• Human brain weighs about 1.5 kilograms (3.3 lbs) and is larger in relation to body size.
• It is the most complex part of the body in human that is responsible to control thoughts, memory and speech, legs and arm movements along with the many functions within the body.
• The brain is located inside the cranium.
• Cranium is the bony covering that protects the brain from external injury.
• The Nervous system:
  • The nervous system in human is divided into central nervous system and peripheral nervous system.
  • The central nervous system comprises of brain, its cranial nerves and the spinal cord.
  • The peripheral nervous system comprises of autonomous nervous system (divisible into the sympathetic and parasympathetic nervous system) and the spinal nerves that branch from the spinal cord.

Cells of the Human brain:

• The brain is composed of two types of cells i.e. nerve cells (neurons) and glial cells also termed as neuroglia or glia.

1. Nerve cells (Neurons):

• Neurons vary in shape and size, however they all consist of cell body, dendrites and axon.
• The neuron transmits the information via the electrical and chemical signals.
• The transmission of information is mediated by a gap called as synapse.
• Dendrites are the arms that plays role as antennae picking up messages from other nerve cells.
• The neurotransmitter after crossing the synapse, fit into special receptors on the receiving nerve cell, that stimulates that cell to convey the message.

2. Glial cells:

• These are about 10-50 times more glial cells than the neurons.
• Glial cells are responsible for nourishing the neurons. It also aids for the protection as well as structural support to neurons.

What are the types of glial cells?

• Astroglia or astrocytes: They are the nurse cells and aids in regulating the blood brain barrier, permitting the nutrients to make contact with neurons.
• They regulate homeostasis, and also have impact on electrical impulses.
• They are also engaged in defense and repair of neurons.
• Oligodendroglia cells forms myelin that aids in the fast transport of electrical impulses.
• Ependymal cells secrete cerebrospinal fluid (CSF) and line the ventricles.
• Microglia cells are the macrophages of brain that are responsible for invading and cleaning up debris.

How is the brain protected in the body?

• The brain is contained in the skull, where a layer of fluid called cerebrospinal fluid is suspended.
• CSF is a transparent watery substance and is produced within the channels in the brain called as ventricles.
• Major portion of CSF is produced by the choroid plexus.
• Choroid plexus is a specialized structure within each ventricle.
• It protects the brain from mechanical shocks and jolts that are mild.
• In addition, it also plays minor immunological functions and provides the brain’s necessary nutrients.

Ventricles in brain:

• There are 4 ventricles of brain that are connected to each other by foramen, and tubes.
• Lateral ventricles (first and second): These are two ventricles that are enclosed in the cerebral hemispheres.
• Third ventricle: It is located at the center of the brain and its wall are made up of the thalamus and hypothalamus. There is a pineal gland behind the third ventricle. It helps control the inner clock and circadian rhythms of the body through the secretion of melatonin. In sexual growth, it has some function.
• Fourth ventricle:
• It is located posterior or dorsal to the pons and medulla oblongata and is anterior to the cerebellum.
• The first and second ventricle connects with the third ventricle through a distinct opening termed as the Foramen of Munro.
• The communication between the third and the fourth ventricle takes place via the Aqueduct of Silvius that is a long tube.

How is blood supplied to the brain?

• Two paired arteries, the internal carotid arteries and the vertebral arteries, bring blood to the brain.
• Most of the cerebrum is supplied by the internal carotid arteries.
• The cerebellum, brainstem, and the cerebrum’s underside are supplied by the vertebral arteries.
• The right and left vertebral arteries join together after passing through the skull to form the basilar artery.
• At the base of the brain, called the Circle of Willis, the basilar artery and the internal carotid arteries interact with each other.
• A significant safety function of the brain is the communication between the internal carotid and vertebral-basilar structures.
• It is possible for collateral blood flow to come through the Circle of Willis and avoid brain damage if one of the main arteries is blocked.
• The brain’s venous circulation varies significantly from that of the rest of the body.
• As they supply and drain particular areas of the body, arteries and veins usually run together.
• Hence one would assume that a pair of vertebral veins and internal carotid veins would be there.
• This is not the case in the brain, however.
• The main vein collectors are integrated into the dura to form venous sinuses.
• Blood from the brain is gathered by the venous sinuses and transferred to the internal jugular veins.
• The superior and inferior sagittal sinuses drain the cerebrum and the anterior skull base is drained by the cavernous sinuses.
• Eventually, all sinuses drain to the sigmoid sinuses, which leave the skull and form the veins of the jugular.
• In reality, these two jugular veins are the sole drainage of the brain.

Meninges of the brain:

• The three layers of tissue called as meninges cover and secure the brain and spinal cord.
• They are the dura mater, arachnoid mater, and pia mater from the outermost layer to inwards.
• Dura mater:
• It is a strong, thick membrane that lines the inside of the skull closely.
• It has two layers i.e. the periosteal and meningeal dura that are fused. They separate only to form venous sinuses.
• Little folds or compartments are formed by the dura.
• Two unique dural folds, the falx and the tentorium, are present.
• The falx divides the brain’s right and left hemispheres and the cerebrum is separated from the cerebellum by the tentorium.
• Arachnoid mater:
• It is a thin, web-like membrane covering the whole brain.
• The arachnoid is made of tissue that is elastic.
• The space between the dura and the arachnoid membranes is termed as the subdural space.
• Pia mater:
• It embraces the surface of the brain following its fold and grooves.
• There are several blood vessels in pia mater that reach far into the brain.
• The subarachnoid space is termed as the space between the arachnoid and the pia.
• The cerebrospinal fluid bathes and cushions the brain in pia mater.

Describe the structure and function of different parts of human brain

• Brain are divisible into the fore brain, the mid-brain and the hind brain.
• The forebrain is further divided into cerebrum, hypothalamus and thalamus.
• The midbrain includes tectum and tegmentum.
• The hind brain is composed of cerebellum, medulla and pons.
• However, the three main components of the brain are:
  • Cerebrum
  • Brain stem
  • Cerebellum

1. Cerebrum:

• It is the largest part of the brain and is divisible into right and left hemispheres.
• The right and left hemispheres is connected by a bundle of nerve fibres called as corpus callosum.
• The outer layer of the cerebrum is termed as cerebral cortex.
• Cerebrum is responsible for many of functions such as learning, emotions, problem-solving, motor control, interpretation of sensory information etc.
• Cerebrum can be classified into four different lobes: the frontal, parietal, temporal and occipital lobes.
• Frontal lobe:
  • It is located in the frontal part of the brain just over the eyes where the largest section of the brain is located.
  • Human frontal lobe is larger and more developed in comparison to any other organism.
  • It is responsible for executive functions such as language, reasons, emotions, personality characteristics and movement.
  • In the frontal lobe, the Broca’s area, one of the areas in speech is located.
  • The area of the brain responsible for controlling the voluntary movement is also present in it.
  • It is because of the frontal lobe that we are able to communicate and form rational thoughts.
• Parietal lobe:
  • It lies just behind the frontal lobe and is separated from frontal lobe by the central sulcus.
  • The two major functions of parietal lobes are:
  • Somatosensation: touch sensations such as pressure, pain, temperature, heat, cold.
  • Proprioception: the sense of how the body parts are oriented in the space.
  • It also regulates the ability to taste.
• Temporal lobe:
  • It lies posterior to the frontal lobe and is separated by lateral fissure.
  • In appropriate terms, it lies in the base of the brain.
  • Primarily, its function is to process and interpret sounds.
  • It is also a center for the cognitive processes for the memory formation and recognition of language.
  • In this lobe, primary auditory cortex is present that receives the sensations related to hearing.
  • Along with it, the processing of complex visual information, such as environments or images having various elements and large variety of colors takes place in the temporal lobe.
  • The key function of temporal lobe is the long-term memory.
  • Hippocampus lies in this lobe that processes memory formation.
• Occipital lobe:
  • It is situated at the back of the brain and is primarily engaged in vision.
  • It is the main area for visual processing.
  • It helps in recognition and identification of the visual world. 

Functions of cerebrum:

• The cerebrum directs the body’s conscious or voluntary motor functions.
• Inside the primary motor cortex and other frontal lobe motor areas where actions are scheduled, these functions originate.
• Upper motor neurons in the primary motor cortex transmit their axons to the lower motor neurons, which innervate the muscles, to synapse into the brain stem and spinal cord.
• In some forms of motor neuron disease, damage to motor areas of the cortex can result.
• Instead of complete paralysis, this sort of harm results in loss of muscle strength and accuracy.
• The olfactory sensory system is unusual in that its axons are sent directly to the olfactory cortex by neurons in the olfactory bulb, rather than to the thalamus first.
• A deterioration of the sense of smell results in damage to the olfactory bulb.
• From such brain areas as the amygdala, neocortex, hippocampus, locus coeruleus, and substantia nigra, the olfactory bulb also receives ‘top-down’ knowledge.
• Its’ possible functions can be classified into four non-exclusive categories:
  • distinguishing between odors
  •  improving odor detection sensitivity
  • filtering out background odors
  • allowing higher areas of the brain involved in arousal and attention to alter odor detection or discrimination.
• Sections of the cerebral cortex are largely attributed to speech and language.
• In the frontal lobe, motor portions of language are attributed to Broca’s field.
• Wernicke’s area, at the temporal-parietal lobe junction, is due to speech comprehension.
• Damage to the area of Broca results in verbal aphasia (non-fluent aphasia), whereas receptive aphasia results in damage to the Wernicke’s area.

