2 – Structure and Functions of Cell Membrane – Biochemistry for Nurses

2

Structure and Functions of Cell Membrane

CHAPTER OBJECTIVES
2.1. FLUID–MOSAIC MODEL

Between the living machinery inside a cell and the harsh conditions of the outside world stands the cell's plasma membrane which serves as a barrier. The plasma membrane consists of both lipids and proteins. While lipids are the fundamental structural elements of membranes, proteins are responsible for carrying out specific membrane functions. Most plasma membranes consist of approximately 50 per cent lipid and 50 per cent protein by weight, with the carbohydrate portions of glycolipids and glycoproteins constituting 5 to 10 per cent of the membrane mass. Since proteins are much larger than lipids, this percentage corresponds to about one protein molecule per every 50 to 100 molecules of lipid. Plasma membrane is surprisingly not solid or hard; it is flexible and in a fluid state. The plasma membrane is lipid bilayer with the lipid tails (the fatty acid part of the lipid is called tail) facing each other while the hydrophilic heads of lipids face outside and inside, interacting with polar molecules.

In 1972, Jonathan Singer and Garth Nicolson proposed the fluid mosaic model of membrane structure, which is now generally accepted as the basic paradigm for the organization of all biological membranes. In this model, membranes are viewed as two-dimensional fluids in which proteins are inserted into lipid bilayers (Figure 2.1).

The fundamental structure of the membrane is the phospholipid bilayer, which forms a stable barrier between two aqueous compartments. In the case of the plasma membrane, these compartments are the inside and the outside of the cell. Proteins embedded within the phospholipid bilayer carry out the specific functions of the plasma membrane, including selective transport of molecules and cell–cell recognition.

 

 

Figure 2.1 Fluid–Mosaic Model of Biological Membrane Conceived by S.J. Singer and Garth Nicolson in 1972 to Describe Structural Features of Biomembrane

Two general features of phospholipid bilayers are critical to membrane function. First, the structure of phospholipids is responsible for the basic function of membranes as barriers between two aqueous compartments. Because the interior of the phospholipid bilayer is occupied by hydrophobic fatty acid chains, the membrane is impermeable to water-soluble molecules, including ions and most biological molecules (because they are charged). Second, bilayer of the naturally occurring phospholipids is viscous fluids, not solids. The fatty acids of most natural phospholipids have one or more double bonds, which introduce kinks into the hydrocarbon chains and make them difficult to pack together. The long hydrocarbon chains of the fatty acids therefore move freely in the interior of the membrane, so the membrane itself is soft and flexible. In addition, both phospholipids and proteins are free to diffuse laterally within the membrane—a property that is critical for many membrane functions. These properties define the essential feature of the fluid–mosaic model of Singer and Nicolson, 1972. Proteins embedded within the phospholipid part of the role of the glycocalyx is to protect the cell surface. In addition, the oligosaccharides of the glycocalyx serve as markers for a variety of cell–cell interactions. A well-studied example of these interactions is the adhesion of white blood cells (leukocytes) to the endothelial cells that line blood vessels—a process that allows the leukocytes to leave the circulatory system and mediate the inflammatory response in injured tissues.

The extracellular portions of plasma membrane proteins are generally glycosylated. Likewise, the carbohydrate portions of glycolipids are exposed on the outer face of the plasma membrane. Consequently, the surface of the cell is covered by a carbohydrate coat, known as the glycocalyx, formed by the oligosaccharides of glycolipids and transmembrane glycoproteins.

Part of the role of the glycocalyx is to protect the cell surface. In addition, the oligosaccharides of the glycocalyx serve as markers for a variety of cell–cell interactions.

2.2 CYTOSKELETON AND CELL–CELL INTERACTION

Cells contain elaborate arrays of protein fibres that serve such functions so as to provide mechanical strength to the cell, establishing cell shape, locomotion, chromosome separation during mitosis and meiosis and intracellular transport of organelles

The cytoskeleton is made up of the following three kinds of protein filaments:

  1. Actin filaments (also called microfilaments)
  2. Intermediate filaments
  3. Microtubules

Microfilaments are long solid fibres 4–6 nm in diameter that are made up of actin. Not only is actin present in muscles, its mRNA is also present in all types of cells. It is the most abundant protein present in mammalian cells, sometimes accounting for as much as 15 per cent of the total protein in the cell.

