Читать книгу Clinical Applications of Human Anatomy and Physiology for Healthcare Professionals - Jassin M. Jouria - Страница 11
ОглавлениеCytology
Learning Objectives
At the completion of this chapter, the student will be able to:
1.Describe the basic structure, including the main components of a composite cell.
2.Characterize each individual organelle’s structure and function.
3.Distinguish between active and passive membrane transport.
4.Identify the stages of cell division.
5.Associate abnormal cell division and cancer.
Case Study Introduction
Erica is a 43-year-old female who has lived in South Florida since her parents migrated from Scandinavia when she was five years old. Erica is an avid scuba diver and loves outdoor sports. After college, she moved to Key West and opened up her own business renting motor boats, jet skis, and scuba gear.
Over the years, Erica has enjoyed growing her business and using her free time to enjoy the sun. One calm, sunny morning, while applying tanning oil to her skin, she noticed a small bump on the side of her left upper arm. Concerned, she called and scheduled an appointment to see her primary care doctor, Dr. Sanderson.
In the office, Dr. Sanderson obtained a history of Erica’s present condition, as well as a full medical, family, surgical, and social history. Dr. Sanderson then proceeded with a focused physical exam. Erica’s vital signs were all within normal limits with no remarkable findings.
Dr. Sanderson reported a 3 mm × 2 mm lesion on the lateral aspect of the patient’s left arm, just inferior to the deltoid muscle. The lesion was raised, dark brown in color, and had an irregular border. Dr. Sanderson decided to do an in-office biopsy and send it to the pathology lab. Erica was then educated on the health risks of repeated, long-term sun exposure and its effects of damaging skin cells. Erica was given a brochure with instructions on how to protect her skin while outdoors. She was also advised to limit sun exposure, and to apply a high SPF sun block product if she must go out in the sun. Erica was scheduled to return to the office in one week, when the results of the biopsy will be available.
■Introduction
Cytology, or the study of cells, was first established in 1665 by Robert Hooke1 (who actually coined the term cell), when he observed some plant substance under a microscope. He found that it resembled a miniature monastery cell, as they both had many sectioned compartments.
Since that time, numerous scientists have studied plant and animal specimens, all of whom have arrived to the same conclusion: all living specimens consist of cells. Therefore, the smallest structural unit of all living things is the cell. The cell, the smallest unit of life, capable of sustaining itself, must be composed of at least one cell.
A unicellular organism, such as bacteria and protozoa are the simplest forms of life. Human beings are multicellular organisms and are consequently much more complex forms of life. The human being is the result of trillions of cells functioning together in order to materialize into the complex structure that is the human body.
Cell biology, as it’s commonly referred to in today’s academic curricula, is the scientific study of the anatomy, physiology, and chemistry of a cell.
■About the Cell
Cells in the human body can be defined by type:
•Static or differentiated
•Expanding or undifferentiated
•Stem cells (responsible for the renewal of cells that can also differentiate or become different kinds of cells)
Undifferentiated cells have the ability to regrow or regenerate, while differentiated or static cells cannot. Once they reach their ‘peak’, they age and die.
A muscle cell is a type of differentiated or static cell.
Skin cells, which can expand, are a type of undifferentiated cell.
Hair is a perfect example of a type of stem cell. Hair cells die and are replaced on a regular basis.
Over 250 different cells are found in the human body. The shape of a cell is based on its specific function. For example:
•Skin (epithelial) cells are flat, much like floor tiles that form an effective barrier against bacteria.
•Skeletal muscle cells are oblong.
•Fat cells are ovoid or round.
•Microphage cells have tendril-like ‘fingers’ protruding from its center which act much like feelers that seek out and capturing damaged or diseased cells or bacteria for consumption/destruction.
Before investigating its intricate structure and function, it is sensible to first learn and know the basic components of a cell. Four main structural components make up a cell: The cell membrane, cytoplasm, organelles, and the nucleus.
Figure 2-1 Cell organelle.
We will consider each component in order to fully explore and appreciate their individual structures and functions.
Basic components of a cell
All cells in the human body have three major parts2:
•Plasma membrane
•Cytoplasm
•Organelles
The cell (plasma) membrane
The cell membrane, or plasma membrane as its sometimes, called, is a physical barrier that separates the internal components of a cell from the cell’s outside environment.
A membrane, by definition, must have two characteristics – it must be pliable, and it must be permeable. Pliability allows the cell to maintain its structural integrity while adapting to the stress of its outside environment.
Permeability allows certain substances to enter and/or leave the cell while preventing others from doing the same; a unique feature of a cell’s plasma membrane, termed selective permeability. For a closer look at how the cell membrane functions, we must examine its structure more closely.
Figure 2-2 Cellular anatomy.
