General Physiology PDF

Dr. ayman aldegwaly 1 ‫شيت رقم‬ General Physiology  Physiology  is study of functions of various systems and different organs of the body.  Physiology (from the Greek physis = nature / logos = study).  Note : physiology is the basis of Medicine  every year Nobel Pri...

Dr. ayman aldegwaly 1 ‫شيت رقم‬ General Physiology  Physiology  is study of functions of various systems and different organs of the body.  Physiology (from the Greek physis = nature / logos = study).  Note : physiology is the basis of Medicine  every year Nobel Prize is given under the field of physiology / Medicine. Homeostasis  Definition : is the maintenance of a nearly constant internal environment within a narrow range of variables.  Homeostasis (homeo = the same / stasis = standing)  Examples : 1. Regualtion of temperature 2. Regulation of body fluids volume 3. Regualtion of blood sugar / blood pressure.  Mechanisms of Homeostasis : two general categories of regulatory mechanisms: (1) Intrinsic mechanism (“built (2) Extrinsic mechanism into )  By the organ itself  by the nervous system  Example :  by endocrine systems. 1. NO  produced by the BVs wall  producing VD 2. Endothein  produced by BVs wall  produced VC > ‫الصفحة‬1 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Components of homeostatic control system 1- Sensors   receptor that can detect changes then  send information to an integrating center. - 2- integrating center :  is specific region that detect changes from a set point.  It is may be :  particular region of the brain  spinal cord  group of cells in an endocrine gland. 3- Effector :  Is specific part of body that cause response to correct the deviations from the set point.  It is may be :  muscles  glands =. ‫الصفحة‬2  Dr. ayman aldegwaly 1 ‫شيت رقم‬ Mechanism of action of homeostatic system  This is achieved by means of feedback signals: a) Negative feedback control b) Positive feedback control Negative feedback control  Definition : is the mechanism that arrest or reverse the direction of change.  examples 1) Secretion of thyroxine hormone 2) Regulation of blood glucose level 3) Regulation of body temperature 4) Maintenance of water balance in the body 5) Regulation of O2 / CO2 Secretion of thyroxine hormone :...  TSH...  is released by pituitary gland  TSH  stimulates thyroid gland to secrete thyroxine  If thyroxine level increases in blood  it inhibits pitutary gland  inhibit the secretion of TSH  if thyroxine level is decreased in blood  it induces pituitary gland to release TSH  stimulates thyroid gland to secrete thyroxine. =x ‫الصفحة‬3 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Regulation of blood glucose level After eating During fasting  blood glucose level is  blood glucose level is increased  chemoreceptors decreased  chemoreceptors detect this change  then sends detect this change  then sends signals into hypothalamus  that signals into hypothalamus  will give order to beta -cells of that will give order to alpha - pancreas  that secrets insulin cells of pancreas  that hormone  increase uptake of secrets glucagon hormone  glucose to liver cells  which increase release of glucose from results that blood glucose level is liver cells  which results that decreased to normal set point blood glucose level is increased to normal set point > ‫الصفحة‬4 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Positive feedback control  Definition : is the mechanism that increase the intensity of the change in the same direction.  Examples :  Blood clotting  childbirth ( parturition) ( labour )  by oxytocin hormone  Milk lactation  by oxytocin hormone  WBCs chemotaxis during immunity  During ovulation  estrogen & LH surge. =@° ‫الصفحة‬5 Some important examples about negative feedback mechanism : 1. Regulation of O2 , CO2 Concentrations in the ECF  Stimulus : ↑ CO2 ( hypercapnia ) , ↓ O2 ( hypoxia )  Receptors : (+) chemorceptors in ( aortic arch , carotid body  afferent nerves : send signals through afferent 9 , 10 CN  Center : (+) RC in medulla oblongata  Efferent nerves : phrenic nerve (+) diaphragm  Response : ↑ respiration  wash out CO2 out of ECF , intake of O 2  ↑ O2 level , ↓ CO2 level to normal  2. Regulation of Arterial Blood Pressure ( simple and rapid )  Stimulus : ↑ BP ( hypertension )  Receptors : (+) baroreceptor