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Recommended Reading Notes: Body Fluid Compartment: Chapter 2, p14- 25 What is the principle chemical elements of the body and their percentage of body weight? Oxygen (65%), Carbon (18%), Hydrogen (10%), Nitrogen (3%), Calcium (1%), Phosphorous (1%), Potassium (0%), Sulphur (0%), Sodium (0%), Chlorin...

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Recommended Reading Notes: Body Fluid Compartment: Chapter 2, p14-25 What is the principle chemical elements of the body and their percentage of body weight? Oxygen (65%), Carbon (18%), Hydrogen (10%), Nitrogen (3.4%), Calcium (1.5%), Phosphorous (1.2%), Potassium (0.28%), Sulphur (0.25%), Sodium (0.17%), Chlorine (0.16%), Magnesium (0.05%), Iron (0.0007%), Zinc (0.002%), Iodine (0.00004%) What are hydrogen bonds? When a hydrogen atom of a polar bond is attracted to a neighbouring oxygen or nitrogen atom a hydrogen bond is formed. They are weaker than covalent and ionic bonds. What is a polar bond? When the shared electrons in a covalent bond are not equally distributed between the 2 atoms, so the electrons are more associated with one atom more than the other. What is the law of conservation of matter? The number of atoms remain the same but their arrangement changes. What is a solvent? A solvent is a liquid that can dissolve a substance (solute) to form a solution. What is molarity? Molarity is the number of moles or millimoles per litre of solution. Eg: 0.1M solution of glucose contains 0.1 moles of glucose per litre of solution

What are some examples of polar substances? NaCl, sucrose, ethanol, acetic acid What are the main strong electrolytes in physiology? Sodium, potassium, calcium, magnesium and chloride ions. What are the main weak electrolytes in physiology? Bicarbonate and phosphate ions. What does rate of diffusion in a solvent depend on? -

Temperature Conc gradient Molecular characteristics of solute and solvent (diffusion coefficient) Area available for diffusion

What is Fick’s law of diffusion? The role of different factors affecting diffusion is expressed in Fick’s law of diffusion. Amount moved = Coefficient x area x conc gradient

Large molecules diffuse slower than small ones. What is osmosis? Osmosis is the movement of water through a semipermeable membrane which allows the movement of water but not other solute particles. What is osmotic pressure? A hydrostatic pressure enough to stop the flow of water through osmosis is called osmotic pressure.

Solutions that have the same molality have the same osmolality. EXCEPTION: aqueous salt solutions, you must double their molality to work out osmolality because they separate into their constituent ions so will exert an osmotic pressure double that of its molal conc. Instead of measuring osmotic pressure directly, the osmolarity/osmolality is stated. Define osmolality: Moles solute particles per kg of water. 1g mole of a non-dissociating substance in 1kg of water has an osmotic pressure of 1 Osmol kg -1. Define osmolarity: Moles solute particles per litre of solution 1M solution of glucose has a concentration of 1 Osmol L-1.

What is the osmolality of the blood plasma? 0.3 Osm kg -1 (300 mOsmol kg -1) Principle ions (Na+, K+, Cl-, HCO3-) = 290 mOsmol kg-1 Glucose and other small molecules = 10 mOsmol kg-1 Proteins = 1 mOsmol kg-1 What is the colloid osmotic pressure/oncotic pressure? The small osmotic pressure exerted by proteins, plays an important role in fluid exchange between body compartments. What is tonicity of solutions? The influence of the osmolality of the solution on the volume of cells. Eg: -

red blood cell placed in 0.9% NaCl solution (0.9g in 100 ml of water) will not change because solution has osmolality of 310 mOsmol kg-1 which is like that of blood plasma. (isotonic saline solution)

Body Fluid Compartment: Chapter 3, p27-43 What are the principle minerals found in tissues? Order of abundance: -

calcium phosphorous potassium sodium

What is lean body mass? Mass of body without adipose tissue What is the water content of the lean body mass? 70-75% But, body fat (adipose tissue) contains 10% water, proportion of body weight contributed by water varies between sexes and age. 60% in adult males and 50% in adult females.

