Proteins| classification | structure and organization| deficiency diseases of proteins|

    PROTEINS    

Proteins are the highly complex chemical compounds present in all living organism. These are the high molecular weight polypeptides, composed of carbon, hydrogen, oxygen, nitrogen, Sulphur and phosphorus. Proteins are the most abundant and essential constituents of living cells. All the basic functions of life depend upon specific proteins. The term protein was first suggested by Swedish chemist Berzelius in 1938 and derived from the Greek word “proteins” meaning ‘first’. Gerardus Mulder for the first time used the term in 1840 and referred it to the complex organic nitrogenous substance found in the cells of living organisms. Proteins are the most significant compound in living beings depending upon their chemical and physical structures they are involved in wide variety of functions i.e. catalysis, conduction, contraction, structure, nutrition, binding and defense.

Chemical Structure of Proteins: -

Proteins are the linear polymers of amino acids. Proteins can be very long polypeptide chains of hundred to several thousand amino acids. When a large number of amino acids join together, they form polypeptides chains. The amino acids molecules in polypeptide chains are linked by polypeptide bonds. 

[Amino Acid] n → Peptide → Polypeptide → Protein

Peptide Bond: The amino acids of a protein are joined to one another by their respective amino and carboxyl groups i.e. the carboxyl group of one amino acid is joined to the amino group of the next amino acid to form a peptide bond or peptide linkage with the release of one molecule of water.

Fig: - formation of peptide bond

CLASSIFICATION OF PROTEINS: -

Proteins can be classified according to their functions, shape, structures and complexity. On the basis of their conformation the proteins can be classified into two major 

1). Fibrous proteins

2). Globular Proteins 

1). Fibrous proteins: - 

In fibrous proteins polypeptide chains are arranged in a parallel manner along a single axis producing long fibers or sheet like structures. Fibrous proteins Fibrous proteins are insoluble inwater or dilute salt solution. These are the basic structural elements in animal tissues. Keratin of hair and skin, elastin of ligament and collagen of tendons and bone matrix all are examples of fibrous proteins.

2). Globular Proteins: - 

Polypeptide chains are tightly folded into compact spherical or globular shapes. Most of the globular proteins are soluble in water example of globular proteins are all the enzymes, certain hormones, and antibodies etc. 

On the basis of their structure and complexity proteins are classified into three major classes: -

1). Simple proteins 

2). Conjugated or Complex proteins 

3). Derived proteins 

1). Simple proteins: - Proteins which consist solely of amino acid are called simple proteins. These are further classified into the following subclasses: -

Albumins: They are soluble in water and coagulate on heating. They are precipitated by dilute acids and alkalis. Albumins are widely distributed in nature stored as food reserved e.g. egg albumin, serum albumin, legumin (legumes), lactalbumin (milk), leucosin (cereals), gliadin (wheat). 

Protamine: They are basic proteins highly soluble in water, dilute acids and ammonium hydroxide. Protamine are not coagulated by heat. These are simplest of all the naturally occurring. proteins, isolated from mature sperms e.g. Sturine and salmine. 

Histones: These are soluble in water and dilute acids but insoluble in ammonia. They are not coagulated by heat. Histones occur as part of nucleoproteins. 

Scleroproteins: These are also known as albuminoids. Scleroproteins are soluble in water and solutions of neutral salts. They are found exclusively in animals e.g. keratin, collagen, elastin and fibroin.

Globulins: These are insoluble in water but are soluble in dilute neutral salt solution such as NaCl. On heating globulin get coagulated. They are precipitated by half saturated with ammonium sulphate examples of globulins are fibrinogen (blood plasma), egg globulin, myogenic (muscles), legumin (peas), tuberin (potato) etc. 

Glutelins: They are insoluble in water but are soluble in dilute acids and Alkalies, Glutelin get coagulate on heating. These are found exclusively in seeds of cereal grains e.g. glutenin (wheat) and oxyzenin (rice). 

Prolamins: These are insoluble in water but are soluble in dilute alkalies and 50-80% of alcohol. They are not coagulated by heat and found in plants only e.g. hordein (barley), gliadin (wheat) and zein (maize)

2. Conjugated Proteins: -These proteins are composed of not only amino acids but also some nonproteins components. This non-protein substance linked to proteins is called “prosthetic group”. Conjugated proteins are further classified into the following subclasses on the basis of their prosthetic group.

Glycoproteins: In glycoproteins simple proteins are covalently linked with carbohydrate group. The percent of carbohydrate group in different glycoproteins may vary from less than1% in egg albumin to as high as 80% in mucoproteins. Glycoproteins which have very high carbohydrate content are called proteoglycans. Examples of glycoproteins are mucin (saliva), heparin (bile juice), and immunoglobulins (plasma). 

Nucleoproteins: In nucleoproteins protein molecules are combined with nucleic acid. The chromatin material of the nuclei of cells is composed of nucleoproteins e.g. nucleohistones. 

Lipoproteins: Lipoproteins are the proteins in combination with lipids. These are present in the brain, egg, milk and plasma.

Phosphoproteins: Phosphoproteins are formed by the combination of simple proteins with phosphoric acid. Examples of phosphoproteins are vitelline (egg) and casein (milk). 

Metalloproteins: These are proteins linked to some metallic prosthetic group, which also gives colour to the proteins. They are also known as chromoproteins e.g. hemoglobin, hemocyanin, cytochromes and flavoproteins.

3. Derived Proteins: These proteins are derived from some previously existing proteins either by its hydrolysis or by its coagulation. Derived proteins can be divided into two major subclasses.

 Primary derived proteins: - These are denaturized or coagulated proteins. The denaturation is caused by heat, acid or alkali treatment. Their molecular weight is same as the native protein, but they differ in solubility, precipitation and crystallization. Examples are proteins, metaproteins, and coagulated proteins.

Secondary derived proteins:- These are formed by the hydrolysis of complex protein of their peptide linkage. The hydrolysis is caused by the action of digestive enzymes, acids or alkalis. Their molecular weight is different from the native proteins. Examples are proteoses, peptones and peptides. On the basis of their biological functions they are classified into seven major classes: 

i) Structural Proteins: Their function is strengthening or protecting biological structures e.g. keratin, fibroin, collagen, elastin etc. 

ii. Storage and Nutrient Proteins: Their function is to provide nourishment to growing e.g. ovalbumin, giadin, ferritin etc.

iii. Enzymatic Proteins: Their function is to transport molecules in body e.g. hemoglobin,serum albumin, myoglobin etc.

iv. Transport Proteins: Their function is to transport molecules or ions in body e.g. haemoglobin, myoglobin and serum albumin.

v. Regulatory Proteins: Their function is to regulate cellular or metabolic activities e.g. hormones, repressors etc.

vi. Contractile Proteins: Their function is in contractile system e.g. actin, myosin, tubulin, etc.

vii. Defense Proteins: Their function is to provide defense against other organisms e.g. antibodies, ricin etc.

Structural Organization of Proteins: -

Proteins are long polypeptide chains formed by the linkages of several thousand molecules of amino acid with a peptide bond. Proteins can be very long polypeptide chains of 100 to several thousand amino acid residues. There are four different structural level of organization are present in proteins, they are:

1). Primary structure

2). Secondary structure

3). Tertiary structure

4). Quartiary structure

GENERAL PROPERTIES OF PROTEINS: - 

SOLUBILITY 

The solubility of protein varies to the native because proteins are colloids of large-sized molecules these form turbine solution in water. These are also soluble in acid and salt solution while insoluble in alcohol. 

AMPHOTERIC NATURE: -

Like a-acid proteins are amphoteric in nature. They behave as acid alkaline solution and alkaline to acidic solution due to presence of several free- NH2 and COOH groups.

ZWITTERION FORMATION: - 

The protein is either positively or negatively charged molecule and in an electric field migrate either towards cathode or towards anode. They are electrically neutral and do not move towards any pole. 

HYDROLYSIS: -

 The protein undergoes hydrolysis by acid, alkali or hydrolytic enzymes which lead the protein to amino acids. Complete hydrolysis with HCl or H2SO4 and yields free a-acid thin breakdown products. 

DENATURATION 

Under certain conditions there is a disruption of secondary tertiary and quaternary structures of functional protein molecule resulting in the changes of its physical, chemical and biological characteristics. These changes occurring in proteins are collectively called denaturation. During denaturation only primary structure of protein is retained. Various physical and chemical elements such as heat, UV-rays, X-rays, ultrasonic waves, high pressure, acids, alkalis, detergents or certain organic solvents can cause denaturation of proteins. Physical and chemical properties of denatured proteins are different then the native proteins and they lose most of their biological activities, in denatured proteins the solubility is decreased or lost. During denaturation the soluble globular proteins are changed into insoluble fibrous proteins. The process of denaturation also destroys enzyme and hormonal activity and the proteins become biologically inactive. The process of denaturation in some proteins is returned to its native stable confirmation and regains their native structure and biological activity, this process is called renaturation.

METABOLISM OF PROTEINS 

Amino acids are the building blocks of proteins and proteins are the building material in the body. Metabolism of proteins involves both biosynthesis of amino acids as well as breakdown of amino acids. 

