KAMPALA INTERNATIONAL UNIVERSITYDAR ER SALAM COLLAGE SCHOOL OF HEALTH SCIENCES DEPARTMENT OF

HUMAN PHYSIOLOGY

The Human Body

Anatomy and physiology is the study of the human body.

Anatomy is concerned with the structure of a part. For example, the stomach is a J-shaped, pouch like organ. The stomach wall has thick folds, which disappear as the stomach expands to increase its capacity.

Physiology is concerned with the function of a part. For example, the stomach temporarily stores food, secretes digestive juices, and passes on partially digested food to the small intestine.

Anatomy and physiology are closely connected in that the structure of an organ suits its function. For example, the stomach’s pouch like shape and ability to expand are suitable to its function of storing food. In addition, the microscopic structure of the stomach wall is suitable to its secretion of digestive juices.

Organization of Body Parts

The structure of the body can be studied at different levels of organization. First, all substances, including body parts, are composed of chemicals made up of submicroscopic particles called atoms. Atoms join to form molecules, which can in turn join to form macromolecules. For example, molecules called amino acids join to form a macromolecule called protein, which makes up the bulk of our muscles. Macromolecules are found in all cells, the basic units of all living things. Within cells are organelles, tiny structures that perform cellular functions. For example, the organelle called the nucleus is especially concerned with cell reproduction; another organelle, called the mitochondrion, supplies the cell with energy. Tissues are the next level of organization.

A tissue is composed of similar types of cells and performs a specific function. An organ is composed of several types of tissues and performs a particular function within an organ system. For example, the stomach is an organ that is a part of the digestive system. It has a specific role in this system, whose overall function is to supply the body with the nutrients needed for growth and repair. The other systems of the body also have specific functions. All of the body systems together make up the organism— such as, a human being. Human beings are complex animals, but this complexity can be broken down and studied at ever simpler levels. Each simpler level is organized and constructed in a particular way.

Human Organization

Human body is organized in terms of, Atom, Molecule, Macromolecule, Organelle, Cell, Tissue, Organ, Organism and Organ system

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Homeostasis

Homeostasis is the relative constancy of the body’s internal environment. Because of homeostasis, even though external conditions may change dramatically, internal conditions stay within a narrow range. For example, regardless of how cold or hot it gets, the temperature of the body stays around 37°C (97° to 99°F). No matter how acidic your meal, the pH of your blood is usually about 7.4, and even if you eat a candy bar, the amount of sugar in your blood is just about 0.1%. It is important to realize that internal conditions are not absolutely constant; they tend to fluctuate above and below a particular value. Therefore, the internal state of the body is often described as one of dynamic equilibrium. If internal conditions change to any great degree, illness results. This makes the study of homeostatic mechanisms medically important.

Negative Feedback

Negative feedback is the primary homeostatic mechanism that keeps a variable close to a particular value, or set point. A homeostatic mechanism has three components: a sensor, a regulatory center, and an effector. The sensor detects a change in the internal environment; the regulatory center activates the effector; the effector reverses the change and brings conditions back to normal again. Now, the sensor is no longer activated.

Mechanical Example

A home heating system illustrates how a negative feedback mechanism works. You set the thermostat at, say, 68°F. This is the set point. The thermostat contains a thermometer, a sensor that detects when the room temperature falls below the set point. The thermostat is also the regulatory center; it turns the furnace on. The furnace plays the role of the effector. The heat given off by the furnace raises the temperature of the room to 70°F. Now, the furnace turns off. Notice that a negative feedback mechanism prevents change in the same direction; the room does not get warmer and warmer because warmth inactivates the system.

Human Example: Regulation of Blood Pressure

Negative feedback mechanisms in the body function similarly to the mechanical model. For example, when blood pressure falls, sensory receptors signal a regulatory center in the brain. This center sends out nerve impulses to the arterial walls so that they constrict. Once the blood pressure rises, the system is inactivated.

Human Example: Regulation of Body Temperature

The thermostat for body temperature is located in a part of the brain called the hypothalamus. When the body temperature falls below normal, the regulatory center directs (via nerve impulses) the blood vessels of the skin to constrict. This conserves heat. If body temperature falls even lower, the regulatory center sends nerve impulses to the skeletal muscles, and shivering occurs. Shivering generates heat, and gradually body temperature rises to 37°C. When the temperature rises to normal, the regulatory center is

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inactivated. When the body temperature is higher than normal, the regulatory center directs the blood vessels of the skin to dilate. This allows more blood to flow near the surface of the body, where heat can be lost to the environment. In addition, the nervous system activates the sweat glands, and the evaporation of sweat helps lower body temperature. Gradually, body temperature decreases to 37°C.