The actin fibres attach to various parts of the cytoskeleton. They reach the tips of the microvilli on the epithelial cells of the intestinal mucosa. They are also abundant in the lamellopodia that cells put out when they crawl along surfaces. The actin fibres intersect with integrin receptors and form focal adhesion complexes, which serve as points of attraction with the surface over which the cell pulls itself. In addition, some molecular motors use microfilaments as tracks.

Intermediate filaments are cytoplasmic fibres of average 10 nm in diameter (and thus are ‘intermediate’ in size between actin filaments (8 nm) and microtubules (25 nm) (as well as of the thick filaments of skeletal muscle fibres).

There are several types of intermediate filaments, each constructed from one or more proteins characteristic of it. Keratins are found in epithelial cells and also form hair and nails. Nuclear lamins form a meshwork that stabilizes the inner membrane of the nuclear envelope.

Despite their chemical diversity, intermediate filaments play similar roles in the cell: providing a supporting framework within the cell. For example, the nucleus in epithelial cells is held within the cell by a basket like network of intermediate filaments made of keratins.

Microtubules are straight, hollow cylinders whose wall is made up of a ring of 13 ‘protofilaments’ and have a diameter of about 25 nm. Microtubules are built by the assembly of dimers of α tubulin and β tubulin.

Microtubules participate in a wide variety of cell activities. Most involve motion. The motion is provided by protein ‘motors’ that use the energy of ATP to move along the microtubule to migrate to the basolateral surface of the cell, and the basolateral set must not be allowed to migrate to the apical surface. Furthermore, the spaces between epithelial cells must be tightly sealed, so that the transported molecules cannot diffuse back into the gut lumen through these spaces.

2.3 TRANSPORT MECHANISM ACROSS PLASMA MEMBRANE

Lipid bilayer is selectively or semi-permeable membrane and is impermeable to most essential macromolecules such as proteins, carbohydrates and ions. The lipid bilayer is permeable to water molecules and a few other small, uncharged, molecules like oxygen (O2) and carbon dioxide (CO2). These diffuse freely in and out of the cell. The diffusion of water through the plasma membrane is of such importance to the cell that it is given a special name. Lipid bilayer is not permeable to ions such as K+, Na+ and Ca2+ unless energy is spent on the transport process.

2.3.1 Diffusion

Diffusion is spontaneous movement of particles from an area of high concentration to an area of low concentration till equilibrium is reached. It does not require energy and occurs via random kinetic movement. Water, while polar, is small enough to freely move across the plasma membrane. Oxygen, H2O, CO2 rapidly diffuse across lipid bilayer. Larger hydrophilic uncharged molecules, such as sugars, do not freely diffuse. Ion channels and specific transporters are required for the transport of charged molecules and larger uncharged molecules.

2.3.2 Osmosis

Plasma membrane is permeable to water but not to solute. Osmosis is the diffusion of water across a semi-permeable membrane. Water moves from solution with lower concentration of dissolved particles to solution with higher concentration of dissolved particles. Water moves from dilute solution to concentrated solution.

2.3.3 Facilitated Diffusion

Facilitated diffusion allows transport of large, membrane-insoluble compounds such as sugars and amino acids. This is mediated by transporters which are transmembrane (membrane spanning) proteins and therefore it is highly specific process for specific molecules. The process is concentration dependent and without expenditure of energy.

2.3.4 Membrane Channels

The definition of a channel (or a pore) is that of a protein structure that facilitates the translocation of molecules or ions across the membrane through the creation of a central aqueous channel in the protein. This central channel facilitates diffusion in both directions depending upon the direction of the concentration gradient. Channel proteins do not bind or sequester the molecule or ion that is moving through the channel. Specificity of channels for ions or molecules is a function of the size and charge of the substance. The flow of molecules through a channel can be regulated by various mechanisms that result in opening or closing of the passageway.

Membrane channels are of three distinct types: The α-type channels are homo- or hetero-oligomeric structures that in the later case consist of several dissimilar proteins. This class of channel protein has between 2 and 22 transmembrane α-helical domains which explains the derivation of their class. Molecules move through α-type channels down their concentration gradients and thus require no input of metabolic energy. Some channels of this class are highly specific with respect to the molecule translocated across the membrane while others are not. In addition, there may be differences from tissue to tissue in the channel used to transport the same molecule. As an example, there are over 15 different K+-specific voltage-regulated channels in humans.