BIOSYNTHESIS OF AMINO ACID 

There are 20 standard amino acids known and these can be classified into the group on the basis of their synthesis in human and animals are called the non-essential amino acid whereas the amino acid which cannot be synthesized by the organisms, and they must be obtained through diet are called the essential amino acids. The pathways for the synthesis of these two types of amino acids are quite different. Non essential amino acids can be synthesized by quite simple reaction while synthesis of essential amino acids is quite complex. 

CATABOLISM OF AMINO ACIDS 

Amino acids are not only served as the building blocks of proteins but also serve as source of carbon and nitrogen, when required. The very first step in their catabolism is removal of –NH2 group and formation of corresponding keto-acid. The ammonia, which is liberated, quickly converted to urea and it is incorporated in some other a-acid. Catabolism of a-acid involves the following process:

1. Transamination

2. Deamination

3. Urea formation

4. Decarboxylation

✅Transamination: Russian workers Braunstein and Bychkov had shown the importance of transamination for the first time in 1939. It is the most important process of conversion of amino acid into keto acid. In this process amino group of one amino acid (donor) is transferred to an αketo acid (recipient) resulting in the formation of a new amino acid and a new keto acid. The donor amino acid is converted into a new keto acid and the recipient keto acid is converted into a new amino acid. Transamination is a reversible process and is catalyzed by the enzyme transaminase or amino transferase. Co-enzyme for the reaction is pyridoxal-5’-phosphate, a derivative of vitamin B6 (Pyridoxine). Transamination takes place principally in liver, kidney, heart and brain. Deamination: Deamination is a process in which amino group (-NH2) is removed from the amino acid, which then changes to a α-keto acid. In this process amino group is removed as ammonia. Deamination usually takes place in liver and kidney cells to catabolize excess of amino acids. 

There are two types of deamination:

i. Oxidative deamination

ii. Non oxidative deamination

✅Oxidative Deamination: When deamination process is accompanied by an oxidative reaction, is known as oxidative deamination. This process is catalyzed by a group of flavin containing enzymes known as amino acid oxidases. This is the two step reaction, in the first step the amino acid is dehydrogenated by the flavoprotein of the enzyme. In the next step with addition of H acid is formed. The enzyme amino acid oxidase is auto oxidizable flavoprotein. Reduced flavoprotein is oxidized to form hydrogen peroxide, which then broken up into H catalase.

✅Non oxidative Deamination: There are certain amino acids which can be deaminated non oxidatively. Non oxidative deamination is catalyzed by specific enzymes and NH3 is liberated in this process. One example of non-oxidative deamination is deamination of glutamate by the enzyme glutamate dehydrogenase. This reaction is reversible in which NAD act as coenzyme. Fate of Deaminated Amino Acids: Acids produced from transamination and deamination of amino acids are channeled to several metabolic routes. Some amino acids are deaminated to produce keto acids which are eventually oxidized to CO2 and H2O through acetoacetate and acetyl-co-A.  Aceto acetone is one of the chemical constituents of ‘ketone bodies’ formed in the pathological conditions of urine. 

Thus the amino acid which leads to the formation of acetoacetate during their metabolism are called ketogenic e.g. leucine & lysine Some amino acids are deaminated to produce keto acids which are broken down to pyruvate, α-keto glutamate, succinyl co-A, fumarate or oxaloacetate which can be utilized for the synthesis of glucose or glycogen. This amino acid is called glycogenic or antiketogenic amino acid example of glucogenic amino acids are called glucogenic or antiketogenic amino acids. Examples of glucogenic amino acids are alanine, glycine, serine, aspartate, glutamate, valine, histidine Argene, proline, methionine, cystine and arginine. Some amino acids are precursors of both glucose and ketone bodies are known as glucogenic and ketogenic amino acids. Examples are phenylalanine, tyrosine, isoleucine, threonine and tryptophan. Fate of Ammonia: Ammonia released during deamination is either converted into ammonium salt or into urea.

Formation of ammonium salts: -Ammonium ions (NH4+) are formed from some of the ammonia released by deamination of amino acids. These ammonium ions are excreted out from the body in the form of ammonium salts.

Formation of Urea (Urea cycle): When production of ammonia exceeds beyond a certain level it become toxic. Excess of ammonia produced during the deamination of amino acids is converted to less toxic substance, urea, before been excreted in the urine. Formation of urea is a cyclic process and the cycle is known as urea cycle. This cycle was first outlined by Hans Krebs and Kurt Henslie in 1932; hence it is also known as Kreb’s Hanseleit cycle. The chief site for urine formation is liver and after its formation urea passes into the blood Strem and form blood to kidneys s and finally excreted into the urine. Urea synthesis takes place in five steps. Each step is catalyzed by a specific enzyme. Out of these five enzymatic reactions, two take place in the mitochondria and three take place in the cytoplasm. This cycle is also known as ornithine cycle as it involves conversion of amino acid ornithine to citrulline though glutamic acid which is derived from aspartic acid by transamination and/or form α- ketoglutaric acid and ammonia.

Decarboxylation: Decarboxylation is the process in which CO2 is removed from the carboxyl group of an amino acid resulting the formation of an amine. Enzyme aminoacidic decarboxylases catalase these reactions which require pyridoxal phosphate as coenzyme. For example, histidine is decarboxylated to histamine by histidine decarboxylase and 3,4- dihydroxyphenylalanine is decarboxylated to dopamine. These types of amines are called, biogenic amines. Many of these amines have strong pharmacological effects and others are important as precursors of hormones or as co-enzymes.

SOURCES OF PROTEINS 

Proteins are widely distributed in plants and animals. Common sources of proteins are milk, yogurt, cheese, fishes, beans, nuts, green peas, meat, eggs, lentils, soy products, quinoa and sea foods.

BIOLOGICAL SIGNIFICANCE OF PROTEINS 

Proteins are the most significant macromolecules in living beings because of the following physiological roles performed by them in all biological processes:

1. Proteins which are involved in the formation and maintenance of various cellular structures are called structural proteins. These proteins form an important part of all membranes and membrane bound organelles of the cell. The cell wall and primary fibrous of the cell have structural proteins e.g. Collagen is the most abundant fibrous protein found in animals forming a major part of the skin, cartilage, ligament, tendons and bones. Keratin is another animal protein involved in the formation of scales, hair, feather, horns, hoofs, fur wool, nails and claws.

2. Capacity of motion and flexibility in the organisms is due to the presence of certain proteins called contractile proteins e.g. Muscle proteins- actin and myosin.

3. Proteins acts as enzymes or biocatalysts and catalyzes a variety of chemical reactions in the living organisms. Almost all the enzymes are protein in nature.

4. Some proteins bind and transport specific types of molecules via blood e.g. hemoglobin is important protein, transports oxygen from lungs to cell tissues. Myoglobin binds and transports oxygen in the muscles. Certain membrane proteins transport ions and small molecules across the cell membrane.

5. Some proteins are stored as reserve food such as albumin in egg and glutelin in rice. In the liver ferritin stores iron.

6. A few proteins functions as hormone e.g. insulin.

7. Proteins also play important role in the immune system of vertebrates. Antibodies are immunoglobulins which combine and neutralize the antigen entering the body.

8. Proteins also take part in blood coagulation e.g. thrombin and fibrinogen.

DEFICIENCY DISEASES OF PROTEINS 

Protein deficiency can lead to weak muscle tone, thin and brittle hair, edema or swelling, skin lesions, fatigue, stunted growth and cognitive development as well as mental health in children. Following diseases can occur due to protein deficiency: 

Marasmus: It affects infants and very young children, often resulting in weight loss and dehydration. People with marasmus appear bony with little muscle tissue.

Kwashiorkor: It usually affects older children. People with Kwashiorkor appear swollen stomach due to fluid retention.

Cachexia: It is a condition that involves protein deficiency, depletion of skeletal muscle and an increased rate of protein degradation. It causes weight loss and mortality and is associated with cancer, AIDS, heart disease and chronic kidney failure.

Synapse| Electrical synapse| Type of synapse| Properties of a synapse| Mechanism of synaptic transmission|

  SYNAPSE 

A synapse is defined as the functional connection between two neurons. It permits a neuron to pass an electrical or chemical signal to another neuron the term “synapse” was given by Charles Sherrington in 1887.The word synapse is derived from the Greek word synapsis meaning conjugation. 

Structure of Synapse 

At a synapse the plasma membrane of the signal passing neuron (presynaptic neuron) comes into close contact with the plasma membrane of the target (postsynaptic neuron) cell but does not fuse with it. Inside the pre-synaptic membrane there are several vesicles filled with neurotransmitters and numerous mitochondria necessary for active synthetic processes occurring in the terminals and at the post-synaptic membrane there are receptor proteins which respond to chemical stimulation and inhibition. The gap between pre-synaptic and post- synaptic membranes is known as synaptic cleft and it is about 20-50nm.

Types of Synapses 

Synapses are of two types: electrical synapses and chemical synapses. Depending upon mode of transmission across the synapse. 