According to the fluid mosaic model proposed by S.J. Singer and G.L. Nicolson in 1972,3 biological properties of the cell membrane can be appreciated as a semi-fluid that allows the movement of lipids, the binding of intrinsic protein molecules, and selective permeability. This arrangement is possible due to the unique phospholipid bilayer composition of the cell’s membrane.
The phospholipid bilayer is essentially two layers of phosphate-containing fat molecules forming a fluid framework, with the addition of another molecule called cholesterol, which helps stabilize the phospholipid molecules. The phospholipid bilayer also contains two types of protein molecules:
•integral proteins
•peripheral proteins
Integral proteins can be located on either surface of the membrane, (inside or outside), or may span the entire membrane. They are “locked” in place, and have many different functions, such as identifying, receiving, and communicating with other molecules and cells.
Peripheral proteins are bound to the plasma membrane or to integral proteins by chemical or covalent bonds, and also aid in cell signaling and receptor modulation. Ultimately, the cell membrane’s unique structure provides a cell with protection, stability, and communication.
Cytoplasm
The cytoplasm can be described as a gel-like fluid matrix that resides inside a cell between the cell membrane and the nucleus, the cell’s spherical epicenter and command center.
The cytoplasm serves as the interior environment that accommodates each cell’s essential structural inclusions, called organelles. Appropriately termed, organelles function like “microscopic organs” within the cell, responsible for the cell’s vitality – similar to how the internal organs are responsible for the human body’s vitality as a whole.
The following organelles, which are found in the cytoplasm, will be discussed further: ribosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, lysosomes, peroxisomes, centrosomes, cilia, flagella, and microvilli.
The cytoplasm is one of numerous important components of cellular structures. Not only does it help to give the cell its shape, but cytoplasm contains three very important components:
•Cytosol (also known as “cell sap”)
•Organelles
•Inclusions
In medical terminology, an inclusion is defined as something that encloses something. Medical dictionaries define a cellular inclusion as a non-living material found in cellular protoplasm. These substances are unable to carry out metabolic activities, nor are they bound by membranes. A few examples of cellular inclusions4:
•Nutritional substances
•Granules of pigment
•Droplets of fat
•Granules of glycogen
Cytosol (aka “cell sap”) Cytosol, often called the cytoplasmic matrix, is the liquid found inside the cell, and makes up a majority of intracellular fluid. Cytosol is often likened to a jelly or gel like substance.
Figure 2-3 Cellular structure.
Organelles literally means “little organs.” Each organelle in the cytoplasm is responsible for performing specific functions. Organelles are defined as a number of different and unique structures found within a living cell.
Organelles found in cytoplasm have specific responsibilities and functions just like the body’s larger organs. Each of these will be described in further detail.
The nucleus of the cell is an organelle. So too is the cellular wall. Other organelles found within a cell include:
•Centrioles – typically found in animal cells.
•Centrosomes – play a role in mitosis and serve as the processing or organizing center of a microtubule. Centrosomes are necessary in the construction of the mitotic spindle. We explore this topic in more depth later in the chapter.
•Chloroplasts – also part of numerous cellular structures including those of plants. They behave in a similar way to an animal cell’s mitochondria. The outer membrane is permeable although the inner membrane typically allows transportation through membrane transporters. A third membrane is found in the chloroplast and is known as an alkaloid membrane, required for energy generation and involves adenosine triphosphate as part of the energy production chain.
•Endoplasmic reticulum (smooth or rough) – smooth endoplasmic reticulum (ER) plays a role in lipid synthesis, while rough ER is vital in the synthesis of proteins.
•Golgi complex – responsible for “receiving” macromolecules from the endoplasmic reticulum and for sorting and processing so that these macromolecules reach their appropriate destinations inside the cell.
•Lysosomes – mainly defined as the primary catabolic organelle.
•Mitochondria – plays a vital role in the production of energy in eukaryotic cells.
•Peroxisomes – contain enzymes involved in a number of biochemical reactions in the body.
•Ribosomes – contain liposomal RNA proteins and molecules that float freely within the cytoplasm or they can be attached or embedded on the outer membrane surfaces of rough ER.
•Vacuoles – fluid-filled structures most commonly found in fungal and plant cells. They’re involved in waste management, detoxification, storage, and molecular catabolism or degradation. They’re responsible for the maintenance of structure and support of a cell, often known as turgor pressure maintenance.
Ribosomes
Ribosomes are organelles constructed primarily of two microscopic subunits. The subunits; one large and one small, are made up of ribosomal RNA (rRNA).
Ribosomes provide the site for synthesis of proteins via a process called translation, where the genetic code, or DNA, is read and translated from an mRNA molecule into a specific amino acid sequence producing the specified protein.
Ribosomes are sometimes found attached to another intracellular organelle called the endoplasmic reticulum or are simply free-floating in the cell’s cytoplasm. At both locations, their function remains the same – the biosynthesis of proteins. Hence, they have been nicknamed the “protein factories” of a cell.