Positive Feedback

Positive feedback is a mechanism that brings about an ever greater change in the same direction. A positive feedback mechanism can be harmful, as when a fever causes metabolic changes that push the fever still higher. Death occurs at a body temperature of 45°C because cellular proteins denature at this temperature and metabolism stops. Still, positive feedback loops such as those involved in blood clotting, the stomach’s digestion of protein, and child- birth assist the body in completing a process that has a definite cutoff point. Consider that when a woman is giving birth, the head of the baby begins to press against the cervix, stimulating sensory receptors there. When nerve impulses reach the brain, the brain causes the pituitary gland to secrete the hormone oxytocin. Oxytocin travels in the blood and causes the uterus to contract. As labor continues, the cervix is ever more stimulated, and uterine contractions become ever stronger until birth occurs.

Homeostasis and Body Systems

The internal environment of the body consists of blood and tissue fluid. Tissue fluid, which bathes all the cells of the body, is refreshed when molecules such as oxygen and nutrients move into tissue fluid from the blood, and when wastes move from tissue fluid into the blood. Tissue fluid remains constant only as long as blood composition remains constant, all systems of the body contribute toward maintaining homeostasis and therefore a relatively constant internal environment.

The cardiovascular system conducts blood to and away from capillaries, where exchange occurs. The heart pumps the blood and thereby keeps it moving to- ward the capillaries. The formed elements also contribute to homeostasis. Red blood cells transport oxygen and participate in the transport of carbon dioxide. Platelets participate in the clotting process. The lymphatic system is accessory to the car- diovascular system. Lymphatic capillaries collect excess tissue fluid, and this is returned via lymphatic veins to the cardio- vascular veins. Lymph nodes help purify lymph and keep it free of pathogens. This action is assisted by the white blood cells that are housed within lymph nodes.

The respiratory system adds oxygen to and removes car bon dioxide from the blood. It also plays a role in regulating blood pH because removal of CO2 causes the pH to rise and helps prevent acidosis. The digestive system takes in and digests food, providing nutrient molecules that enter the blood and replace the nutrients that are constantly being used by the body cells. The liver, an organ that assists the digestive process by producing bile, also plays a significant role in regulating blood composition. Immediately after glucose enters the blood, any excess is removed by the liver and stored as glycogen. Later, the glycogen can be broken down to replace the glucose used by the body cells; in this way, the glucose com- position of blood remains constant.

The liver also removes toxic chemicals, such as ingested alcohol and other drugs. The liver makes urea, a nitrogenous end product of protein metabolism. Urea and other metabolic waste molecules are excreted

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by the kidneys, which are a part of the urinary system. Urine formation by the kidneys is extremely critical to the body, not only because it rids the body of unwanted sub- stances, but also because urine formation offers an opportunity to carefully regulates blood volume, salt balance, and pH. The integumentary, skeletal, and muscular systems protect the internal organs we have been discussing. In addition, the integumentary system produces vitamin D, while the skeletal system stores minerals and produces the blood cells.

The muscular system produces the heat that maintains the internal temperature. The nervous system and the endocrine system regulate the other systems of the body. They work together to control body systems so that homeostasis is maintained. We have already seen that in negative feedback mechanisms, sensory receptors send nerve impulses to regulatory centers in the brain, which then direct effectors to become active. Effectors can be muscles or glands. Muscles bring about an immediate change. Endocrine glands secrete hormones that bring about a slower, more lasting change that keeps the internal environment relatively stable.

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INTRODUCTION

Levels of Organization

1. Chemical Level :

Everything on this planet, living or not, is composed of the same basic building blocks called atoms. Atoms aren't content to exist in isolation; they have this wonderful tendency to “shamelessly” combine with each other in a myriad of forms. We call the larger chemical grouping of atoms, molecules. When molecules combine to form an even larger structure, we term that a macromolecule. Examples of biological macromolecules include proteins, carbohydrates, and fats. Plastics are an excellent non-biological example of a macromolecule. Atoms, molecules and macromolecules interact with one another in varied and complicated manners. We understand some interactions very well, but not all. It is these interactions that are the basis of physiological processes without which life would not exist.

2. Organelle Level:

Biological macromolecules can and do combine into nearly anything. Amongst the simplest (simple being a relative term) structures found in living organisms that biological macromolecules form is a class of structures called organelles. Organelles are the underlying machinery found within cells that are responsible for the functioning of the cell. Organelles are reliant on the cell for their survival, as they will die if removed. At the same time, the cell too will die if the organelles are removed from it.