in ( aortic arch , carotid body )  afferent nerves : send signals through afferent 9 , 10 CN  Center : (-) VMC in medulla oblongata  Efferent nerves : ↑ parasympathetic , ↓ sympathetic nerve  Response : VD  ↓ BP to normal  Stimulus : ↓ BP ( hypotension )  Receptors : (+) baroreceptor in ( aortic arch , carotid body )  afferent nerves : send signals through afferent 9 , 10 CN  Center : (+) VMC in medulla oblongata  Efferent nerves : ↑ sympathetic, ↓ parasympathetic nerve  Response : VC  ↑ BP to normal Dr. ayman aldegwaly 1 ‫شيت رقم‬ Body fluids  Total body water (TBW) : is approximately  85% in infant / newborn  80% in children  60% in adult male  50% in adult female  45% in old age  Factors affecting TBW : 1) Age 2) Gender 3) degree of obesity.  Note :  Muscles contain high water contents  Adipose tissue contain low water contents  Males have high muscles than females  Females have high adipose tissue than males  Old age have more adipose tissue than muscles  Athelets have high muscles ( & have high TBW )  TBW  in males = 60% of weight ( 42L in 70 kg man )  TBW  in female = 50% of weight ( 30 L in 60 kg woman ) ‫الصفحة‬6 -> Dr. ayman aldegwaly 1 ‫شيت رقم‬ Compartments of TBW : Extracellular fluid (ECF) :  20% of weight ( 1/3 of TBW )  14 L in 70 kg man  one-third of TBW.  composed of : a) interstitial fluid (ISF )  15 % / 10.5 L in 70kg man b) plasma  5 % / 3.5 L in 70kg man  The major cation of ECF is Na+  The major anions of ECF are Cl- and HCO3-  Note : Plasma = one-fourth of the ECF / one-twelfth of TBW Intracellular fluid (ICF) :  40% of weight ( 2/3 of TBW )  28 L in 70 kg man  The major cations of ICF = K+ and Mg2+  The major anions of ICF = protein and organic phosphates ATP/ ADP /AMP NOTES :  80% of ECF = interstitial fluid (10.5 L)  20 % of ECF = blood plasma (3.5 L)  ISF is similar in composition to plasma, except that interstitial fluid has almost no protein. Thus, interstitial fluid is an ultrafiltrate of plasma. > ‫الصفحة‬7  Dr. ayman aldegwaly 1 ‫شيت رقم‬  ECF is high in NaCl and low in K  ICF is high in K+ and low in NaCl.  Osmolarity is the same in all compartments. Transcellular fluid :  It is fluid in cavities  Like : synovial cavity / peritoneal cavity / pericardial cavity / intraocular cavity / cerebrospinal fluid  it is specialized type of extracellular fluid.  about 1 to 2 liters.. ‫الصفحة‬8  Dr. ayman aldegwaly 1 ‫شيت رقم‬ =-> ‫الصفحة‬9 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Measuring the volumes of the fluid compartments Characteristics of Marker Substances a. nontoxic b. Must mix with the fluid compartment thoroughly within reasonable time. c. excreted completely after reasonable time / slowly d. not alter the volume of the body fluid. e. not change the color of the body fluid. Dilution or Indicator dilution method Steps : 1- A known amount of a substance is given whose volume of distribution is the body fluid compartment of interest. 2- The substance is allowed to equilibrate. 3- The concentration of the substance is measured in plasma, and the volume of distribution is calculated as follows: where:  Volume = volume of distribution, or volume of the body fluid compartment (L)  Amount = amount of substance present (mg)  Concentration = concentration in plasma (mg/L) > ‫الصفحة‬10 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Body fluid Fraction Markers used Major Major compartment of TBW to measure cations anions volume TBW 1.0  Tritiated H2O  radioactive water  deuterium oxide ECF 1/3 Mannitol, Na+ Cl- & HCO3- inulin sucrose Plasma 1/12 Evans blue Na+ Cl- & HCO3- (1/4 of Plasma ECF) proteins Interstitial ¼ (3/4 ECF-plasma Na+ Cl- & HCO3- Fluid ( ISF ) of ECF) volume (indirect) ICF 2/3 TBW-ECF K+ Organic (indirect) phosphates & proteins > ‫الصفحة‬12  Dr. ayman aldegwaly 1 ‫شيت رقم‬ Osmosis Definition : is the flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration. There are two requirements for osmosis: (1) There must be a difference in the concentration of a solute on the two sides of a selectively permeable membrane. (2) The membrane must be relatively impermeable to the solute. Types of Solutes : 1. osmotically active = that cannot freely pass through the membrane can promote the osmotic movement of water 2. osmotically inactive = that free pass through the membrane , so : can not promote osmotic movement of water Types of Osmosis a. Endosmosis b. Exosmosis -=> ‫الصفحة‬13 Dr. ayman aldegwaly 1 ‫شيت رقم‬ Osmolarity Osmolality is concentration of osmoles per is concentration of osmoles per liter of water. kilogram of water.  