Endoplasmic reticulum
The endoplasmic reticulum (ER) is a system of membranes arranged into a network of tubules, canals, and connecting sacs that form a convoluted channel in the cytoplasm that travels from the nucleus of a cell and stretches almost to the outer plasma membrane.
As briefly mentioned, there are two types of ER: the rough endoplasmic reticulum (RER) and the smooth endoplasmic reticulum (SER).
The RER is named due to the ribosomes that are attached to its outer surface, giving it a studded or “rough” appearance. It should be mentioned here that ribosomes are not permanently docked on the RER; they dock only in preparation of synthesizing a protein designed for the secretory pathway. This pathway describes a process of steps that transport proteins out of a cell.
Once synthesized, the proteins are dropped off into the interior of the RER and packaged into vesicles bound for the Golgi apparatus. Two types of proteins are made in the RER:
•secretory proteins
•integral membrane proteins
Figure 2-4 Endoplasmic reticulum structure.
The SER, true to its namesake and discernibly lacking the rough exterior, serves to synthesize fats, carbohydrates, and steroids. The SER also metabolizes steroids, adjoins receptors to integral membrane proteins, and detoxifies drugs. Its ultimate responsibility, however, is to manufacture new plasma membrane.
Golgi apparatus
The Golgi apparatus, sometimes called the Golgi complex, is a distinctive intracellular organelle located near the nucleus that serves a variety of complex functions. It is composed of a series of membrane-covered, flattened sacs stacked on top of each other, forming a three-dimensional convoluted structure. The flattened sacs are actually vesicles called cisternae.
The Golgi apparatus serves to receive and modify molecules manufactured in the endoplasmic reticulum, and packages them into tiny vesicles destined for the plasma membrane, where the vesicle will fuse and release its contents to the outside of the cell.
One specific example of a molecule packaged and shipped from the Golgi apparatus is mucus (a relatively thick, liquid substance secreted generally for protective purposes). The Golgi apparatus has been known to be called or nicknamed, “the shipping and packaging center”. This author refers to it as the “FedEx of cell”.
Figure 2-5 Golgi apparatus.
Lysosomes
Lysosomes are membranous organelles that roam the intracellular cytoplasm as “digestive sacs”. They are usually crafted and developed from the endoplasmic reticulum, where they bud off - circulating through the cytosol, seeking the digestion of cellular waste products and/or damaged cellular components.
They contain acidic enzymes (which are constructed in the endoplasmic reticulum and modified in the Golgi apparatus) such as hydrolase, lipase, and amylase, among others, that can break down food particles, waste materials, and cellular debris. Lysosomes also aid in protection by engulfing and digesting microorganisms that have invaded the cell.
Lysosomes play an essential role in cellular maintenance and recycling macromolecules – breaking them down and assimilating them to be reused by the cell in order to continue functioning. A crucial structure in the normal operation of lysosomes is their membrane, which allows for the potentially hazardous digestive enzymes to remain contained inside the lysosome and not leak out where they would be toxic to and destroy the cell in a process known as “auto-digestion”.
Peroxisomes
Peroxisomes are also membranous, or membrane-contained organelles that roam the interior of a cell, performing many different metabolic reactions at the cellular level. Structurally, they are similar to lysosomes except for one keynote difference; peroxisomes do not bud off of the endoplasmic reticulum. Instead, they are manufactured by free-floating ribosomes and released into the cytosol as completed polypeptide chains.
The main function of peroxisomes – and most significant role – is in the production of hydrogen peroxide during oxidative reactions.
Toxic to cells, hydrogen peroxide is contained by peroxisomes and kept in check with the enzyme catalase (also included in peroxisomes), which converts hydrogen peroxide into water or another harmless biological compound. Peroxisomes thereby contribute a major role in several metabolic pathways, including fatty-acid oxidation, lipid and bile-acid synthesis, and aiding in cholesterol production.
Another vital function of lysosomes is the production of plasmalogen, the most prevalent phospholipid found in myelin sheaths – which is essential in carrying out the proper communication purposes of the central nervous system.
Mitochondria
Mitochondria is a unique structural component found within cells. Mitochondria (plural: mitochondrion) is a vital and crucial part of cellular structures, and therefore tissues and organs. Mitochondria take in food to provide energy for use by the cell.
The mitochondria organelle found inside complex cellular structures is responsible for actually producing the energy required by that cell.
The number of mitochondria found in cells differs: simple cells might contain one or perhaps two mitochondria. A cell that requires high levels of energy – like muscle – can contain thousands.
The primary mechanism of action of mitochondria involves energy production. The molecule utilized for energy (adenosine triphosphate or ATP), is found inside the mitochondria.
Mitochondria synthesizes energy through cellular respiration. This is achieved when the mitochondria consume food molecules such as carbohydrates and combines them with oxygen. This produces ATP. Protein enzymes are responsible for this action.