✅Electrical synapse: In electrical synapse, synaptic cleft is only 0.2 mm, so action potential can directly be transmitted to the next neuron. Electric synapse is quite rare and occurs in neural system that requires fastest possible response

✅Chemical synapse: in chemical synapses, neurotransmitters are present. Each synaptic vesicle is of about 50 mm. diameters and stores about 10,000 molecules of a neurotransmitter. It is the most common type of synapse and allows the nervous system to connect and control other systems of the body. Acetylcholine, adrenaline and noradrenaline are chemical transmitters, released at synapses. Dopamine, serotonin and sympathy are some other excitatory neuron transmitters. Most synapses are chemical synapse. 

✅Conjoint synapse: the synapses where transmission of nerve impulse is both chemical and electrical are, called conjoint synapse. According to the nature of connections the synapse is of the following types: -

1. Axo-axonic synapse: A synapse between axon of one neuron and axon of another neuron is Axo-axonic synapse. 

2. Axo-dendritic synapse: A synapse between axon of one neuron and dendrite of another neuron is known as Axo-dendritic Synapse. It is found in the cerebellum where the climbing fibers form connections with dendrite of Purkinje cells. 

3. Axo-dendrosomatic synapse: A synapse between axon of one neuron and dendrites and cell body of other neuron is known as axo-dendrosomatic synapse. 

4. Axo somatic synapse: A synapse between axon of one neuron and cell body of another neuron is axosomatic synapse. 

5. Dendro-dendritic synapse: A synapse between dendrites of two different neurons is known as dendro-dendritic synapse. 

Properties of a Synapse: -

✔An impulse can be transmitted only in one direction across the synapse i.e. from presynaptic neuron to post synaptic neuron. This is known as the law of forward conduction.

✔The minimum time required for the transmission of impulse from one neuron to next is known as synaptic delay and it is about 0.5miilisecond. 

✔Synapse is a site where impulses are received and discharged, it is therefore, regarded as relay station.

✔ Summation is an important characteristic of synapse. It means adding up of the effects of multiple impulses at the synapses. It is of two types: Spatial and temporal summation. 

✔ Synapses bring about convergence and divergence of nerve impulses. Suppose many neurons synapse with a common post synaptic membrane, then impulses coming from various directions get converged at the synapse. All the impulses are further transmitted in a single uniform direction. This is known as convergence. 

Suppose a neuron makes synaptic contact with many postsynaptic neurons, the impulse coming through the first neuron in a single direction get diverted at the level of synapse and transmitted further in different directions. This is known as divergence.

✔Sometimes when impulses are transmitted repeatedly across a synapse it stops transmitting impulses after sometimes. This is fatigue and it is due to neurotransmitter. However, it is a temporary phenomenon. 

✔The phenomenon of passage of impulses from presynaptic to post synaptic neuron and back to presynaptic neuron is known as reverberation .As a result of continous transmission of impulses, a circuit is maintained.

Mechanism of synaptic transmission: -

When a nerve impulse travelling along an efferent peripheral nerve reaches the synaptic terminals it produces a characteristic response in the effector tissue (increased or decreased activity of smooth muscle or cardiac muscle, secretion of glands, contraction of skeletal muscles). The current in the presynaptic membrane is too weak to excite the post synaptic membrane directly and there is evidence that the activity is now conveyed to the effector organs by the release of chemical transmitters into the synaptic cleft.

The process of chemical transmission across the synapse was first revealed by Loewi in 1921.Later Henry Dale (1936) worked out the chemical nature of these neurotransmitters and their mode of action is mentioned below:

✔ When a nerve impulse reaches the interneural or the neuromuscular junction, the weak action potential that it has carried to the synapse causes the calcium ions to move from the extracellular fluid into the membranes of the axon terminals.

✔The calcium ions in turn, cause the synaptic vesicle to rupture through the membrane and release the neurotransmitter. 

✔Within approx.2-3 milliseconds after the chemical transmitter (which is either excitatory or inhibitory in nature) is released by the axon terminal, it traverses the synaptic gap, combines with a specific receptor on the post synaptic membrane and causes a local depolarization. 

✔The local depolarization creates a synaptic potential across the synapse and when this reaches a certain magnitude it fires off an action potential in the next neuron or in the effecter cell. 

✔The weak presynaptic potential is thus sufficient to release the transmitter which then greatly lowers the resistance of the post synaptic membrane by increasing the membrane permeability to Na+ and K+.The post-synaptic membrane gets depolarized. A fresh action potential is generated in the post synaptic neuron and is propagated further. Transmission of impulses across the synapse is chemical in nature.

Factors affecting synaptic transmission: - 

✔Hypoxia: As synaptic transmission requires energy expenditure, so oxygen deficiency stops it. 

✔ Acidosis: It depresses neuronal activity. A fall in pH from 7.4-7 may cause comma stage. 

✔ Alkalosis: It increases neuronal activity 

✔ Drugs: Like caffeine, theophylline and theobromine found in coffee, tea and cocoa increases neuronal activity 

✔Hypocalcemia: or lack of calcium increase synaptic transmission while hypercalcemia retards synaptic transmission.

Nerve impulse| classification| structure| function| nervous system|

    TRANSMISSION OF NERVE IMPULSE  

In a neuron, nerve impulse is conducted from axon terminal of one neuron to dendrites of next neuron, so it a unidirectional process. The nerve impulse travels along axon in the form of a self-propagative wave of certain fixed electrochemical changes, The conduction of nerve impulse depends upon following facts like: Permeability of axolemma., Osmotic equilibrium between axoplasm and extracellular fluid, Electrical equivalence between axoplasm and extracellular fluid. In thin nerves the impulses travel at less than 1m/sec, but in large nerves they travel much faster at 100m/sec.

✅Resting Membrane Potential (Polarization) 

Membrane of nerve cells have electrical potential difference (voltage), known as membrane potential. Resting nerve cell has -70mv (ranging from – 40 to – 90mv) electrical potential on the inner side of membrane. It is called resting membrane potential. This state of nerve cell is, called polarized state. Resting membrane potential is the unequal distribution of ions on both sides of the membrane of neuron determined by the concentration of ions. During polarized state, membrane is negatively charged from inner side and positively charged on outer side. The resting membrane potential is determined primarily by three factors: -

1) Concentration of ions on the inside and outside of the cell. 

2) Permeability of membrane to the ions through specific ion channels 

3) By the activity of the electrogenic sodium potassium pump. Thus, polarization is established by maintaining excess sodium ions (Na+) on the outside and an excess of potassium ions K+ on the inside. A certain amount of Na+ and K+ ions is always leaking across the membrane through leakage channels but the sodium –potassium pumps in the membrane actively restore the ions to the appropriate side. The main factor that determines the resting membrane potential is the difference in permeability of K+ and Na+. The resting membrane is more permeable to K+ than to Na+ resulting in slightly more net K+ diffusion (from inside of the neuron to the inside) causing a slight difference in polarity along the membrane. 

Graded potential: -

It is a change in the resting potential of the plasma membrane in response to a stimulus. A graded potential occurs when the stimulus causes Na+ or K+ gated channels to open. If Na+ channels open Na+ enters inside and the membrane depolarizes (becomes more positive). If K+ Channels open K+ exit across the membrane and the membrane hyperpolarizes (becomes more negative). A grade potential is a local event that does not travel far from its origin. It occurs in cell bodies and dendrites. Light, heat, mechanical. Pressure and chemicals may generate potential depending upon the neuron.

When a nerve fiber is stimulated it propagates a nerve impulse and the conduction of such an impulse along the axon is associated with an action potential. The factors which can elicit an action potential of a nerve fiber are: -

✅Chemical stimulation: Certain chemicals such as acids, bases, salt solutions of strong concentrations and some hormones stimulate nerve fires by disturbing resting potential.

✅ Mechanical stimulation: - Crushing, pinching or pricking a nerve fiber can cause a sudden surge of Na+ influx and cause stimulation of the nerves. There are numerous mechanoreceptors found distributed throughout the body which pick up even slightest sensation of pressure, pain, or vibrations.

✅ Electrical stimulation: - Electrical charge can also initiate an action potential because it causes an excess flow of ions across the membrane. 

 Action Potential: -

Any factor that suddenly increases the permeability of the nerve membrane to sodium ions is likely to elicit a sequence of changes in the membrane potential lasting a fraction of a minute. followed immediately by the return of the membrane potential to its resting value. This sequence of potential changes by a factor or stimulus is called action potential. Following sequence of events occur during an action potential. 

Depolarization: When the stimulus picked up by a nerve is strong enough the sodium channels in the trigger zone open increasing the flow of Na+. The permeability of the nerve membrane to Na+ increases and the ions rush to the inside of the membrane. This is known as activation of the membrane at the onset of action potential. As sodium diffuse into the interior the internal negativity becomes less and there is reversal potential. Thus, the membrane become depolarized.

✅Repolarization: -

Almost immediately after depolarization the sodium channels close and the nerve membrane again become impermeable to Na+. As soon as sodium channels close potassium channels open, thus allowing K+ from inside to rush out of the cell. This causes repolarization by restoring g the original membrane polarization. Unlike the resting potential, in repolarization the K+ are on the outside and Na+ are on the inside. 