3. Cellular Level

The cell is the smallest unit that possesses and exhibits the basic characteristics of living matter. The cell is also the most numerous of units, with estimates being in excess of 100 trillion cells in the average adult human (that would be a 1 followed by 14 zeroes!). To put that in perspective: if you counted 1000 cells every second until you counted them all, it would take you nearly 3171 years before you made it to 100 trillion. Most cells possess the same basic characteristics in common, but also have the amazing ability to differentiate according to the function needed in a given tissue type. Differentiation is the "process of the development of cell specialization". We begin life as a single cell and only become more than just that single cell type because of this ability to differentiate. Stem cells are the progenitors of the various cell lines, albeit prior to differentiation. Thus, a stem cell can be encouraged to develop into any type of tissue through the process of differentiation.

4. Tissue Level

A cell grouping that has differentiated slightly (both in purpose and in morphology [structure]) from the surrounding region is known as a tissue. The cells that comprise a tissue interact together in a coordinated manner. All tissues in the human organism can be grouped into one of four main types: epithelial ("surface", or "lining" tissue), connective, muscle and nervous. Each of these tissue types can be subdivided into specialized subtypes, each of which plays an important role in the proper functioning of the human body.

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5. Organ Level

An organ is defined as "a structure made up of several different kinds of tissues so arranged that, together, they can perform a special function." Great! Now that we have a definition, what does it mean? Really, organs relate to tissues in much the same manner as cells do to tissues. The arrangement and interaction between them allows for a much more specialized and varied number of functions to be performed. Examples of organs include the heart, the lungs, the liver, and even the skin.

6. System Level

A system involves the interaction of multiple and diverse organs that perform complex functions for the body. Each system in the body does not function independently; they are all inter-reliant. For example, the cardiovascular and respiratory systems are so tightly inter-twined that we can justifiably consider them extensions of each other. The eleven major systems of the body (integumentary, skeletal, muscular, nervous, endocrine, circulatory, lymphatic/immune, respiratory, digestive, urinary and reproductive) form the basis of all the lectures in anatomy and physiology.

7. Organism Level

This is the highest level of organization in this hierarchy. It is the coordinated interaction of each of these chemicals, in each of these cells, in each of these tissues, in each of these organs, in each of these systems that enables us to exist as anything greater than a puddle of goo. Quite clearly, we are far more than merely the sum of our parts. This coordinated effort of the systems to interact is another way of describing the process of homeostasis. Control of function. Function is variable – capable of being started and stopped. Nerves, chemicals in the blood (hormones) or “auto regulation”

Anatomy and Physiology has all of these separate properties but the dominant aspect is the balance between all systems of the body. Balance provides stability in the face of change in the environment or the variation in the bodies needs. “Level playing field” Achieved by keeping the bodies internal environment constant in terms of its temperature, chemistry and physical parameters. This is called homeostasis (Cannon 1930) – the maintenance of the internal environment - the “milieu interieur” of Claude Bernard 1860. The internal environment is the fluid outside all cells – the extracellular fluid.

Homeostasis

Homeostasis is the relative constancy of the normal body's internal environment". Homeostasis is probably the most elegant concept in all of physiology that I can think of. The word homeostasis itself only refers to the steady state of values of properties. Yet it is the combined effects of bodily processes that maintain homeostasis. The concept of homeostasis is integral to the study of physiology. Unfortunately, it also happens to be one of the hardest concepts to teach.

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CELL PHYSIOLOGY

All living creatures are made of CELLS _ small membrane bound units filled with concentrated aqueous solution of chemicals and endowed with extraordinary ability to create copies of themselves by growing and dividing in two. The simplest forms of life are solitary cells. Higher organisms, such as mammals, are communities of cells derived by growth and division from a single founder cell (a doctrine sometimes referred to as cell theory). Cells, therefore, are fundamental units of life, and it is to cell biology that we must turn for an answer to the question of what life is and how it works.

Function of the cell

• A. Serves as the structural building block to form tissues and organs.

• B. Each cell is functionally independent- it can live on its own under the right conditions.

1. It can define its boundaries and protect itself from external changes causing internal changes.

2. It can use sugars to derive energy for different processes which keep it alive.

3. It contains all the information required for replicating itself and interacting with other cells in order to produce a multicellular organism 4. It is even possible to reproduce the entire organism from almost any single cell of the organism.

Types of cells.

A. Prokaryotic cells- eg. Bacteria.

1. Very simple-there are no organelles and everything functions in the cytoplasm.

B. Eukaryotic cells.

1. All contain the organelles that sub-compartmentalize the cell 2. Includes unicellular algae and protists (e.g. amoeba) that live alone or in colonies.  3. Includes multi-cellular organisms - animals, plants, fungi - where cells work together.

What is a cell made from?