2. Amygdala:

• This is another aspect of the limbic system that is a functional portion of the cerebrum.
• In the temporal lobes, the amygdala lies and is engaged in several functions of the autonomic nervous system, including physiological responses to fear (the “Fight or Flight response) and hormone secretion.
• In each hemisphere, one amygdala is found (plural: amygdalae).
• In particular, this structure is concerned with controlling the emotions of fear, anger, and pleasure.
• The amygdala is the structure which decides what memories are stored and where they are stored in the brain.
• The amygdala is the mechanism which decides what memories are stored and where they are stored in the brain.

3. The thalamus:

• It is a gray matter which is located between the cerebral cortex and the midbrain.
• The thalamus, placed under the cerebral cortex, is involved in various sensory and motor functions.
• It also regulates the circadian rhythm partly by signaling to the brain during sleep to decrease those physiological functions.

4. Hypothalamus:

• It is a small but necessary region of the brain.
• It is situated at the base of the brain, in the proximity to the pituitary gland.
• It is located in the third ventricle’s floor and is the autonomic system’s master control.
• In regulating behaviors such as starvation, hunger, sleep, and sexual response, it plays a major role.
• It also controls the temperature of the body, blood pressure, emotions, and hormone secretion.

5. Basal ganglia:

• The basal ganglia are a collective term for a group of subcortal nuclei that are central to motor control, learning and executive functions as those regulated by the frontal lobe.
• The putamen, caudate, globus pallidus, subthalamic nucleus, and substantia nigra are the parts which make up the basal ganglia collectively.
• The caudate and putamen are referred to as the striatum together.
• These systems are best known for their role in movement, considering all they’re associated with.

6. Olfactory bulb:

• The olfactory bulb is a structure found in the anterior part of the brain, in the lower (bottom) part of the cerebral hemisphere.
• There is one olfactory bulb per hemisphere, and an elongated structure known as the olfactory stalk or the olfactory peduncle binds them to the cerebrum.
• The olfactory bulb is as the name implies, central to the sense of smell and is also partially involved in taste.

7. Brain stem:

• The distal portion of the brain that consists of the midbrain, pons, and medulla oblongata is the brain stem (brain stem).
• Each of the three parts has a particular structure and feature of its own.
• Together, they help to monitor breathing, heart rate, blood pressure, and a variety of other main functions.
• A stalk-like projection that stretches caudally from the base of the cerebrum is the brainstem.
• It favors the communication between the cerebrum, cerebellum, and the spinal cord.
• At its proximal end, the brainstem is broader and becomes smaller towards the distal end.
• Three parts of the brainstem exist:

i) Medulla oblongata:

• The narrowest and most distal section of the medulla is the medulla oblongata.
• The narrowest and most caudal portion of the brainstem is the medulla oblongata or medulla.
• It is a funnel-like structure that stretches from the decussation of the broad pyramids to the inferior pontine sulcus (pontomedullary groove) through the foramen magnum (which is the largest of all the foramina and fissures of the skull).
• The narrowest and most caudal portion of the brainstem is the medulla oblongata or medulla.
• It is a funnel-like structure that stretches from the decussation of the broad pyramids to the inferior pontine sulcus (pontomedullary groove) through the foramen magnum (which is the largest of all the foramina and fissures of the skull).
• As the medulla in the posterior cranial fossa proceeds upward it stops at the fourth ventricle inferior pontine sulcus (anteriorly) and medullary striae (posteriorly).

ii) Pons:

• To the anterior, pons lies in the middle segment of the brainstem.
• Another comparatively short part of the brainstem located in the posterior cranial fossa is the pons.
• The arrangement of approximately 2.5 cm rests against the skull clivus, below the tentorium cerebelli.
• The metencephalon, which is a secondary brain vesicle developed from the hindbrain (rhombencephalon), produces the pons.
• Caudal to the mesencephalon, and cranial to the myelencephalon (medulla), the metencephalon is located.

iii) Midbrain:

• The midbrain is the section that is broader and superior.
• The midbrain is the brainstem’s shortest section.
• It stretches caudally from the thalamus base to the fourth ventricle’s superior roof.
• In the tentorium cerebelli (an extension of the dura mater), it passes through an opening.
• The structure emerges from the mesencephalon, which is one of three primary brain vesicles that emerge (above the fourth pair of somites) from the cranial portion of the closed neural tube.
• Between the forebrain (prosencephalon) and the hindbrain (rhombencephalon) the mesencephalon is located.
• This part of the brainstem is split into tectum (the Latin word for roof), tegmentum (the Latin word for covering) and crus cerebri.
• The tectum is the dorsal component of the midbrain to the cerebral aqueduct of Sylvius (a conduit linking the third and fourth ventricles).
• In comparison, the tegmentum is ventral to the aqueduct of Sylvius.
• Wide arrays of ascending and descending tracts moving to and from the brain are the crus cerebri.
• The substantia nigra separates each crus from the tegmentum.
• This is a pigmented lamina that consists of neurons that are dopaminergic and GABAergic.
• These are cells that create unique neurotransmitters they are named for.
• It is important to note that the tegmentum is continuous throughout the midline of the midbrain, even though each crus cerebri is separate from each other.
• Some texts collectively refer to the crus cerebri and tegmentum as the cerebral peduncles.

Functions of brain stem:

• The brainstem has three essential functions:
• To act as a conduit for pathways to and from the brain to ascend and descend
• To house the nuclei of cranial nerves
• To merge the roles of many critical systems with each other

8. Cerebellum:

• It is a comparatively small region of the brain, about ten percent of the total weight, but it includes approximately half of the neurons of the brain, specialized cells that convey electrical signal information.
• The cerebellum is split into two lateral hemispheres, which are connected by a medial portion called the vermis.
• Each of the hemispheres is composed of a white matter central core and a gray matter surface cortex and is divided into three lobes.
• The flocculonodular lobe is the first portion of cerebellum to develop.
• The flocculonodular lobe receives sensory input from the vestibules of the ear.
• From the spinal cord, the anterior lobe receives sensory input.
• The posterior lobe is last to arise and receives nerve impulses from the cerebrum.
• Within the cerebellar cortex, all these nerve impulses are incorporated.
• The superior, middle, and inferior peduncles that link the cerebellum with the midbrain, pons, and medulla, respectively, transmit information to and from the cerebellum via three paired bundles of nerve fibres.
• The cerebellum has traditionally been regarded a motor structure as cerebellar damage contributes to impairments in motor function and posture and as the majority of the outputs of the cerebellum are part of the motor system.
• In the cerebellum, motor commands are not initiated; rather to make movements more adaptive and precise, the cerebellum modifies the motor commands of the descending pathways.

Functions of cerebellum:

• Balance and posture management:
  • In order to maintain equilibrium, the cerebellum is essential for making postural changes.
  • It modulates commands to motor neurons through its feedback from vestibular receptors and proprioceptors to compensate for changes in body position or changes in load on muscles.
  • Balance problems are suffered by patients with cerebellar injury, and they frequently develop stereotyped postural strategies to compensate for this issue (e.g. a broad-based stance).
• Voluntary movement synchronization:
  • Most movements consist of a variety of distinct muscle groups behaving in a temporarily organized manner together.
  • One of the cerebellum’s key functions is to coordinate the timing and force to produce fluid limb or body movements of these various muscle groups.
• Motor learning:
  • In adjusting and fine-tuning motor programs to make precise movements in a trial-and-error process e.g. learning to hit a baseball), the cerebellum plays a major role.
• Cognitive roles:
  • Though the cerebellum is most commonly understood in terms of its contribution to motor regulation, some cognitive functions, such as language, are also involved.
  • The cerebellum is therefore regarded historically as part of the motor system, like the basal ganglia, but its functions extend beyond motor control in ways that are not yet well understood.

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• The glands that secrete digestive juices for the digestion of food are termed digestive glands.
• Besides the number of gastric glands present in the lining of the stomach, there are many other related digestive glands that pour their secretions into the alimentary canal.
• The digestive glands include salivary glands, gastric glands, liver, pancreas, and intestinal glands.