The transport of molecules through α-type channels occurs by several different mechanisms. These mechanisms include changes in membrane potential (termed voltage-regulated or voltage-gated), phosphorylation of the channel protein, intracellular Ca2+, G-proteins and organic modulators.

Aquaporins (AQP) are a family of α-type channels responsible for the transport of water across membranes. At least 11 aquaporin proteins have been identified in mammals with 10 known in humans (termed AQP0 through AQP9). A related family of proteins is called the aquaglyceroporins which are involved in water transport as well as the transport of other small molecules. AQP9 is the human aquaglyceroporin. The aquaporins assemble in the membrane as homotetramers with each monomer consisting of six transmembrane α-helical domains forming the distinct water pore. Probably the most significant location of aquaporin expression is in the kidney. The proximal tubule expresses AQP1, AQP7 and AQP8, while the collecting ducts express AQP2, AQP3, AQP4, AQP6 and AQP8. Loss of function of the renal aquaporins is associated with several disease states. Reduced expression of AQP2 is associated with nephrogenic diabetes insipidus (NDI), acquired hypokalemia and hypercalcemia.

The β-barrel channels (also called porins) are so named because they have a transmembrane domain that consists of β-strands forming a β-barrel structure. Porins are found in the outer membranes of mitochondria. The mitochondrial porins are voltage-gated anion channels that are involved in mitochondrial homeostasis and apoptosis.

The pore-forming toxins represent the third class of membrane channels. The defensins are a family of small cysteine-rich antibiotic proteins that are pore-forming channels found in epithelial and hematopoietic cells. The defensins are involved in host defense against microbes (hence the derivation of the name) and may be involved in endocrine regulation during infection. Although this is a large class of proteins first identified in bacteria, there are a few proteins of this class expressed in mammalian cells.

2.3.5 Membrane Transporters

Transporters are distinguished from channels because they catalyze (mediate) the movement of ions and molecules by physically binding to and moving the substance across the membrane. Transporter activity can be measured by the same kinetic parameters applied to the study of enzyme kinetics. Transporters exhibit specificity for the molecule being transported as well as show defined kinetics in the transport process. Transporters can also be affected by both competitive and non-competitive inhibitors. Transporters are also known as carriers, permeases, translocators, translocases and porters. Mediated transporters are classified based upon the stoichiometry of the transport process. Uniporters transport a single molecule at a time, symporters simultaneously transport two different molecules in the same direction, and antiporters transport two different molecules in opposite directions.

The action of transporters is divided into two classifications: passive-mediated transport (also called facilitated diffusion) and active transport. Facilitated diffusion involves the transport of specific molecules from an area of high concentration to one of low concentration which results in an equilibration of the concentration gradient. Glucose transporters are a good example of passive-mediated (facilitative diffusion) transporters.

In contrast, active transporters transport specific molecules from an area of low concentration to that of high concentration. Because this process is thermodynamically unfavourable, the process must be coupled an exergonic process, for example, hydrolysis of ATP. There are many different classes of transporters that couple the hydrolysis of ATP to the transport of specific molecules. In general, these transporters are referred to as ATPases. These ATPases are so named because they are auto-phosphorylated by ATP during the transport process. There are four different types of ATPases, but most studied example is Na+/K+-ATPase.

2.3.6 Active Transport: Na+-K+ Pump

The active transport is always against a higher concentration and needs input of energy. The energy is provided by the hydrolysis of ATP. The transport of Na+-K+ the cell provides a good example of active transport. The transport of Na+/K+- is carried out by an enzyme called Na+/K+-ATPase, because it behaves as a ATP cleavage enzyme and simultaneously transports 3 Na+ from inside to outside and 2 K+ from outside to inside. This process is responsible for maintaining the large excess of Na+ outside the cell and the large excess of K+ ions on the inside. The Na+/K+-ATPase is also called a pump because the ions are transported from a region of lower concentration towards region of higher concentration. The sodium–potassium pump is an important contributor to action potential produced by nerve cells. This pump is called a P-type ion pump because the ATP interaction phosphorylates the transport protein and causes a change in its conformation.

A cycle of the transport process is schematically shown in Figure 2.2. The binding and subsequent phosphorylation of the enzymes results in conformational changes and the enzymes expels 3 Na+ while 2 K+ bind Na+/K+-ATPase. This is followed by dephosphorylation of the enzymes which brings about changes in the structure of the enzyme and release of K+ inside.