Four groups of biologically important molecules: lipids, carbohydrates, nucleic acids and proteins. Tissues is divided into thousands of small cells, which may either be closely packed or separated from one another by a material known as extracellular matrix. The cell has a sharply defined boundary, suggesting the presence of an enclosing membrane. In the middle, a large round body, the nucleus, is prominent. Around the nucleus lies a transparent substance that fills the rest of the cell’s interior, the cytoplasm.

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Plasma membrane

• encloses every human cell

Functions include:

1. Supporting and retaining the cytoplasm

The concentration of solutes, sugars, ions, and other substances are much higher within the cell than outside. A fundamental principle of nature however is that solute concentrations will tend to equilibrate. In this case, causing water to flow into the cell (a process known as osmosis) and the solutes to flow out. The cell membrane prevents free flow of material and thus serves as an osmotic barrier.

2. Being a selective barrier

The cell is separated from its environment and needs to get nutrients in and waste products out. Some molecules can cross the membrane without assistance, most cannot. Water, non-polar molecules and some small polar molecules can cross. Non-polar molecules penetrate by actually dissolving into the lipid bilayer. Most polar compounds such as amino acids, organic acids and inorganic salts are not allowed entry, but instead must be specifically transported across the membrane by proteins.

3. Transport

Many of the proteins in the membrane function to help carry out selective transport. These proteins typically span the whole membrane, making contact with the outside environment and the cytoplasm. They often require the expenditure of energy to help compounds move across the membrane

4. Communication (via receptors)

5. Recognition

STRUCTURE OF THE CELL

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2 Primary building blocks include protein (about 60% of the membrane) and lipid, or fat (about 40% of the membrane). The primary lipid is called phospholipid, and molecules of phospholipid form a 'phospholipid bilayer (two layers of phospholipid molecules).

This bilayer forms because the two 'ends' of phospholipid molecules have very different characteristics: one end is polar (or hydrophilic) and one (the hydrocarbon tails below) is non-polar (or hydrophobic):

Cytoplasm and organelles

Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell's cytoskeleton) and organelles (literally 'little organs). Cells do not contain the same organelles in the same proportion.

The nucleus is usually the most prominent organelle in a eukaryotic cell within which is found DNA (deoxyribonucleic acid) in the form of chromosomes plus nucleoli (within which ribosomes are formed).It is enclosed within two concentric membranes that form the nuclear envelope. DNA acts as the genetic information store.

Organelles

Endoplasmic reticulum. Comes in 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not.

functions include: mechanical support, synthesis (especially proteins by rough ER), and is the site at which most cell membrane components, as well as materials destined for export from the cell, are made.

Golgi complex. Consists of a series of flattened sacs (or cisternae)

Functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes

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Lysosomes - membrane-enclosed spheres that contain powerful digestive enzymes

Functions include destruction of damaged cells (which is why they are sometimes called 'suicide bags') & digestion of phagocytosed materials (such as bacteria)

Mitochondria - have a double-membrane: outer membrane & highly convoluted inner membrane, inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production. primary function is production of adenosine triphosphate (ATP) Mitochondria contain their own DNA and reproduce b dividing in two, and because of their many resemblances to bacteria they are thought to derived from bacteria that were engulfed by some ancestor of the present day eukaryotic cells.

Ribosomes. Composed of rRNA (ribosomal RNA) & protein, may be dispersed randomly throughout the cytoplasm or attached to surface of rough endoplasmic reticulum often linked together in chains called polyribosomes or polysomes whose primary function is to produce proteins

Centrioles paired cylindrical structures located near the nucleus, play an important role in cell division

Flagella & cilia - hair-like projections from some human cells, cilia are relatively short & numerous, a flagellum is relatively long and there's typically just one (e.g., sperm)

Villi - projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)

COMPONENTS OF THE CELLULAR ENVIRONMENT

Water: , comprises 60 - 90% of most living organisms (and cells). important because it serves as an excellent solvent & enters into many metabolic reactions

Ions = atoms or molecules with unequal numbers of electrons and protons: found in both intra- & extracellular fluid examples of important ions include sodium, potassium, calcium, and chloride.

Carbohydrates: about 3% of the dry mass of a typical cell, composed of carbon, hydrogen, & oxygen atoms (e.g., glucose is C6H12O6) an important source of energy for cells

Lipids: about 40% of the dry mass of a typical cell, composed largely of carbon & hydrogen. generally insoluble in water involved mainly with long-term energy storage; other functions are as structural components (as in the case of phospholipids that are the major building block in cell membranes) and as "messengers" (hormones) that play roles in communications within and between cells

Subclasses include:

Triglycerides - consist of one glycerol molecule + 3 fatty acids

Fatty acids typically consist of chains of 16 or 18 carbons (plus lots of hydrogen).

