Cell Physiology

Cell Physiology Dr. Kyaimon Myint Physiology Department University Malaya

Lecture Objectives • • • •

Basic Cell structure Organelles and their functions Structure and Functions of cell membrane Transport processes across cell membrane Passive, active, special • Distribution of ion between extracellular and intracellular fluids • Resting Membrane Potential 2

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Total Body Water and Body Fluid Compartments • The chief constituent of living tissue is…….. Water • The percentage of water varies with sex, age and lean body mass

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Approximate Composition of the body

Normal adult man

Normal adult women

Water %

65- 70

55- 60

Fat %

5

18

Lean (Fat free) body mass

25

22 5

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Body Fluid Distribution Intracellular

K+ PO4= Prot-

Extracellular

Na+ ClInterstitial

Intravascular ‘plasma’ 7

The internal environment • Is the fluid environment of the cells • Thus, ECF constitutes ‘the internal environment’

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Cell Structure and Function

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Basic structure: • Size: 10-20 m • Greatly varies in size and shape according to their function

Physical structure: • Organelles: nuclear and cytoplasmic • Inclusion bodies 10

Chemical structure • Water (70- 80%) …….. Act as a medium for chemical reactions and transport of substances • Electrolytes: Cations: K+ , Na++, Mg++ Anions: HCO3=, PO4=, Cl• Proteins (10- 20%) • Lipids • Carbohydrates 11

Nuclear Organelles

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Cytoplasmic membranous organelles • • • • • •

Cell Membrane Endoplasmic reticulum Mitochondria Golgi apparatus or complex Lysosomes Peroxisomes

Cytoplasmic Non- membranous organelles • Ribosomes • Centrioles • Microtubules and microfilaments

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Mitochondria

‘Power- generating units’ 14

‘Intracellular circulatory System’

Sites of synthesis of Protein such as hormones

Metabolic Functions: as site of • Steroid synthesis • Detoxification e. g. in liver cells • Glycoprotein synthesis As sarcoplasmic reticulum: plays role in initiating contraction and relaxation of skeletal and cardiac muscle 15

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Functions: • Directs intracellular trafficking of proteins by attaching carbohydrate ‘destination labels’

Particularly prominent in actively secreting cells 17

Lysosomes Functions:

Housekeeping Role • Defense and scavenger function by digesting the phagocytosed foreign particles • Engulf and remove worn- out component of the cells • Autolysis of dead cells • Help in cellular differentiation and regression of tissue Contains variety of enzymes; can cause destruction of most cellular components

‘Digestive system of the cell’ 18

Defense and scavenger function 19

Microtubules and Microfilaments Functions: • Provides tracks along which substances can move ‘Intracellular traffic’ • Maintain cell shape ‘Cytoskeleton’ • Play role in muscle contraction and movement of microvilli • help cell to resist external pressure 20

Cell Membrane Dynamic fluid mosaic model

thickness: 6-10 nm

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Characteristics of Cell Membrane

‘Amphiphatic molecule’

Semi permeable/ Selective permeability 22

Cell Membrane Proteins • Mostly glycoproteins 1) Integral (intrinsic) Proteins …. Integral components of the membrane …. Pass through the membrane …. Many specific functions 2) Peripheral Proteins …. Attach inside and outside of the membrane …. Weakly bound to integral protein 23

Functions of Cell Membrane ANTIGENS

Seperates ECF from ICF

Regulates movement of substances • channels (voltage-,ligand-, mechanically-gated) • carriers • pumps

Connects adjacent cells

Binding sites for Catalyzing • neurotransmitters reactions • hormones • drugs 24

Transport Proteins: Functional Classification

Transport only one substances, direction depends on the gradient Eg. Glucose transporter (GLUT) in muscle cells

Moves 2 or more substances in the same direction Eg. Sodium dependent glucose transporter (SGLT) in intestinal mucosa and renal tubular cells

Counter transporter: Moves 2 or more different substances in opposite direction Eg. Sodium Potassium Pump

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Intercellular Connections 2 Types of Junctions:

• That tie cells together giving strength and stability to tissues … Tight junction … Desmosomes … Hemidesmosomes • That permit transfer of ions and molecules from one cell to another … Gap Junction 26

Holds adjacent cell, usually in constantly stretched areas (e.g. skin)

Prevents free movement of substances between cells 27

Forms protein channels between cells Allows transfer of electrical activity 28

Transport Across Cell Membrane

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Passive Transport Mechanisms • Diffusion Simple or free diffusion Facilitated or carrier- mediated diffusion Non ionic diffusion • Osmosis

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Diffusion Continuous random movement of molecules and ions from a region of higher concentration to a region of lower concentration along concentration or chemical gradient; or in case of ions, to an area having the opposite charge along electrical gradient 31

Facilitated Diffusion Is the passive transport of substances across the plasma membrane with the help of transport proteins such as the channel protein and the carrier protein.

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• Small uncharged polar (hydrophilic) molecules such as CO2 diffuse rapidly • Lipid soluble and non- polar (hydrophobic) molecules such as O2, N2 diffuse with ease

Some polar and charged molecules such as water diffuse through protein channels

Large, uncharged molecules bind to a protein, triggering a change in protein shape that transport across the membrane. Glucose enters the cell by this transport.