1. Salivary glands:

• Three pairs of salivary glands are present.
• They are the parotid, submandibular and sublingual glands.
• Parotid glands:
  • The largest of the salivary glands are parotid glands.
  • They are located one on each side of the face, just below and in front of the ears.
  • Parotid glands secrete saliva via a parotid duct into the mouth and help in mastication and swallowing,
  • The secretion of each parotid gland passes through Stensen’s duct which opens into the mouth opposite the site of second upper molar tooth.
  • Mumps is the disease caused by the viral infection of parotid gland.
  •  It is characterized by swelling, irritation, and pain.
• Submandibular glands:
  • These are located embedded in the mucous membrane on the floor of the buccal cavity, under the tongue.
  • Duct of these glands open into the sublingual part of the mouth under the tongue.
  • It secretes mixture of the serous fluid and mucus.
  • This secretion passes into the oral cavity via the submandibular duct or Wharton’s duct.
  • Despite being much smaller than the parotid glands, it accounts for the production of 65-70% of saliva in the oral cavity.
• Sublingual glands:
  • It is the smallest of all the salivary glands.
  • It also includes the parotid and submandibular glands.
  • It is located between the muscles of the oral cavity.
  • It is different from other salivary glands as it lacks striated ducts, hence the saliva is secreted directly via the ducts of Rivinus.
  • It is the only unencapsulated major salivary gland.
  • Primarily, it secretes a thick mucinous fluid that lubricates the oral cavity and aids for swallowing, buffering the pH, initiate digestion, and dental hygiene.

Saliva and its fuctions:

• The salivary glands secrete saliva which is a viscous fluid.
• The saliva of man is a viscous, colorless, cloudy, and opalescent liquid.
• The optimum pH value is 6.8 with a range of 5.6 to 7.6 and specific gravity ranges from 1.002 to 1.008.
• It is uniformly secreted in small quantities to keep the buccal cavity moist.
• When food is present the rate of secretion is increased as the saliva helps both moistening the food and lubricating its subsequent passage through the alimentary canal.
• It also initiates digestion.
• The saliva contains 98.5 to 99% water and 1 – 1.5 % of a dense residue.

Enzymes of saliva:

• Saliva possesses a large number of enzymes such as amylase, lysosome acid phosphatase, aldolase, cholesterase, lysozyme, maltase, catalase, lipase, urease, and protease.
• Among them, amylase and lysozyme show physiological importance.
• Salivary amylase carries out the hydrolysis of starch and glycogen to maltose, isomaltose, dextrin and some glucose.
• Some particular complex polysaccharides present in the cell wall of different species of bacteria are hydrolysed by lysozyme, thereby killing and dissolving them.

Functions of saliva:

• The saliva is responsible for a number of functions:
• The dry food is moistened and facilitates swallowing by a lubricating action. It prevents desiccation of the oral mucosa, since water evaporates slowly from saliva.
• One of the enzymes present in saliva, salivary amylase, or ptyalin play a role in the digestion of starch.
• It keeps the mouth and teeth clean.
• The soluble substance such as sugar and salts get dissolved by it.
• It makes the food delicious to taste.
• The excretion of certain substances such as lead, mercury, and iodides take place in the saliva.
• It makes rapid articulation possible by facilitating movements of the tongue and lips.
• It enhances the sense of taste by acting as a solvent. The taste buds can be stimulated only when the substances having pleasant taste are actually present in the solution.
• It consists of three buffering systems, bicarbonate, phosphate, and mucin of which the bicarbonate is most important.
• When the salivary flow increases particularly at the time of eating, the concentration of bicarbonate and the buffering system rises.

2. Gastric glands:

• The wall of the stomach has various gastric glands.
• They are simple or branched tubular glands.
• About 2-3 litres of gastric juice is secreted daily by these gastric glands in adults.
• At least three different types of gastric glands are present in the gastric mucosa. These are: parietal cells (oxyntic cells), chief cells, and mucous cells.
• The parietal cells supply the hydrochloric acid of the gastric juice.
• The chief cells provide pepsin and other enzymes such as rennin and gastric lipase and the mucous cells secrete mucin.
• The Castle’s intrinsic gastric factor is secreted by the parietal cells that help in the absorption of vitamin B₁₂.
• All these secretions altogether form an acidic gastric juice with pH=2 and low specific gravity ranging from 1.002 to 1.006.
• The gastric juice comprises about 0.5% of solid matter including sodium chloride with traces of potassium chloride and phosphates, mucin and enzymes pepsin, rennin and gastric lipase, hydrochloric acid and mucin.
• The secretion of gastric juice is under both nervous and hormonal control.
• Gastric secretion is triggered by the thought of food, the smell of food, chewing of food and contact of food with the stomach wall.
• The gastric glands also have two uncommon types of gland cells:
• Argentaffin cells that are normally situated at the base of the glands and secrete serotonin, a potent vasoconstrictor.
• Endocrine cells that are present in the pyloric antrum and produce gastrin. The gastrin triggers the secretion of enzymes and HCl.

3. Liver:

• It is the largest gland of the body.
• It generally weighs about 1.6 kg.
• It is chocolate colored and is located just behind the diaphragm on the right side of the upper abdominal cavity.
• The liver has two main lobes, the right lobe which is larger, and the left lobe along which is smaller with two small lobes, the quadrate lobe and the caudate lobe present behind the main lobes.
• Hepatic artery supplies to the liver.
• The blood is drained into the inferior venacava by the hepatic vein.
• On the undersurface of the right lobe of liver, a pear-shaped structure is located called as a gall bladder.
• The gall bladder serves as a reservoir that stores the bile juice secreted by the liver.
• The right and left hepatic ducts from the liver join to form a common bile duct or ductus choledochus.
• The common bile duct and pancreatic duct join to form the hepatopancreatic duct, near the duodenum.
• This opens in the duodenum via an opening guarded by the sphincter of Oddi.
• The dilation of short common hepatopancreatic duct forms hepatopancreatic ampulla or Vater’s ampulla.
• The ampulla opens into the duodenum.
• The bile duct is surrounded by a strong sphincter muscle of Boyden before it is joined by the pancreatic duct.
• When there is no food in the duodenum, this muscle closes.
• This forces the bile into the gall bladder through the cystic duct for storage.

Functions of the liver:

• The liver being a multipurpose organ, performs several important functions:
• Production of bile:
  • Liver secretes bile which is an alkaline dark green-colored fluid having several organic and inorganic salts as well as some waste substances.
  • The bile performs the following functions:
  • It makes the chyme alkaline, better suited for the action of pancreatic juice.
  • It is responsible for the emulsification of fats.
  • It helps in removing the excretory products like bile pigments, inorganic salts, toxins, etc. from the body.
  • It stimulates peristalsis.
  • Some bile salts are necessary for the absorption of vitamin K and other vitamins soluble in fats.
  • Bile acts as an antiseptic, therefore, it does not allow the growth and multiplication of bacteria.
• Regulation of blood sugar level:
  • Liver regulates the blood sugar level (normal 90-120mg per ml of blood) either by the process of glycogenesis or by the glycogenolysis.
  • Glycogenesis is the conversion of glycogen into glucose by the liver cells with the help of glucagon secreted by the pancreas.
  • It is also a center for gluconeogenesis and glyconeogenesis.
• Lipogenesis:
  • Liver also controls lipogenesis. The conversion of the excess of glucose and amino acids into the fats is termed as lipogenesis. It also takes place into the liver.
• Deamination:
  • Liver decomposes the excess and harmful amino acids of blood into toxic NH₃ and metabolically useful keto acids by the process of deamination in the presence of oxidase enzyme.
  • In the liver cells, toxic NH₃ is combined with CO₂ to form less toxic urea by the process of detoxification.
  • Liver also detoxifies the alcohol and converts it into acetaldehyde and then harmless acetyl CoA.
• Absorption and metabolization of bilirubin:
  • Liver transforms hemoglobin of dead RBCs into bile pigments such as biliverdin and bilirubin which are egested out along with feces. Thus, liver helps in excretion.
• Aids in blood clotting:
  • Liver produces an anticoagulant called heparin which prevents the coagulation in the blood vessels.
  • Liver produces two main proteins fibrinogen and prothrombin which help in clotting of blood at injury to check excess of bleeding.
• Erythropoesis and hemolytic function:
  • Liver acts as an erythropoietic organ. It forms RBCs in the foetus.
  • Liver also acts as hemolytic organ. It breaks old RBCs.
• Immunological functions:
  • Kupffer’s cells of liver act as phagocytes which feed on dead cells and bacteria by the phagocytosis process.
• Vitamin and mineral storage:
  • Liver synthesizes vitamin A from beta carotene in the presence of an enzyme carotenase. Beta carotene is an orange yellow substance of carrot.
  • Liver stores minerals like copper and iron, vitamins like A, D, E, K and B12, glycogen, fats and water.
• Maintains body temperature:
  • Liver is the major heat producing centre of the body. Because of high metabolic activities of the liver, sufficient heat is generated, which is very important for maintaining the optimum body temperature.
• Blood reservoir:
  • It serves as the second reservoir of blood.
• Angiotensinogen synthesis:
  • Liver secretes a protein called angiotensinogen which helps kidney to maintain body fluid, osmoregulation.
• Blood filtration:
  • It helps in eliminating several unwanted substances like carbolic acid, cresol, etc. from the blood coming from alimentary canal.
  • It is the important seat of lymph formation.
  • It also produces certain substances which check anemia.