Osmole(osm): the total number of particles in a solution.  Milliosmoles (mOsm)= 1/1000 osmole and is commonly used. Note: Osmolarity is dependent on the number of particles in solution but independent of the nature of the particles. Example : If in 1 liter of water  add :  1 mole glucose dissolved  osmolarity = 1 osm /L  1 mole glucose + 1 mole sucrose dissolved  osmolarity = 2 osm/L  1 mole NaCl were dissolved  osmolarity 2 osm/L  1 mole Na2SO4 dissolved  osmolarity = 3osm/L > -> ‫الصفحة‬14  Dr. ayman aldegwaly 1 ‫شيت رقم‬  Normal Plasma osmolarity = 290-300 mOsm/l.  solution has an osmolarity of 300 mOsm/l = iso-osmotic  Solution has an osmolarity of ˂300 mOsm/l = hypo- osmotic  Solution has osmolarity of ˃300 mOsm/l= hyper- osmotic.  Pure water (distilled) has no osmoles  osmolarity = zero (hypo- osmotic )  ECF ( Plasma ) osmolarity is determined by Na+ concentration  ICF osmolarity is determined by K+ concentration ????????????? Osmotic pressure = ‫الصفحة‬15  Dr. ayman aldegwaly 1 ‫شيت رقم‬ Calculating osmotic pressure (van’t Hoff’s law)  π = osmotic pressure (mm Hg)  g = number of particles in solution (osm/mol)  C = concentration (mol/L)  R = gas constant (0.082 L—atm/mol—K)  T = absolute temperature (K) Tonicity  This term is used to describe the effect of a solution on the osmotic movement of water, thus it affects the cell volume.  It is determined by osmolarity of the solution and by the permeability properties of the cell membrane.  In terms of tonicity the solutions are classified into three categories: Isotonic solution  Fluid which has the same effective osmolality (tonicity) as blood fluids is called isotonic fluid (300mOsm/l). Examples : 1. 0.9% NaCl solution (normal saline) 2. 5% glucose solution. ( dextrose saline )  When red blood cells or other cells are placed in isotonic fluid, neither gain nor lose water by osmosis. - ‫الصفحة‬16  Dr. ayman aldegwaly 1 ‫شيت رقم‬ Hypertonic solution  fluid has high osmolality than the body fluid. ( ˃ 300 mosm / L ) Example : 1. ˃ 0.9% Nacl solution ( normal saline ) 2. ˃ 5 % glucose solution ( dextrose saline )  When red blood cells or other cells are placed in hypertonic fluid  water moves out of the cells resulting in shrinkage (crenation). Hypotonic solution  Fluid has less osmolality than the body fluids ( ˂ 300 mosm /L ) Example : 1. ˂ 0.9% Nacl solution ( normal saline ) 2. ˂ 5 % glucose solution ( dextrose saline )  When red blood cells or other cells are placed in hypotonic fluid,  water moves into the cell and causes swelling of the cells. Eventually, red blood cell become globular (spherocytic) and get ruptured (hemolysis). > ‫الصفحة‬17  Dr. ayman aldegwaly General physiology part 2 Transport of molecules Classification(types) of membrane transport a) -According to presence of a carrier: 1. Carrier-mediated transport a) Facilitated diffusion b) Active transport 2. Non-carrier-mediated transport a) Simple diffusion of lipid-soluble molecules through the phospholipid layers of the plasma membrane b) Simple diffusion of ions through membrane channel proteins in the plasma membrane c) Osmosis: through aquaporin (water) channels in the plasma membrane b) - According to energy requirement: 1) Passive transport 2) Active transport Passive transport Simple ( lipid ) diffusion : Simple ( aqeous ) diffusion : Lipophilic molecules  cross Hydrophilic molecules  cross through hydrophobic lipid bilayer through protein layer Examples : O2 /CO2/steroids Examples : electrolytes ->> ‫الصفحة‬1  Dr. ayman aldegwaly General physiology part 2 Types of protein channels or ion channels 1. Ungated ( leaky) channels  continuously opened. 