Figure 2-6 Mitochondria.
Mitochondria can take on different appearances depending on how the section of mitochondria is orientated within the cellular structure. Mitochondria are essential not only for energy production but also oxidation of nutrients.
Mitochondria is composed of an inner and outer membrane. The outer membrane effectively controls what enters and exits the mitochondria, as well as substrate uptake and release of ATP.
The structure of mitochondria is similar, although the shape of the mitochondria itself can differ:
•Outer membrane – Often takes on different appearances. Mitochondria is not a consistently rigid shape, but is rather flexible and takes various shapes dependent upon its environment. It can be shaped similar to pill capsule or tablet, long and slender like a pencil, or rounded like a kidney bean.
•Inner membrane – Differentiation of mitochondria organelles from others is due to the inner membrane. The inner membrane takes on a wrinkled appearance like cloth folded on top of itself. These folds are called cristae and are packed inside the mitochondria. These ‘folds’ increase the overall surface of the inner mitochondrial membrane.
•Mitochondrial DNA is also found within the inner membrane, as are a number of other components including ribosomes and ATP synthase, an enzyme responsible for the synthesis of ATP from adenosine diphosphate (ADP) and inorganic phosphate (Pi).
•Matrix – Located inside the inner membrane, the matrix is home to most of the proteins of mitochondria as well as mitochondrial DNA and ribosomes.
The inner and outer membranes of the mitochondria are formed by the joining of components from two separate cellular compartments: the nucleus and the mitochondria.
Mitochondria is responsible for a number of cellular functions including but not limited to:
•Heat production (thermogenesis)/cellular metabolism
•Maintenance of calcium concentrations
•Citric acid cycle
Mitochondria are able to alter their shape and relocate around cells when necessary. When a cellular structure requires more energy, the mitochondria reproduce, expand, and divide. In cases where a cellular structure requires less energy, the mitochondria either become inactive or die. In some ways, mitochondria are similar to some forms of bacteria.
Different types of mitochondria produce different types of proteins; some are capable of producing hundreds of proteins used for a variety of body functions.
The cytoskeleton supports the cellular structure. The cytoskeleton is a network of rod-like substances that pass through the cytoplasm. Proteins link these ‘rods’ to other cellular structures. Three major types of ‘rods’ are found in the cytoskeleton:
•Microfilaments
•Intermediate filaments
•Microtubules
Microfilaments are the thinnest, semi-flexible type of rod constructed of a special protein called actin. No two cells’ microfilament arrangements are identical. However, most do contain a web-like structure much like a net or web that attaches to the cytoplasmic side of the cell membrane.
Figure 2-7 Interior cell components.
Microfilaments serve to strengthen the surface of cells, resist crushing, and are capable of cellular movements that can influence shape.
Intermediate filaments can be likened to rope in its structure – also constructed of protein fibers twisted together to enhance strength. They’re responsible for resisting external forces often placed on cells.
Microtubules are literally hollow tubes much like a straw that are constructed from round protein subunits. These subunits are called tubulin. They extend from the center part of the centrosome. Microtubules are responsible for the overall shape of a cell and can change form; at times they can break apart and then form again, even at a different location inside the cell.
Centrosomes
Centrosomes is a Latin word defining “center of the body” and is another organelle located close to the cell’s nucleus within the cytoplasm. The centrosome was discovered by Theodor Boveri5 (also spelled Boyeri) in 1888, who identified it as a special organism that facilitated cellular division.
Centrosomes are involved in a number of functions including:
•Regulating progression of cell cycles
•Mitotic spindle formation – the mitotic spindle is a macromolecular process that separates chromosomes into two daughter cells during mitosis. The spindle itself is constructed of microtubule polymers with intrinsic polarity (minus and plus).
Figure 2-8 Microtubules.
Microtubule formation is defined as any minute tubule found in eukaryotic cytoplasm. The microtubules are composed of tubulin protein and are vital components of the cytoskeleton, mitotic spindle, cilia, and flagella.
Figure 2-9 Cilia extending from cellular surface.
The structural form of centrosomes is based on an assembly of nine microtubules. Microtubules appear as hollow, cylinder-like structures constructed of rings of proto-filaments. They’re involved in a number of cellular functions and activities including motion. The motion aspect of microtubules is the result of proteins that utilize energy from ATP to literally propel movement along the microtubule.
The microtubule at the attached end is defined as the “minus” end while the other is the “plus” end. Microtubules are slender but can grow up to one thousand times longer than they are wide.
Microtubules are constructed of alpha (α) and beta (β) tubulin dimers. A dimer is defined as a molecule or complex molecular structure that consists of two identical molecules linked together. More simply defined, a dimer is an oligomer that is formed from two similarly structured monomers joined by a bond that can be intermolecular, covalent, weak, or strong.