4. Pancreas:

• The pancreas is an elongated and yellowish gland.
• It is located behind the stomach lying horizontally in the curvature of duodenum.
• It is about 12-15cm long and 2.5 cm wide and weighs about 60gms.
• It comprises of head, body and tail.
• The head is located in the curve of the duodenum, the body lies behind the stomach and the tail links the spleen.
• The smaller ducts within the pancreas form the main pancreatic duct.
• Into the hepatopancreatic ampulla (ampulla of Vater), the main pancreatic duct opens.
• In pancreas, an accessory pancreatic duct (duct of Santorini) is also present and opens directly into the duodenum.
• The pancreas is exocrine as well as endocrine in nature.
• A large number of branching tubules or lobules are present in the exocrine tissue called acini.
• Acini are embedded in connective tissue containing blood and lymph vessels, nerves and pancreatic ductules.
• The acinus comprises of cuboidal epithelial cells and secretes an alkaline pancreatic juice with pH 8.8.
• About 500-800 ml of pancreatic juice is secreted every day.
• The main pancreatic duct carries the pancreatic juice into the duodenum through the hepatopancreatic ampulla.
• The pancreatic juice is directly poured into the duodenum by the accessory pancreatic duct.
• The pancreatic juice contains sodium bicarbonate, three proenzymes: trypsinogen, chymotrypsinogen and procarboxypeptidase and several enzymes: pancreatic amylase, pancreatic lipase and nucleases such as DNAse and RNAse.
• The pancreatic juice aids in the digestion of starch, proteins, fats and nucleic acids.
• The activity of chyme caused by HCl is neutralized by the sodium bicarbonate.
• The endocrine tissue of pancreas consists of several group of cells, called Islets of Langerhans, found situated in between the acini.
• Each Islet of Langerhans comprises of the following types of cells.  
• These secrete hormones to be poured in the circulating blood.
• i) Alpha cells (a-cells) are more numerous towards the periphery of islet and constitute about 25% of the Islet of Langerhans. These cells produce glucagon hormone which converts glycogen into glucose in the liver.
• ii) Beta cells (b-cells) are more numerous towards the middle of the islet and constitute about 60% of the islet and constitute about 60% of the islet of Langerhans. These cells supply insulin hormone that converts glucose into glycogen in the liver and muscles. Deficiency of insulin causes diabetes mellitus.
• iii) Delta cells (d-cells) are found towards the periphery of islet and constitute about 10% of islet of Langerhans. These cells produce somatostatin hormone which halts the secretion of glucagon by alpha cells and to some extent secretion of insulin by beta cells.
• iv) Pancreatic polypeptide cells (PP cells) are also found in the pancreas. Pancreatic polypeptide (PP) are secreted by these cells which inhibits the release of pancreatic juice.
• Thus, the pancreas serves two main functions:
  • i) secretion of pancreatic juice which contains digestive enzymes and
  • ii) production of hormones

5. Intestinal glands:

• They are numerous, microscopic glands present in the mucosa of small intestine.
• They are of two types i.e. crypts of Lieberkuhn and Brunner’s glands.
• Crypts of Lieberkuhn:
  • These are simple tubular glands.
  • They occur throughout the small intestine between villi.
  • Digestive enzymes and mucus are secreted by it.
  • These secretions are slightly alkaline with pH in the range of 7.5 to 8.0.
  • They contain several types of cells that secrete mucus and a large number of enzymes.
  • The secretion of these glands is termed as succus entericus or intestinal juice.
  • Each day about 2-3 litres of intestinal juice is secreted.
  • It is alkaline (pH 8.3) in nature and is poured into the intestine.
  • The intestinal juice contains several enzymes: aminopeptidases, intestinal amylase, maltase, isomaltase, dipeptidases, limit dextrinase, sucrase, intestinal lipase, nucleotidases or nucleophosphatases, lactase, nucleosidases and enteropeptidase (enterokinase).
  • These enzymes digest all types of food.
• Brunner’s glands:
  • These are branched tubular glands.
  • These are restricted to the submucosa of the duodenum.
  • These glands secrete mucus.
  • The mucus lubricates and sticks the food together.
  • The digestive tract is therefore lubricated so that food quickly slips into it. This protects the duodenal mucosa from the stomach-derived acidic chyme.
  • The mucus also protects mucosal cells from digestive enzymes.
  • Along with the glands mentioned, the entire alimentary canal has mucous glands that produce mucus.
  • The mucus lubricates the food and digestive tract and protects the mucosa of the stomach from damage.

The post Digestive glands in Human digestive system, their secretions and functions appeared first on Online Biology Notes.

• The lymphatic system is a part of the circulatory system, comprising a network of conducts called lymphatic vessels that carry a clear fluid called lymph, uni-directionally towards the heart.
• The cells of the body are bathed in interstitial fluid which leaks constantly out of the blood stream through the permeable walls of blood capillaries.
• It is hence very alike in composition to blood plasma.
• Some tissue fluid returns to the capillaries at their venous ends and the remainder diffuses through the more permeable walls of the lymph capillaries, forming lymph.
• Lymphatic system does not have central pump organ.

Lymph:

• Lymph is a clear colorless watery fluid, similar in composition to plasma, with the important exception of plasma protein.
• Lymph contains less proteins than blood.
• It is identical in composition to interstitial fluid.
• The hydrostatic pressure of blood in the blood vessel force our water and small protein into the interstitial space.
• Once carried by the lymphatic capillaries, it is known as lymph.
• Its main function is to nourish and bath tissues.
• It transports the plasma protein that sweeps out of the capillary bed to the blood stream.
• It also carries away larger particles such as bacteria and cell debris from damaged tissues, which can then be filtered out and destroyed by the lymph node.
• Lymph consists of lymphocytes, which circulates in the lymphatic system permitting them to patrol the different regions of the absorbed into the lymphatics give the lymph, a milky appearance.
• Lymph is the most common route for cancer cell spread (metastasis). (second common route is via the blood).
• Flow of lymph is affected by:
  • The presence of fluid in the tissue.
  • The smooth and longitudinal muscle contraction of lymphatic capillaries.
  • Lymphatic system runs parallel to the venous system which enters sub-atmospheric pressure “Pull factor”.
  • The valves of lymphatic vessels.
  • Pressure exerted by skeletal muscle.
  • Auxillary respiratory pump.

Functions of lymphatic system:

1. Tissue drainage:
   • It accounts for the removal of interstitial fluid from tissues.
   • Everyday around 21 liters of fluid from plasma protein, escape from the arterial end of the capillaries and into the tissues.
   • Most of this fluid is returned directly to the blood stream via the capillary at its venous end, but the excess, about 3-4 times of fluid, is drained away by the lymphatic vessels.
   • In absence of this, the tissues would rapidly become waterlogged and the cardiovascular system would start to fail as the blood volume falls.
2. Absorption and transportation:
   • It absorbs and transports fats and fat-soluble minerals (fat soluble vitamins) as chyle from the small intestine (central lacteals of the villi).
3. Immunity:
   • The lymphatic organs are concerned with the production and maturation of lymphocytes, the WBC responsible for immunity.
   • Bone marrow is therefore concerned to be lymphatic tissue since lymphocytes rae produced there.
   • The lymph transports antigen presenting cells (APCs) such as dendritic cells, to the lymph node where an immune response is stimulated.

What are organs of lymphatic systems?

• Lymphatic system consists of:
  • Lymphatic capillaries (lacteals)
  • Lymphatic vessels
  • Lymph node (lymph gland)
  • Lymphoid organs:
    • Tonsil
    • Spleen
    • Thymus gland
    • Aggregated payer patches

1. Lymphatic capillaries:

• These originates as blind end tubes in the interstitial space.
• They have the same structure as blood capillaries i.e. a single layer of endothelial cells, but their walls are more permeable to all interstitial fluid constituents including proteins and cell debris.
• The tiny capillaries join up to form larger lymph vessels.
• Nearly all tissues have a network of lymphatic vessels, important exception being the central nervous system, the cornea of the eyes, the bones and the most superficial layers of the skin.

2. Lymph vessels:

• Lymph vessels are often found running along-side the arteries and veins serving the area.
• These walls are about the same thickness as those of small veins and have the same layers of tissues.
• The layers of tissue consists of fibrous covering, a middle layer of smooth muscle and elastic tissue and an inner lining of endothelium.
• Similar to veins, lymph vessels have large number of cup shaped valves to make sure that lymph flows in a one-way system towards the thorax.
• There is no pump like the heart, involved in the onward movement of lymph, but the muscle layer in the walls of larger lymph vessels has an intrinsic ability to contract rhythmically.
• In addition, lymph vessels are compressed by activity in adjacent structures such as contraction of muscles and the regular pulsation of large arteries.
• This milking action on the lymph vessel walls helps to push lymph along.
• Lymph vessels become larger as they join together eventually forming two large ducts, the thoracic duct and right lymphatic duct, which empty lymph into the subclavian veins.
• Thoracic duct:
  • This duct begins at the cisternae chyli which is a dilated lymph channel situated in front of the bodies of the first two lumbar vertebrae.
  • The duct is about 40cm long and opens into the left subclavian vein in the root of the neck.
  • It drains lymph from both eyes, the pelvic and abdominal cavities, the left half of the thorax, head and neck and the left arm.
• Right lymphatic duct:
  • This is a dilated lymph vessel of about 1cm long.
  • It lies in the root of the neck and opens into right subclavian vein.
  • It drains lymph from right half of the thorax, head and neck of the right arm.