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Factors affecting Diffusion Q = D (C1-C2) • Concentration gradient

Q = rate for diffusion D = diffusion coefficient

C1 - C2 = concentration gradient

• Electrical gradient • Size of molecules • Lipid solubility • Surface area

• Thickness of membrane • Temperature 34

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Osmosis • the movement of water molecules from an area of high concentration to an area of low concentration across a membrane selectively permeable to it Water • a polar molecule • size 0.3nm • crosses membrane very rapidly or through channels (aquaporins) 36

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Osmotic pressure The pressure required to stop movement of water (osmosis); Unit = mmHg • Depends on the number rather than type of particles in a solution Number of particles in a solution depends on: • i. Molarity of molecules in a solution • ii. Whether the molecule dissociates or not in solution 38

Units for Measuring Solute Concentration • The concentration of osmotically active particles is expressed in Mole or Osmoles • Mole = g molecular weight of a substance molecular weight of substance in grams • 1 osml = number of freely moving particles each molecule liberate in solution 39

For non-dissociable molecules • 1 osmol = 1 mol of solute particles • 1 M solution of glucose has concentration of 1 Osm (1 osmol per liter)

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For molecules that dissociate in solution Osmolarity of the solution (Osm/L) = Concentration in molarity per litre

X

No. of solutes after dissociation

Eg. In solution, 1 M Na+ Cl- dissociates into 1 M Na+ & 1 M Cl- ions

•1 M solution of Na+ Cl- = 1 Osm/L Na+ + 1 Osm/L Cl= 2 osmol / liter 41

Osmolarity • Is the measure of solute concentration • Defined as the number of osmoles per liter of solution (Osmol/L)

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Osmolality • Is the number of osmoles of per kilogram of solvent (osmol/kg) • Not affected by volume of various solutes and temperature • Normal plasma osmolality: 290 _+ 5 mOsm/Kg or mmol/l 43

Tonicity • Osmolal concentration of Plasma • Is used to describe the osmolality of solution relative to plasma • Is the concentration of only the solutes that cannot cross the membrane ‘Only considers the non-penetrable solutes’ Permeant solutes ….. do not affect tonicity Impermeant solutes ….. do affect it 44

Isotonic solution • contains 300 mOsmol/L of non penetrating solutes, regardless of the concentration of membrane penetrating solutes

Hypertonic solution • contains greater than 300 mOsmol/L of non penetrating solutes

Hypotonic solution • contains less than 300 mOsmol/L of non penetrating solutes 45

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Isosmotic solution • solution containing 300 mOsmol/L of solutes, regardless of its composition of membrane penetrating and non- penetrating solutes Hyperosmotic solution • solution containing greater than 300 mOsmol/L of solutes, regardless of its composition of membrane penetrating and non- penetrating solutes Hyposmotic solution • solution containing less than 300 mOsmol/L of solutes, regardless of its composition of membrane penetrating and non- penetrating solutes 47

Filtration

Process in which fluid is forced through a membrane or barrier (a capillary wall) due to difference in hydrostatic pressure on the two sites 48

Active Transport Mechanisms: • Primary Active Transport Sodium- Potassium pump H+ - K + ATPase Ca++ ATPase • Secondary Active Transport Sodium- Dependent glucose Transport Sodium- Dependent calcium Transport • Endocytosis, Exocytosis, Vesicular transport 49

Sodium- Potassium Pump • One of the major energy- using processes in the body • Found in almost all cells • Extrudes 3 Na+ from the cell and take 2 K+ into it (coupling ratio= 3:2) for each mole of ATP hydrolysed ‘ELECTROGENIC’

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H+ - K+ ATPase • Extrudes H+ from the cells in exchange for K+ • Found in acid- secreting cells in the gastric mucosa and the renal tubules

Ca++- ATPase • Pumps Ca++ out of cytoplasm into the endoplasmic reticulum in skeletal and cardiac muscle cells 52

Secondary Active Transport ‘the transport of a substance is coupled to active transport of Na+’ Na+- K+ pump maintains the Na+ gradient, and the energy of this gradient drives the carrier which transports both that substance (either into or out of the cells) and the Na+ (into the cells)

e.g. Sodium dependent glucose transport in intestinal and renal tubular cells 53

The process by which proteins and large molecules enter the cells without disruption of the cell membrane

Transport of large particulate matter such as bacteria, dead tissue, or other bits of material visible under microscope ’cell eating’

Transport of large molecules in solution such as protein

Responsible for internalization of macromolecules such as proteins, hormones (insulin, growth factor), LDL and Toxins ‘cell drinking’ 54

The extrusion process by which cellular secretion (proteins and large molecules) are liberated to the exterior

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Resting Membrane Potential At equilibrium, a slight excess of cations on the outside anions on the inside creating a resting membrane potential. ECF

ICF

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Genesis of RMP • The nature of cell membrane …….. provide explanation of RMP

• Operation of the Na+- K+ Pump …….. maintain high intracellular [K+] high extracellular [Na+]

ECF (mmol/L)

ICF (mmol/L)

Na+ 150

Na+ 15

K+ 5. 5

K+ 150

Cl- 125

Cl- 9 Anion Protein

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K+ ions • diffuse out along concentration gradient through ion channels selectively permeable to them ‘K+ leak channels’ Intracellular anions • ‘proteins and organic phosphate’ ……non diffusible, and not able to move along with K+ Create a potential difference across the cell membrane 58

Na+ ions • being more concentrated on outside, tends to diffuse in • but Na+ influx does not compensate for the K+ efflux because K+ channels make the membrane more permeable to K+ than to Na+

ECF

ICF

ECF

Na+

K+

Thus K+ efflux effectively outbalances the Na+ influx 59

Cl- ions • tends to diffuse in • Increase the negativity of membrane potential

ECF

ICF

ECF

Cl-

Direct electrogenic effect of Na+ - K+ pump • 3 Na+….out for every 2 K+ in …….loosing one positive charge from the cell • Contribute very little, only 4%

- 70 mV 60

THANK YOU

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