Alpha (α) tubulin dimers and beta (β) tubulin dimers are assembled into microtubules, which are in turn involved in numerous functions and processes in the cytoskeleton including:
•DNA segregation
•Intracellular transport
•Structural support
Cilia and flagella are rope-like appendages that extend outward from the surface of numerous types of eukaryotic cells. Their main function is to move liquids over the surface of cells.
Microtubule “motors” facilitate movement. The two major motor groups are defined as:
•Dyneins – move toward the “minus” end of the microtubule
•Kinesins – move toward the “positive or plus” end of the microtubule
A prime example of such function is sperm. Cilia and flagella enable single-celled sperm to “swim”. In a multicellular structure, such as those lining bronchial tubes, the cilia and flagella move or encourage movement of mucus upward toward the throat.
The structure of cilia and flagella are identical and each contain nine filaments situated in a cylindrical array. These filaments contain a fully structured microtubule, a partial microtubule, and what are known as cross bridges of dynein, or one of the “motor” proteins that facilitate movement.
A membrane encloses the entire assembly of cilia and flagella like a sheath.
The functions of mitochondria and its components are vital, but so too are microvilli. These tiny, hair-like projections jut out from the surface of plasma membranes that serve to enhance the overall surface area of numerous types of cells.
The endomembrane system (including the organelles already mentioned) work as a team to:
•Produce
•Degrade
•Store
•Transfer (export) molecules
They also destroy potentially damaging substances.
■The Cell Nucleus
The nucleus is composed of five major parts, each with a specific role to play.
The largest organelle is the nucleus of a cell. The nucleus is responsible for regulating the activities or functions of a cell, whether it be a blood cell, a muscle cell, or a brain cell. The nucleus is responsible for two specific functions:
•Storing hereditary material (DNA)
•Coordinating cellular activities including but not limited to reproduction, protein synthesis, growth, and intermediary metabolism
Most cells only have one nucleus, although some types of algae and slime molds have more. Bacteria and cyanobacteria (prokaryotes) are known as one-celled organisms and don’t have a nucleus. Rather, in such organisms, the cytoplasm contains all the “instructions” for function as well as cellular information.
The five major parts of the nucleus include:
•Nuclear membrane or envelope
•Nuclear “sap”
•Chromatin fibers
•Nucleolus
•Endosomes
Nuclear membrane or envelope – The nucleus is typically spherical and takes up approximately 10% of the volume of a eukaryotic cell.6 The nucleus is separated from other parts of the cell by a nuclear envelope, or more specifically, a double-layered membrane. This space between the double layers is defined as the perinuclear space and connects with the endoplasmic reticulum. The inner surface area of the nuclear envelope is lined with protein. This lining is called the nuclear lamina. In turn, the lamina binds to chromatin and other components found inside the nucleus.
Very small holes occupy the surface of the envelope. These holes are called nuclear pores and allow for the passage of molecules between the cytoplasm and the nucleus. The nuclear pores are responsible for overseeing passage of molecules between the cytoplasm in the nucleus. Some of these molecules are allowed to pass through the membrane.
Eukaryotic and prokaryotic cells both contain common features such as DNA, cytoplasm, a plasma membrane, a nuclear weight region, a nucleus, and ribosomes.
DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are allowed to pass into the nucleus through these nuclear pores, and so too are molecules that will provide the energy for genetic material construction.
During cellular division (mitosis) the nuclear envelope disintegrates, but will later form again as the two cells formed from mitosis complete formation and as the chromatin unravels and also eventually evaporates.
Chromatin or chromatin fibers are defined as a complex arrangement of DNA and proteins found inside the cell nucleus. The nucleus contains molecules that when laid out would encompass nearly 2 meters (6 feet) of DNA.7 They’re literally packed inside every nucleus of every human cell. The chromatin fibers are an extraordinary feat of “packaging” wonder that is precisely structured and organized into very dense fibers or streams called chromatin.
This packaging is facilitated by special proteins that bind and fold DNA into an incredibly complex series of loops and coils.
Nuclear “sap” is considered similar to the cytoplasm of a cell, but it’s not exactly the same. Nuclear sap is a substance found inside a new nucleus, also known as nucleoplasm. Its main function is to act as a suspension substance for organelles that also helps the nucleus maintain its structure and shape. It’s also a major component of transportation for cellular metabolism. Enzymes and nucleotides are dissolved in the nucleoplasm.
This fluid is typically found in the nuclei of eukaryotic cells. This sap-like structure is likened to protoplasm and is constructed of various molecules, dissolved ions, and water. Nuclear sap is completely encompassed within the nuclear membrane, also known as the nuclear envelope. This fluid, also gel-like in nature as cytoplasm or cytosol, contains chromatin materials.
The nucleolus is an organelle found within the nucleus. The nucleolus is responsible for the manufacture of ribosomes. Ribosomes are structures that produce protein. The nucleus of a cell may contain as many as four nucleoli, but every species has a predetermined set or fixed number of nucleoli.