3. Lymph node:

• Lymph nodes are oval or bean shaped organs that are found often in groups, along the length of lymph vessels.
• The lymph drains through a number of nodes, usually 8 to 10 before returning to venous circulation.
• These nodes vary considerably in size, some are small as a pin head and the largest ate about the size of an almond.
• Lymph nodes are the lymphatic tissues covered by the fibrous tissue.
• The outer capsule of fibrous tissue dips down into the node substance forming partitions trabeculae.
• Many lymphocyte and macrophage are found inside lymph node.
• As many as four or five afferent lymph vessels may enter a lymph node while only one efferent vessel carries lymph away from the node.
• Each node has a concave surface called the hilum where an artery enters and a vein and the efferent lymph vessel leave.
• Histologically, it has outer layer cortex and inner layer medulla.
• Cortex predominantly consists of B-lymphocytes that are responsible for humoral immunity whereas medulla predominantly contains T-lymphocytes responsible for cell mediated immunity.
• Lymph nodes are particularly numerous in the mediastinum in the chest, neck, pelvis, axilla (armpit), inguinal (groin) region and in association with the blood vessels of the intestine.
• Lymph from various regions passes through:
  • Head and neck region —> deep and superficial cervical node
  • Upper limbs —-> nodes of elbow region and then to superficial axillary node.
  • Organs and tissue of thoracic cavity —–> Nodes close to mediastinum
  • Breast —-> axillary nodes
  • Pelvic and abdominal cavity —> lymph nodes —> cisternae chyli
  • Lower limbs —-> inguinal nodes
• Functions of lymph node:
• Filtering and phagocytosis:
  • Lymph is filtered by the reticular and lymphoid tissues as it passes through lymph nodes.
  • Particulate matters may include bacteria, dead and live phagocytes containing ingested microbes, cells from malignant tumors, worn out and damaged tissue cells and inhaled particles.
  • Organic material is destroyed in lymph nodes by macrophages and antibodies.
  • Some inorganic inhaled particles cannot be destroyed by phagocytosis.
  • These stay inside the macrophages, either causing no damage or killing the cell.
  • Material not filtered out and dealt with in one lymph node passes on to successive nodes and by the time lymph enters the blood it has usually been cleared of foreign matter and cell debris.
  • In some cases where phagocytosis of bacteria is incomplete, they may stimulate inflammation and enlargement of node (lymphadenopathy).
• Proliferation of lymphocytes:
  • In lymph nodes, activated T and B lymphocytes multiply.
  • Antibodies produced by sensitized B-lymphocytes enter lymph and blood draining the node.

4. Lymphoid organs:

• Tonsil:
  • Tonsil are lymphoid tissue around the pharynx but unlike lymph node they don’t have fibrous capsule, cortex and medulla.
  • There are three types of tonsils:
  • Pharyngeal tonsil —> upper posterior wall of pharynx behind nose
  • Palatine tonsil —-> on the side of the soft palate
  • Lingual tonsil —-> at the base of the tongue
  • Tonsil prevents microorganisms by destroying invading microorganisms.
• Spleen:
  • Spleen is the largest lymphoid organ and contains reticular and lymphatic tissues.
  • The spleen is located in the left hypochondriac region of the abdominal cavity.
  • It lies between the fundus of the stomach and the diaphragm.
  • It is purplish in color and varies in size in different individuals, but it is usually about 12 cm long, 7 cm wide and 2.5 cm thick.
  • It weighs about 200gm.
  • The spleen is more or less oval in shape with the hilum on the lower medial border.
  • The anterior surface is covered with peritoneum.
  • A fibroelastic capsule encloses spleen that dips into the organ, forming trabeculae.
  • Splenic pulp is the term for the cellular material consisting of lymphocytes and macrophages.
  • Red pulp is the part suffused with blood and white pulp consists of areas of lymphatic tissues where there are sleeves of lymphocyte and macrophages around blood vessels.
  • The structures entering and leaving the spleen at hilum are:
  • Splenic artery: a branch of coeliac artery
  • Splenic vein: a branch of portal vein
  • Lymph vessels: (efferent only)
  • Functions of spleen:
  • Phagocytosis:
    • In the spleen, old and abnormal erythrocytes are mainly destroyed.
    • The breakdown products, bilirubin and iron are transported to the liver via the splenic and portal veins.
    • Other cellular materials e.g. leukocytes, platelets and bacteria are phagocytosed in the spleen.
    • Unlike lymph nodes, the spleen lacks afferent lymphatics entering it.
    • So, it is not exposed to disease spread by lymph.
  • Storage of blood:
    • Spleen contains upto 350ml of blood and in response to symphatetic stimulation can rapidly return most of the volume to the circulation in hemorrhage.
  • Immune response:
    • The spleen contains T and B-lymphocytes, which are activated by the presence of antigens. E.g. in infection.
    • Proliferation of lymphocytes during serious infection can result in enlargement of the spleen.
  • Erythropoiesis:
    • The spleen and liver are essential sites of fetal blood cell production.
    •  The spleen can also fulfil this function in adults in times of much need.
• Thymus gland:
  • The thymus is pinkish grey ductless gland lies in the upper part of the mediastinum behind the sternum and extends upwards into the root of the neck.
  • It weighs about 10-15gm at birth and grows until puberty when it begins to atrophy.
  • Its maximum weight, at puberty, is between 30 and 40 gm and by the middle age it has returned to approximately its weight at birth.
  • The thymus consists of two lobes joined by areolar tissue.
  • A fibrous capsule encloses the lobes which dips into their substance, dividing them into lobules that consists of an irregular branching framework of epithelial cells and lymphocytes.
• Functions of thymus gland:
  • Lymphocytes originate from stem cells in red bone marrow.
  • Those that enter the thymus develop into activated T-lymphocytes.
  • Thymic processing produces mature T-lymphocyte that can differentiate self tissue from foreign tissue.
  •  These mature T lymphocytes also provides each T-lymphocyte with the ability to react to only one specific Ag from the millions it will encounter.
  • T-lymphocytes then leave the thymus and enter the blood.
  • Some enter lymphoid tissues and other circulate in the bloodstream.
  • Although T-lymphocyte production is most prolific in youth, it probably continues throughout life from a resident population of thymic stem cells.
  • The maturation of thymus and other lymphoid tissue is stimulated by thymosin, a hormone secreted by the epithelial cell of thymus.
  • Shrinkage of gland begins in adolescence, so the effectiveness of the T-lymphocytes response to Ag declines.

Lymph and Lymphatic system: functions and role in immunity

The post Lymph and Lymphatic system: functions and role in immunity appeared first on Online Biology Notes.

• The sequence of events related to the flow of blood or blood pressure that occurs from the beginning of one heartbeat to the beginning of another can be referred to as cardiac cycle.
• Average heart beat per minute= 75 beats
• Then, cardiac cycle= 60secs/75 beats= 0.8 sec/beat.
• The frequency of the cardiac cycle is explained by the heart rate:
• Each cardiac cycle has four major events:
  • Atrial Systole = 0.1 sec
  • Atrial Diastole = 0.7 sec
    • Total = 0.8 sec
  • Ventricular Systole = 0.3 sec
  • Ventricular Diastole = 0.5 sec
    • Total = 0.8 sec

Atrial systole:

• It is the contraction of heart muscle (myocardium) of left and right atria.
• Generally, both atria contract at the same time.
• As the atria contract, the blood pressure in each atrium increase forcing additional blood into the ventricles.
• The additional flow of blood is also known as atrial kick.

Atrial diastole:

• It is the phase when the atria are in relaxing mode.

Detection of atrial systole:

• Electrical systole of the atria begins with the onset of the P wave on the Electrocardiogram.
• The wave of bipolarization or depolarization that stimulates both atria, to contract at the same time is due to sinoatrial node (SA node) which is located on the upper wall of the right atrium.

Ventricular systole:

• Ventricular systole events contains:
  • Isomeric contraction (0.05sec)
  • Maximum ejection (0.11sec)
  • Reduced ejection (0.14sec)
• First sound of heart produced by closure of AV valve.
• For certain period, semi lunar valve also stays closed.
• The period when both AV and semilunar valve stay closed is known as isovolumetric contraction as there is no change in volume.
• It occurs for about 0.05sec.
• Then semilunar valve opens and blood flows from ventricle to aorta and pulmonary artery through left and right ventricle respectively which is known as maximum ejection (0.11 sec).
• Then reduced ejection occurs (0.14sec).
• After which sharp closure of semilunar valve occurs producing second sound of heart.