✅Hyper polarization: -

By the time potassium channels close more K+ have moved out of the cell than is actually necessary to establish original polarized potential. Thus, the membrane is said to be hyperpolarized(-80mV). Na+ and K+ diffuse through sodium and potassium channels present in the membrane. The sodium channels are believing d to be oval in shape and having a diameter of 3x5ang while potassium channels are rounded, with a diameter of 3x3Aº.Each channel is believed to be guarded by a gate which can open and close the channel. Under resting condition both sodium and potassium channels are completely closed. The sodium and potassium gates are positively charged. The positive charge creates a positive electric field that spread far into the channels and thus blocks ion permeability. The opening and closing of the gate is caused by electrical potential called gating potential.

✅All or none response: -

Once an action potential has been set up by a stimulus above the threshold potential at any point on the membrane of a resting nerve fiber, the process of nerve depolarization will travel over the entire membrane. This process of impulse formation and transmission is independent of the strength of stimulus. Had the stimulus been less strong than the threshold value (sub-threshold potential), the impulse would have not generated at all. This is because the conduction follows an all or none response.i.e.the stimulus either fails to set up an impulse or it sets up a full-sized impulse.

TRANSMISSION OF NERVE IMPULSE 

Nerve impulse is transmitted from axon of one neuron to dendrites of next neuron, though. synapse. If dendrites of more than one neuron are in contact of one axon, then nerve impulse will be transmitted to all neurons with same velocity. This transmission of nerve impulse from is a chemical process that is stored in synaptic vesicles.

At a synapse, telodendrion of one axon are not in direct contact of dendrites of next neuron but are separated by a space called synaptic cleft. Synaptic cleft is from 200 to 400 E wide. Tissue fluid is filled in the synaptic cleft. When nerve impulse reaches telodendrion Ca++ from tissue fluid diffuse into synaptic vesicles. The concentration of Ca++ is 10,000 times more outside the cells than in the axoplasm. After entering inside synaptic vesicles, Ca++ stimulates release of neurotransmitters at the synapse. Many synaptic vesicles fuse with the plasma membrane and release the neurotransmitters in the fluid of synaptic cleft. The molecules of neurotransmitters bind to some surface receptors of dendrites, which change the permeability of postsynaptic membranes and generate nerve impulse in the next neuron. In this manner neurotransmitters transmit nerve impulse to next neuron. 

Neurotransmitters are also called neurohumor. Adrenaline, dopamine, serotonin and sympathy are some other excitatory neuron transmitters that are secreted at some nerve endings. Glycine and GABA (gamma amino butyric acid) are impulse inhibitory substances. Nerve impulse is transmitted from one neuron to next neuron within milliseconds after which neurotransmitters are hydrolyzed. Enzyme acetylcholinesterase (AChE) breaks acetylcholine at synaptic cleft of cholinergic neurons. At synapse of adrenergic neurons, norepinephrine is released. Norepinephrine is disintegrated by catechol-O-methyltransferase enzyme (COMT). The time required for the impulse to cross at the synapse is, called synaptic delay. Synaptic delay is of about 0.8 milliseconds.

✅Propagation of the impulse: -

Once elicited at one spot on an excitable membrane, the action potential then excites adjacent portions of the membrane resulting in propagation of the action potential. The fig A shows a rating nerve and a nerve excited in its middle portion has been shown in fig B which has developed a local circuit of current flow between the polarized and the resting membrane, show that more areas on the membrane become depolarized and the process of depolarization occur in both directions along the nerve fiber. The transmission of this depolarization along a nerve fiber is called a nerve impulse. 

✅The Refractory Period: -

After a nerve impulse has passed, there is a short period of time during which the nerve is not able to respond to another stimulus as it is still depolarized from the previous action potential. This brief interval of in excitability is known as absolute refractory period and it is about 1/1000 second for a large, myelinated nerve. Thus, there is limit to the frequency of the impulses the nerve fiber can transmit and it is usually 500-1000 impulses per second. In the later part of the refractory period second stimulus of higher intensity can generate a fresh action potential by it, second stimulus of same intensity cannot. This is known as relative, refractory period. 

✅The velocity of conduction: -

The velocity of conduction through nerve fibers varies from as little as 0.5 meter per second in small unmyelinated fibers up to as high as 130metres per second in large, myelinated fibers. 

Saltatory conduction: - 

In 1925, Lillie observed that when the velocity of propagation of nerve impulse in an unmyelinated axon is compared with that in a myelinated axon of the same diameter, it is found that the impulse travels at a much greater rate in myelinated fiber. This suggests that the mechanism of propagation may be different and has led to the hypothesis of saltatory conduction. Saltatory means “Leaping” (saltire-jump) and the term is used to describe a process in which the active process of conduction ‘leaps ’from one node of Ranvier to another node of Ranvier where the membrane is some 500times more permeable. Saltatory conduction is of physiological importance for two reasons: First, by causing the depolarization process to jump long intervals along the axon, which greatly increases the velocity of conduction in myelinated fibers. Second, saltatory conduction conserves energy for the axon, for only the nodes depolarize and that metabolic energy is saved which would have been otherwise required to re transport the ions across the membrane.

Nervous system| Type| function| classification| structure| characters|

  NERVE FIBRE  

A nerve fiber is a cord like structure containing bundles of axons in the peripheral nervous system. It provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons to peripheral organs. Within a nerve, each axon is surrounded by a layer of connective tissue called endoneurium. The axons are bundled together into groups called fascicles and each fascicle is wrapped in layer of connective tissue called Perineurium. Finally, the entire nerve is wrapped in a layer of connective tissue called epineurium. Nerves are bundled along with blood vessels since the neurons are of a nerve have fairly high energy requirements. A blood vessel carrying blood to a nerve is known as vasal nervosa. Within the endoneurium, the individual nerve fibers are surrounded by a low protein liquid called endo neural fluid.it constitutes a blood nerve barrier similar to the blood brain barrier. Molecules are thus prevented from crossing the blood into the endo neural fluid. During the development of nerve oedema (swelling)due to nerve injury, the amount of epineural fluid may increase at the site of injury. This can be visualized using magnetic resonance neurography.

Histologically nerves are of two kinds:

✒ MYELINATED NERVE FIBRE: -

The nerve fiber which are surrounded by a lipid rich insulating layer, so it appears white called myelin sheath. Myelin sheath is an electrical insulator, its purpose is to speed the transmission of nerve impulse. A neuron having myelin sheath means faster conduction, faster transmission and faster transfer of nerve impulses. Myelin sheath is interrupted at some places; these are called nodes of Ranvier, which is always constant in number. The space between two nodes of Ranvier is called internode. Speed of conduction of nerve impulse is faster in myelinated fiber. These nerves are more than 1µ in diameter.

✒NON-MYELINATED NERVE FIBRE: -

Nerve fibers without myelin sheath are, called non-myelinated nerve fibers. In non-myelinated nerve fibers, nodes of Ranvier are absent. They appear grey because of the absence of myelin sheath: post ganglionic sympathetic nerves are non-modulated. The nerve fibers, which carry nerve impulse from receptor organs to the central nervous system are, called afferent nerve fibers or sensory neurons. The nerve fibers, which carry nerve impulse from the central nervous system to effecter organs are, called efferent nerve fibers or motor neurons. The nerve fiber that contains, both afferent and efferent axons and thus conduct both incoming sensory information and outgoing muscle commands in the same bundle.

Types of Neurons 

The nerve cells have been classified either on the basis of their structure or function as follows: - 

✅Functional type of Neurons: On the basis of their functional or their physiological properties, the neurons may be divided into following types: -

✔Sensory or afferent neurons: These neurons carry a stimulus from the peripheral or visceral receptors to the central nervous system.

✔Motor or Efferent Neurons: These neurons carry impulses away from CNS to the 

effectors like muscles and glands. 

✔Neurosecretory neurons: These cells are specialized for producing neurohormones. 

✔Internuncial neurons: These are generally located in the central nervous system and serve to link the sensory and motor neurons.

✅Structural classification of neurons 

✔Multipolar Neurons: -

These neurons have an axon and many dendrites. Examples of multipolar neurons are motor neurons and inter neurons found in brain and spinal cord. 

 ✔Bipolar Neurons: - 

When one axon and one dendrite arise from one soma i.e. they have an axon and a dendrite. The bipolar neurons are found in retina and in the ganglia of VIII nerve. 

✔Unipolar or Pseudo unipolar Neurons: -

All developing neuroblast cells pass through a stage in which they have only one process the axon. During the later development it may be divided into two processes, one terminating in the central nervous system while another moves out. The unipolar neurons are found in the posterior roots of spinal nerves, in the mesencephalic nucleus of V cranial nerve and in the nerve roots of IX and X cranial nerve. 

✔Non-polar Neurons: -  

When many processes arise from the soma and all are equal without any distinction of axon or dendron, the neuron is called non-polar neuron. These nerve cells are unpolarized and cannot be differentiated into dendrites and axon. In non-polar neurons, nerve impulse can be conducted in any direction. Non-polar neurons are found in nerve net of coelenterates.