2. Gated channels   opened only when required  Types : Voltage - gated channels Ligand - gated channels Open when there is a change Open when there is chemical in the electrical potential. substance binds to receptor ( hormone / neurotransmitter) Example : Example : in the neuromuscular junction in the neuromuscular junction when action potential reaches when acetylcholine (Ach) is axon terminal, the calcium released from the vesicles and channels are opened, and moves through the presynaptic calcium ions diffuse into the membrane and reaches the interior of the axon terminal synaptic cleft. Then, the Ach from ECF. molecules cause opening of sodium channels in the postsynaptic membrane and sodium ions diffuse into the neuromuscular junction from ECF. -> ‫الصفحة‬2 Dr. ayman aldegwaly General physiology part 2 Facilitated diffusion  Characters : a. It occurs down an electrochemical gradient (“downhill”), similar to simple diffusion. b. it is passive = no energy c. Is more rapid than simple diffusion. d. Types of facilitated diffusion: 1. Channel mediated facilitated diffusion  ions 2. Carrier mediated facilitated diffusion  glucose / amino acids transport  notes :  Glucose or amino acid molecules cannot diffuse through the channels because the diameter of these molecules is larger than the diameter of the channels.  Glucose transport in muscle and adipose cells is “downhill,” is carrier-mediated, and is inhibited by sugars such as galactose  In diabetes mellitus, glucose uptake by muscle and adipose cells is impaired because the carriers for facilitated diffusion of glucose require insulin. The characters of carriers :  Specificity: D-glucose (the natural isomer) is transported by facilitated diffusion, but the L-isomer is not. Simple diffusion, in contrast, would not distinguish between the two isomers because it does not involve a carrier.  Saturation: The transport rate increases as the concentration of the solute increases, until the carriers are saturated.  Competition: Structurally related solutes compete for transport sites on carrier molecules. For example, galactose is a competitive inhibitor of glucose transport in the small intestine ‫الصفحة‬3 => Dr. ayman aldegwaly General physiology part 2 Factors affecting rate of diffusion: o Permeability of the cell membrane o Temperature o Concentration gradient or electrical gradient of the substance across the cell membrane o Solubility of the substance Diffusion is directly proportional to the previous factors. o Size of the molecules o Thickness of the cell membrane o Size of the ions o Charge of the ions Diffusion is inversely proportional to the previous factors. Active transport Charcters :  movement of substances against the chemical or electrical or electrochemical gradient.  uphill transport.  requires energy ( ATP mainly ). Types of active transport o Primary active transport o Secondary active transport > ‫الصفحة‬4 Dr. ayman aldegwaly General physiology part 2 Primary active transport Characters : o against an electrochemical gradient (“uphill”). o Requires direct input of ATP o Is carrier mediated o exhibits specificity, saturation, and competition. o Examples :  Na+/ k+ pump (ATPase )  Ca++ pump ( ATPase )  H+ / K+ pump ( ATPase ) a. Na+, K+-ATPase (or Na+–K+ pump)  in cell membranes of all cells  transports 3 Na+ from intracellular to extracellular fluid  transport 2 K+ from extracellular to intracellular fluid  it maintains low intracellular [Na+] and high intracellular [K+].  against their electrochemical gradients.  Energy is provided from the terminal phosphate bond of ATP.  The usual stoichiometry is 3 Na+/2 K+. b. Ca2+ -ATPase (or Ca2+pump)  in the sarcoplasmic reticulum (SR) or cell membranes ( mainly muscles )  transports Ca2+ against an electrochemical gradient. c. H+, K+-ATPase (or proton pump)  in gastric parietal cells  transports H+ into the lumen of the stomach against its electrochemical gradient. -> ‫الصفحة‬5  Dr. ayman aldegwaly General physiology part 2 Secondary active transport Characters  The transport of two or more solutes is coupled.  One of the solutes (usually Na+) is transported “downhill” and provides energy for the “uphill” transport of the other solute(s).  Metabolic energy is not provided directly but indirectly from the Na+ gradient that is maintained across cell membranes.  Thus, inhibition of Na+, K+-ATPase will decrease transport of Na+ out of the cell, decrease the transmembrane Na+ gradient, and eventually inhibit secondary active transport.  