Ventricular diastole:

• Ventricular diastole events:
  • Proto-diastole (0.04sec)
  • Isometric relaxation (0.08sec)
  • 1^st rapid filling (0.113sec)
  • Diastasis (0.107sec)
  • Last rapid filling (0.1sec)
• For certain period before diastole, semilunar valve close, the AV are open and the whole heart is relaxed.
• This period is known as prodiastole and it lasts for about 0.04 sec.
• During isovolumetric ventricular relaxation (0.08sec), both AV and SLV closed, pressure decreases, no blood enters the ventricles, the ventricles stop contracting and begin to relax.
• 3^rd sound of heart is produced by 1^st rapid filling (0.113).
• Diastasis is the intermediate period when the pressure lowers.
• 4^th sound of heart is produced by last rapid filling (0.1sec).

Detection of ventricular systole or heart sound:

• The closure of the mitral and tricuspid valve at the beginning of ventricular systole cause the first part of the Lubb-dubb sound made by the heart as it beats.
• Formally, this sound is termed as the first heart tone or S1.
• This first heart tone is created by the vibration of leaves of the valves during the closure of mitral and triscuspid valve and is actually a two component sounds H1, T1.
• The second part pf the lubb-dubb (the second heart tone or S2) is caused by the closure of the aortic and pulmonary valves at the end of ventricular systole.
• As the left ventricle empties, its pressure falls below pressure in the aorta, and the aortic valve closes.
• The second heart sound is also of two components A2 and P2 i.e. aortic valve closes prior to the pulmonary valve and they are audibly separated from each other in the second heart sound.
• The splitting of S2 is only audible during inhalation.
• But, some cardiac conduction abnormalities such as left bundle branch block (LBBB) permit the P2 sound to be heard before the A2 sound during respiration.
• With LBBB, inhalation brings A2 and P2 together where they cannot be audibly distinguished.

Cardiac output:

• The cardiac output is the amount of blood ejected from each ventricles every minute.
• The amount expelled by each contraction of each ventricle is the stroke volume.
• Cardiac output is expressed in litres per minute and is calculated by:
  • Cardiac output = stroke volume X heart rate
• In a healthy adult at rest, the stroke volume is approximately 70ml and if the heart rate is 72 per minute, the cardiac output is 5 litre/min.
• This can be greatly increased to meet the demands of exercise to around 25litre/minute and in athletes up to 35 litre/min.
• This enhancement during exercise is called the cardiac reserve.

What is Blood pressure?

• Blood pressure is the force or pressure that the blood exerts on the wall of the blood vessels.
• It is also known as systematic arterial blood pressure and it maintains the essential flow of blood into and out of the organs of the body.
• Blood pressure = cardiac output X peripheral resistance
• The blood pressure in a healthy person is 120/80mm Hg.
• The blood pressure is measured by an ausculatory method with the help of an instrument called sphygmomanometer. It was invented by Karot kolff in 1905. It is the indirect method of measurement of blood pressure.
• It is of two types:
  • Systolic blood pressure
  • Diastolic blood pressure

Systolic blood pressure:

• When the left ventricle contracts and pushes blood into the aorta, the pressure produced within the arterial system is called the systolic blood pressure.
• In a healthy resting adult man, it is about 120mm Hg.
• It is maximum in arteries because arteries because arteries are always stretched.
• It indicates the force with which the left ventricle pushes the blood in the aortic arch.
• It is the higher limit of arterial blood pressure (or 16kpa).

Diastolic blood pressure:

• When complete cardiac diastole occurs and the heart is resting following the ejection of blood, the pressure within the arteries is much lower and is called diastolic blood pressure.
• At this time, ventricle is maximally relaxed.
• In a healthy resting adult man, it is about 80mm Hg or 11 kpa.
• It indicates the elasticity of blood vessels.
• It is called the lower limit of arterial blood pressure.
• Therefore, during each heartbeat, the arterial blood pressure rises to about 120mm Hg in systolic phase and falls to about 80mm Hg in diastolic phase.

Pulse pressure:

• The difference between the systolic and diastolic pressure is called pulse pressure which is 40mm Hg.

The effects of the autonomic nervous system on heart and blood vessels:

	Sympathetic stimulation	Parasympathetic stimulation
Heart	Rate increases       strength of contraction increases	Rate decreases    strength of contraction decreases
Blood vessels	Most constrict but arteries supplying skeletal muscles and brain dilate.	Most blood vessels do not have a parasympathetic blood supply.

Elasticity of arterial walls:

• There is a considerable amount of elastic tissue in the arterial walls especially in large arteries.
• Therefore, when the left ventricle ejects blood into the already full aorta, the aorta expands to accommodate it and then recoils because of the elastic tissue in the wall.
• This rushes the blood forwards into the systemic circulation.
• This distension and recoil occur throughout the arterial system.
• During cardiac diastole the elastic recoil of the arteries maintains the diastolic pressure.
• If BP becomes too high, blood vessels can be damaged, causing clots or bleeding from sites of blood vessel rupture.
• The blood flow through tissue beds may be inadequate if BP falls too low.
• This is especially critical for such essential organs as the heart, brain or kidneys.

Blood pressure disorders:

Hypertension:

• It is the condition in which a person has persistent high blood pressure.
• In this condition, blood pressure is high 150/90mm Hg.
• The main factors responsible for hypertension are:
  • Tension
  • Fear
  • Exercise
  • Obesity
  • Anxiety
  • Sorrow
  • Other emotional stress
• It can also be caused due to intake of cholesterol rich diet, smoking, nephritis etc.
• Constriction of arteries, loss of elasticity and fatty deposition (cholesterol) inside arteries narrowing the lumen results in high blood pressure.

Hypotension:

• Hypotension is a condition in which a person has persistent low blood pressure.
• In this condition, blood pressure becomes low as 100/50mm Hg.
• The main factors responsible for hypotension are the loss of blood by hemorrhage, failure of the pumping action of the heart.
• It may cause a person senseless.

Artificial pacemakers:

• It is an artificial instrument to keep the pace of heart.
• It generates heartbeat somewhat at a normal rate.
• At first Chardack implanted it in 1960.
• A pacemaker is implanted when heart rate of a patient falls to about 30-40 percent has to certain reason.
• The implanted pacemaker raises the heartbeat rate and maintains to a normal.
• This device is being widely used and has become a boon in the history of medical science.
• A pacemaker is made of a pulse generator and an electrode.
• The pulse generator is a sealed box that contains lithium halide cells to generate power for more than ten years and an electric circuit to regulate the heart beat rate.
• The electrode is a fine metallic string that is connected to the pulse generator.
• Its special tip remains in contact with the interior of right ventricle.
• The pacemaker is placed under the collar bone below the skin.
• It is done by a simple operation.
• A pacemaker can be replaced or removed easily.

Distribution of blood volume in body:

• Total blood volume = 5 liter (approx.)
• Systemic circulation= 64% in veins and venules,
• 13% in arteries,
• 7% in systemic arterioles and capillaries.
• Heart = 7%
• Pulmonary vessels = 9%
• The whole course of circulation is shown as follows:
  • Organs —-> venous capillaries —-> venules (deoxygenated blood) ——> veins ——-> pre and post cavals ——> right auricle —–> right ventricles —-> pulmonary aorta m -> lungs (for oxygenation) ——> pulmonary veins —–> left auricle (oxygenated blood) —–> left ventricle ——> systemic aorta —–> arteries —–> arterioles and arterial capillaries —–> organs

Cardiac cycle and heart sound

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• One drawback of a circulatory system such as ours, in which the liquid blood is under high pressure, is that serious bleeding can take place after even a slight injury.
• To prevent the possibility of uncontrolled bleeding, we have a three-part hemostatic mechanism consisting of:
  • The constriction of blood vessels
  • The clumping together (aggregation) of platelets
  • Blood clotting
• Overall, hemostasis is a specific type of homeostasis that prevents blood loss.

1. Vasoconstrictive phase:

• Normally, when a tissue is damaged and blood escapes from a blood vessel, the vessel wall constricts in order to narrow the opening of the vessel and slow the flow of blood.
• This vasoconstriction is due to contraction of the smooth muscle of the vessel wall as a direct result of the injury and the release of vasoconstrictor chemicals from platelets.
• Proper vasoconstriction is also enhanced by pain reflexes, producing constriction in proportion to the extent of the injury.
• Constriction of capillaries, which donot have muscular layers, is due to the vascular compression caused by the pressure of lost blood that accumulates in surrounding tissues.
• Injured blood vessels may continue to constrict for 20 min or more.

2. Platelet phase:

• The next event in hemostasis is the escape from blood vessels of platelets, which swell and adhere to the collagen in adjacent connective tissues.
• This attachment stimulates vasoconstriction.
• By now, the platelets have become very sticky, so that as more and more of them move into the injured are they stick together.
• In about a minute they can clog a small opening in the vessel with a platelet plug.
• The process is called platelet aggregation.
• It is important partly because it successfully stops hundreds of small hemorrhages every day and partly because it triggers the blood-clotting mechanism.