During cellular division, this nucleolus literally disappears.
Endosomes are small areas found inside eukaryotic cells. They’re located in the cytoplasm. Endosomes are described as part of the pathway utilized in the rejuvenation or recycling of surface receptors. Endosomes can be characterized as a collection of organelles that serve in the function of identifying, sorting, and as a delivery vessel of materials from the cellular surface, and even as a transport vehicle from the Golgi apparatus to the lysosome.
Endosomes play a role in the “recycling” of molecules from the plasma membrane through the endoplasmic pathway. This pathway is composed of unique compartments; each involved in the replenishment of degraded molecules. Three types of endosomes are typically defined as:
•early endosome
•recycling or sorting endosome
•late endosome
Molecules are transported along this pathway for degradation in the lysosome (think of a lysosome as a trash truck pulling up to the curb for garbage disposal). They are then recycled back into the plasma membrane.
The process is known as endocytosis and follows the endocytic pathway. Endocytosis is a necessary component of cellular structures because the majority of substances that are vital for optimal function are large, polarized molecules that are unable to passively make their way through the plasma membrane.
■Characteristics of all Cells
Cells share a number of common characteristics depending on various responses to their environment, among which is their ability to move and engage in metabolic processes. They have the ability to grow (anabolism)as well as literally self-destruct (catabolism). One of the most fascinating aspects of cellular characteristics is their ability to reproduce (mitosis.)
Every cell has the potential to respond to their environment. They can literally be irritated into responses or stimulated by a number of factors. They have the potential to sense changes in their immediate environment and respond to those changes. This response to environment is achieved through their nuclear receptors, which can trigger a number of controlled responses.
This type of “communication” between cells as well as their environment is known as homeostasis.
Cells are capable of receiving and processing simultaneous signals. Cells don’t only receive signals, but can transmit them. For example, signaling molecules known as neurotransmitters can travel short distances between adjacent neurons or between a neuron and a muscle cell. Others can send signals much further. A prime example is FSH or follicle-stimulating hormone, which is sent by the hypothalamus to the female ovary, signaling (via FSH) the ovary to release an egg.
In the skin, sensory cells respond to external cues such as touch. Cells inside the ear respond to sound waves. Cells found in blood vessels identify and respond to changes in blood pressure.
This is done through the presence of protein receptors. These receptors bind to “signaling” molecules to trigger physiological responses.8 Some receptors are found deep inside a cell while others are found on its surface, while still others are located in the nucleus.
Motility
How do cells move? They migrate. Cells utilize two basic methods of transportation: contractibility or self-propulsion. Contractibility is contraction. For example, think of contraction of a muscle cell or fibers in the act of bending the elbow and bringing the hand to the face. This contracting ability helps divide daughter cells during mitosis. Contraction occurs when molecular “motors” act on cytoskeletal filaments or microtubules, compelling them to draw toward one another.
Cells can move in specific directions. This directional mobility is called chemotaxis and describes how cells move after triggering by an external signal or stimulus. In many cases, this external signal is caused by the influence of a short peptide or molecule (known as a chemoattractant). The cells automatically move toward the direction of the increased signal concentration. This type of movement is typical in wound-healing scenarios. A damaged or injured cell releases a chemoattractant. This signals the attraction of microphages and fibroblasts of the immune system.
For example, a chemical “scent” or trail is left by the movement of a damaged cell. Like bloodhounds following a scent, leukocytes, vital for defense, respond to the area ready to do battle. This is known as positive chemotaxis.9
Another type of cellular movement in eukaryotic cells occurs via tiny appendages nicknamed “false feet”. Imagine a caterpillar’s tiny legs propelling it across the surface of a leaf or twig. Also known as pseudopods, these tiny appendages attach to a surface in the direction the cell is moving. During chemotaxis, pseudopods are extended in several directions, but they’ll only attach to surfaces that exhibit higher concentrations of chemical signals.
On the other hand, bacterial cells facilitate movement through flagellum. Flagellum move almost like a boat propeller, urging the cell forward.
Metabolism
Metabolism is another common characteristic of all cells. Metabolism in cells occurs through a number of chemical processes.
Cellular metabolism defines chemical changes in living cells through which a number of activities and processes are achieved. It’s a constant state of growth and destruction, which is how energy is produced and provided, as well as involves how new materials are assimilated by a structure.
These biochemical reactions inside the cell can either accelerate or decelerate the functions of a cell based on need. A number of pathways are involved in these functions. Metabolism inside cells must be carefully balanced and coordinated.
The importance of enzymes and their influence in these biochemical reactions is vital. Enzymes are protein-based catalysts or triggers that accelerate biochemical reactions. They do this by expediting rearrangement of molecules supporting cellular functions.
Enzymes are defined as flexible proteins. They can change shape when binding to substrate molecules. This binding and “shape shifting” capability is how an enzyme can influence responses or reactions inside the cell.
