General Physiology PDF

GENERAL PHYSIOLOGY Dr. S.O. Elias BSc (Hons), MSc, MBChB, MPH, PhD Figure: A Typical Human Cell  Cells ❑A cell is a structure as well as a functional unit of life ❖Every living thing has cells Some organisms are made up of just one cell are called unicellular e....

GENERAL PHYSIOLOGY Dr. S.O. Elias BSc (Hons), MSc, MBChB, MPH, PhD Figure: A Typical Human Cell  Cells ❑A cell is a structure as well as a functional unit of life ❖Every living thing has cells Some organisms are made up of just one cell are called unicellular e.g. bacteria and protozoans but animals, including human beings, are multi-cellular An adult human body is composed of billions of cells  There are about 200 different kinds of specialized cells in the human body When many identical cells are organized together it is called a tissue e.g muscle tissue, nervous tissue etc Various tissues organized together for a common purpose are called organs e.g. the stomach, skin, brain, uterus  Types of Specialized Cells ❖Nerve Cells: Also called Neurons these cells are in the nervous system and function to process and transmit information They are the core components of the brain, spinal cord and peripheral nerves. They use chemical synapses that can evoke electrical signals, called action potentials, to relay signals throughout the body. ❖Epithelial cells Epithelium lines both the outside (skin) and the inside cavities and lumen of bodies Their functions include ✓Secretion ✓sensation detection ✓ selective permeability ✓Absorption ✓Protection ✓ transcellular transport, ❖Exocrine cells These cells secrete products through ducts, such as mucus, sweat, or digestive enzyme The products of these cells go directly to the target organ through the ducts Example ✓the bile from the gall bladder is carried directly into the duodenum via the bile duct ❖Endocrine cells These cells are similar to exocrine cells, but secrete their products directly into the bloodstream instead of through a duct Endocrine cells are found throughout the body but are concentrated in hormone- secreting glands such as the pituitary gland, adrenal gland etc  The products of the endocrine cells go throughout the body in the blood stream but act on specific organs by receptors on the cells of the target organs For example, the hormone oestrogen acts specifically on the uterus and breasts of females because there are oestrogen receptors in the cells of these target organs ❖Blood Cells The most common types of blood cells are: – red blood cells (erythrocytes): main function is to collect oxygen in the lungs and deliver it through the blood to the body tissues; Gas exchange is carried out by simple diffusion – white blood cells (leukocytes): there are various types of these; they are produced in the bone marrow and help the body to fight infectious disease and foreign objects in the immune system. White cells are found in the circulatory system, lymphatic system, spleen, and other body tissues  CELL MEMBRANE Cells are delineated by unit membranes that separate it from the sorrounding It separates internal metabolic events from the external environment and controls the movement of materials into and out of the cell This membrane is very selective about what it allows to pass through; this characteristic is referred to as "selective permeability."  Cell Membrane contd Cell membrane appears as dark parallel lines under light microscope Cell membrane is a thin, pliable, elastic structure About 7.5 to 10nm in thickness Consists of lipid bi-layers between which are protein molecules  LIPID BI-LAYER ❑This provides the basic structure of the membrane ❑It is a thin film of lipids, only two molecules thick, and continuous over the entire cell surface ❖Lipids make up about 90% to 99% of the molecules in the cell membrane 75% = phopholipids 20% = cholesterol 5% = glycolipids Figure: Molecular structure of a lipid-bilayer Figure: Lipid bi-layer of the plasma membrane  Phospholipids of the lipid bi-layer ❑These are described as amphiphilic because ❖One end of the molecule is hydrophilic - the phosphate head These cover the surfaces of the CMs and are thus in contact with water of ECF and cytoplasm These heads retain water and help cells stick together ❖The other end is hydrophobic - the fatty acid tails The tails repel water but are mutually attracted to each other and thus