Types : cotransport or symport counter-transport or antiport or exchanger If the solutes move in the If the other molecule or ion is same direction moved in the opposite direction Examples : Examples :  SGT 1 / 2  Na+ / Ca2+ exchanger  SAAT 1 /2/3/4/5  Na+ / H+ exchanger  Na+/ Mg+ exchanger  Na+/ K+ exchanger  Cl- / HCO3 exchanger  Ca- Mg exchanger = ‫الصفحة‬6  Dr. ayman aldegwaly General physiology part 2 Na+–glucose cotransport ( SGT ) Site :  luminal membrane of intestinal mucosal (SGT1  for absorption of glucose )  renal proximal tubule cells (SGT2  for reabsorption of glucose ) Mechanism :  Glucose is transported “uphill”; Na+ is transported “downhill.”  Energy is derived from the “downhill” movement of Na+. Na+/ Ca2+counter transport or exchange.  Site : Many cell membranes  Mechanism :  transports Ca2+ “uphill” from low intracellular [Ca2+] to high extracellular [Ca2+].  Ca2+and Na+ move in opposite directions across the cell membrane.  The energy is derived from the “downhill” movement of Na+.  As with cotransport, the inwardly directed Na+ gradient is maintained by the Na+–K+ pump. Note :  Uniport: if one specific ion or molecule moves across CM  Symport: If the solutes move in the same direction across CM  Antiport: if two ions or molecules move in opposite directions.. ‫الصفحة‬7  Dr. ayman aldegwaly General physiology part 2 Transport of large molecules (Vesicular transport) includes :  endocytosis  exocytosis. Endocytosis:  it means a transport of macromolecules into the cell.  It is a special active process.  three types: 1) Phagocytosis 2) Pinocytosis 3) Receptor – mediated pinocytosis Phagocytosis:  it means cell-eating or ingestion of solid particles, such as bacteria, cell debris, or foreign substances  significance : elimination of harmful substances from the body by few cells like monocytes, neutrophils, and tissue macrophages  Mechanism of phagocytosis: 1) a part of the plasma membrane extends around a particle & fuses so that the particle is surrounded by the membrane (pseudopodium). 2) That part of the membrane then pinches off to form a phagocytic vesicle containing the particle which is called phagosome. 3) Phagosome travels into interior of the cell. 4) Primary lysosome fuses with this phagosome and forms secondary lysosome. 5) Hydrolytic enzymes present in secondary lysosome are activated resulting in digestion degradation of phagosomal contents. ⑤ ‫الصفحة‬8 Dr. ayman aldegwaly General physiology part 2 Pinocytosis:  it means cell-drinking or uptake of small droplets of extracellular fluid, and the materials contained in the fluid, by the formation of small endocytic vesicles.  Pinocytosis often forms vesicles near the tips of deep invaginations of the plasma membrane.  Endosome travels into interior of the cell.  Primary lysosome fuses with this endosome and forms secondary lysosome.  Hydrolytic enzymes present in secondary lysosome are activated resulting in digestion and degradation of endosomal contents. Site : kidneys, intestines, liver, and cells that line capillaries. Phagocytosis and pinocytosis can exhibit specificity. Cells that phagocytize bacteria do not phagocytize healthy cells. Receptor – mediated pinocytosis:  It is the transport of macromolecules with the help of a receptor protein.  Mechanism of receptor-mediated pinocytosis: 1) Ligand molecules approach the cell and bind to receptors in the coated pits and form ligand receptor complex. 2) Ligand receptor complex gets aggregated in the coated pits. Then, the pit is detached from cell membrane and becomes the coated vesicle. This coated vesicle forms the endosome. 3) Endosome travels into interior of the cell. =@ ‫الصفحة‬9  Dr. ayman aldegwaly General physiology part 2 4) Primary lysosome fuses with this endosome and forms secondary lysosome. 5) Hydrolytic enzymes present in secondary lysosome are activated resulting in digestion and degradation of endosomal contents. 6) Receptor may move to a new pit of the cell membrane. Examples : uptake of cholesterol and hormones, toxins and bacteria, antibodies, viruses are taken up by the cells. Exocytosis:  is the movement of materials out of cells by vesicles.  Secretory vesicles accumulate materials for release from cells.  The secretory vesicles move to the plasma membrane, where the vesicle membrane fuses with the plasma membrane, and the material in the vesicle is eliminated from the cell.  