What is meant by fluid and what is it divided into? Fluid is the water plus the dissolved materials of cells and tissues. Can be divided into extracellular fluid and intracellular fluid. What is the extracellular fluid divided into? Plasma – the liquid fraction of the blood Interstitial fluid – fluid that lies outside the blood vessels and bathes the cells, contribution of lymph is also within this fluid What is meant by transcellular fluid? The extracellular fluid in the serosal spaces (ventricles of the brain, abdomincal cavity, joint capsules, ocular fluids) What does the interstitial space consist of? -

Connective tissue Chiefly collagen Hyaluronate Proteoglycan filaments

What does the water of the interstitial fluid do and what is the purpose of this? It hydrates the proteoglycan filaments and forms a gel. This stops the extracellular fluid from flowing to the lower regions of the body due to gravity. How is the body water divided?

How can the amount of water in the main fluid compartments be determined? By diluting specific markers. What qualities must the marker have? -

The marker disperses only in the compartment measured The marker disperses evenly in the compartment Must have no effect of its own o the distribution of fluids Marker is metabolically inert

How is the plasma volume estimated? Dilution of Evans Blue – does not readily pas across capillary walls into interstitial space and is bound to albumin Radio-labelled albumin is also used How is the total body water estimated? Known amount of radioactive (tritiated) water 3H2O or deuterium oxide 2H2O is injected and given time to be distributed throughout the whole body. A sample of blood is taken and the concentration of the marker is calculated. How is the extracellular fluid volume measured? Inulin/mannitol – passes freely between circulation and the interstitial fluid but does not enter cells. How is the volume of intracellular fluid measured? Difference between total body water and volume of extracellular fluid How is the volume measured? Individual with a body weight of 70 kg was injected with 10 ml of a 1 per cent (w/v) solution of the dye. Further assume that a sample of blood was taken after 10 min, and the plasma was found to contain 0.037 mg ml−1 of dye. What is the plasma volume? Volume = amount of dye/concentration Total amount of dye injected = 1% of 10 ml = 0.1 g = 100 mg Plasma conc after 10 mins = 0.037 mg ml -1 therefore: Plasma volume = 100/0.037 = 2702 ml What are some assumptions made and limitations doing this method? -

Dye is evenly distributed All of the dye remains in circulation Some dye is lost via excretion and corrections for that loss have to be made Water in bone and dense connective tissue equilibrates slowly so are nit included in estimates

How is the limitation overcome to give an accurate estimate of total body water? Volume = amount of marker infused – amount excreted / concentration in plasma

The Transport Functions of Cells: Chapter 5, p66-81 -

The nature of the cell membrane. How molecules cross the cell membrane. – Channels, carriers and metabolic pumps The difference between active and passive transport. How ion gradients are established across the cell membrane. How these gradients are exploited by cells. The mechanisms of constitutive and regulated secretion. Endocytosis.

How does the intracellular fluid composition differ from the extracellular fluid? Rich in potassium ions but poor in both sodium and chloride ions. Rich in protein enzymes, structural proteins and small organic molecules involved in metabolism and signalling such as amino acids, ATP, fatty acids. What is the overall ionic composition of the intracellular and extracellular fluid of mammalian skeletal muscle?

What is the resting membrane potential? -90 mV What is the membrane potential? Mammalian cells have an electrical potential across plasma membrane and its magnitude varies from -35 mV to -90 mV. Inside of the cell is always negative with respect to the outside. Existence of membrane potential influences diffusion of charged molecules and ions, positively charged molecules are attracted inside whilst negatively charged molecules are repelled. What factors determine the direction of movement of ions and charged molecules across a cell membrane? -

Conc gradient Charge of molecule or ion Membrane potential

What is an electrochemical gradient? A combination of conc gradient, charge of molecule or ion and membrane potential gives the electrochemical gradient. Can be calculated by from difference between equilibrium potential for an ion and the membrane potential.

