Regulation of the intracellular Ca2+

Regulation of intracellular [H]:

Cell volume regulation It depends on the total amount of intracellular solute (Na + and K + ionic gradients) generated by the Na + /K + pump Following cell shrinkage  Intracellular solute concentration increasing mechanism is activated  The synthesis of osmotically active molecules (eg, sorbitol or taurine)  The transport of ions inside the cell through the Na + -H + exchanger or the Na + -H + -Cl − cotransporter Following cell swelling  transport mechanisms that extrude solutes out of the cell (eg, K + or Cl - channels or the K + -Cl - cotransporter) will be activated.

Cell Apoptosis = Cell suicide  Genetically determined Cell Necrosis = Cell murder  External cause

Cell structure and Functions

Interesting facts about body fluids and water: Water is key to life. Humans can survive more than a month without food, but only a few days without water. Transportation: Water transports glucose, oxygen, and fat to body tissues and waste products, such as carbon dioxide, and lactic acid away from body tissues. Body temperature regulation: Your body produces enough heat in only thirty minutes to boil a half-gallon of water. The body wants to keep a constant temperature of approximately 37ºC. If the body temperature increases to >41ºC, cells will die. To prevent overheating, the body regulates temperature by sweating. Water absorbs heat from the working muscles and dissipates this heat to circulating blood and ultimately through the skin and by sweat evaporation. Digestion: Water is an important component of saliva, intestinal, and gastric juices, which help digest food. Lubrication: Water is a good lubricator of joints, organs, and tissues.  Drinking too much water too quickly can lead to water intoxication. Water intoxication occurs when water dilutes the sodium level in the bloodstream and causes an imbalance of water in the brain. Water intoxication is most likely to occur during periods of intense athletic performance.  Pure water (solely hydrogen and oxygen atoms) has a neutral pH of 7, which is neither acidic nor basic. Water dissolves more substances than any other liquid  Wherever it travels, water carries chemicals, minerals, and nutrients with it.  By the time a person feels thirsty, his or her body has lost over 1 percent of its total water amount.

After the end of these lectures, you should be able to...  Know the composition of extracellular and intracellular body fluids.  Explain osmosis, osmolarity and osmotic pressure, and tonicity of the body fluids.  Know the forces producing movement of substances between compartments.  Describe the process of endocytosis and exocytosis.  Describe the primary factors (Starling forces) that determine fluid movement through the capillary membrane and the formation of interstitial fluid and lymph.  Describe the intake versus output of water.

Body fluids and compartments Water = 60% of TBW ECF20% ICF40%

Body fluids and compartments Extracellular fluid (20% of the TBW): 1. The interstitial fluid 15% of the TBW. 2. Plasma 4% of the TBW. 3. Transcellular fluids 1% of the TBW. Intracellular fluid (40% of the TBW 15%4%40%

Body fluids and compartments Extracellular fluid (20% of the TBW): 1. The interstitial fluid 15% of the TBW. 2. Plasma 4% of the TBW. 3. Transcellular fluids 1% of the TBW. Intracellular fluid (40% of the TBW 15%4%40%

Osmosis, Osmolarity and Osmotic pressure of the body fluids Osmosis is the diffusion or flow of water molecules across a membrane into a region in which there is a high concentration of a solute to which the membrane is impermeable

The number of the solute particles determines the magnitude of the osmotic pressure of the solution in which it is dissolved.

 Each mole of a substance contains Avogadro's constant (6.022×10 23 ) of molecules.  Molarity of a substance is the concentration of non-dissociated substance (in moles) per one L (kg) of water.  The osmolarity (osmole) is the concentration of osmotically active particles (the molecules or the particles which attract water to it) in one liter of a solution (mol/L H 2 O).  The osmolality (osmole) is the concentration of osmotically active particles (the molecules or the particles which attract water to it) in one kg of a solution (mol/Kg H 2 O).  The number of osmotically active particles in any fluid is determined by: The number of moles per liter (or kg) of water X the numbers of osmotically active particles released into solution when the solute is dissolved. Therefore; One Avogadro's constant molecules of a substance/L H 2 O = 1 Mole of substance/L H 2 O (MOLARITY) = 1 Mole X the numbers of osmotically active particles released into solution when the solute is dissolved (OSMOLARITY, Osmole of substance /L H 2 O). 1M glucose = 1 OsM/L 1M NaCl = 2 OsM NaCl/L, because NaCl dissociates to 2 ions in solution, Na+ and Cl-.