line up at the centre of the lipid bi-layer ❖Middle of the cell membrane is therefore impermeable to water-soluble substances like ions, glucose and urea but permeable to fat-soluble substances like O2, CO2 and alcohol ❖Movement of the phospholipids keep the membrane in a fluid state so that portions of the membrane can literally flow from one point to the other along the surface of the membrane  Therefore, phospholipid bilayer is selectively permeable Only small, uncharged polar molecules can pass freely across the membrane ✓Some of these molecules are H2O and CO2, hydrophobic (nonpolar) molecules like O2, and lipid soluble molecules such as hydrocarbons Other molecules need the help of a membrane protein to get across  Cholesterol molecules These are located in the middle of the lipid bi- layer, in between the fatty acid tails of the phospholipids Main Function: To determine the degree of permeabiltiy of the membrane to water-soluble constituents of the body fluids Also controls much of the fluidity of the cell membrane  Glycolipids These are phospholipids with short oligosaccharide chains covalently bonded together They are found only on the extracellular face of the membrane  MEMBRANE PROTEINS ❖ These make up 1% to 10% of the cell membrane ❑ INTEGRAL (TRANSMEMBRANE) PROTEINS These are through and through proteins in that they span the entire length of the plasma membrane They have hydrophilic portion which is at the ends in contact with the ECF and ICF They have hydrophobic portion in the middle and these pass back and forth through the lipid membrane They are mostly glycoproteins which are conjugated with oligosaccharides on the extracellular side of the membrane Some are anchored to the cytoskeleton  PERIPHERAL PROTEINS ❖These do not protrude into the phospholipid layer ❖They adhere to the intracellular face of the membrane in different ways: i. Attached to glycosylated forms of phosphatidylinositol ii. They may be lipidated ie they have specific lipids attached to them e.g. Myristolated, palmytoylated ❖They are usually associated with an integral protein ❖They are usually tethered to the cytoskeleton  FUNCTIONS OF MEMBRANE PROTEINS i. RECEPTORS: Some messengers (hormones, neurotransmitters) can not enter the target cell directly to exert their effect and so require receptors on the cell surface These receptors initiate specific cell responses once hormones or other trigger molecules bind to them Figure: Some functions of Membrane Proteins ii. SECOND MESSENGERS: This may be produced by the activity of the first messenger (hormones, neurotransmitters) on the receptor They are usually formed in the cytoplasm and involve both the transmembrane proteins (receptors) and the peripheral proteins  1. A messenger binds to a receptor Second Messenger in the plasma membrane 2. The receptor releases a G protein which then travels feely in the cytoplasm causing various effects in the cell 3. G protein binds to adenylate cyclase in the membrane. This converts ATP to cAMP, the 2nd messenger 4. cAMP activates a kinase in the cytoplasm 5. Kinases add PO4 groups (Pi) to other cytoplasmic enzymes and deactivates others leading to varied metabolic effects in the cell  FUNCTIONS OF MEMBRANE PRROTEINS contd iii. ENZYMES: Found in the plasma membranes of cells involved with the final stages of starch and protein digestion that play a part in producing second messengers that break down hormones and neurotransmitters once the job of the latter is done  FUNCTIONS OF MEMBRANE PRROTEINS contd iv. CHANNEL PROTEINS: These are mainly integral proteins that provide passageways through the membranes for certain hydrophilic or water-soluble substances such as polar and charged molecules. No energy is used during transport, hence this type of movement is called facilitated diffusion.  