Examples : secretion of digestive enzymes by the pancreas, of mucus by the salivary glands, and of milk from the mammary glands. =. ‫الصفحة‬10 Cell Communication 1. Inter cellular communications a) Gap junctions  These are channels (pores )  allow for exchanging chemical and electrical information  Aim : coordination of cardiac excitation and contraction b) Chemical messangers ( ligands ): 1. Neurotransmitters : chemical messangers produced by neuron & act on another neuron / muscles e.g : Ach , NA 2. Endocrine hormone : chemicals produced by endocrine glands and some non endocrine tissues  secreted into blood  act on distant targets e.g : Insulin 3. Paracrines : chemicals released from cells into ISF & act on in very close proximity target. e.g : NO ( EDRF ) 4. Autocrines: chemicals released from cell & act on the same cell that released it  important in negative feedback pathway 2. Intra cellular communication  By binding the ligand to its receptor :  Types of receptors 1. Ligand gated ion channel 2. G-protein -coupled receptor 3. Enzyme linked receptor ( catalytic ) 4. Intracellular receptor ( genetic receptor ) A Ligand-gated ion channels :  Aim : facilitate communication between neurons and target cells, example, the nicotinic receptor on NMJ ( skeletal muscle )  Mechanism : Ach binds to Nicotinic receptors  conformational change  opens the Na+ channel  depolarization  sk.ms. contraction /3 G protein-coupled receptors  commonest type  found in both neural and non-neural tissues  activates one or more second messenger pathways.  Second messengers include : 1. cyclic 3- _5 adenosine monophosphate (cAMP), 2. cyclic3_5_-guanosine monophosphate (cGMP) 3. inositol trisphosphate (IP3) 4. di acyl glycerol ( DAG ) 5. ca++ -calmodulin 1) CAMP signaling pathway: 1. hormone binds to receptor on CM 2. Hormone-receptor interaction  (+) G-proteins to stimulate the activity of adenylate cyclase on the cytoplasmic side of the membrane 3. Activated adenylate cyclase catalyzes the conversion of ATP to cyclic AMP (CAMP) within the cytoplasm. 4. Cyclic AMP activates protein kinase 5. Activated protein kinase  (phosphorylates) other enzymes in the cytoplasm 6. The activity of specific enzymes is either increased or inhibited  7. Altered enzyme activity mediates the target cell's response to the hormone Hormones that works through activation of cAMP: 1. Adrenocorticotropic hormone (ACTH) 2. Angiotensin II 3. Calcitonin 4. Catecholamines (B 1,2,3 receptors) 5. Corticotropin-releasing hormone (CRH) 6. Follicle-stimulating hormone (FSH) IP3 signaling pathway: 1. hormone binds to receptor on CM 2. Hormone-receptor interaction  (+) G-proteins to stimulate the activity of phospholipase. C  liberates IP3, DAG, and Ca? 3. Inositol triphosphate enters the cytoplasm and diffuses to the endoplasmic reticulum, where it binds to its receptor proteins and causes the opening of Ca2+ channels  ca++ release from SER into cytoplasm 4. Ca2+ that enters the cytoplasm binds to and activates a protein called calmodulin. 5. Activated calmodulin  activates protein kinase C , which phosphorylates other enzyme proteins 6. Altered enzyme activity mediates the target cell's response to the hormone  Hormones that work through this pathway: 1. Angiotensin II (vascular smooth muscle) 2. Catecholamines (a receptors) 3. Gonadotropin-releasing hormone (GnRH) 4. Growth hormone-releasing hormone (GHRH) 2C. Catalytic receptors  ligands bind to membrane receptors that either associate with an enzyme mainly  For example : 1. natriuretic peptides  (+) guanylyl cyclase and cGMP formation 2. Insulin  (+) tyrosine kinases DD. Intracellular receptors Lignad should be lipid insoluble  binds to receptor in cytoplasm or nucleus  (+) genetic expression Example : 1. Estrogen 2. Testosterone 3. Vitamin D 4. Cortisol  Dr. ayman aldegwaly General physiology part 2 Cell Physiology  A single cell is the smallest unit that  Cell is defined as the structural and functional unit of the living body.  Each type of cells is specially adapted to perform one or a few particular functions.  examples : the red blood cells, numbering about 25 trillion in each human being, transport oxygen from the lungs to the tissues. The entire body, then, contains about 100 trillion cells. Cell Organization and Functions  Each cell is a highly organized unit.  A cell is composed of: 1. plasma membrane, or cell membrane forms the outer boundary of the cell, through which the cell interacts with its external environment. 