Razi Kittaneh & Tamer Barakat. Bayan Abusheikha. Faisal Mohammed

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1 3 Razi Kittaneh & Tamer Barakat Bayan Abusheikha Faisal Mohammed

Transport and Osmolality In the last lecture we briefly talked about Transport, there are 2 types of transport: 1) Passive Transport 2) Active Transport.

2 Transport and Osmolality In the last lecture we briefly talked about Transport, there are 2 types of transport: 1) Passive Transport 2) Active Transport. The main difference between the 2 types of transport is the usage of energy. No energy is used in Passive Transport in contrast to Active Transport which uses energy. The other difference between Active and Passive transport is that Passive Transport involves the transport of molecules along (or with) the gradient (whether it s a concentration gradient, electrical gradient, pressure gradient etc.) meanwhile Active Transport involves the transport of molecules against the gradient. 1)Passive Transport (downhill) a) Simple Diffusion: It s the movement of LIPID SOLUBLE substances through the cell membrane, so for a substance to move through a membrane by simple diffusion, it must be Lipid soluble. Gases are the best example for a lipid soluble substance including O 2 and CO 2 which pass easily through the membrane by simple diffusion. However, ions like Na+ or K+ can t pass through the cell membrane by simple diffusion. Page1

Another feature for gases in Anesthesia is that the gases leave the body quickly, because they are transported by simple diffusion, so the patient will recover quickly and at the suitable time.

3 n And that s why gases are used in Anesthesia. Nitrous oxide (N 2 O) is mainly used in anesthesia because it passes quickly through the membrane, so it reaches the lung quickly and the patient becomes anesthetized. Another feature for gases in Anesthesia is that the gases leave the body quickly, because they are transported by simple diffusion, so the patient will recover quickly and at the suitable time. If other chemicals were used in anesthesia they might not leave the body easily and might harm other organs like kidney or liver because their movement is slower in the body through the membranes and the recovery time for an anesthetic person will be long. When the gas source in anesthesia is removed from the patient s mouth, the gases will move in the other direction in his body to leave it. n We mentioned, in the last lecture, that this kind of diffusion (simple diffusion) depends on many factors as shown below: J J J J J concentration gradient (Dc) solubility of the substance (s) area which the substance can pass through (A) 1 Dmolecular wight R STU STVWXYUZZ [\ STU ]U]^_`YU ( Dx) These factors can be summarized in J DC S A (thickness of the memb) Dmolecular weight Page2

4 n Since the thickness of the membrane is inversely proportional to the rate of diffusion, the respiratory membrane which separates the alveoli from the blood is very thin, so the air can move quickly to the blood in the lung. n There is a condition that occurs when there is too much fluid in the interstitial space that separates 2 areas, this condition is called edema. A specific type of this condition is pulmonary edema which is caused by excess fluids in THE LUNG. The other type is peripheral edema. Edema causes the membrane to become thicker, which results in the transport becomes slower and harder in the lung, this leads to difficulties in breathing and an increase in CO 2 concentrations in the blood this causes hypoxia (hypo=little oxia= oxygen) n The previous factors can be combined to form Fick s law: J = D Do Dp = P(c1-c2) A D is a constant that takes in consideration the solubility of the molecule in the lipid and Its molecular weight. C is the concentration. X is thickness. P is the permeability (solubility) b) Facilitated Diffusion (carrier mediated transport): It s the passive movement of molecules across the cell membrane via the aid of membrane proteins. This protein is called carrier protein and they are specific. n For carrier proteins, the number of the transport proteins in a cell is fixed under standard conditions. If the amount of the substance that must be transported is much higher than the number of transporters, the extra amount of substance will not pass, which means that carrier proteins can be saturated (facilitated diffusion is saturable) and that s a difference between simple and facilitated diffusion. n For channel proteins, which are other type of transport proteins, if the channels are open, the substance will move according to its concentration gradient, otherwise it won t function. Transport through channels is a case of simple diffusion. n Let s take Glucose transportation as an example: Page3 a carrier protein will move Glucose along its concentration gradient, once a carrier protein finishes moving a Glucose molecule it attaches to other one and so

Since carrier proteins are saturable, there is a value called Transport Maximum Tmax or Vmax (velocity max), which means after a

5 on. This transportation is an example of facilitated diffusion and it doesn t need energy. Glucose has to be transported through this method because it isn t lipid soluble. Since carrier proteins are saturable, there is a value called Transport Maximum Tmax or Vmax (velocity max), which means after a specific amount of concentration, no more substances can be transported through carrier proteins because all carriers are busy(full). For simple diffusion, higher concentrations always lead to a higher transport rate. Page4