These channels could be ❖Open channels i.e. Continuously open ❖Gated channels: 1. ligand-gated which respond to specific ligands External ligand e.g. NT, hormones Internal ligand e.g. Intracellular Ca++, cAMP, lipids etc  Channel Proteins contd 2. voltage-gated which respond to changes in electrical potential (voltage) across the plasma membrane e.g. Na+ channel 3. mechanically-gated which respond to physical stress on a cell e.g. stretch and pressure. Important in the movement of the cell  Transport proteins: These are membrane proteins that utilize energy in the form of adenosine triphosphate (ATP) to transfer materials across the membrane When energy is used to provide passageway for materials, the process is called active transport  FUNCTIONS OF MEMBRANE PRROTEINS contd v. CARRIERS: These are integral proteins that bind to glucose, electrolytes and other solutes and transfer these to the other side of the membrane down electochemical gradients Pumps: these are carriers that consume ATP in the process of their action, transport against the electrochemical gradient vi. MOTOR MOLECULES: These are proteins that produce movement by changing shape and pulling on other molecules e.g. they enable white blood cells to crawl around in the body’s tissues  FUNCTIONS OF MEMBRANE PRROTEINS contd vii. CELL IDENTITY MARKERS: The glycoproteins present within the glycocalyx act like “identification tags” that alllows the body to distinguish “self” from “non-self” viii. CELL-ADHESION MOLECULES: These are membrane proteins that allow cells to adhere to one another or to basal lamina and to extracellular material They attach cells to neighbouring cells They provide anchors for the internal filaments and tubules that give stability to the cell  GLYCOCALYX This is the loose carbohydrate coat on the entire outside surface of the cell It is rich in neutral and amino sugars It is made up of the carbohydrate moieties of the membrane glycolipids and glycoproteins which serve as backbone molecules for support Glycocalyx is unique to each person though identical in identical twins The CHO portion of the glycocalyx usually retains a layer of water at the cell surface which enables the cell to absorb water and dissolved solutes from the ECF Figure: Glycocalyx  Generally, the CHO portion of the glycolipids found on the surface of plasma membranes helps these molecules contribute to cell-cell recognition, communication, and intercellular adhesion Glycocalyx is a Sugar Coating  FUNCTIONS OF THE GLYCOCALYX i. Identification Tag ii. Basis of Transplant Compatibility or Rejection of tissue grafts, organ transplants, blood trasfusion iii. Recognition of cancer cells iv. Cell adhesion v. Fertiization: enables sperm cells to recognise and bind egg cells vi. Receptor substances for binding hormones vii. Guides cell migration during development viii. Confers overall negative charge on cell surface  CELL ORGANELLES MEMBRANOUS ORGANELLES NON-MEMBRANOUS ORGANELLES Nucleus Ribosome Mitochondria Centriole Endoplasmic Reticulum Centrosome Golgi Complex Basal bodies Lysosomes Peroxisomes  NUCLEUS Largest organelle in the cell Enclosed within two unit membranes referred to as nuclear envelope permeable to only ions and small molecules Space between these membranes = perinuclear cistern Most cells have one nucleus Average diametre = 5µm Nuclear pore complexes = about 30nm to 100nm in diametre which: i. allow transport of proteins and mRNA ii. hold the unit membrane together at regular intervals  Nucleosome ❑Nucleosome is a core of histone proteins around which the DNA strand is wrapped The nucleus is made up of chromosomes mainly Each chromosome consists of a giant DNA molecule The DNA strand, about 2m long, fits in the nucleus because it is wrapped around a histone proteins at intervals ❖There are about 25 million nucleosomes in each nucleus  Nucleolus Accumulation of granules rich in RNA Has no membrane There is at least one nucleolus in each mucleus of most cells Becomes enlarged and numeorus when the cell is actively synthesizing proteins FUNCTION Site of ribosome production  FUNCTIONS OF THE NUCLEUS i. Replication of DNA ii. Synthesis of ribosomes and RNA iii. The genes in the nucleus determine the characteristics of the cell proteins and structural proteins and the enzymes of the cytoplasm that control cytoplasmic activities iv. Genes control reproduction by undergoing meiosis followed by mitosis  Mitochondrion Powerhouse of the cell Spheroid or thread-like in shape Size: a few hundred nm to 1µm in diametre & 7µm long Inner membrane is folded into shelves – cristae Intracristal space – space between the two membranes Matrix - space inside the inner memrane Matrix contains mitochondrial DNA, ribosomes & multi-enzyme assembly Figure: Structure of a Mitochondrion  Mitochondria contd ❖Outer membrane has enzymes cocerned with oxidation Provides raw material for reactions inside the