3. Coagulation phase: Basic mechanism of blood clotting

• If the blood vessel damage is so extensive that the platelet plug cannot stop the bleeding, the complicated process of blood clotting- the coagulation phase- begins.
• The basic clotting mechanism involves the following events:
• Supported by a plasma globulin called antihemophilic factor (AHF), blood platelets disintegrate and release the enzyme thromboplastinogenase and platelet factor 3.
• Thromboplastinogenase combines with AHF to convert the plasma globulin thromboplastinogen into the enzyme thromboplastin.
• Thromboplastin combines with calcium ions to convert the inactive plasma protein prothrombin into the active enzyme thrombin.
• Thrombin acts as a catalyst to convert the soluble plasma protein fibrinogen (‘giving birth to fibrin’) into the insoluble, stringy plasma protein fibrin.
• The fibrin threads entangle the blood cells and create a clot.
• The basic process may be summarized as follows:
  • Thromboplastinogen —–Thromboplastinogenase+ antihemophilic factor——-> Thromboplastin
  • Prothrombin ——-Thromboplastin+ calcium ions-——-> Thrombin
  • Fibrinogen ——thrombin————> Fibrin

List of Blood clotting factors:

Platelet coagulation factors:

Extrinsic and intrinsic pathways:

• Two partially independent pathways were identified in 1960s for the triggering of a blood clot:
• The extrinsic pathway is a rapid clotting system activated when blood vessels are ruptured and tissues are damaged.
•  The intrinsic pathway is activated when the inner walls of blood vessels become damaged or irregular.
• Damaged tissue triggers the extrinsic pathway, which initiates blood clotting by the release of thromboplastin, known in this form as tissue factor. (A somewhat different form of thromboplastin is at work at the site of ruptured vessels, triggered by the disintegration of platelets).
• Tissue factor combines with a mixture of enzymes and the phospholipids from damaged cell membranes released by the injured tissue to produce a substance called pro-thrombin activator.
• At this point, the extrinsic system merges with the intrinsic system to activate yet another mechanism (called the common pathway) that actually produces the clot.
• The common pathway includes steps 3, 4, and 5 described above.
• The intrinsic pathway for initiating blood clotting uses only substances found in the blood.
• These substances are called clotting factors.
• Injury to the inner wall of a blood vessel activates clotting factor XII, which triggers a series of rapid chemical reactions usually called the ‘cascade effect’.
• Each step activates the next step in the sequence until prothrombin activator is produced.
• After prothrombin activator is formed in the extrinsic and intrinsic pathways, the basic blood-clotting process proceeds through the common pathway.
• The extrinsic pathway usually produces a clot in as little as 15 sec, while the intrinsic pathway requires 2 to 6 min.
• At this point, the fibrin threads form only a weak mesh, and the clot must be strengthened if it is to hold.
• Platelets and plasmaglobulins release a fibrin-stabilizing factor that responds to thrombin to create an interlacing pattern of fibrin threads.
• Within a few minutes after the clot is formed, it begins to contract, squeezing out serum and helping the clot solidify.
• The power to contract comes from platelets, which contain actin and myosin, the same proteins that make muscle contraction possible.
• Platelets contain more actin and myosin than any tissue in the body except muscle.
• Most of the serum is drained within an hour, and the solid clot is finally complete.
• A ‘scab’ forms, dries up, and in a few days falls off as the underlying tissue heals.
• A well-known dietary substance involved with blood clotting is vitamin K.
• It is found in leafy green vegetables, tomatoes, vegetable oils and also produced by intestinal bacteria, vitamin K is necessary for the production of prothrombin and other clotting factors by the liver.

Blood clotting inhibitors

i. Anticoagulant:

• As many as 35 compounds may be required for blood coagulation.
• Such a complex system of checks and balances is necessary to prevent clotting when there is no bleeding.
• An unwanted clot in a blood vessel that cuts off the blood supply to a vital organ is one of the body’s worst enemies.
• Most of the body’s anticoagulant substances circulate within the blood, and the blood vessels themselves help prevent clotting.
• The blood vessels contribute in two ways.
• First, the smoothness of the inner walls normally prevents activation of the intrinsic clotting mechanism.
• Second, a thin layer of negatively charged protein molecules attached to the inner walls repels the clotting factors, preventing the initiation of clotting.
• Injury to a blood vessel removes both of these safeguards.
• The rough damaged wall of the vessel and the negatively charged collagen layer beneath the smooth endothelium initiate the platelet phase of hemostasis.
• If the platelet plug that forms cannot stop the loss of blood, factor XII is activated, along with the rest of the intrinsic pathway.

ii. Heparin and antithrombin:

• One of the most powerful anticoagulants in the blood is heparin, a polysaccharide produced by mast cells and basophils.
• Heparin is concentrated mostly in the liver and lungs.
• Minute quantities of heparin in normal circulating blood also prevent clotting by combining with the antithrombin-heparin cofactor (also called antithrombin or antithrombin III) to induce the co-factor to combine with thrombin 1000 times more rapidly than usual.
• Such a rapid binding to thrombin removes it almost instantly from the bloodstream and makes clotting almost impossible.
• Without heparin, antithrombin-heparin cofactor binds to thrombin molecule for molecule, removing it from the blood in about 15min.
• The combination of heparin and antithrombin-heparin cofactor also reacts with several clotting factors in the extrinsic and intrinsic pathways, further inhibiting blood clotting.
• Thrombin itself acts as an anticoagulant.
• When its concentration becomes too high, it destroys factor VIII to prevent clotting.

iii. Fibrinolysis by plasmin:

• Clot prevention is important, but so is clot destruction, or fibrinolysis (‘fibrin breaking’).
• Small blood clots form continually in blood vessels throughout the body.
• If they are not removed promptly, the blood vessels become clogged.
• In the process of fibrinolysis, a blood protein called plasminogen is activated into an enzyme called plasmin.
• The plasmin digests the threads of fibrin by first making them soluble and then breaking them into small fragments.
• The fragments are removed from the bloodstream by phagocytic white blood cells and macrophages.
• Excessive amounts of coagulants are routinely removed by the liver.

Anticoagulant drugs:

• When used under medical supervision, anticoagulant drugs can sometimes remove blood clots in the body.
• The best-known anticoagulant drug is aspirin (acetylsalicylic acid), which works by preventing platelets from sticking together to form a plug.
• It also inhibits the release of clot-promoting substances from platelets.
• One drug that digests the fibrin threads of a clot is streptokinase, which is released by certain streptococcal bacteria.
• Streptokinase activates plasminogen to speed fibrinolysis.
• It is used to dissolve blood clots (thrombi) in veins and arteries.
• Streptokinase also helps dissolve the fibrin threads in a blood clot by converting plasminogen into plasmin, the fibrin-destroying enzyme.
• Genetically engineered (recombinant) tissue-plasminogen activator (rt-PA) is effective in dissolving intravascular blood clots when delivered directly to a clotted area through a catheter.
• For example, if rt. PA is used within the first several hours after a blood clot forms in a coronary artery, the heart is often spared a serious damage.
• When vitamin K is in short supply, the liver produces enough prothrombin and other clotting substances for normal clotting.
• Dicumarol is a compound that resembles vitamin K to such an extent that the liver enzymes that form prothrombin will pick up dicumarol instead of vitamin K.
• The anti-coagulatory effect of dicumarol is often used to prevent clotting after surgery.
• In addition to being used to remove blood clots and keep blood from coagulating during surgery, anti-coagulant drugs may be necessary to prevent clotting in blood that will be used later for blood transfusions.
• To avoid such clotting, a dilute sterile solution of a citrate or an oxalate salt is added to collected blood.
• Clotting doesnot occur because citrate ions or oxalate ions combine with the available calcium ions, making calcium unavailable for its usual blood-clotting functions.

Blood coagulation tests:

• Several tests are used to determine blood-clotting time.
• The most popular ones are platelet count, bleeding time, clotting time, and prothrombin time.
• The blood platelet count must be greater than 150,000 per cubic millimeter in order for normal coagulation to take place.
• Also, if platelet function is not normal, normal coagulation may not occur.
• A pierced fingertip or earlobe usually bleeds for 3 to 6 min.
• A longer bleeding time for this wound generally indicates a platelet deficiency.
• Clotting time is determined by placing blood in a test tube and tipping it back and forth every 30sec or until it clots.
• This usually occurs in 5 to 8 min.
• Because the condition and size of test tubes vary, standardization is necessary to obtain accurate results.
• The test for prothrombin time (PT) indicates the amount of prothrombin in the blood.
• Immediately after blood is removed, oxalate is added to prevent the prothrombin from being converted into thrombin.
• Then calcium ions and tissue extract containing thromboplastin are added to the blood.
• The calcium offsets the effect of the oxalate, and the tissue extract activates the conversion of prothrombin.
• The time usually required for blood to clot, referred to as the prothrombin time, is about 12 sec.
• A longer prothrombin times also mean a decreased quantity of some factor other than prothrombin.
• Similar tests are used to determine the relative quantities of other clotting factors.

Blood clotting: factors, mechanism and inhibitors

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• Hormones are the chemical messenger produced in small amount by endocrine glands, secreted into blood stream to control metabolism and biological activities in target cell or organs.