 

 

Figure 2.2 Transport of Na+ and K+ Across Membrane by Na+ / K+ Pump

2.4 ACID–BASE BALANCE: BLOOD pH, BUFFERING AND DIAGNOSIS

As the acidity and alkalinity are displayed by a pH scale from 0 to 14, the neutral pH is 7.0. An important property of the blood is its maintenance of pH. Body acidity increases when the level of acidic compounds in the body rises due to either increased uptake of acid producing food ingredients or due to decreased excretion through kidney. Body alkalinity increases due to reverse of this process. The body's balance between acidity and alkalinity is referred as acid–base balance. Due to a fine mechanism, the blood pH is closely maintained around pH 7.4, in the range from 7.35 to 7.45, below or above which acidosis or alkalosis begins. The acidosis refers to decrease in blood pH below 7.35 while above pH 7.45, alkalosis condition begins.

The blood pH is maintained close to 7.4 by bicarbonate buffering system of the body and by elimination of excess acids by the kidney. Arterial blood gas analysis is used to detect acidosis. The concentration of blood bicarbonate is maintained by the dissolved CO2 to 24 mM (of blood).

The formation of bicarbonate ion in blood from CO2 and H2O allows the transfer of relatively insoluble CO2 from the tissues to the lungs, where it is expelled. The major source of CO2 in the tissues comes from the oxidation of ingested carbon compounds.

Carbonic acid is formed from the reaction of dissolved CO2 with H2O. The relationship between carbonic acid and bicarbonate ion formation is shown in the two equations below:

 

 

The reactions shown occur predominately in the erythrocytes, since nearly all of the CO2 leaving tissues via the capillary endothelium are taken up by these cells. This reaction is catalyzed by carbonic anhydrase. Ionization of carbonic acid then occurs spontaneously (second equation above), yielding bicarbonate ion.

Carbonic acid is a relatively strong acid with a pKa of 3.8. However, carbonic acid is in equilibrium with dissolved CO2. Therefore, the equilibrium equation for the sum of the above equations requires a conversion factor, since CO2 is a dissolved gas. This factor has been shown to be approximately 0.03 times the partial pressure of CO2 (pCO2).

According to the Hendersson–Hasselbalch equation, the pH of blood will be

 

 

As the pKa of bicarbonate formation is 6.1, the blood pH can be calculated as follows:

 

2.4.1 Symptoms and Diagnosis

The symptoms of acidosis are non-specific clinically and include chest pain, palpitation, headache, nausea, vomiting and abdominal pain. Extreme acidosis induced by excess acid production in the body leads to coma and seizures. Arterial blood gas sampling, bicarbonate levels in the blood (normal being 24 mM) and electrolyte balance, like sodium, chloride and anion gap are the useful tool to identify acidosis. The anion gap is calculated as follows:

There are two organs primarily involved in maintaining acid–base balance of blood. The lungs control bicarbonate-carbonate buffering system of blood. The gas is constantly exhaled through lungs. The excess metabolic activity and increased release of carbon dioxide gas may contribute in acidosis

 

 

The kidney is responsible for releasing excess acids from blood but kidney acidosis results due to problems in acids excretion. Diabetic acidosis occurs due to release of ketone bodies (keto acids) as a result of excess utilization of fats during diabetic mellitus. Smoking is a major contributor of respiratory acidosis.

2.5 CHEMISTRY OF WATER, pH AND BUFFERS

Water is a universal solvent and medium of life because most biomolecules are solubilized by water except oils and fats. Water acts as a universal solvent primarily because of its unique properties.

Water is comprised of two atoms of hydrogen and one atom of oxygen held together by covalent bond.

The water molecule maintains a bent shape (bent at 104.5 degrees) actually because of two considerations. First the tetrahedral arrangement around the oxygen and second the presence of lone pair electrons on the oxygen which are not involved in the covalent bonds. The pairs of electrons are left alone. These lone pairs are very negative—containing two negative electrons each—and want to stay away from each other as much as possible. These repulsive forces act to push the hydrogen closer together.

 

 

If we do a similar arrangement of water, putting oxygen in the centre, and using the two hydrogens and two lone pairs at the corners, we also come up with a tetrahedral arrangement. However, there is one important difference—the bond angles for water are not 109.5. Because of the presence of the very negative lone pair electrons, the two hydrogens are squeezed together as the two lone pairs try to get away from each other as far as possible. The resulting angle gives water a 104.5 bond angle.

