Cell Physiology For PC1 Black lion .pptx

For pc1 students Cell physiology black lion hospital

1. Addis Ababa University School of Medicine Department of Medical Physiology Lecture Notes on Cell Physiology and transportation for PC I Medical students 1

2. Objectives At the end: Able to discus the structures of the a cell Able to discuses the functions of the structures of a cell Able to list the types and functions of membrane proteins Able to discus cell transport Able to discuses about body fluid 2

3. Cell Physiology The human body composed of non-cellular and cellular components Non-cellular components Water Macro -nutrients: carbohydrate, protein, lipid, nucleic acid Micro- nutrients: vitamins, electrolytes Cells: Smallest structural & functional unit of life Small in size  10-20um Large in number  75-100 trillion Arranged in d/f functional structures 3

4. Structural or functional classification 4 Fig1: C ell types

5. Fundamental theories and cell types Types Eukaryotic Blood, nerve, muscle, fat and glandular cells Prokaryotic cells Bacteria, virus Have many functions Transportation, Defenses, protection 5

6. Structures of the human cells 1) Plasma/cell membrane Double, thin, flexible ( fluid mosaic model ) structure surrounding animal cell Composed of biological macromolecules Carbohydrates, proteins, lipids and cholesterol Functions: Selective barrier (semi-permeable) and transport Support, protect the cell & retain cytoplasmic contents Recognition (identity proteins) Pattern recognition receptors Detect molecules on pathogens Maintains chemical & electrical gradients Communication Controls and directs cellular activities 6

7. Major compositions of cell membrane Phospholipids (25%) Form double membrane, lipid bilayer (outer and inner) Asymmetry ( variation in composition and arrangement ) Amphipathic molecule Hydrophilic and hydrophobic properties Carbohydrates(3%) Combined (glycoprotein and glycolipid): recognition and blood clotting E.g Glycocalyx ( blood clotting) Proteins (55%): membrane proteins Intrinsic and extrinsic Cholesterol (13%) For immobilization of lipid molecules and give extra support 7

8. F luid mosaic model of cell membrane 8 The mosaic model states that a membrane is a fluid structure with a “mosaic” of various proteins embedded in it. Fibers (collagen) where cell rest is called basal lamina Fig 2: Fluid mosaic model

9. Membrane proteins i- Integral proteins Transmembrane, intrinsic proteins Strongly bonded with lipid bilayer Not removed easily with out affecting the membrane Most of them are glycoproteins Receptors (GPCR) Ion channels Carriers (permease, pumps) 9

10. ii- Peripheral proteins Attached to the inner membrane Not penetrate the hydrophobic core of the membrane Easily removed Enzymes Protein kinases, Phospholipases Important Cell signaling Anchoring (integral proteins and cytoskeleton) 10 Membrane proteins con’t

11. Membrane proteins con’t 11 Fig 3: Integral and peripheral membrane proteins

12. Functions of membrane proteins: summary Receive chemicals and transport substances Receptor and transporter proteins Transporters proteins (uniport, symport and antiport) Link structures: Linkers proteins Communication(gap junctions) and recognition (identity) Immune cells can recognize self cells Enzymatic reaction and signal transduction Cell adhesion: one cell to an other Platelet attached on endothelial cells Connect the cell with the cytoskeleton Keeping the integrity of membrane: structural proteins 12

13. Membrane proteins and their functions con’t 13 Fig 4: Functions of membrane proteins

14. Parts of human cell... 2) Cytoplasm Space b/n the nucleus and cell membrane Contains fluid: cytosol/ICF with d/f compositions and Suspended structures : organelles (except red cells) The machinery of the cells Has their own functions 14 Cytoplasm cytosol Water, glucose, proteins, electrolytes Dispersed particles Smaller: FA Larger: neutral fat, glycoprotein, excretory granules Organels Some cells lack organelles ( RBCs)

15. Red blood cells Lack most of the organelles Nucleus (DNA) No cellular division and protein synthesis Mitochondria N o ATP production in oxidative phosphorylation Glycolysis source of energy One glucose molecule  2ATP 15

16. Organelles Nucleus Largest organelle at the center of the cell Has nuclear membrane with nuclear envelop Controls the cell functions The genes Genes : molecules on the DNA that carry and express traits Each gene has its own triplet code word The functional unit of gene Gene Gene I Gene II Gene III code word with sequence CAG AGC GAC Specific proteins (hormones, enzymes,activitors, inhibitors) Protein type I Protein type II Protein type III 16

17. DNA structure Fig 5 : DNA structure( alpha double helix of two polynucleotide strands). 17

18. Ribosomes and Endoplasmic reticulum 18 Free Exocytosis (active) sER store Ca ++ (SR in muscle cells) Steroids Glycogen phosphatase Glucokinase Phosphoglucomutase phospholipids GA More in secretary cells (plasma B cells and acinar cells ) Fig 6: Ribosmomes and ER

19. Mitochondria and ATP production 19 Fig 7: Mitochondrion 38 ATP’s from one glucose molecule but 2ATP used for preparation steps Nicotinamide adenine dinucleotide  ( NAD ): NADH is the reduced form of NAD and carry energy 2NADH 2