Characteristics or properties of hormone:

• Low molecular weight
• Small soluble organic molecules
• Rate of diffusion is very high and are readily oxidized but the effect does not remains constant
• It is effective in low concentration
• Travels in blood
• It has its target site different from where it is produce and  is specific to a particular target
• Hormones are non-specific for organisms and may influences body process of other individuals

Functions of hormones

• Regulatory and homeostasis functions
• Maintain consistency of interior of cell
• Permissive functions; movement of substance in and out of cell
• Integrative function; usually balance two system
• Developmental function; helps in development of foetus

Classification of hormone

Hormones are classified

1. On the basis of chemical nature
2. On the basis of mechanism of hormone action
   1. Group I hormone
   1. Group II hormone

A. On the basis of chemical nature:

1. Protein hormones: insulin, glucagon
2. Steroid hormone: sex hormones, glucocorticoids
3. Aminoacids derivatives hormones: epinephrine, nor epinephrine etc

B.  On the basis of mechanism of hormone action

1. Group I hormone (lipophilic hormone):

• These hormones are lipophilic in nature.
• They are mostly derivatives of cholesterol.
• These hormones binds to intracellular receptors
• Example: Steroid hormones, Estrogen, androgen, glucocorticoids, cholcalciferol, thyroxine etc

2. Group II hormones (water soluble hormone):

• These hormones binds to cell surface receptors and stimulates the release of certain molecules (secondary messengers) to perform biochemical functions

On the basis of secondary messengers group II hormones are of 3 types;

i. Secondary messenger is cAMP:

• eg. Adrenocorticotropic hormone, FSH, LH, PTH,ADH, calcitonin, glucagon,

ii. Secondary messenger is phosphotidylinocitol/calcium or both:

• eg. Acetylcholine, vasopressin, cholecystokinin, gastrin, gonadotropin releasing hormone, thyrotropin releasing hormone,
• Insulin, chorynoic somato mamotropin, epidermal growth factors, fibroblast growth factors, GH, prolactin

iii. Secondary messenger is cGMP:

• Atrial natriuretic peptide (ANP)

Hormones- Properties, functions and classification

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• Electrocardiogram refers to the recording of electrical changes that occurs in heart during a cardiac cycle. It may be abbreviated as ECG or EKG.

Electrocardiograph:

• It is an instrument that picks up the electric currents produced by the heart muscle during a cardiac cycle of contraction and relaxation.

Working principle of electrocardiograph:

• It works on the principle that a contracting muscle generates a small electric current that can be detected and measured through electrodes suitably placed on the body.
• For a resting electrocardiogram, a person is made to lie in the resting position and electrodes are placed on arms, legs and at six places on the chest over the area of the heart. The electrodes are attached to the person’s skin with the help of a special jelly.
• The electrode picks up the current and transmit them to an amplifier inside the electrocardiograph. Then electrocardiograph amplifies the current and records them on a paper as a wavy line.
• In an electrocardiograph, a sensitive lever traces the changes in current on a moving sheet of paper.
• A modern electrocardiograph may also be connected to an oscilloscope, an instrument that display the current on a screen.

Normal ECG wave:

• A normal ECG makes a specific pattern of three recognizable waves in a cardiac cycle. These wave are- P wave, QRS wave and T-wave, P-R interval, S-T segment

• P-wave:

  • It is a small upward wave that appears first
  • It indicates atrial depolarization (systole), during which excitation spreads from SA node to all over atrium
  • About 0.1 second after P-wave begins, atria contracts. Hence P-wave represents atrial systole

• QRS wave:

  • It is the second wave that begins as a little downward wave but continues as a large upright triangular wave and ends as downward wave
  • It represents the ventricular depolarization (systole)
  • Just after QRS wave begins, ventricles starts to contracts. Hence QRS wave represents ventricular systole

• T- wave:

  • It is third small wave in the form of a dome-shaped upward deflection.
  • It indicates ventricular repolarization (diastole)
  • It also represents the beginning of ventricular diastole
  • ** ATRIAL DIASTOLE MERGES WITH QRS-WAVE

• P-R interval:

  • It represents the time required for an impulse to travel through the atria, AV node and bundle of his to reach ventricles.

• S-T segment:

  • It is measured from the end of S to the beginning of T- wave
  • It represents the time when ventricular fibres are fully depolarized.

Application of ECG:

• it indicates the rate and rhythm or pattern of contraction of heart
• it gives a clue about the condition of heart muscle and is used to diagnose heart disorders
• it helps the doctors to determine whether the heart is normal, enlarged or if its certain regions are damaged
• it can also reveal irregularities in heart’s rhythm known as ‘arrhythmia’
• it is used by doctors to diagnose heart damage in conditions like high blood pressure, rheumatic fever and birth defects
• an ECG also helps to determine the location and amount of injury caused by heart attack and later helps to assess the extent of recovery

Significance of different waves in an ECG deviating from normal ECG

• Enlarged P-wave:
  • It indicates enlarged atrium (it occurs in a condition called mitral stenosis in which due to narrowing of mitral valve, blood backs up into left atrium)

• Enlarged Q-wave: downward wave
  • It indicates a myocardial infraction ( heart attack)
• Enlarged R- wave:
  • It indicates enlarged ventricles

• Long P-Q interval:
  • It indicates more time taken by impulse to travel through atria and reach ventricles
  • It happens in coronary artery disease and rheumatic fever when a scar tissue may form in heart
• Elevated S-T segment:
  • When S-T segment is above the base line, it may indicates acute myocardial infraction

• Depressed S-T segment:
  • It indicates that heart muscles receive insufficient oxygen

• Flatter T-wave:
  • It indicates insufficient supply of oxygen to heart muscle as it occurs in coronary artery disease
• Elevated T-wave:
  • It may indicates increased level of potassium ions in blood as in hyperkalemia

Electrocardiogram (ECG): working principle, normal ECG wave, application of ECG

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Principle of ESR:

When an anticoagulant is added to the blood and this well mixed venous blood is placed in a vertical tube, erythrocytes tend to settle towards bottom leaving clear plasma on top. This rate of sedimentation of red blood cells in a given interval of time is called erythrocyte sedimentation rate (ESR).

As the erythrocytes sediments, in a period of one hours, 3 stages can be observed.

• Stage I: first 10 minutes
  • It is initial period of aggregation during which rouleaux are formed and the sediment rate is low
• Stage II: next 4o minutes
  • It is a period of fast setting. Sedimentation occurs at a constant rate during this period

• Stage III: next 10 minute or more
  • The sedimentation again slows as it is the final period of packing of cells at the bottom of the tube

Factors affecting ESR:

• There are several factors that affects sedimentation of erythrocytes.

• Factors that increases ESR:

  • Anemia:
    • anemia increase ESR because the change in erythrocyte-plasma ratio favors rouleaux formation.
    • Rouleaux is aggregation of RBCs together due to their discoid shape.
    • Rouleaux have a decrease surface area and accelerate ESR
  • Increase level of fibrinogen:
    • it decreases the negative charge of erythrocyte, so RBC tend to remain apart and this promotes formation of rouleaux and increase ESR
  • Immunoglobulin:
    • increase antibody level in blood increase ESR
  • Increase cholesterol level
  • Rheumatoid arthritis
  • Chronic infections
  • Carcinoma
  • Tissue destruction and other disease

• Factors that decrease ESR:

  • Defibrinigenation:
    • removal of fibrinogen decreases ESR
  • Increase albumin and lecithin in blood
  • Abnormal or sickle shape RBCs:
  • abnormal or irregular shape of RBC lower ESR
  • Congestive heart failure

Method for ESR estimation:

Westergren method for ESR estimation is widely used method. Wintrobe method is also used for ESR determination. Wintrobe tube is smaller than westergren tube

Materials required:

1. Westergren tube or wintrobe tube
2. Anticoagulant: 0.1 M sodium citrate
3. ** in modified westergren method EDTA is used as anticoagulant

Procedure for ESR estimation:

• Withdraw 4 ml of venous blood
• Mix exact 10ml of sodium citrate with 4ml of venous blood in a tube
• Invert the tube 2-3 times to mix the blood thoroughly with anticoagulant
• Fill the westergren tube up to mark 0 and place in the rack at room temperature undisturbed and away from sunlight.
• Take the reading exactly after 1 hour. Record in millimeters from top surface of column to top of RBC sediments.

Result:

• Normal value of ESR
  • Female:
    • under 50 years- 20 mm/hr
    • above 50 years- 30mm/hr
  • Male:
    • Under 50 years- 15mm/hr
    • Above 50 years- 20 mm/hr

Clinical application of ESR estimation:

• ESR test is non-specific test although it is used as indication of presence of disease
• ESR value increase during rheumatoid arthritis, chronic infection, carcinoma, tissue destruction and nephritis
• During pregnancy, ESR increase moderately from 10^th or 12^th weeks onwards and return to normal after delivery.
• ESR value decreases in sickle cell anemia and congestive heart failure (CHF).

Erythrocyte sedimentation rate (ESR): principle, method, procedure and clinical application

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further reading: difference between diabetes mellitus and diabetes insipidus

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Disorders/diseases caused by deficiency or over secretion of various hormones

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