The shape and structure of a molecule is an important determinant of its function. The importance of the bent structure of water is that it provides water with two distinct ‘sides’: One side of the water molecule has two negative lone pairs, while the other side presents the two hydrogens which are partially positively charged as follows:

 

 

Thus, water is highly polar with a dipole created by negatively charged oxygen and positively charged protons. This property of water is responsible for hydrogen bonding between water molecules and consequently water is liquid and has a higher boiling point compared to acetone, methanol and ethanol, in spite of the fact it has low molecular weight of 18 (Figure 2.3). All molecules like oxygen, nitrogen, carbon dioxide, etc., in spite of higher molecular weight than water, are in gaseous state.

Because water has a slightly negative end and a slightly positive end, it can interact with itself and form a highly organized ‘inter-molecular’ network. The positive hydrogen end of one molecule can interact favourably with the negative lone pair of another water molecule. This interaction is called ‘hydrogen bond’(Figure 2.3). It is a type of weak electrostatic attraction (positive to negative). Because each and every one of the water molecule can form four hydrogen bonds, an elaborate network of molecules is formed. And to interact with other polar molecules—which is how substances become dissolved in water. Thus, because of continuous hydrogen bonding, the water behaves as continuous polymer. The ability of water to be bonded through hydrogen bonding explains its ability to solubilize polar molecules such as glucose, as explained below in Figure 2.4.

 

 

Figure 2.3 Hydrogen Bonding in Water

 

 

Figure 2.4 Structure of Glucose Soluble in Water

2.5.1 Buffers

Consider an acid HA that ionizes as follows:

 

 

HA is an acid as per the definition of Bronsted because it donates a proton (H+).

According to the Law of Mass action, the dissociation constant (Ka) for a weak acid, HA, is defined as

 

 

Multiplying both the sides with–log and then replacing–log with ‘p’ as per Sorenson, gives the Henderson–Hasselbalch equation, which describes pH in terms of pKa

 

 

In this equation, [A] is the concentration of the conjugate base and [HA] is the concentration of the acid.

Thus, under the condition, when the concentrations of acid (HA) and conjugate base (A) are equal, often described as half-neutralization, pH = pKa. In general, the pH of a buffer solution may be easily calculated, knowing the composition of the mixture.

The calculated pH may be different from measured pH. Glass electrodes found in common pH metres respond not to the concentration of hydrogen ions ([H+]), but to their activity, which depends on several factors, primarily on the ionic strength of the media. For example, calculation of pH of phosphate-buffered saline would give the value of 7.96, whereas the actual pH is 7.4.

The same considerations apply to a mixture of a weak base, B and its conjugate acid BH+.

 

 

The pKa value to be used is that of the acid conjugate to the base.

2.5.2 Buffering Action

An acid is considered as weak if it is poorly ionized, while strong when it is strongly ionized. A buffer is defined as solution which resists a change in pH. The buffer, in general, may be made up of more than one weak acid and its conjugate base. If the individual buffer regions overlap, a wider buffer region is created by mixing the two buffering agents.

In order to understand how buffers resist a change in pH upon addition of an acid or a base, it is necessary to understand the reactions of weak acid, its salts, or, for that matter, weak base and its salts.

First, let us consider a buffer made from weak acid (HA, like acetic acid) and its salt (like sodium acetate). This is called acid buffer.

 

 

Let us consider its dissociation since CH3COOH is a weak acid, it is sparingly soluble and hence the equilibrium lies to the left. That means, the concentration of undissociated CH3COOH is more than the dissociated acid (CH3COO) as follows:

 

 

When the salt, CH3COONa too is added to it, the above equation is shifted more towards the left as the common ion CH3COO from the salt suppresses the equilibrium according to Le Chatelier's principle.

As a result, the buffer solution will have much undissociated CH3COOH, CH3COO from the salt and some H+.

When externally strong acid like HCl [i.e. H+ and Cl] is added to this buffer solution, the H+ from HCl combines with the CH3COO from the salt as under H+ + CH3COO → CH3COOH which is sparingly soluble. Thus, the externally added H+ (as HCl) are converted to CH3COOH. Thus, this solution acts as buffer.

Similarly, a buffer made from weak base and its salt is called basic buffer. For example, NH4OH + NH4Cl.