20. Lysosome … 20 Fig 8 : Actions of lysosome phagosome Intracellular digestive system: stomach of the cell Suicide Acid hydrolic enzyme (pH<7) cytosol pH =7.2

21. Secretory vessicels Similar structure with lysosomes Contain enzymes not used in the cell, released out Glandular cells have secretory vesicles Pancreatic gland Salivary gland Other endocrine gland 21

22. Peroxisomes ( from ER) and action of catalase 22 harmless Harmless Fig 9 : Action of catalase and peroxidase Fe losses O 2 Oxidized : Facilitate the formation of H 2 O 2 Peroxisomes Replicated from ER Release catalase Shorter and smoother Oxidation : 0 2 gaining and reduction loss of O 2 . iron reduced 0 2 this is b/se CO receive oxygen Thus CO : reducing agent as it facilitates Fe to loss O 2 Fe: oxidizing agent as it facilities CO to gain 0 2 and oxidized Oxidized substrate: reducing agent Reduced substrate: oxidizing agent

23. Cell junctions and types 23 Sheet epithelial cells, BBB Fig 10: Cells communication provide strong mechanical attachments between adjacent cells. Electrical signal conducted 1 2 3 4

24. Transport across the cell membrane 24

25. Membrane transport Passage of substances across the cell membrane Into the cell: influx and Out the cell: efflux The passage can be through:  Lipidbilayer  Proteins Cells differ in their permeability: Variation in : Composition and arrangement 25

26. Transport across the cell membrane 26 Nutrients Ions and Water are through With out proteins Gas Lipid soluble substances Alcohol Protein Fig 11: Transportation across the cell membrane

27. Types of m embrane transport Passive transport No energy required Movement down concentration gradient The forces are concentration & electrical gradients Substances follow their concentration gradient Concentration gradient reduced /eliminated Filtration , simple or carrier mediated diffusion and osmosis 27

28. Types of the passive transport... 1 - Simple diffusion Through lipid bilayer or leaky channels- not gated ion channels Lipid soluble, gas and alcohol (via lipid bilayer) Vitamin A, D, E and K Lipid insoluble ( via water filled channels) Ions , water No interaction b/n channel and transported substance 28

29. Transport across the cell membrane 29 Fig 12: Types of Transport

30. Properties of channels Water field proteins Mostly, allow substances to move down (passive channels- leaky ion channels ) Dissipate potential difference Opened and closed by gate ( gated channels ) Active channels Prolonged activation desensitizes the channels Select influx and efflux substances Connected with receptors E.g ion channels Important for excitable cells 30

31. Gated Ion channels con’t 31 Voltage gated ( charge difference sensors) Ligand or Chemical gated (Ach, GABA, glutamate) Light gated (photo sensitive channels) Mechanical gated ( stretched sensitive channels)

32. Bases of selectivity Channels are specific and selective The selection is based on Size (size of Na + channel: 0.3 x 0.5 nm) The bond nature of the proteins The charge Hydration/ unhydration of ions Na + channel (-ve Q) allows unhydrated sodium to pass But hydrated potassium still pass through its channel The selectivity is less than the carriers Not have binding site 32 Unhydrated ion Hydrated ion ion ion H 2

33. Factors affecting the diffusion rate: rate of transport Cell membrane thickness Molecular Size Temperature The gradient (electrical and concentration: opposite forces) Net influx, F = k p A (C -C i ) The net efflux, F= k p A (C i -C ) k p (Permeability constant) The lipid solubility Membrane surface area Permeability 33 1 2

34. Passive transport… 2- Facilitated diffusion It is carrier (permease ) mediated Solute binds to the carrier (conformational changes) Rotate, open The substance is released into the low concentration side Substances attached from high concentration region 34

35. Facilitated diffusion… 35 The unique feature of facilitated diffusion 1. Specificity 2. Competition 3. Inhibition 4. Saturation 5. Transport maximum Fig 13: Facilitated diffusion

36. Facilitated Diffusion… Differ from simple diffusion mainly Transport maximum(V max ) achieved Diffusion rate elevated until transport maximum Proteins are saturated Diffusion rate constant after V max 36 Fig 14: Transport maximum(v max ) Rate of transportation increased as the concentration of the substance getting high

37. Passive transport: osmosis and osmotic pressure 3- Osmosis Net movement of water from The region of high water molecules to low water molecules Low solute to the high solute concentration Hypotonic to hypertonic solution Equalizes water concentration across the membrane This movement is there if there is Water and solute concentration difference 37

38. Solution tonicity Tonicity The osmotic activity of body fluid Ability of a solution affecting cell volume The solution: Isotonic, hypotonic and h ypertonic against cytosol Affects the osmotic pressure of the solution 38

39. A cell in different solution 39 Solution concentration compared with concentration of intracellular fluid What will be the cell volume if you add different solution into the ECF? isotonic solution Hypertonic solution Hypotonic solution Fig 15: a cell in different solutions