Specific enzymes can either activate or inhibit a molecule’s activity or function. Metabolism often occurs along metabolic pathways, which are simply defined as a coordinated process of chemical reactions that trigger a continual process from point A to point B. Enzymes are involved in every step of this reaction pathway and have the ability to transform molecules into different forms depending on the presence of certain enzymes. In such a way, these chemical processes are involved in biosynthesis or creation of new molecules. They can also be involved in catabolism or degradation of molecules.
Some enzymes are involved in physically connected metabolic pathways. Chemical reactions in cellular structures are balanced through anabolic or catabolic pathways. Synthesis of new molecules requires the input of energy to become an anabolic pathway.
The catabolic pathway triggers the breakdown of molecules and results in energy release. In this way, cells break down polymers that include polysaccharides and proteins, and in turn, sugars and amino acids.
Molecules created by organic or enzymatic activities are known as metabolites. Metabolites ensure that energy is consistently available for both anabolic and catabolic pathway balances.
This careful balance as well as maintenance of biochemical reactions of cells by enzymes is a vital component to cellular functions. Activity of enzymes enables cells to respond to ever-changing demands on their environment as well as in the regulation of metabolic pathways. Both are vital to the survival of every cell.
Cellular mitosis
Mitosis is a process that all cell life undergoes. It was first observed in 1855 by German researcher Rudolph Virchow.10 Mitosis defines division of eukaryotic nuclei, although the term is used broadly in defining cellular duplication.
Cellular division differs between eukaryotes and prokaryotes. Prokaryotes (single-celled organisms) rely on asexual reproduction, producing offspring with the same genetic makeup of the parent through binary fission.
Figure 2-10 Cellular mitosis.
Eukaryotic cells undergo mitosis or cellular division and production by manufacturing identical copies that duplicate their DNA sequences through specific phases known as the cell cycle.
Cellular mitosis is most simplistically defined as reproduction. Technically, mitosis is recognized as the division of nuclear cells in the production of two identical “daughter” cells during numerous phases (cell cycle):
•Interphase – generally defined as a ‘pre-mitosis’ preparation activity
•Prophase
•Prometaphase
•Metaphase
•Anaphase
•Telophase
•Cytokinesis
Each of these phases involved in mitosis is a vital aspect of growth and rejuvenation or replacement of older or damaged, or otherwise literally “worn out” cells.
During mitosis, the cell divides and creates identical copies of itself. The process involves a parent cell that divides and produces identical daughter cells.
This process enables the parent cell to translate or pass on its genetic coding to each daughter cell.
Before this happens, the cells duplicate their DNA, and mitosis is defined as the process through which the cell separates identical copies or duplications of its nucleus.
In many circles, Interphase is not technically defined as the first stage or phase of mitosis, but is generally further broken down into three separate yet distinct stages: G1 (first gap), S (synthesis phase), and G2 (second gap phase).
During Gap 1 stage, the cells that will divide perform a number of metabolic activities, including growth. During the synthesis phase (S. phase) the cell effectively duplicates its DNA. Each chromosome creates its own copy known as a sister chromatid. The two chromatids fuse together in the shape of a X, with the intersection known as the centromere.
During the second gap phase (G2), the cell grows and manufactures proteins necessary for mitosis.
In Prophase, some structures inside the cell dissolve, while others are formed. Chromosomes will condense and mitotic spindles start to form. The spindle is responsible for organizing chromosomes, growing as the centrosomes gradually move apart. During this phase, the nucleolus also dissolves, triggering the next stage, typically called late prophase or prometaphase. As the nuclear envelope breaks down, the chromosomes are released. At this point, some microtubules bind to patches of protein (kinetochore) on the centromere of each sister chromatid.
During metaphase, the spindle has lined up the chromosomes in the middle of the cell in preparation for actual division. At this time, chromosomes are aligned with kinetochores and attached to microtubules. This process is vital in order to ensure that the sister chromatids divide evenly between the two daughter cells. If chromosomes are not aligned properly, the cell will trigger this division process to stop until they are properly arranged.
Anaphase occurs when the sister chromatids actually separate from one another. They drift to opposite sides of the cell, each now becoming its own chromosome. Each pair of chromosomes drift to opposite sides of the cell.
This movement activity is compelled by motor proteins as defined earlier. The motor proteins literally transport chromosomes during this phase.
Telophase is the point in time when the cell is nearly finished with the division process and once again reestablishes its normal structure. The division of the cellular contents actually takes place in a process known as cytokinesis. Cytokinesis is defined as the actual point at which division of the cytoplasm occurs, creating two new cells.
At this point, the mitotic spindle is disassembled and two new nuclei form; one nuclei for each set of chromosomes. Following that, nuclear membranes reappear.
When cells don’t divide properly, abnormal cellular growth processes go awry, creating cancer.