6 c) Osmosis: a special kind of passive transport, it s the movement of water through semi-permeable membrane from higher concentration of water to the lower one. (lower concentration of solutes to the higher one). n Water can pass through plasma membrane in 2 ways (mentioned in slides but Dr.Faisal didn t mention them) 1. Through lipid bilayer by simple diffusion. 2. Through aquaporins which are integral membrane proteins. n Osmole: the molecular weight of any substance in water (1 mole) = Avogadro's Number. in other words, 1 Osmole = 1 Mole IF the molecule doesn t dissociate in water. Osmolality= Number of Osmoles per kilogram of water. Osmolarity= Number of Osmoles per Liter of water. Note: since water s density is 1000kg/m 3 we can approximate that: Osmolarity Osmolality In Osmolality/Osmolarity, we don t care about concentrations, neither about weight in grams. We care about the number of osmoles. n Examples: o how many osmoles does 140 mmoles of NaCl equel? Since NaCl dissociates into ions, we will have 140 mosmoles of Na mosmoles of Cl - = 280 m osmoles. o what s the osmolarity/ osmolality of 140 mmoles of glucose(c 6 H 12 O 6 )? Since glucose doesn t dissociate, Its 140mOsm/L 140 mosm/kg. o which has more Osmolarity? 1 gram of K + or 1 gram of Na +? Since Osmolarity depends on the number of osmoles, we need to know the Molecular Weight ( from periodic table, Na is 23,K is 39). Now we can calculate the Number of cataions as the following: For Na + = 1/23 x 6.02x10 23 for K + = 1/39 x 6.02X10 23 So Na + cataions > K + cataions which means Na + has more Osmoarity. o which one has more Osmoles 180g of Glucose or 23g of Na +?( Molecular weight for glucose= 180, Na=23) Since they make the same number of molecules, they have the same osmoles. Page5

n Osmolarity in our body: Plasma and interstitial fliud have approximatly the same number of anaions and cataions. However, plasma has more proteins.

ECF osmolarity equals 300 mosm/l ( or /Kg for Osmolality). The Osmolarity of the ICF is roughly the same.

7 n Osmolarity in our body: Plasma and interstitial fliud have approximatly the same number of anaions and cataions. However, plasma has more proteins. To calculate the osmolarity of the extracellular fluid, we add all of the numbers of none-permeable solutes (i.e. proteins, anaions and cataions), we don t ignore molecular weight. ECF osmolarity equals 300 mosm/l ( or /Kg for Osmolality). The Osmolarity of the ICF is roughly the same. Since both ICF and ECF have the same osmoles, they are Isotonic (iso= same, tonic= tension). You can use the following picture to calculate the Osmolarity of each. n Osmotic Pressure If we have two solutions seperated by a semi-permeable membrane (permeable to water, non-permeable to solutes) as the picture above, three steps will occur: Page6

In (a) The left side of the U-tube has less osmolarity than the right side (osmolarity of water is zero), so water moves from the left side to the right side (osmosis) until the water level

8 In (a) The left side of the U-tube has less osmolarity than the right side (osmolarity of water is zero), so water moves from the left side to the right side (osmosis) until the water level (pressure) is enough to stop the movement of water, we call the pressure that is enough to stop osmosis, Osmotic Pressure. In (b), water keeps moving from lower osmolarity (left) to the higher osmolarity (right until the Osmotic Pressure in the right side of the U-tube prevents movement of more water molecules. In which we reach a state of equilibrium. As shown in (c), we can prevent the movement of water by applying pressure to the right side of the U-tube, the pressure we must apply is equal to Osmotic Pressure. n We calculate the osmotic pressure by the following law: Where is the osmotic pressure, M is the molarity, R is the gas consant and T is the absolute temperature. n Additional info (only for acquaintance): we can use the method in the previous figure (c), to filter water (when pressing on the right side more than osmotic pressure, the water in the left side will rise in pure state because of the membrane which wont allow solutes through) n The Osmolality inside the cell is 300 mosm/l so: First solution is isotonic, because Osmolality is equal. there is no net movement of water Second solution is hypotonic or hyposmolar-solution (hypo=less), water will move into the cell (by osmosis) causing hemolysis (hemo=blood, lysis=bursting) -Note: we say hemolysis to RBCs, the rupture of other cells is simply called lysis The third solution is hypertonic or hyperosmolar solution (hyper= more), so the cell will lose water (by osmosis) and shrink, we also call that crenation of the cell. Page7