NEUROTRANSMITTERS 

Neurotransmitters are the endogenous chemical messengers that enable neurotransmission liberated at the nerve ending. They transmit signals across a chemical synapse from one neuron (nerve cell) to another target neuron a, muscle cell, or a gland cell. They play an important role in shaping everyday life and functions. 

✅Types of neurotransmitters: -

There are about 40 neurotransmitters and they have been classified into two types: - 

✔Rapidly acting neurotransmitters

✔Slowly acting neurotransmitters 

✅Rapidly acting neurotransmitters are small molecules and cause acute response. 

 It includes: -

i) Acetylcholine 

ii) Amines: Norepinephrine, epinephrine (Catecholamines), Dopamine, Serotonin.

iii) Amino acids like GABA (glycine and gamma amino butyric acid), glutamate, aspirate 

✅Slowly acting neurotransmitters are neuropeptides having prolonged effect: - 

It includes: -

✔Neuroactive peptides which are releasing hormones secreted by hypothalamus, for eg. TRH, LH, somatostatin 

✔Pituitary peptides like ACTH, vasopressin, oxytocin, endorphins 

✔ Peptides acting on gut and brain like leucin, methionine, cholecystokinin, neurotensin, insulin, and glucagon. 

✔ Neuropeptides from other tissues like angiotensin-II, bradykinin, and bombesin.

Excretory system| Nephrons| Micturition| Loop of Henle| Ultra filtration| -Learning hub

 EXCRETORY SYSTEM 

The following steps are involved in the excretory system.

STRUCTURE OF VERTEBRATE KIDNEY: -

The main excretory organs of vertebrates are kidney. Kidneys are mesodermal in origin. Each adult kidney is composed of a number of structural and functional units called nephrons or, nephric tubules or the uriniferous tubules. Basically, there are three types of kidneys met within the vertebrates. 

(i) Pronephros: It is the embryonic kidney of all vertebrates except Myxine and Belladona, it is the head kidney that remains functional in the larvae of cyclostomes, fishes and amphibians but later degenerates 

(ii) Mesonephros: It is the opisthonephric kidney of adult cyclostomes, fishes and amphibians and also serves to be the embryonic excretory organ in amniotes. 

(iii) Metanephros: It is the functional kidney of the adult, reptiles, birds, mammals and man. The detailed study of metanephric kidney is discussed below.

✅In man, the two kidneys lie behind the peritoneum on either side of the vertebral column extending from 12th thoracic to 3rdlumbar vertebrae. In man and most mammals, the left kidney is usually a little higher than the right kidney, reaching the level of the eleventh rib. In healthy man, each dark red bean shaped kidney weighs between 120-170 gms and measures from 11-13 cm in length. Each kidney is covered by a layer of fibrous connective tissue, called renal capsule.

✅The physiological anatomy reveals that each kidney comprises about 1.2 million nephric tubules or nephrons, functional unit of kidney. Each nephron is 4–5 cm. long. It is divisible into an outer granular cortex and inner paler medulla. Hilus is the inner medial border of the kidney which is somewhat concave and has an indentation through which passes the renal arteries, veins, nerves and the lymphatics, the pelvis or the ureter.

✅The funnel shaped upper end of pelvis is formed by the joining together of about three or four major calyces each of which is intern made up of several short branches or minor calyces. The medulla of kidney comprises of some ten to fifteen pyramids which project into the calyces and separated by the renal columns of Bertini.

Structure of single nephron: - 

The renal tubule or nephron was first described by Marcello Maiphigi (1666) and later by Bowman (1842). Approximately 2.2million nephrons are present in both kidneys i.e., (1.1 million in each kidney). In an adult person, a single nephron measures about 5-6 cm and is divisible into two parts.

1) Malpighian or renal corpuscle 

2) Renal tubule.

(1) Malpighian or renal corpuscle: Each nephric tubule begins as a blind dilated cup shaped sac called Bowman’s capsule. It is double layered and situated in the cortex of kidney. The Bowman’s capsule is invaginated by a tuft of some 40-50capillary loops, each covered by special epithelial cells known as Podocytes. Podocytes have slit pores through which ultra-filtration occurs and forms the Glomerulus. The glomerular capillary tuft surrounded by its capsule is termed as Malpighian corpuscle. Blood enters the capsule through afferent renal arteriole and after passing through glomerular capillary network it is collected by the efferent renal arteriole. 

(2) Renal tubule: The long portion of the nephron following the Bowman’s capsule is termed as renal tubule. It is divided into the following regions.

✅ The proximal convoluted tubule, 

✅The loop of Henle (Descending limb and ascending limb) 

✅ The distal convoluted tubule 

✅Collecting duct 

• PCT: The proximal convoluted tubule lumen of which is continuous with Bowman’s capsule is about 12-24mm in length lies in the cortex of kidney. It consists of large columnar cells with a brush border produced into numerous microvilli of 1 to 4mµ in size. 

• The loop of Henle: It is a hair pin-shaped part of nephron after PCT. The loop of Henle consists of one descending limb and one ascending limb Descending limb of loop of Henle is permeable for water and is impermeable for salts while ascending limb of loop of Henle is impermeable for water. Ascending limb of loop of Henle is called diluting segment of nephron.

• DCT: The next part of nephron that is again highly convoluted is, called distal convoluted tubule (DCT). It lies in renal cortex. It is made up of cuboidal epithelial cells but have few scattered microvilli. DCT opens into collecting tubule. 

✅Collecting tubule (CT): All collecting tubules receive many functional tubules from other nephrons and finally open into the renal pelvis as the papillary duct of Bertinii. 

✅Types of nephrons in mammalian kidney 

(a) Cortical Nephrons: -

The nephrons situated in cortical region are, called cortical nephrons. In cortical nephrons, loop of Henle is short. In a kidney 15 to 35% nephrons are cortical nephrons. 

(b) Juxtamedullary nephrons: -

Nephrons situated near medulla part are, called juxtamedullary nephrons. It is formed by the DCT and glomerular afferent arteriole. It is so named because it lies next (juxta)to the glomerular. In juxtamedullary nephrons, loop of Henle is long and parallel blood vessels, called vasa recta are present. In a kidney 65 to 85% nephrons are juxtamedullary nephrons. It works only in condition of stress.

It consists of three types of cells. 

(1) The macula dense, a part of the distal convoluted tubule of the same nephron. It acts as a chemoreceptor and are stimulated by decreased NaCl concentration and thereby cause release of rennin.

(2) Juxtaglomerular cells or granular cells which secrete rennin. These cells are smooth muscle cells of afferent arteriole which supply blood to the glomerulus. They are baroreceptors and respond to changes in the pressure gradient. They are innervated by sympathetic nerves. 

(3). Extraglomerular mesangial cells (Laci’s cells) These cells are located at the junction. between afferent and efferent arterioles. They are contractile and play a role in regulation of GFR. 

MECHANISM OF RENAL EXCRETION (URINE FORMATION): -

As mentioned above, kidneys are the chief organs of nitrogen excretion invertebrates. Each minute, the two kidneys filter approximately 1200 ml of blood to collect 125 ml of filtrate and form about 1 to 2 ml of urine (per minute) and thus eliminate extra water, nitrogenous wastes and inorganic salts from the body. The entire mechanism of renal excretion involves three main steps. 

• Ultra filtration 

• Selective reabsorption 

• Tubular secretion 

(A) Ultra-Filtration: -

Described first by Ludwig (1844) and later modified by Richards (1942), the ultra-filtration or glomerular filtration is the first step in urine formation. The glomerular capillaries receive the renal blood supply through afferent renal arteriole which form a high-pressure bed in glomerulus, and it is approximately 60 mm Hg (Guyton,2003). Opposing the effects of blood pressure in the glomerulus are- 

(1) Colloidal osmotic pressure of plasma proteins 

(2) Tubular pressure of the Bowman's capsule itself, which are approximately 32 mm Hg and 18 mm Hg, respectively. Thus, in the Bowman's capsule a blood pressure of about 60 mm Hg is being opposed by an internal pressure of approximately 50 mm Hg (colloidal osmotic pressure plus the tubular pressure) and this spares a filtration pressure of about 10 mm Hg (called the net filtration pressure) which is sufficient to cause filtration of the non-protein substances of plasma across the glomerulus (fig. 4.6). Everything except plasma proteins is filtered and the fluid collected is called ultrafiltrate. The total amount of glomerular filtrate formed each minute in all the nephrons of both kidneys is known as the glomerular filtration rate. It is approximately 125 ml/min or 180 liters/day.

Filtration Coefficient (Kf) is defined as total amount of ultra-filtrate formed by all the nephrons of both kidneys per minute per 1mm of Hg of net Filtration pressure. 

Kf = 125/10 = 12.5 ml/min/mm of Hg 

Another noteworthy feature of ultrafiltration is the tremendous permeability of the glomerular capillary membrane which is several hundred times higher than any capillary membrane inhuman body. Histologically it is made up of three layers:

(1) endothelium of the capillary, 

(2) basement membrane, and 

(3) A layer of epithelial cells that line the surface of Bowman's capsule. The fenestrae and slit pores of these layers increase permeability but prevent the filtration of all particles having an average diameter greater than 70 A. Since plasma proteins are slightly larger than 70 Aº diameter, it is possible for the glomerular membrane to prevent the filtration of all those substance with molecular weight equal to or higher than those of the plasma proteins.