Examples: ʘ 5% of glucose in water has a molarity of 300 mMoles/L H 2 O, and because the glucose molecules in water do not dissociated, it has an osmolarity of 300 mOsmol/L H 2 O. ʘ 0.9% NaCl in water has a molarity of 150 mMoles/L H 2 O, and because each NaCl molecule in water is dissociated into two osmotically active particles (Na + and Cl - ions); it has an osmolarity of 300 mOsmol/L H 2 O. Therefore, 5% of glucose in water and 0.9% NaCl in water have different molarity but identical osmolarity and consequently identical osmotic pressure.

Cell keeps the same volume in an isotonic solution. Cell gains volume in a hypotonic solution Cell looses volume in a hypertonic solution Isotonic - both solutions have the same solute concentrations. Hypotonic - solution with the lower solute concentration. Hypertonic - solution with the higher solute concentration.

Solution containing: NaCl 150 mmol/L = 300 mOs  Non-Penetrating substances Urea 100 mmol/L = 100 mOs  Penetrating substance Total Osmolarity = 400 mOs Total Tonicity = 300 mOs

During intavenous injection: 0.9% (normal) saline  isotonic 5% dextrose  isotonic 0.45% saline  hypotonic

Forces producing movement of substances between compartments Simple diffusion Simple diffusion Filtration Filtration Osmosis Osmosis Carrier-mediated transport Carrier-mediated transport Endocytosis and exocytosis Endocytosis and exocytosis

Simple diffusion  through cell membrane lipid bilayer or through cell membrane channel proteins Simple diffusion  through cell membrane lipid bilayer or through cell membrane channel proteins Affected by:  Concentration gradient  Electrical gradient  Thickness of the boundary  Cross sectional area of the boundary  Temperature  Membrane permeability

Filtration  Is the process by which water and water soluble substances is forced through an epithelial layer due to a difference in hydrostatic pressure on the two sides Filtration  Is the process by which water and water soluble substances is forced through an epithelial layer due to a difference in hydrostatic pressure on the two sides Affected by the:  Pressure gradient  Surface area of the membrane  Diameter of the membrane pores  Size of the filtered molecules

Carrier-mediated transport Carrier-mediated transport characterize by: [i] Stereospecificity [ii] Saturation [iii] Competition Classified according to the direction of transport:

Carrier-mediated transport Carrier-mediated transport Facilitated diffusionActive transport primary active transport Secondary active transport

Facilitated diffusion Transport occurs according to electrochemical gradient, energy is not required (passive), Animation

Simple diffusionFacilitated diffusion Diffusion according to electrochemical gradientSame Energy is not requiredSame Does not require a carrier proteinRequires a carrier protein Simple diffusion is not saturableHave saturation limited (Tm)

Primary active transport Transport occurs against electrochemical gradient, the process requires energy. High energy phosphate compound, ATP, provides directly the energy required for the transport process Animation Na-K-ATPase pump, H-ATPase pump (proton pump) and Ca-ATPase pump Animation

Secondary active transport: Co-transport or symport The transport of one substances (e.g. Na+) provides the energy to transport another substance. Transport occurs against electrochemical gradient, the process requires energy. Animation Na co-transport of glucose and amino acids Na-K-2Cl co-transport Na-Ca counter-transport Na-H counter transport

Secondary active transport: Counter-transport or antiport The transport of one substances (e.g. Na+) provides the energy to transport another substance. Transport occurs against electrochemical gradient, the process requires energy. Animation

Secondary active transport: Co-transport or symport

Facilitated diffusionActive transport Transport according to electrochemical gradient Transport against electrochemical gradient Does not require energyRequires energy Uniport transportUniport, Antiport, or symport transport