2. Organelles (little organs) Within cells 3. Cytoplasm (cell + plasma, a thing formed), located between the nucleus and plasma membrane, contains many organelles. The main functions of the cell are: 1. Cell metabolism and energy use. 2. Synthesis of molecules. 3. Communication 4. Reproduction and inheritance > => ‫الصفحة‬17 Dr. ayman aldegwaly General physiology part 2 Protoplasm is composed mainly of five basic substances: a. Water b. Electrolytes c. Proteins d. lipids e. Carbohydrates A cell can be divided into three principal parts: 1. Plasma (cell) membrane  It is a protective sheath, enveloping the cell body.  It separates the fluid outside the cell called extracellular fluid (ECF) and the fluid inside the cell called intracellular fluid (ICF).  is a semipermeable membrane. So, there is free exchange of certain substances between ECF and ICF.  Thickness of the cell membrane varies from 7.5- 10 nanometer.  It is selectively permeable membrane surrounds the cell, gives it form, and separates the cell’s internal structures from the extracellular environment. Composition of cell membrane Cell membrane is composed of three types of substances: a. Proteins (55%) b. Lipids (40%) c. Carbohydrates (5%) ⑤?. ‫الصفحة‬18 Dr. ayman aldegwaly General physiology part 2 Membrane proteins  Most of proteins are present in form of glycoproteins. There are two types: a. Integral proteins, extending into the membrane. b. Peripheral proteins that are attached to the inside or outside of the membrane. Functions of membrane proteins 1. Integral proteins provide the structural integrity of the cell membrane. 2. Channel proteins help in the diffusion of water- soluble substances like glucose and electrolytes. 3. Carrier or transport proteins 4. Pump 5. Receptor proteins serve as the receptor sites for hormones and neurotransmitters 6. Enzymes 7. Antigens 8. Cell adhesion Membrane lipids  The central lipid layer is a bilayer structure.  The characteristic feature of lipid layer is that it is fluid in nature and not a solid structure.  So, the portions of the membrane move from one point to another point along the surface of the cell.  The materials dissolved in lipid layer also move to all areas of the cell membrane.  Lipids are of two types: 1. Phospholipids 2. Cholesterol. => ‫الصفحة‬19  Dr. ayman aldegwaly General physiology part 2  Phospholipid molecules are arranged in two layers. Each phospholipid molecule resembles the headed pin in shape. The outer part of the phospholipid molecule is called the head portion and the inner portion is called the tail portion.  Head portion is the polar end, and it is soluble in water (hydrophilic). Tail portion is the non-polar end. It is insoluble in water and repelled by water (hydrophobic).  Two layers of phospholipids are arranged in such a way that the hydrophobic tail portions meet in the center of the membrane. Hydrophilic head portions of outer layer face the ECF and those of the inner layer face ICF (cytoplasm).  Cholesterol molecules are arranged in between the phospholipid molecules. It is responsible for the structural integrity of lipid layer of the cell membrane. It represents 20% to 25% of the total lipid content of the membrane Functions of lipid layer in cell membrane  Lipid layer of the cell membrane is a semipermeable membrane. It allows only fat-soluble substances to pass through it.  Thus, the fat-soluble substances like oxygen, carbon dioxide and alcohol can pass through this lipid layer.  The water-soluble substances such as glucose, urea and electrolytes cannot pass through this layer. => ‫الصفحة‬20 Dr. ayman aldegwaly General physiology part 2 Membrane carbohydrates  Carbohydrates attached to the outer surface of the membrane as glycoproteins and glycolipids.  Functions of carbohydrates in cell membrane a. Certain glycolipids on the plasma membrane of red blood cells serve as antigens that determine the blood type. b. Carbohydrate molecules are negatively charged and do not permit the negatively charged substances to move in and out of the cell. c. Carbohydrate molecules form glycocalyx (thin and loose cover the cell membrane). It helps in tight fixation of cells with one another. d. Some carbohydrate molecules act like receptors for some hormones. Cytoplasm  The cytoplasm is the aqueous content of a cell inside the plasma membrane but outside the nucleus.  