Let us consider its dissociation. Since NH4OH is a weak acid, it is sparingly soluble and hence the equilibrium lies to the left, that is, the concentration of undissociated NH4OH is more than the dissociated.

When the salt, NH4Cl is added to it, the above equation is shifted more towards the left as the common ion NH4+ from the salt suppresses the equilibrium, according to Le Chatelier's principle.

As a result the buffer solution will have much of NH4OH, NH4+ from the salt and some OH. When externally strong base like NaOH [i.e. OHand Na+] is added to this buffer solution, the OH from NaOH combines with the NH4+ from the salt as under OH + NH4+ → NH4OH, which is sparingly soluble. Thus, the externally added OH are converted to undissociated NH4OH. Thus, this solution acts as buffer.

2.6 WATER ELECTROLYTE BALANCE

Electrolytes are metal and non-metal charged particles that readily dissolve in water. The predominant positively charged ions in the body are sodium, potassium, calcium and magnesium, while negatively charged electrolytes include chloride, phosphates and bicarbonate. The concentration of electrolytes must be maintained within a narrow range within the blood, otherwise deleterious physiological effects may occur. Electrolyte concentrations of extracellular fluid can be measured in a blood sample.

The electrolytes involved in disorders of salt balance are most often sodium, potassium, calcium, phosphate and magnesium. The concentration of blood chloride is usually similar to the blood sodium concentration, while bicarbonate is related to acid–base balance. The concentration of sodium is critical to maintain electrical voltage during heart function and the concentration of sodium in blood is maintained at 14–146 mEq (milli equivalent)

The most common electrolyte disorder is hyponatremia, which is characterized by low sodium in the blood, below 136 mEq per litre of blood. Lethargy and confusion are typically the first signs of hyponatremia. Muscle twitching and seizures may occur as hyponatremia progresses with risk of stupor, coma and death in the most severe cases.

Hypernatremia is a condition characterized by a high concentration of sodium in the blood, above 145 mEq per litre of blood. There is too little water compared to the amount of sodium in the blood, often resulting from a low intake of water. Profuse sweating, vomiting, fever, diarrhoea, or abnormal kidney function may result in hypernatremia.

Potassium plays a major part in cell metabolism and in nerve and muscle cell function. Most of the body's potassium is located intracellularly, not extracellularly or in the blood. Too high or low concentrations of blood potassium can have serious effects such as an abnormal heart rhythm or cardiac arrest. The potassium concentration in the blood is maintained with the assistance of intracellular potassium.

Calcium is necessary for proper functioning in many areas of the body including nerve conduction, muscle contraction and enzyme functions. Like other electrolytes, the body controls calcium levels both in blood and cells. Calcium from the diet is absorbed in the gastrointestinal tract while the excess is excreted in the urine. A minimum of 500–1000 mg of calcium is required daily in order to maintain a normal calcium concentration.

A low potassium blood level is referred to as hypokalemia. It occurs when the blood potassium concentration falls below 3.8 mEq per litre of blood. Hypokalemia is common in the elderly. Common causes include decreased intake of potassium during acute illness, nausea and vomiting, and treatment with thiazide or loop diuretics. About 20 per cent of patients receiving thiazide diuretics develop hypokalemia, which is dose-dependent but usually mild. Since several foods contain potassium, hypokalemia is not typically due to a low intake. It is usually due to malfunction of the kidneys or abnormal loss through the gastrointestinal tract. People with heart disease have to be especially cautious regarding hypokalemia (particularly, when taking digoxin), because they are prone to developing abnormal heart rhythms.

A high level of potassium in the blood is referred to as hyperkalemia. It occurs when the blood potassium concentration rises above 5.0 mEq per litre of blood. The kidney's ability to excrete potassium is over-whelmed due to a rapid influx into the blood, resulting in life-threatening hyperkalemia. Generally, hyperkalemia is more dangerous than hypokalemia. A blood potassium concentration above 5.5 mEq/litre starts to affect the electrical conducting system in the heart. If the concentration continues to increase, the heart rhythm becomes irregular which may cause the heart to eventually stop.

Mild hyperkalemia often may not produce any symptoms. Symptoms may include an irregular heartbeat that could be experienced as palpitations. Hyperkalemia is typically first diagnosed during a routine blood test or by examining changes in an electrocardiogram. Severe deficiencies may lead to muscular weakness, twitches and paralysis.