✅Factor affecting Glomerular Filtration Rate (GFR) 

Any change in any of these pressures affects GFR. 

✔ When the blood pressure in the glomerulus raises GFR increases. 

✔ When colloidal osmotic pressure (CPO) increases, GFR decreases provided other two factors are constant (COP decreases in starvation and due to under nutrition). 

✔ When the tubular pressure in the Bowman's capsule increases, GFR decreases. 

✔ Increase in blood volume increases GFR. 

✔ Increase in cardiac output increases GFR.

✔ Decrease in the number of functional nephrons will decrease GFR (Some nephrons become non-functional due to old age). 

✔ Sympathetic discharge will produce constriction in afferent arteriole and this decreases GFR.

 Determination of GFR: -

GFR is taken as one of the kidney function tests. By quantifying GFR one can understand how the kidney handles various substances. Thus, substances with excretory rate less than filtration rate must undergo tubular reabsorption whereas substances with excretion rate more than filtration rate must undergo secretion. 

✅Clearance Test: - 

The clearance of a substance may be defined as the concentration of that substance in plasma same as in glomerular filtration and is neither reabsorb nor secreted by the tubular epithelium. It is a measure of the rate of glomerular filtration. Inulin, a polymer of fructose found in the roots of certain plants is easily filtered, it is neither reabsorbed nor secreted and has a clearance equal to GFR. 

✅Transport Maximum (Tm): -

Another parameter of renal excretory function is the transport maximum which is the maximum ability of the kidney either to reabsorb or secrete a given material. For example, Tm of glucose is defined as the maximum amount of glucose that can be reabsorbed by all nephrons of both the kidneys per minute. Average TmG = 360 mg/min (320 mg/min in females and 375 mg/min in males). If the tubular load of glucose becomes 400 mg then it will be excreted in urine at the rate of 40 mg/min. When tubular load of glucose is less than TmG then no glucose is lost in urine.

Glucose lost in urine = tubular load of glucose - TmG 

= 400-360 

= 40 mg/min

(B). Selective reabsorption: -

 The filtered fluid in the Bowman's capsule and in the tubule is called the glomerular filtrate. It has almost the same composition as the fluid that filters from the arterial end of capillaries into the interstitial fluids. The glomerular filtrate has no red blood cells but consists of about 0.03 percent proteins, a great amount of glucose, salts, nitrogenous end-products and water. About 99 percent of the water and almost all other useful substances present in the glomerular filtrate are to be reabsorbed back into the blood as the filtrate passes through various parts of the convoluted tubule. 

✅ Reabsorption in the proximal convoluted tubule 

About 65 to 80 percent of the glomerular filtrate is reabsorbed in the proximal convoluted tubule and this fraction is referred to as the obligatory reabsorption. The epithelial cells of the proximal tubule have a brush border composed of thousands of very minute microvilli which facilitate a rapid and active diffusion of sodium from the peritubular capillary blood. Each time a positively charged sodium ion is pumped out of the tubule, a negatively charged ion follows it and it is usually a chloride ion which thus leaves the tubule, since it is the most abundant negatively charged ion in the tubular fluid. 

The peritubular capillary bed has a mean blood pressure of about 13 mm Hg which is slightly higher than the filtration pressure. The peritubular fluid now has a higher osmotic pressure because of an increased concentration. Both these factors influence the movement of water from the filtrate which also carries away, passively, substance like glucose, amino acids, and potassium, calcium and phosphate ions from the filtrate.

✅ Reabsorption in the loop of Henle 

At the end of proximal tubule, the fluid is almost isotonic with blood. In the rest of its course, it is converted into urine of the appropriate concentration through a complicated sequence of events termed as the counter-current mechanism. The mechanism is basically associated with the anatomy of the loop of Henle which is a hair-pin loop between the proximal and distal convoluted tubules of nephrons. Entire mechanism of the counter-current system is as follows: 

(a) The ascending limb of loop of Henle with thicker walls is impermeable to water but actively transports sodium and chloride ions passively from the tubular wall into the renal medulla. This causes an increase in the osmolarity of the interstitial fluid in the medulla. 

(b) The increase in the osmolarity due to the sodium pump causes water to leave the thin-walled descending limb. This makes the filtrate increasingly hypertonic as it proceeds from the renal cortex towards the papilla. 

(c) The Na+ secreted by the cells of the ascending limb of the loop of Henle into the interstitial fluid escape passively into the adjacent blood vessels or the descending limb of the loop following a concentration gradient. 

(d) Thus, by this re transport of the sodium (and chloride) again and again the counter-current multiplier mechanism increases the concentration of sodium chloride in the medulla, and consequently determines the concentration of urine.

(3) Reabsorption in the distal convoluted tubule: -

The fluid reaching the distal tubule of the nephron is hypotonic and it is the antidiuretic hormone (ADH) from the hypothalamic pituitary which now controls the concentration of the urine. This ADH controlled water reabsorption is the distal and collection tubule is termed as facultative reabsorption, and its mechanism is simple. In water diuresis very little ADH is present in the blood, so the distal and collecting tubules become relatively impermeable to water and a dilute urine is excreted but when the body has little water (or say when the blood is more concentrated) a larger amount of ADH is present in the blood and the kidneys conserve more water because of tubular reabsorption Hence the urine becomes concentrated. Mechanism of urine formation in mammal.

✅Tubular Secretion: -

Tubular secretion is the final step in the urine formation. The epithelial lining of the tubule is able to collect electrolytes and water from the fluid but at the same time many foreign substances are readily secreted by the tubule. It is believed that some creatinine, potassium, phenol red, H ion and penicillin are the main substances secreted by the tubular epithelium in man. 

✅Composition and characteristics of urine: -

The concentrated fluid entering the collecting tubule is called Urine. Through the way of pelvis and ureters, it is usually stored in the urinary bladder and is discharged from the body from time to time. The normal volume and composition of urine varies widely from day to day and is being governed by, among other things, the type of food and fluid taken and the amount of fluid lossby other agencies, a factor which itself depends upon environmental temperature, humidity, exercise and sweating etc. 

Micturition: -

Micturition is the mechanism by which the urinary bladder empties itself when it becomes filled with the urine. The urine is basically collected in the pelvis of the kidney where all the nephrons of a kidney open through their collecting tubules. As urine collects in the pelvis, its pressure increases and initiates peristaltic waves occurring every 10 sec or so and travelling through the ureters at a velocity of about 3.0 cm/sec and pushing a little spurt of urine into the bladder, the stretch receptors located in the bladder wall and proximal urethra become stimulated creating a micturition reflex. The detrusor muscles, which make-up the body of urinary bladder, contract during the micturition reflex; the internal sphincter of the urethral opening relaxes and the urine  is evacuated.

Reproductive health; problems and strategies| Population explosion| Birth control methods|

  Reproductive Health: Problems and Strategies 

Reproductive Health simply refers to healthy reproductive organs with normal functions. According to the World Health Organization (WHO), reproductive health means a total well-being in all aspects of reproduction, i.e., physical, emotional, behavioral and social. The improved reproductive health of society requires following factors. 

✔ Better awareness about sex-related matters. 

✔ Increased number of medically assisted deliveries and better postnatal care so, as to decrease maternal and infant mortality rates. 

✔ Increased number of couples with small families. 

✔ Better detection and cure of STDs (Sexually Transmitted Diseases). 

✔ Overall increased medical facilities for all sex-related problems. 

✒Awareness of Reproductive Health: -

Some of the measures taken for the awareness of reproductive health are as follows: -

(i) The family planning programmes were initiated in India in 1951 and were periodically assessed over the past decades. The programmes were improved and covered reproduction-related areas under the popular name Reproductive and Child Healthcare (RCH) programmes. It was launched in 1997. Major tasks of RCH programme are: -

✅Creating awareness among the people about reproduction related aspects. 

✅ Providing facilities and support for building up a reproductively healthy society. Governmental and non-governmental agencies have taken various important steps to create awareness among people about reproduction-related aspects. 

(ii) In schools, introducing sex education is a good step to provide right information to adolescents to discourage them from believing in myths and misconceptions about sex-related issues. Adolescents should be informed about reproductive organs, adolescence and related changes, safe and hygienic sexual practices, sex abuse, STDs, AIDS, etc.

 (iii) Married couple or those in marriageable age group should be educated about available birth control options, care of pregnant mothers, postnatal care of the mother and child, importance of breast feeding, equal opportunities for the male and female child, etc. This will lead to the formation of socially conscious healthy families of desired size. 

(iv) Successful implementation of action plans like providing medical assistance and care to reproduction-related problems, pregnancy, delivery, STDs, abortions, contraception, menstrual problems, infertility, etc. need strong support and infrastructural facilities.

(v) Statutory ban on amniocentesis It is a prenatal diagnostic technique based on chromosomal pattern in which a sample of amniotic fluid is taken from the uterus of a pregnant woman to detect the early development of foetus. The benefits of amniocentesis include the diagnosis of chromosomal abnormalities and developmental disorders of it foetus. However, is being misused for sex-determination of foetus that leads to female foeticides. Therefore, statutory ban on for amniocentesis sex-determination keeps check on female foeticides. 