What is passive transport? When ions/molecules diffuse across a plasma membrane down their electrochemical gradient. What determines the rate at which a substance crosses a plasma membrane? Number and properties of channels and carrier proteins present. The more channels/carriers present the greater the permeability of the membrane. What is the equilibrium potential? It is the potential where the tendency of the ion to move down its conc gradient is exactly balanced by the membrane potential. The rate at which ions enter the cell is exactly balanced out by the rate at which they leave. How is equilibrium potential measured? Nernst Equation: E = RT/zF ln[C]o/[C]I F is 96,487 C mol-1 What are ion channels? Specific membrane proteins with pores that span the membrane and provide a route for a specific ion to diffuse down its electrochemical gradient. What are some main features of ion channels? -

Allow high permeability of natural membranes to various ions such as sodium, potassium and chloride Exists in 2 states: open and closed High capacity for transport High selectivity Named after the principle ion which they are permeable for

What are non-selective cation channels? Allow passage of a variety of positively charged ions to cross plasma membrane but do not allow negatively charged ions What are carrier proteins? Bind to specific substances (small organic molecules like gluclose) and undergo a conformational change. What is the capacity of a cell to transport a molecule limited by? -

Number of carrier proteins available Number of molecules each carrier can translocate in a given period of time (turnover number)

What are some features of carrier proteins? -

Transport fewer molecules than channels (typical values are between 102 and 103 Selective for molecules, can differentiate between optical isomers Some can transport molecules/ions against electrochemical gradients this is active transport.

What are uniports, symports and antiports? Uniports: bind to a specific molecule on one face of the membrane and then transfer it to the other side Symports: Type of cotransport/coupled transport, both molecules move in the same direction across the membrane Antiport: Type of cotransport/coupled transport, movement of an molecule into a cell is coupled to the movement of a second molecule out of the cell.

What is active transport? Requires a cell to expend embolic energy either directly or indirectly and involved carrier proteins. What is primary active transport? When the activity of a carrier protein is directly dependent on metabolic energy derived from hydrolysis of ATP. What is secondary active transport? When the transport of a substance against its conc gradient occurs by the coupling of its uphill movement to the downhill movement of sodium ions into the cell, and this depends on the ability of the sodium pump to keep intracellular conc of sodium lower than the ECF. What experiment was done on the giant squid axon? -

Rate at sodium ions being pumped out of axon was worked out by injecting the axon with radioactive sodium ions Adding cyanide stopped the pumping of sodium because it is an inhibitor for ATP generation Injecting ATP into cyanide poisoned axon restored sodium pumping

What did the experiment on squid axon show? -

Sodium pump requires intracellular ATP If potassium was removed from extracellular fluid then sodium efflux is inhibited Shows that intake of potassium is coupled to efflux of sodium

How can the sodium pump be inhibited? Glycoside – ouabain, binds to extracellular face of the protein Why is the intracellular sodium ion conc kept low? The sodium pump maintains the total osmolality of the intracellular compartment equal to that of the extracellular fluid so the cell volume is kept relatively constant. If this was not the case, then there is a tendency for the intracellular conc of ions to become equal to that of extracellular fluid by diffusing down electrochemical gradient. This means the osmolality of the intracellular fluid would increase as the large impermeant molecules cannot pass out of the cell to compensate for the inward movement of small ions. Why are intracellular hydrogen ion conc regulated? -

Readily react with and bind to proteins such as enzymes Change function of ion channels and contractile proteins like actin and myosin

How do cells regulate intracellular hydrogen ion conc? -

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Cell maintain intracellular conc close to 10-7 moles/l Extracellular fluid conc = 4 x 10-8 mol/l Sodium-hydrogen ion exchange – antiport (outward movement of hydrogen against electrochemical gradient and inward movement of sodium down electrochemical gradient) – secondary active transport Cotransport of sodium and bicarbonate ions into cells to increase intracellular bicarbonate – symport: transports sodium and bicarbonate ions into the cell against electrochemical gradient, bind to excess hydrogen ions to form carbonic acid. 1 molecule of CO2 leaving = 1 H+ used to make molecule of water Chloride-bicarbonate exchange – At high altitudes = low CO2 conc so cell are more alkaline. Intracellular bicarbonate exchanged for extracellular chloride (reversible)

How do cells regulate intracellular calcium? -

Intracellular conc of calcium = 10-7 – mol/l Extracellular conc of calcium = 1-2 x 10-3 mol/l Low level conc maintained at rest 1. Calcium pump: uses ATP to pump ions against conc gradient 2. Sodium-calcium exchanger: Influx of Na+ down conc gradient provides energy for efflux of Ca2+ - secondary active transport 3. SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase): Ca2+ stored in sarcoplasmic reticulm 4. Mitochondria: Ca2+/H+ antiporter which is high affinity but low capacity OR calcium uniport which is low affinity but large capacity