9 (The osmolality of water is zero since there aren t any osmoles) n -Question: if we want to make the plasma of a patient hypotonic, what do we inject him with? We inject him with water, which will cause RBCs to hemolyze and the person might end up dead. n For this reason, when we inject patients with solutions that are isotonic to our ECF and ICF (both 300 mosm/l), for example: % NaCl (9 grams per 1L of water) => Rq rq.r 300 mosm/l. 18: 9 from Na + and 9 from Cl - we multiply the percentage with 1000 so the unit becomes (gram/l) m Molar solution of CaCl 2 => 100 x 3 (Ca 2+, Cl -, Cl - )= 300mOsm/L m Molar of glucose => 300 mosm/l All the previous solutions have the same osmolality of our body. 2) Active Transport (uphill transport): it s the transport that needs energy to move solutes against their concentration/electrical/etc. gradient. It has two types: a) Primary active transport (Direct): These pumps are specific saturable proteins that pump solutes against their gradients. For instance: Na + /k + pump, Ca ++ pump and H + pump. they can also be called Na + /k + ATPase, Ca ++ ATPase and H + ATPase since they use ATP as a source of energy, they hydrolyze ATP directly for energy. These pumps can be electrogenic (genic= formation). Pumps generate voltage by unequal distribution of charge, the most common electrogenic pump is Na + /k + (moves 3 Na + cations out of the cell and 2 K + into the cell against their concentration gradient where the concentration of Na+ outside the cell is already higher than the inside). b) Secondary Active transport (indirect): In this type of active transport, the energy isn t used directly, the pump uses the energy stored in Na + or H + concentration gradients which is maintained by ATPases as Na + /k + ATPase (that s how its indirect). Na+/ Ca++ exchange: Na+ enters and Ca++ leaves. Page8

Na enters passively (by diffusion) but overall, it s active because the Na+/K+ pump is what maintains the Na+ outside in higher concentrations.

solutes: a) Symporter (sym= same): Also called Cotransport, both solutes move in the same direction.

Quiz 1- Emphysema is a lung disease, as in the picture, how does it affect gas exchange (diffusion): a- It doesn t affect it b- It increases

10 Na enters passively (by diffusion) but overall, it s active because the Na+/K+ pump is what maintains the Na+ outside in higher concentrations. The pump is active so Na+/Ca++ exchange does use ATP but indirectly There are two types of secondary transport according to the movement of solutes: a) Symporter (sym= same): Also called Cotransport, both solutes move in the same direction. b) Antiporter: Also called Counter transport: it moves the solutes in opposite directions. Quiz 1- Emphysema is a lung disease, as in the picture, how does it affect gas exchange (diffusion): a- It doesn t affect it b- It increases diffusion because of the space increasement C- It decreases diffusion because the surface area decreases 2- Pneumonia is a lung disease, which diffusion factor does it affect A- Thickness b- molecular weight c- concentration gradient d- electrical charge Page9

3-How does insulin help to increase glucose absorption by cells from blood? a- It sends signals to cells to build more carrier proteins for glucose to increase Vmax b- CHOOSE A!! c- CHOOSE A!

11 3-How does insulin help to increase glucose absorption by cells from blood? a- It sends signals to cells to build more carrier proteins for glucose to increase Vmax b- CHOOSE A!! c- CHOOSE A!! d- CHOOSE A!! 4-In the following picture, when does osmosis stop? a- When all the water in the right moves to the left b- When the osmolarity of the right side = osmolarity Of the left side c- When both sides have the same concentration of H 2 O D- When there is enough pressure on the left side (Osmotic pressure) 5-The solvent of the U-tube is a-plasma b-blood C-water d-fats 6-What is crenation A- Shrinking c- bursting a- Normal d- plasmolyzing 7-What would happen to Na + /glucose co transport if there is no Na + /k + pump? A-The cotransport would eventually stop because the Na gradient is lost. b-the cotransport would eventually stop because the glucose gradient is lost. c-na + /glucose is independent of any other pump *CORRECT ANSWERS ARE IN UPPERCASE* The End (finally!!) Page10

Chapter 4 Cell Membrane Transport

Chapter 4 Cell Membrane Transport Plasma Membrane Review o Functions Separate ICF / ECF Allow exchange of materials between ICF / ECF such as obtaining O2 and nutrients and getting rid of waste products