Phospholipids - a phosphate group (-PO4) substitutes for one fatty acid & these lipids are an important component of cell membranes.

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Steroids - include testosterone, estrogen, & cholesterol

Proteins: about 50 - 60% of the dry mass of a typical cell. subunit is the amino acid & amino acids are linked by peptide bonds. 2 functional categories = structural & enzymes.

Nucleic Acids:

• DNA

• RNA (including mRNA, tRNA, & rRNA).

Transport/ Movement Across Membranes

A. Passive processes - require no expenditure of energy by a cell:

Simple diffusion = net movement of a substance from an area of high concentration to an area of low concentration. The rate of diffusion is influenced by:

– concentration gradient

– cross-sectional area through which diffusion occurs

– temperature

– molecular weight of a substance

– distance through which diffusion occurs

Facilitated diffusion = movement of a substance across a cell membrane from an area of high concentration to an area of low concentration. This process requires the use of 'carriers' (membrane proteins), for example, a ligand molecule (e.g., acetylcholine) binds to the membrane protein. This causes a conformational change or, in other words, an 'opening' in the protein through which a substance (e.g., sodium ions) can pass.

• Secondary active transport uses an ion gradient across a membrane as an energy source to provide the uphill movement of the actively transported solute.

Osmosis = diffusion of water across a semi permeable membrane (like a cell membrane) from an area of low solute concentration to an area of high solute concentration

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Characteristics of Facilitated Diffusion & Active Transport

Both require the use of carriers that are specific to particular substances (that is, each type of carrier can 'carry' one type of substance) and both can exhibit saturation (movement across a membrane is limited by number of carriers & the speed with which they move materials)

B. Active processes - require the expenditure of energy by cells:

Active transport = movement of a substance across a cell membrane from an area of low concentration to an area of high concentration using a carrier molecule.

Endo- & exocytosis - moving material into (endo-) or out of (exo-) cell in bulk form. Initially, the membrane transport protein (also called a carrier) is in its closed configuration which does not allow substrates or other molecules to enter or leave the cell.

Movement of Substances across Lipid Bilayers

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Cell Junctions

Specialized cell junction occur at many points of cell-cell and cell matrix contact in all tissues. But they are particularly important and plentiful in epithelia.

Cell junction can be classified into 3 functional groups:

1. Occluding junctions [tight junction], which can seal cells together in an epithelial cell sheet in a way that prevents even small molecules from leaking from one side of the sheet to the other. Tight junctions play two distinct roles in selective barrier functions;

They function as barriers to diffusion of membrane proteins between apical and basolateral domains of plasma membrane _ Transcellular transport-e.g_gluc trasport.

2. Anchoring junctions, which mechanically attach cells (and their cytoskeletons) to their neighbors or to the extracellular matrix. They are widely distributed in animal tissues. They enable group of cells, such as those in the epithelium, to function as robust structural units by connecting cytoskeleton elements of a cell either to those of another cell or to the extracellular matrix. They are most abundant in tissues that are subjected to severe mechanical stress, such as heart muscle and skin epithelium (epidermis). They occur in 2 structurally and functionally different forms:

3. Communicating junctions [Gap Junctions], which mediate the passage of chemical or electrical signals from one interacting cell to its partner. It is one of the most widespread, being found in large numbers in most animal tissues and practically in all animal species. It allows inorganic ions and other small water soluble molecules to pass directly from cytoplasm of cell to the cytoplasm of the other. Thereby coupling the cells both electrically and metabolically. Such cell coupling has important functional implications, many of which are only beginning to be understood.

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Excitable Tissues/Muscles

Introduction

Neurons - single cells specialized for carrying information rapidly from one place to another and/or integrating information from various sources. Also known as nerve cells. Neurons have the capacity to generate and conduct electrical signals and the ability to manufacture and secrete neurotransmitters. The human nervous system consists of billions of nerve cells (or neurons) plus supporting (neuroglial) cells. Neurons are able to respond to stimuli (such as touch, sound, light, and so on), conduct impulses, and communicate with each other (and with other types of cells like muscle cells).

Basic Structure and Function of Nerve Cells

Cell body - also known as the soma or perikarya containing the cell nucleus (DNA) and organelles necessary to maintain the survival of the cell. Extending out from the cell body are processes called dendrites and axons. These processes vary in number & relative length but always serve to conduct impulses (with dendrites conducting impulses toward the cell body and axons conducting impulses away from the cell body).

Dendrites - thin, tube-like extensions of a neuron that typically branch repeatedly near the cell body and are specialized for receiving signals from other neurons.

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Axon - tube-like extension specialized to carry action potentials from the cell body to the terminals (longest axon is about 1 meter from spine to toe).