mitochondrion ❖Internal mitochondrial membrane houses enzymes involved with conversion of products of CHO, Proteins and lipid metabolism to CO2 and H 2O i. NADH dehydrogenase ii. Succinic dehydrogenase iii. Cytochrome C iv. Cytochrome oxidase  Mitochondria contd These enzymes operate in association with the oxidative enzymes to cause oxdation of the nutrients to form CO2 and H2O Protons (H+) are pumped from the matrix to the intracristal space leading to a proton gradient The protons tend to diffuse back into the matrix along this gradient leading to the formation of ATP by ATP synthase ATP is a high-energy compound that drives many metabolic processes ENDOPLASMIC RETICULUM Little network of cytoplasm or system of (ER) branching channels/tubules Continouos with the outer nuclear membrane Rough ER i. Site of protein synthesis ii. Initial folding of polypeptide chains with the formation of disulfide bonds iii. Membrane factory Smooth ER i. Free of ribosomes ii. Liver: Converts alcohol, drugs to less toxic water-soluble forms iii. Steroid secretion in steroid-secreting cells iv. Sarcoplasmic reticulum in muscle: Act as storage reservoir for Ca2+ in Skeletal Muscle v. Synthesis of lipids: TGAs, cholesterol  Ribosome Complex structures containing many different proteins and 3 rRNAs Measure about 22nm by 32nm in eukaryotes Has two subunits: 60S and 40S FUNCTION Site of protein synthesis: On rER, they produce all transmembrane proteins, most secreted proteins, most proteins stored in Golgi apparatus, lysosomes and endosomes Free ribosomes: synthesize cytoplasmic proteins e.g. haemoglobin and proteins found in peroxisomes and mitochondria GOLGI COMPLEX Membranous organelle found in the cell in close relation to the ER Collection of membrane-enclosed sacs, about 6 sacs in each pparatus It is a polarized structure with cis and trans sides Resemble a stack of pancakes or dinner plates Usually located close to the nucleus FUNCTIONS: i. Formation of Golgi vesicles – Lysosomes and secretory vesicles ii. CHO factory iii. Synthesis of some hormones and lipids iv. Involved in the concentration of Figure: Golgi Complex protein  LYSOSOME Package of over 50 enzymes contained in a single unit membrane Formed by breaking off from the Golgi apparatus and then dispersing into the cytoplasm The interior is more acidic than the rest of the cytoplasm Called the “suicide bag” of the cell as the enzymes are hydrolases which are capable of killing the cell Contained in a single unit membrane Variable shape, round or oval, usually 250nm to 750nm in diametre  Table: Some enzymes and Substrates in Lysosomes Enzyme Substrate 1. Ribonuclease 1. RNA 2. Deoxyribonuclease 2. DNA 3. Phosphatase 3. Phosphate esters 4. Glycosidases 4. Complex CHOs, glycosides, polysaccharides 5. Arylsulfatases 5. Sulfate esters 6. Collagenase 6. Proteins 7. Cathepsins 7. Proteins NOTE: Congenital absence of any enzyme leads to Lysosome Storage Disease in which there is accumulation of that substrate  LYSOSOME contd FUNCTION i. Autophagy ii. Glycogenolysis iii. Immune System iv. Digestion of surplus cells v. Digestion of food particles that had been ingested by the cell  PEROXISOMES Similar to lysosomes although they are formed by budding off from sER About 0.5mm in size Matrix of the peroxisome contains >40 enzymes The enzymes are different (oxidases) from those in lysosomes and thus perform different functions Abundant in the liver and kidney cells FUNCTIONS i. Detoxification of alcohol and drugs ii. Formation of hydrogen peroxide iii. Neutralization of free radicals  CENTRIOLE Short cylindrical assembly of microtubules arranged in nine groups of 3 microtubules each Two centrioles lie perpendicular to each other within the centrosome CENTROSOME = clear area of cytoplasm FUNCTION Centrioles play a role in cell division Figure: Centriole  BASAL BODY Consists of a single centriole oriented perpendicular to the plasma membrane This is the content of cilia and flagella  CYTOSKELETON This is a collection of protein filaments and cylinders: microfilament, intermediate filaments, microtubules FUNCTIONS i. Lend structural support to the cell ii. Help to organize the cell content iii. Move substances through a defined course through the cell iv. Contribute to the movement of the entire cell Figure: Cytoskeleton  Bibliography https://en.wikipedia.org/wiki/Glycocalyx