What is constitutive secretion? -

Performed by all cells to release/insert newly synthesised lipids and proteins such as carriers and ion channels into their plasma membranes Tightly regulated Happens over many minutes

What is regulated secretion? -

Triggered by chemical or electrical signal such as rise in intracellular Ca2+ like hormone or neurotransmitter release (physiological event) Happens over seconds/ fractions of a second

What is endocytosis? Membrane retrieval where small areas of the plasma membrane are pinched off to form endocytotic vesicles. Is a response to high levels of exocytosis What is pinocytosis? Called cell drinking as the formation of vesicle traps extracellular fluid What is fluid phase endocytosis? When proteins and macromolecules are absorbed with extracellular fluid during vesicle formation. What is receptor mediated endocytosis? -

Protein binds to specific surface receptors Activation of a cell surface receptor causes structural changed in the protein in the cytosolic side and induces internalisation

What is phagocytosis? -

Large particles are ingested by the cell Only triggered when receptors on surface of cells are bound to particle to be engulfed

The Membrane Potential: Chapter 5, p73-81 The origin of the membrane potential Define membrane potential: -

Sodium pump causes accumulation of potassium inside cell Plasma membrane is slightly permeable to potassium ions but less permeable for sodium ions Potassium ions leak outside of plasma membrane but sodium cannot replace them by diffusing into cell Loss of potassium cells causes a negative charge inside the membrane Negative charge causes a potential difference across membrane and this is called the membrane potential

What is meant by the potassium equilibrium potential? -

Negative value of membrane potential attracts positively charged potassium into the cell but they diffuse out of the cell down conc gradient, the potential at which these tendencies are exactly balanced is eqm potential, this is very close to resting membrane potential.

The relationship between the ionic permeability of the membrane and the membrane potential How does changes in ionic permeability alter the membrane potential? -

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Electrochemical gradients for different ions differ because they have different eqm potentials Membrane potential depends on ionic gradients across the cell membrane and on the permeability of the membrane to the different ions present For potassium at resting membrane potential, the potassium ion distribution is close to the eqm potential so tendency for potassium to diffuse out is balanced by the tendency of inward movement due to membrane potential (charge) For sodium, at resting the electrochemical gradient favours influx but the channels are not open so permeability is low. When channels open permeability is high so membrane potential is close to sodium’s eqm potential (depolarised = less negative)

What shows the relationship of membrane potential, ionic gradients and permeability of membrane to specific ions? Goldman equation:

The properties of ion channels: – ligand-gated channels – voltage-gated channels What is a ligand-gated channel? -

When ion channels open when they bind to specific agonist or ligand Used to send signals from one cell to another Cell is specialised and is adapted to respond to specific agonist

What is the difference between ligand and agonist? -

Ligand binds to another molecule Agonist binds to and activates a physiological system

What is a voltage gated ion channel? -

When ion channels open when the membrane potential changes when it becomes depolarised Channels spontaneously close after a short period of time – inactivation Channel exists in 3 different states: closed/resting sate, open and allow ions to cross, inactivated state

Cell signalling: Chapter 6, p83-97 The main types of signalling between cells. – paracrine, endocrine, and synaptic signalling What is paracrine signalling: The chemical signals are released by local mediators which act on neighbouring cells through diffusion over short distances. What is autocrine signalling: Secreted chemicals also act on cells that secreted it.

What is endocrine signalling? When hormones are secreted into the blood by specialised glands (endocrine glands) and this acts on various tissues around the body. What is synaptic signalling? When nerve cells release chemicals at their endings and affect the cells they contact. How cells detect chemical signals. How do cells detect chemical signals? -

Specific receptor molecules Process of transduction happens where there is a link between the detection of the signal and the response

What are some properties of receptors? -

Are proteins Located in plasma membrane where hydrophilic molecules from extracellular fluid can bind to Cells have cytoplasmic and nuclear receptors for hydrophobic signalling molecules Receptors exist intracellularly too for secondary messengers

How cells respond to various chemical signals. How do cells respond to various chemical signals? -

Individual cells have different types of receptors so they respond to different types of extracellular signals Response of a cell to a signal depends on which receptor is activated

How does the response to acetylcholine differ? -