Myelin sheath - casing of fatty cells wrapped tightly around the axon (contains 80% fat and 20% protein) and involved in speeding up the conduction velocity of action potentials and as support and protection of the nerves axon.

Schwann cell - Surrounds and insulates axons in PNS. Provides myelin [80% fat; 20% protein]. Wraps only a single axon; is able to regenerate.

Nodes of Ranvier- This is the exposed patch of axon in between adjacent segments of myelin sheath. Most of the Na+ ion channel of the axon are confined to this site.

Axon terminal - swelling at the end of an axon that is designed to release a chemical substance (neurotransmitter) onto another neuron, muscle cell, or gland (also known as a bouton, or button).

Three Main Functional Classes of Neurons (input - output).

Sensory neurons carry information from the sensory organs to the central nervous system (CNS). Cell body exists outside of the CNS; axon extends in both directions from cell body. Dendrites transduce different sensory stimuli exist as branches at one end of the axon, total number (human) ~2 million.

Motor neurons carry information from the CNS to the body's muscles and glands. Cell body and dendrites exist within the CNS, axon exits CNS by way of spinal nerves and terminates on different muscle cells.

Interneurons – carry information from one set of neurons to another. Exist entirely within the CNS; come in an enormous variety of shapes and sizes. Total number (human) ~100 billion.

Types of Neurons

The three main types of neurons are;

Multipolar neurons are so-named because they have many (multi-) processes that extend from the cell body: lots of dendrites plus a single axon.

Functionally, these neurons are either motor (conducting impulses that will cause activity such as the contraction of muscles) or association (conducting impulses and permitting 'communication' between neurons within the central nervous system).

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Unipolar neurons have but one process from the cell body. However, that single, very short, process splits into longer processes (a dendrite plus an axon). Unipolar neurons are sensory neurons - conducting impulses into the central nervous system.

Bipolar neurons have two processes - one axon & one dendrite. These neurons are also sensory. For example, bipolar neurons can be found in the retina of the eye.

Establishment of the Resting Membrane Potential

Nerve cells, like all other cells in the body, are bounded by a plasma membrane that characterize the limit of each cell identity. The plasma membrane serves several important functions. Most importantly, the membrane regulates the intracellular and extracellular ionic environment crucial to the development and maintenance of signaling properties of nerve cells on which nervous system function depends. Neurons can respond to stimuli and conduct impulses because a membrane potential is established across the cell membrane. In other words, there is an unequal distribution of ions (charged atoms) on the two sides of a nerve cell membrane.

And, in this example, the voltmeter reads -70 mV (mV = millivolts). In other words, the inside of the neuron is slightly negative relative to the outside. Such charge differences can result from both electrogenic pumping and from passive ion diffusion. This difference is referred to as the Membrane Potential [MP]. Membrane potentials represent the force required to separate charged ion species. Measured MP of neurons are in the order of -40 to -90 mV, the minus means that the inside is negative relative to (or compared to) the outside. It is called a RESTING MEMBRANE POTENTIAL [RMP] because it occurs when a membrane is not being stimulating or conducting impulses (in other words, it's ‘resting’).

How is this potential established?

Membranes are polarized or, in other words, exhibit a RESTING MEMBRANE POTENTIAL. This means that there is an unequal distribution of ions (atoms with a positive or negative charge) on the two sides of the nerve cell membrane. Concentration gradients and electrical voltage differences drive transmembrane movement of ions. Both factors contribute to the electrochemical energy of an ion in solution. If a suitable pathway exists for passage of an ion species across the membrane, a net movement

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down the electrochemical gradient results. Ion channels afford such pathways, and their ability to discriminate among ion species is directly responsible for generating normal membrane voltages. The selective movement of a single ion species across a cell membrane generates a membrane potential that can be predicted from knowledge of the concentration difference for that ion species between intracellular and extracellular compartments.

What factors contribute to this membrane potential?

Two ions are responsible:

Sodium (Na+) and potassium (K+).

An unequal distribution of these two ions occurs on the two sides of a nerve cell membrane because carriers actively transport these two ions: Sodium from the inside to the outside and potassium from the outside to the inside.

AS A RESULT of these active transport mechanisms (commonly referred to as the SODIUM PUMP and the POTASSIUM PUMP, respectively), there is a higher concentration of sodium on the outside than the inside and a higher concentration of potassium on the inside than the outside.