Magnesium influences the function of many enzymes. Dietary intake is essential to maintain normal levels. The body's magnesium stores are predominately found in bone with little appearing in the blood. A low level of magnesium in the blood is known as hypomagnesemia. The level of magnesium in the blood decreases below 1.6 mEq per litre of blood. Metabolic and nutritional disorders are usually the culprit of hypomagnesemia, most often when intake of magnesium is decreased during starvation or intestinal malabsorption compounded with greater kidney excretion.

A high level of magnesium in the blood is referred to as hypermagnesemia. The blood magnesium concentration rises above 2.1 mEq per litre of blood.

Phosphorus occurs in the body almost solely in the form of phosphate, which is composed of one phosphorus and four oxygen atoms. Phosphate is found mostly in bones, although a significant amount is found intracellularly. It plays an active role in energy metabolism and acid–base regulation, and it is used as a building block for DNA. Phosphate is excreted in the urine.

EXERCISES
  1. Discuss in detail the structure of fluid membrane.
  2. Write short notes on:
    1. Membrane assembly
    2. Disorders of membrane
    3. Acid–base balance
    4. Active transport
    5. Buffers and pH
  3. Write the difference between:
    1. Osmosis and diffusion
    2. Acidosis and alkalosis
  4. Write in detail about the bicarbonate buffer system.
  5. Give an account of plasma lipid and plasma protein.
  6. Write the structure of water and show its hydrogen bonding with the help of a diagram.
Multiple Choice Questions
  1. The pH of gastric juice in infants is
    1. 2.0
    2. 4.0
    3. 4.5
    4. 5.0

     

    Ans. d

  2. The pH of blood is 7.4 when the ratio between [NaHCO3] and [H2CO3] is
    1. 10:1
    2. 20:1
    3. 25:1
    4. 30:1

     

    Ans. b

  3. The difference in pH between arterial and venous blood is rarely more than
    1. 0.02
    2. 0.03
    3. 0.04
    4. 0.06

     

    Ans. c

  4. The chief buffering system in the blood is
    1. K2HPO4 and KH2PO4
    2. B. Protein and H. Protein
    3. NaHCO3 and H2CO3
    4. B. Haemoglobin and H. Haemoglobin

     

    Ans. c

  5. During severe muscular exercise, when the blood lactic acid content rises over 100 mg per 100 ml the pH of blood
    1. Slightly increases
    2. Highly increases
    3. Slightly decreases
    4. Markedly decreases

     

    Ans. d

  6. The pH of urine usually is
    1. 5.6
    2. 6.0
    3. 6.4
    4. 6.8

     

    Ans. b

  7. The osmotic pressure of a solution increases with the rise in
    1. Temperature
    2. Cold
    3. Humidity
    4. Rancidity

     

    Ans. a

  8. The osmotic pressure of a solution relating to solute molecules depends on the
    1. Size
    2. Shape
    3. Number
    4. Volume

     

    Ans. c

  9. If a cell is immersed in a concentrated solution, it follows the phenomenon
    1. Turgor
    2. Plasmolysis
    3. Hemolysis
    4. Paralysis

     

    Ans. b

  10. Osmosis is opposite to
    1. Effusion
    2. Transport
    3. Confusion
    4. Diffusion

     

    Ans. d

  11. The intracellular fluid of red cells and the red cell membrane in 0.92 per cent NaCl solution maintains a relation
    1. Hypertonic
    2. Hypotonic
    3. Isotonic
    4. None of the above

     

    Ans. c

  12. Hemolysis is caused by the dilution of RBC by
    1. Diffusion
    2. Osmosis
    3. Effusion
    4. Imbibation

     

    Ans. b

  13. The surface tension of a solution is decreased by
    1. Calcium sulphate
    2. Barium sulphate
    3. Magnesium phosphate
    4. Potassium permanganate

     

    Ans. d

  14. The surface tension of a solution is lowered by
    1. Ammonia
    2. Sodium hydroxide
    3. Potassium hydroxide
    4. Aluminium hydroxide

     

    Ans. a

  15. The surface tension of a solution is increased by
    1. Bile salts
    2. Bile acids
    3. Concentrated sulphuric acid
    4. Acetic acid

     

    Ans. c

  16. Bile salts make emulsification with fat for the action of
    1. Amylase
    2. Lipase
    3. Pepsin
    4. Trypsin

     

    Ans. b