It is a jelly – like material formed by 80 % of water.  Organelles (excluding the nucleus) are subcellular structures within the cytoplasm that perform specific functions.  The term cytosol is a fluid portion of the cytoplasm—that is, the part that cannot be removed by centrifugation. - ‫الصفحة‬21 Dr. ayman aldegwaly General physiology part 2 Nucleus  Nucleus is the most prominent and the largest cellular organelle.  It has a diameter of 10 μ to 22 μ and occupies about 10% of total volume of the cell.  Nucleus is present in all the cells in the body except the red blood cells.  The cells with nucleus are called eukaryotes and those without nucleus are known as prokaryotes.  Presence of nucleus is necessary for cell division.  Most of the cells have only one nucleus (uninucleated cells).  Few types of cells like skeletal muscle cells have many nuclei (multinucleated cells).  Generally, nucleus is located in the center of the cell.  It is mostly spherical in shape. However, the shape and situation of nucleus vary in some cells.  It contains the DNA, or genetic material, of the cell and thus directs the cell’s activities.  The nucleus also contains one or more nucleoli.  Nucleus is composed of the following parts: 1. Nuclear envelope 2. Nucleoplasm: 3. Nucleolus  Each nucleus contains one or more nucleoli.  The nucleolus contains RNA and some proteins, which are similar to those found in ribosomes.  The RNA is stored in the nucleolus. Later, it is condensed to form the subunits of ribosomes.  All the subunits formed in the nucleolus are transported to cytoplasm through the pores of nuclear membrane. In the ->?* ‫الصفحة‬22 Dr. ayman aldegwaly General physiology part 2 cytoplasm, these subunits fuse to form ribosomes, which play an essential role in the formation of proteins.  Nucleus functions: 1. Control of all activities of the cell 2. Synthesis of RNA 3. Sending genetic instruction to cytoplasm for protein synthesis 4. Formation of subunits of ribosomes 5. Control of cell division Endoplasmic reticulum  Endoplasmic reticulum is connected with nucleus.  There are two types of endoplasmic reticulum: Rough endoplasmic reticulum: membranous tubules and flattened sacs with attached ribosomes transports and modifies proteins. Smooth endoplasmic reticulum: membranous tubules and flattened sacs with no attached ribosomes. Manufactures lipids and carbohydrates; detoxifies harmful chemicals; stores calcium. Golgi complex  Golgi apparatus or Golgi body is a membrane bound organelle.  It is present in all cells except red blood cells.  Each Golgi apparatus consists of 5 to 8 flattened membranous sacs called the cisternae.  It is situated near the nucleus.  It has two ends namely cis face and trans face. The processed substances exit from Golgi complex through trans face. => ‫الصفحة‬23  Dr. ayman aldegwaly General physiology part 2  Function of Golgi complex Processing, packaging, labeling and delivery of proteins and lipids to different parts of the cell. Lysosomes  Lysosomes are the membrane-bound vesicular organelles found throughout the cytoplasm.  They are formed by Golgi apparatus.  They are often called ‘garbage system’ of the cell because of their degradation activity. W  About 50 different hydrolytic enzymes, known as acid hydroxylases, are present in the lysosomes, through which lysosomes execute their functions  Functions of lysosomes  Digest foreign molecules and worn and damages organelles. Mitochondria o Mitochondria vary in size and shape, but all have the same basic structure. o The outer mitochondrial membrane is smooth, but the inner membrane is characterized by many folds, called cristae, which project like shelves into the central area (or matrix) of the mitochondrion. o The cristae and the matrix compartmentalize the space within the mitochondrion and have different roles in the generation of cellular energy. ATP is made by a process called oxidative phosphorylation.  Functions of mitochondria: 1. Synthesis of ATP =? ‫الصفحة‬24  Dr. ayman aldegwaly General physiology part 2 2. Initiation of apoptosis (programed death of the cell t under genetic control). ⑧3. Storage of calcium and detoxification of ammonia in liver. - ‫الصفحة‬25