Movements of Sodium and Potassium ions

The nerve cell membrane also contains special passageways for these two ions that are commonly referred to as GATES or  CHANNELS. Thus, there are SODIUM GATES and POTASSIUM GATES. These gates represent the only way that these ions can pass through the nerve cell membrane. IN A RESTING NERVE CELL MEMBRANE, all the sodium gates are closed and some of the potassium gates are open. AS A RESULT, sodium cannot diffuse through the membrane & largely remains outside the membrane. HOWEVER, some potassium ions are able to diffuse out. OVERALL, THEREFORE, there are lots of positively charged potassium ions just inside the membrane and lots of positively charged sodium ions PLUS some potassium ions on the outside. THIS MEANS THAT THERE ARE MORE POSITIVE CHARGES ON THE OUTSIDE THAN ON THE INSIDE. In other words, there is an

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unequal distribution of ions or a resting membrane potential. This potential will be maintained until the membrane is disturbed or stimulated. Then, if it's a sufficiently strong stimulus, an action potential will occur.

ACTION POTENTIAL

Perhaps the most important functional property of the neuronal cell membrane is the property of electrical excitability. It is this property that underlies the basic nerve impulse, or action potential, which is the fundamental unit of signaling in the nervous system. An action potential is a very rapid change in membrane potential that occurs when a nerve/muscle cell membrane is stimulated. Specifically, the membrane potential goes from the resting potential (typically -70 mV) to some positive value (typically about +30 mV) in a very short period of time (just a few milliseconds).

What causes this change in potential to occur?

The stimulus causes the sodium gates (or channels) to open and, because there's more sodium on the outside than the inside of the membrane, sodium then diffuses rapidly into the nerve cell. All these positively-charged sodium rushing in causes the membrane potential to become positive (the inside of the membrane is now positive relative to the outside). The sodium channels open only briefly, then close again.

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The potassium channels then open, and, because there is more potassium inside the membrane than outside, positively-charged potassium ions diffuse out. As these positive ions go out, the inside of the membrane once again becomes negative with respect to the outside.

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Threshold stimulus & potential

Action potentials occur only when the membrane is stimulated (depolarized) enough so that sodium channels open completely. The minimum stimulus needed to achieve an action potential is called the threshold stimulus. The threshold stimulus causes the membrane potential to become less negative (because a stimulus, no matter how small, causes a few sodium channels to open and allows some positively-charged sodium ions to diffuse in). If the membrane potential reaches the threshold potential (generally 5 - 15 mV less negative than the resting potential), the voltage-regulated sodium channels all open. Sodium ions rapidly diffuse inward, & depolarization occurs.

All-or-None Law

Action potentials occur maximally or not at all. In other words, there's no such thing as a partial or weak action potential. Either the threshold potential is reached and an action potential occurs, or it isn't reached and no action potential occurs.  

Refractory periods

ABSOLUTE

During an action potential, a second stimulus will not produce a second action potential (no matter how strong that stimulus is), corresponds to the period when the sodium channels are open (typically just a millisecond or less)

RELATIVE

Another action potential can be produced, but only if the stimulus is greater than the threshold stimulus

corresponds to the period when the potassium channels are open (several milliseconds)

the nerve cell membrane becomes progressively more 'sensitive' (easier to stimulate) as the relative refractory period proceeds.

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So, it takes a very strong stimulus to cause an action potential at the beginning of the relative refractory period, but only a slightly above threshold stimulus to cause an action potential near the end of the relative refractory period.

Impulse conduction

An impulse is simply the movement of action potentials along a nerve cell. Action potentials are localized (only affect a small area of nerve cell membrane). So, when one occurs, only a small area of membrane depolarizes (or 'reverses' potential). As a result, for a split second, areas of membrane adjacent to each other have opposite charges (the depolarized membrane is negative on the outside & positive on the inside, while the adjacent areas are still positive on the outside and negative on the inside).

Conduction Velocity

Impulses typically travel along neurons at a speed of anywhere from 1 to 120 meters per second the speed of conduction can be influenced by:

– the diameter of a fiber

– temperature

– the presence or absence of myelin

Neurons with myelin (or myelinated neurons) conduct impulses much faster than those without myelin. Schwann cells are located at regular intervals along the process (axons) & so a section of a myelinated axon would look like this:

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An electrical circuit (or 'mini-circuit') develops between these oppositely-charged areas (or, in other words, electrons flow between these areas). This 'mini-circuit' stimulates the adjacent area and, therefore, an action potential occurs. This process repeats itself and action potentials move down the nerve cell membrane. This 'movement' of action potentials is called an impulse. Between areas of myelin are non-myelinated areas called the nodes of Ranvier. Because fat (myelin) acts as an insulator, membrane coated with myelin will not conduct an impulse. So, in a myelinated neuron, action potentials only occur along the nodes and, therefore, impulses 'jump' over the areas of myelin - going from node to node in a process called saltatory conduction (with the word saltatory meaning 'jumping'). Because the impulse 'jumps' over areas of myelin, an impulse travels much faster along a myelinated neuron than along a non-myelinated neuron.