40. Osmol, osmolarity, osmolality Osmol N umber of osmotically active particles of solute in a solution Osmolarity : solute pr kg of solution and is the concentration of the solution with the unit of mOsmol/L of solution The total osmolarity of the body is 280mOsm/L of solution And one milliossmole has an osmotic pressure of 19.3mmHg Osmolality : solute per kg of water 40

41. Atomic and molecular weight Atomic weight of elements Molecular weight of compound Table 1: atomic and molecular weight 41

42. Osmosis and osmotic pressure Osmotic pressure Force applied by solution to oppose the net movement of water Affected by osmole and the tonicity of solution : One mole of glucose= 1 osmole/L One mole of NaCl = 2 osmole/L One mole of HCl = 2 osmole/ L One mole of Na 2 SO 4 = 3 osmole/L The more the osmotic pressure The less movement of water into other compartment Size of the molecule in the solution not affect osmotic pressure One mole of glucose (C 6 h 12 O 6 ) ? One mole of NaCl ? 42

43. Osmosis and osmotic pressure... Determination of osmotic pressure of a solution Osmolarity (mOsmol/L) = concentration x number of dissociable particules E.g a 150 mmol/L ( conc ) solution of NaCl has an osmolarity of 300 mOsm /L Then the osmotic pressure = 5,795mmHg 43

44. Relation between osmol and osmotic pressure A solution with 1 miliosmol /L opposes the net movement of water by 19.3mmHg force The osmolarity of the body fluid is 280-300 miliosmol/L Then the calculated body fluid osmotic pressure = 19.3 x 300 = 5790mmHg But the actual total body fluid osmotic pressure is 5500mmHg (contributed by ions, proteins….) The reduction is due to some ions attract to each other like Na + and Cl - in that their full osmotic effect is reduced 44

45. Molarity and osmotic pressure of a solution Calculate the osmolarity and the osmotic pressure of a solution of 0.9 % NaCl Assume the membrane is impermeable to other solutes 0.9% NaCl solution means the solution contains 0.9gm of NaCl in 100ml of the solution or 9gm/L Osmolarity = concentration x osmol (9gm/L)/(58.5 gm/mole)= 0.1538mole/L, then for two osmole = 2x 0.1538mole/L = 0.308 osmole/L Osmotic pressure 1mosmle , the osmotic pressure required is 19.3 mmHg Then for 0.308 osmole/L = 308mosmole/L = 308 mosmole /L X 19.3 mmHg = 5, 944.4mmHg 45

46. Determination of fluid shift and osmolarities of a solutions after an other solution infused Assume : 2L of hypertonic solution with 3.0% of NaCl infused into ECF of a 70kg patient whose initial plasma osmolarity is 280mosmole/L. Then determine Osmolarity of body after infusion Intra and extracellular fluid volumes 46

47. Steep one: Determine the initial conditions before solution given 47 Table 2: Initial condition of subject

48. 3.0% Nacl solution means , solution contain 3mg of NaCl in 100ml or 30gm/L Osmol / conc = 30gm/L/58.5gm/mole = 0.513mol/L x 2 =1.023mol/L For 2 L= 2x 1.023mol/L = 2.051mol/L = 2051mosmol/L Thus the total ECF osmole = 3,920 + 2,051mosmo/L = 5,971mosmol/L 48 Steep two: determination of milliosmoles added

49. 49 Step 3: Determine the concentration in each L of solution Table 3: Conditions after infusion before equilibrium

50. Concentration= total miliosmoles in the body/ total volume 13,814/44 = 313.9mosml/L The fluid compartments will have the same concentration, 313.9mosml/L ICF volume = Total miliosmoles in ICF/ its concentration = 7840/313.9 = 24.89L ECF volume = total milimoles in ECF/ its concentration = 5971/313.9 = 19.02L 50 Steep 4: determination of volume & concentration after osmotic equilibrium is developed

51. The result (after infusion and equilibrium) 51 Table 4: conditions after equilibrium

52. Active Transport Transporter proteins (pumps) use energy Pump mediated and bulk transport Energy sources: ATP and ions Against concentration gradient. Gradient elevated Example Na + -K + pump, Ca ++ pump, movement of amino acids into cell and movement of calcium into SR 52

53. Transporter proteins Proteins Cotransporter Uniportor Symporter Antiporter /exchanger Example Na + , Ca ++ , K + , H + channels Na + -glucose or Na + -amino acid transporters ,Na + - K + and 2Cl - Na + -K + (neurons), Na + -Ca ++ (heart cells), K + -H + ( kidney and stomach) exchangers 53 Table 5: Transporter proteins

54. Ion driven Down hill ion movements uphill the solutes Indirect source of energy is ATP ATP-driven : primary or direct ATP hydrolyzed by ATPase to drive uphill solute Two types active transport 54

55. Mechanism of Na + - K + pump and the functions 55 Regulate cell volume Create membrane potential (electrogenic effect): electrogenc effect Maintain ion diffusion gradient Contribute for 2 active transport Fig 19: Sodium- potassium pump

56. 2) H + -K + pump on parietal cells apical membrane 56 Fig 20: Hydrogen- potassium pump

57. Secondary active transport 57 Na + Secondary active transport Fig 21 : 2 active transport