Population Explosion: -

The tremendous increase in the size and growth rate of population is called population explosion. It occurs due to increased health better living conditions.

(i) Reasons of population explosion include 

✅ Decreased death rate. 

✅ Declined Maternal Mortality Ratee (MMR). 

✅ Decreased Infant Mortality Rate (IMR). 

✅Increase in the number of people in reproductive age. 

(ii) According to the 2001 census report, the population growth rate was around 1.7%, i.e. 17/1000/year. By this rate, our population could double in 33 years. 

Methods to prevent population explosion include 

✔ Raising the marriageable age now, it is 18 years for females and 21 years for males. 

✔ Couples with small families should be given some incentives. 

✔ Birth control is an important step to control the population growth by motivating smaller families by using contraceptive methods. 

Birth Control (Contraception) Methods: - 

Contraceptive methods are ideal if they are user friendly, easily available, effective, reversible with no side effects and non-interferring with the sexual drive, desire and the sexual act. There are several methods of birth control that can be categorised as follows: - 

Natural Methods: -

Natural method of birth control involves avoiding ances of sperm and ovum meeting. It can be achieved by 

•  Periodic abstinence in which couples avoid coitus from day 10-17 (fertile period) of the menstrual cycle. In this period, ovulation 1s expected to occur and chances of fertilization are very high. This method is also called rhythm method. 
•  Coitus interruptus is also called 'rejected Sexual intercourse' or 'pull-out'/withdrawl method. In this method, the penis is withdrawn from the vagina just before ejaculation, so that semen is not deposited in the vagina.

• Lactational amenorrhea is the absence of menstruation during the period of intense lactation following parturition. As ovulation does not occur in this period, the chances of conception are nil. This method is reliable for a maximum period of 6 months after delivery. Main advantage of these methods is that, they do not cause any type of side effect. The main disadvantage is that, these methods are not 100% reliable, as these depend on chance. 

Barrier Methods: -

These methods are based on the prevention of ovum and sperm from physically meeting with the help of barriers. Barriers may be mechanical or chemical and uscd by both males and females 

(i) Mechanical Barriers: -

✅Condoms:-

 They are made of thin rubber or latex sheath to cover the penis in male or vagina and cervix in females (femidom) They prevent meeting of sperm and ova. Condoms provide protection from sexually transmitted discases. They are disposable and can be self-inserted and thereby gives privacy to the user. 

✅Diaphragms, Cervical Caps and Vaults: - They are made up of rubber that are inserted into the female reproductive tract to cover the cervix during coitus. They are reusable. 

(ii) Chemical Barriers: -

They include spermicidal creams, jellies and foams. They are usually used along with the barriers to increase their contraceptive efficiency.

Intra Uterine Devices (IUDS): - 

These devices are introduced in the uterus through vagina by doctors or expert nurses. These are of following types: -

✅Non-medicated IUDs, e.g. Lippes loop. 

✅ Copper-releasing IUDs, e g. Cu-T, Cu-7 and multiload 375. 

✅ Hormone-releasing IUDs, e.g. progestasert, LNG-20.

IUDs prevent contraception in the following ways: -

✅ Increase phagocytosis of sperms within the uterus. 

✅ Some IUDs suppress sperm motility and fertilizing ability of sperm by releasing copper ions. 

✅The hormone releasing IUDs make uterus unsuitable for implantation and make the cervix hostile to sperms. IUDs are ideal Contraceptives for females who want to delay pregnancy. It is one of the most widely accepted contraception method in India.

Oral Contraceptives: -

These are hormonal preparations in the form of pills. Their major fecatures include 

(i) Pills are of two types-combined pills and mini pills. Combined pills (Mala-D and Mala-N) contain synthetic progesterone and oestrogen whereas mini pills contain progestin (progesterone like synthetic hormone) only. 

(ii) Oral pills inhibit ovulation and modify the quality of cervical mucus to prevent/retard the entry of sperms. They also modify uterine endometrium by making it unsuitable for implantation. 

(iii) Oral pills have to be taken daily for a period of 21 days starting within the first five days of menstrual cycle. 

(iv) Saheli an oral contraceptive pill developed by scientists at Central Drug Research Institute (CDRI), Lucknow, contains a non-steroid called centchroman. It is a once-a-week pill, with very few side effects and high contraceptive value. 

Implants or injections: -

These are effective for longer period, although their mode of action is similar to thal of oral contraceptives. Progesterone alone or in combination with oestrogen are used by females as injections (Depo Provera) or implants under the skin. 

Emergency Contraceptives: -

It includes administration of high dose of progesterone or progestogen-Oestrogen Combinations within 72 hours of coitus. It has been found to be very effective to avoid possible pregnancy due to unprotected intercourse.

Sterilisation or Surgical Methods: -

Sterilisation methods are used by male/female partner as a terminal/ permanent/stable method to prevent any more pregnancies. These methods block the transport of gametes and prevent Contraception. There are of following two types 

(i) Vasectomy is applied in case of males. In this method, a small portion of vas deferens is removed or tied up through an incision on the scrotum to prevent the passage of sperms.

 

(ii) Tubectomy is applied in case of females, where a small part of Fallopian tube is removed or tied up through a small incision in the abdomen or through vagina to prevent the passage of ova. Both of these methods are highly effective. but poorly reversible. 

Fertilisation | Implantation | Changes during pregnancy | Embryonic development | lactation |

     Fertilization    

The process of fusion of a sperm with an ovum is called fertilization: - 

✔ Semen of a male is transferred by the penis to the vagina of female during copulation (coitus) and this process is called insemination. 

✔ Spermatozoa move through the cervix, enter the uterus and reach the ampullary-isthmic junction of Fallopian tube, where fertilization takes place. 

✔ Fertilization occurs only if the ovum released by the ovaries and sperms are transported simultaneously to the ampullary-isthmic junction of the Fallopian tube. 

✔ During fertilization, a sperm comes in contact with zona pellucida layer of the ovum and induces changes in the membrane that block the entry of other sperms ensuring that only one sperm fertilizes an ovum. 

✔ The secretions of the acrosome help the sperms enter into the cytoplasm of the ovum through the zona pellucida and the plasma membrane. 

✔This induces the completion of the meiotic division of the secondary oocyte which results into the formation of a haploid ovum (ootid) and a small second polar body. 

✔ The haploid nucleus of the sperms and that of ovum fuse together to form a diploid zygote. 

✔ After fusion of the male and female gametes, the zygote would carry either XX or XY depending on whether the sperm carrying X or Y fertilized the ovum. The Zygote carrying XX would develop into a female baby and XY would form a male baby. Hence, the sex of the baby is determined by the father and not by the mother. 

✅Implantation: -

 The zygote implantation in uterus occurs in the following steps: - 

• The mitotic division within the zygote termed cleavage starts as the zygote moves Towards the uterus through the isthmus of the oviduct. 
•  It forms 2, 4, 8 and 16 daughter cells called blastomeres. 
• The embryo with 8-16 blastomeres is called a morula. 
•  Morula continues to divide and transforms into blastocyst as it moves further into the uterus. 
•  Blastomeres in the blastocyst are arranged into an outer layer called trophoblast. 

 The inner group of cells attached to trophoblast constitute the inner cell mass.

• Trophoblast layer then gets attached to the endometrium and the inner cell mass gets differentiated as the embryo. 
• After attachment, the uterine cells divide rapidly and cover the blastocyst. This leads to embedding of blastocyst in the endometrium of the uterus. This is called implantation.

✒ Changes During Pregnancy 

After implantation, following changes occur during pregnancy. 

✅The finger-like projections appear on the trophoblast called chorionic villi, surrounded by the uterine tissue and maternal blood. 

✅ Both the uterine tissue and chorionic villi become interdigitated with each other and jointly form a structural and functional unit between developing embryo and internal body called placenta.

✅ Placenta transports oxygen and nutrients to the fetus and removes carbon dioxide and excretory waste materials produced by the embryo.

✅ Placenta also acts as an endocrine tissue and secretes hormones like human Chorionic Gonadotropin (hCG), human Placental Lactogen (hPL), oestrogen, progesterone, etc. 

✅ A hormone called relaxing is secreted by the ovary, in later phase of pregnancy. 

✅Umbilical cord connects the placenta with fetus and helps in transport of substances to and from embryo. 

✅ During pregnancy, the levels of other hormones like oestrogen, progesterone, cortisol, prolactin, thyroxine, etc., are increased many times in the maternal blood. These hormones support the foetal growth, maintenance of pregnancy and metabolic changes in mother.

✒Embryonic Development: -

It starts after pregnancy and involves the following changes: -

☑ The inner cell mass (embryo) differentiates into an outer layer called ectoderm and an inner layer called endoderm,

☑ Middle layer called mesoderm appears between the ectoderm and endoderm. 

☑ Primary germ layers give rise to all the tissues and organs of the adult. The inner cell mass contains certain cells called stem cells, which have the potency to give rise to all the tissues and organs.