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Synapse

Point of impulse transmission between neurons; impulses are transmitted from pre-synaptic neurons to post-synaptic neurons. Synapses usually occur between the axon of a pre-synaptic neuron & a dendrite or cell body of a post-synaptic neuron. At a synapse, the end of the axon is 'swollen' and referred to as an end bulb or synaptic knob. Within the end bulb are found lots of synaptic vesicles (which contain neurotransmitter chemicals) and mitochondria (which provide ATP to make more neurotransmitter). Between the end bulb and the dendrite (or cell body) of the post-synaptic neuron, there is a gap commonly referred to as the synaptic cleft. So, pre- and post-synaptic membranes do not actually come in contact. That means that the impulse cannot be transmitted directly. Rather, the impulse is transmitted by the release of chemicals called chemical transmitters (or neurotransmitters).

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When an impulse arrives at the end bulb, the end bulb membrane becomes more permeable to calcium. Calcium diffuses into the end bulb & activates enzymes that cause the synaptic vesicles to move toward the synaptic cleft. Some vesicles fuse with the membrane and release their neurotransmitter (a good example of exocytosis). The neurotransmitter molecules diffuse across the cleft and fit into receptor sites in the postsynaptic membrane. When these sites are filled, sodium channels (also called chemically gated ion channels) open & permit an inward diffusion of sodium ions. This, of course, causes the membrane potential to become less negative (or, in other words, to approach the threshold potential). If enough neurotransmitter is released, and enough sodium channels are opened, then the membrane potential will reach threshold. If so, an action potential occurs and spreads along the membrane of the post-synaptic neuron (in other words, the impulse will be transmitted). Of course, if insufficient neurotransmitter is released, the impulse will not be transmitted.

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The operation of the nervous system, the most powerful and sophisticated computer known, relies principally on the synaptic mechanisms described above. Synaptic events provide the links between individual neurons that make possible higher processes such as sensation, motor control, behavior, learning, and thought.

MUSCLE

Characteristics of muscle

• excitability - responds to stimuli (e.g., nervous impulses)

• contractility - able to shorten in length

• extensibility - stretches when pulled 22

• elasticity - tends to return to original shape & length after contraction or extension

Functions of muscle

• motion

• maintenance of posture

• heat production

Types of muscle

1. Skeletal, attached to bones & moves skeleton

– also called striated muscle (because of its appearance under the microscope,)

– voluntary muscle

2. Smooth.

– involuntary muscle

– muscle of the viscera (e.g., in walls of blood vessels, intestine, & other 'hollow' structures and organs in the body)

3. cardiac:

– Muscle of the heart, involuntary.

Structure of Skeletal Muscle

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Skeletal muscles are usually attached to bone by tendons composed of connective tissue. This connective tissue also ensheaths the entire muscle & is called epimysium. Skeletal muscles consist of numerous subunits or bundles called fasicles (or fascicles). Fascicles are also surrounded by connective tissue (called the perimysium) and each fascicle is composed of numerous muscle fibers (or muscle cells). Muscle cells, ensheathed by endomysium, consist of many fibrils (or myofibrils), and these myofibrils are made up of long protein molecules called myofilaments. There are two types of myofilaments in myofibrils: thick myofilaments and thin myofilaments.

SMOOTH MUSCLE

Involuntary muscle; innervated by the Autonomic Nervous System (visceral efferent fibers), found primarily in the walls of hollow organs & tubes, spindle-shaped cells typically arranged in sheets, cells do not have t-tubules & have very little sarcoplasmic reticulum. Cells do not contain sarcomeres (so are not striated) but are made up of thick & thin myofilaments. Thin filaments in smooth muscle do not contain troponin. Calcium does not bind to troponin but, rather, to a protein called calmodulin. The calcium-calmodulin complex 'activates' myosin which then binds to actin & contraction (swiveling of cross-bridges) begins.

Types of smooth muscle

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• 1 - Visceral, or unitary, smooth muscle, found in the walls of hollow organs (e.g., small blood vessels, digestive tract, urinary system, & reproductive system) multiple fibers contract as a unit (because impulses travel easily across gap junctions from cell to cell) &, in some cases, are self-excitable (generate spontaneous action potentials & contractions)

• 2 - Multiunit smooth muscle consists of motor units that are activated by nervous stimulation. Found in the walls of large blood vessels, in the eye (adjusting the shape of the lens to permit accommodation & the size of the pupil to adjust the amount of light entering the eye), & at the base of hair follicle (the 'goose bump' muscles).

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