☑ In humans, after one month of pregnancy the embryo's heart is formed. The sign of growing foetus can be ensured by listening to the heartbeat. 

☑ By the end of second month, limbs and digits develop 

☑ By the end of third month (first trimester). most of the major organ systems are formed. 

☑ During the fifth month, the first movement of fetus and appearance of hair on the head are observed. 

☑ By the end of sixth month (second trimester the body is covered with fine hair. eyelids separate and eyelashes are formed. 

☑ By the end of eight months, the testes in male fetus descend into the scrotum. 

☑ By the end of nine months, the fetus is fully developed and ready for birth.

 ✒ Parturition: -

The process of delivery of fetus (childbirth) is called parturition. 

✔ The average duration of human pregnancy is about 9 months, which is called gestation period. 

✔Vigorous contraction of the uterus at the end of pregnancy causes expulsion/delivery of the fetus. 

✔ Parturition is induced by complex neuro endocrine mechanism. 

✔ Relaxin hormone is secreted by the ovary to facilitate parturition by softening the connective tissue of symphysis pubica. 

✔ Fetus and the placenta induce mild uterine contractions called fetal-ejection reflex. This initiates the release of oxytocin hormone from the posterior pituitary.

✔ Oxytocin acts on uterine muscle to cause stronger contractions, which in turn stimulate further secretion of oxytocin. This causes more stronger contractions leading 1o the expulsion of the baby out of the uterus through the birth canal. 

✔ After the baby is delivered, the placenta is also expelled out of the uterus.

✒Lactation: - 

Parturition is followed by the lactation which requires certain changes in the mother's body. 

•  Mammary glands of the female undergo differentiation during pregnancy 
•  By the end of pregnancy, this start producing milk by the process called lactation. 
•  During the initial few days of lactation, the milk produced is called colostrum.

 It contains several antibodies (IgA) and nutrients essential to develop resistance in the newborn baby.

Spermatogenesis | Sperm | Oogenesis | Menstrual cycle |

  Gametogenesis  

It is the process of producing haploid gametes from diploid germ cells in the gonads, i.e. sperms and ova are produced in the testis and ovary, respectively. It is of the following two types (7) Spermatogenesis (17) Oogenesis 

💥Spermatogenesis: -

It is the production of sperms in males. 

(i), In tastes the immature male germ cells (spermatogonia) produce sperms by spermatogenesis that begins at puberty. 

(ii) Spermatogonia (sing. spermatogonium) present on the inside wall of seminiferous tubules multiply by mitotic division and increase in numbers.

(iii) Each spermatogonium is diploid and contains 46 chromosomes. Some of the spermatogonia called primary spermatocytes periodically undergo meiosis. 

(iv) The primary spermatocytes undergo first meiotic division leading to two equal, haploid cells called secondary spermatocytes, which contains only 23 chromosomes each.

(v)The secondary spermatocytes undergo the second meiotic division to produce four equal, haploid spermatids which contain only 23 chromosomes each.

(vi) The spermatids are transformed into spermatozoa (sperms) by the process called spermiogenesis. Thus, each sperm too contains only 23 chromosomes.

(vii) Sperm heads are embedded in the Sertoli cells and are finally released from the seminiferous tubules by the process called spermiation.

Role of Hormones in Spermatogenesis: -

The following hormones play an essential role in spermatogenesis.

(i) Spermatogenesis starts during puberty with the significant increase in hypothalamic hormone called Gonadotropin Releasing Hormone (GnRH). 

(ii) The increased level of GnRH acts on the anterior pituitary gland and stimulates the secretion of two gonadotropins, i.e., LH (Luteinizing Hormone) and FSH (Follicle stimulating Hormone) 

(iii) LH acts on the Leydig cells and stimulates the synthesis and secretion of androgens, which in turn stimulate the process of spermatogenes1s. 

(iv) FSH acts on Sertoli cells and stimulates the secretion of some factors, which help in the process of spermiogenesis.

💥Structure of a Sperm: -

(i) A sperm is composed of a head, neck, a middle piece and a tail. 

(ii) A plasma membrane encloses the whole body of sperm. 

(ii) Head contains an elongated haploid nucleus, the anterior portion of which is covered by a cap-like structure called acrosome. 

(iv) The acrosome is filled with enzymes that help in fertilization of the ovum. 

(v) Neck contains two centrioles, a proximal centriole, which is necessary for first cleavage division of zygote and a distal centriole, that gives rise to axial filament of tail. 

(vi) Middle piece possesses many mitochondria to produce energy for the movement of tail to facilitate sperm motility. 

(vii) Tail of the sperm consists of an axial filament. It helps in the movement of sperm inside the female reproductive tract towards the ovum for fertilization.

0ogenesis: -

It is the process of formation of a female gamete or ova in the ovary. 

(i) It starts during embryonic stage in a female. 

(ii) About a million oogonia are formed in the ovary of the female fetus which is 25 weeks old. No new oogonia are formed after birth.

(iii) The oogonial cells start meiotic division, enter into prophase I, get temporarily arrested at that stage and are called as primary oocytes.

(iv) Each primary oocyte then gets surrounded by a layer of granulosa cells called primary follicle.

(v) A large number of primary follicles degenerate during the phase from birth to puberty. As a result, about 60,000-80,000 primary follicles are left in each ovary at puberty.

(vi) The primary follicles get surrounded by more layers of granulosa cells and a new theca and are called secondary follicles.

 

(vii) The thecal layer in secondary follicles becomes organized into an outer theca externa and an inner theca interna. This stage is called tertiary follicle. 

(viii) Tertiary follicle is characterized by a fluid-filled cavity called antrum. 

(ix) At this stage, the primary oocyte within the tertiary follicle grows in size and completes its first meiotic division. 

(x) The first meiotic division, which is unequal results in the formation of haploid secondary oocyte and tiny first polar body. 

(xi) Secondary oocyte retains bulk of the nutrient rich cytoplasm of the primary oocyte. 

(xii) The tertiary follicle develops into a mature follicle or Graafian follicle. 

(xiii) The secondary oocyte forms a new membrane called zona pellucida surrounding it.

(xiv) The Graafian follicle ruptures to release the secondary oocyte (ovum from the ovary by the process called ovulation.

Ovum: -

Human egg or ovum is non-cleidoic (i.e. without shell), alecithal (i.e. yolk is absent), microscopic with about 0.1 -0.13 mm or 100-130 um diameter. The ovum possesses three coverings, i.e. inner plasma membrane, middle glycoprotein, zona pellucida and outer cellular corona radiata with radially elongated scattered cells held in mucopolysaccharide (hyaluronic acid).

✒ Menstrual Cycle: -

It is a rhythmic change in the reproductive organs of the female primates (monkey, apes and humans). 

(i) The first menstruation begins at puberty and is called menarche. 

(ii) Average interval of menstruation in human female is about 28-29 days. 

(iii) The cyclic events starting from one menstruation till the next one constitutes one menstrual cycle. 

(iv) The four phases of menstrual cycle are: -

✅Menstrual Phase: -

(a) Cycle starts with this phase and the menstrual flow occurs for 3-5 days.

 (b) It occurs due to breakdown of endometrial with lining of the uterus and blood vessels which along unfertilized ovum comes out through the vagina. 

(c) Menstruation occurs only if fertilization does not take place.

(d) Lack of menstruation generally indicates pregnancy, but may also be due to stress, poor health, diseases, etc. 

✅Follicular or Proliferative Phase: - 

(a) Menstrual phase is followed by the follicular phase.

(b) The primary follicle in the ovary grows to become a fully mature Graafian follicle and simultaneously the endometrium of uterus regenerates through proliferation.

(c) Pituitary and ovarian hormones induce the changes in ovary and uterus. 

(d) LH and FSH levels increase gradually during this phase and stimulates follicular development. 

(e) The growing follicles secrete oestrogens. 

(f) Both LH and FSH attain highest level during mid-cycle (about 14th day)

✅Ovulatory Phase: -

(a) Rapid secretion of LH leading 1o its maximum level during the mid-cycle is called LH surge. 

(b) The LH surge induces rupture of Graafian follicle, releasing the ovum and this process is called ovulation.

✅Luteal Phase/Secretory Phase: -

(a) Ovulatory phase is followed by the luteal phase. 

(b) The remaining parts of the ruptured Graafian follicle change into corpus luteum. 

(c) Corpus luteum secretes large amount of progesterone, which is required for the maintenance of endometrium. 

(d) The thickened endometrium is necessary for the implantation of fertilized ovum and maintenance of pregnancy. 

(e) During pregnancy, all the events of menstrual cycle stop, and menstruation does not occur. 

(f) In case of no fertilization, the corpus luteum degenerates and now known as corpus albicans, which does not secrete progesterone. This causes rupture of endometrium leading to menstruation - initiation of a new cycle. 

(v) In human females, menstrual cycle stops around the age of 50 years and this phase is called as menopause. 

(vi) Menstrual cycle is absent temporarily during pregnancy and lactation periods and permanently after menopause. 

(vii) Menstruation is also called 'Weeping of uterus for the lost ovum' or "Funeral of unfertilized eggs'.