■Abnormal Cell Division
Cancer is defined as the abnormal growth of a single cell or group of cells that have lost their ability to control their growth. A malignant cancer cell can appear in any tissue or organ in the body. As that cancer cell develops, grows, and then multiplies, it forms a mass. This mass of cancerous tissue is called a tumor.
Figure 2-11 Abnormal cell development.
Tumors can attack, invade, and then destroy adjacent tissues that are otherwise normal and healthy. Tumors, in most cases referring to abnormal growth or masses, are either classified as cancerous (malignant) or noncancerous (benign). Cancer cells that migrate from their initial point of origin can spread through a number of ways through the body. This is known as metastasizing.
Development of cancer cells
A normal and healthy cell can turn into a cancerous cell through a molecular process known as transformation. Transformation occurs in steps that include:
•Initiation
•Promotion
Figure 2-12 Skin cancer.
Initiation occurs when an alteration in the genetic material of the cell occurs. This alteration can be triggered in the chromosomal structure or the DNA. This will cause the cell to become cancerous or “abnormal”. The alteration of cellular genetic material is typically caused by carcinogens, or environmental agents, or spontaneously. The most common carcinogens that contribute to cancerous growth include:
•Tobacco
•Over-exposure to sunlight
•Radiation
•Chemicals
Not everyone is susceptible to carcinogens. For example, a smoker may never develop lung cancer, although a non-smoker can. In many cases, it’s a matter of genetics as to whom is more susceptible to carcinogens.
Promotion defines the latter step of cancerous development. Any agent that triggers promotion is called a promoter. In many cases, these are environmental substances or even drugs. Unlike carcinogens, a promoter doesn’t necessarily cause cancer all by itself, but it will “promote” or enable a cell that has undergone initiation to develop into a cancerous cell. Some cancers develop without the influence of promotion.
Cancers can develop and grow by spreading directly into adjacent tissues or organs. It can also travel great distances within the body through the lymphatic system, which is the more typical in metastatic cancers.
As an example, breast cancer typically migrates (metastasizes) into the lymph nodes nearby, and through the lymph, spreads through the body.
Cancers can also spread through the bloodstream, typical of most sarcomas.
■Different Types of Cancer
Malignant cancers are typically divided into either blood-forming tissue (such as lymphoma or leukemia) or a solid tumor such as with sarcoma or carcinoma.
Cancers such as those that form in the blood or blood-forming tissues such as lymphomas or leukemias don’t form a mass or lump, but often remain as individually separated abnormal cells. However, they multiply to a point where they can overcrowd or overcome normal blood cells in the bloodstream or bone marrow. Over time, the number of damaged or abnormal cancerous cells gradually overcome and replace healthy cells.
A carcinoma is defined as a cancer of epithelial cells. Carcinomas also affect endocrine glands or any gland that secretes hormones. Some of the most common types of carcinomas include:
•Skin cancer – such as melanoma
•Stomach cancer
•Lung cancer
•Prostate cancer
•Colon cancer
Carcinomas are more commonly found in older individuals than younger individuals.
Sarcomas are defined as cancers of muscle dermal cells or the cells that form connective tissues and muscles.
This type of cancer can form in smooth muscles found in digestive organs (Leimyosarcoma) or in bone cells, resulting in bone cancer (osteosarcoma).
This type of cancer is more commonly found in younger people than older people.
A number of factors can contribute to an increased risk of developing cancer:
•Genetics
•Environment
•Diet
•Geography
| Men | Women |
| Prostate | Breast |
| Lung | Lung |
| Colon and rectum | Colon and rectum |
| Bladder | Uterus |
| Non-Hodgkin’s lymphoma | Non-Hodgkin’s lymphoma |
Some cancers are often gender specific. For example, see the list above. Other causes of cancer include viral infections and inflammatory diseases.
Body defenses against cancer
The body’s immune system is the front line of defense against a cancerous cell. In most cases, it is believed that the immune system is able to recognize the development of common abnormal cell structures and destroy them before they can reproduce or replicate and spread.
Figure 2-13 Different types of Sarcoma.
However, cancers are not limited to individuals with compromised immune systems or system function. Otherwise healthy individuals with strong immune systems may also develop cancers.
When the body senses a cancerous or abnormal cell, it responds to tumor antigens. Antigens are described as a foreign substance that is quickly recognized by the immune system and targeted for destruction. While antigens are typically found on all cellular surfaces, the body’s immune system doesn’t typically react to its own cellular structures. However, when the cell becomes cancerous, new or previously unknown antigens appear on the surface of that cell.
Think of these antigens as a beacon that attract components of the immune system, much like a great white shark attracted to the scent of blood in the water, which them prepare for attack.
In some cases, the body’s own immune system, through this mechanism of action, is capable of destroying abnormal cellular development and even cancerous cells before they become established in the body. However, after a cancerous cell reproduces or forms a mass, the body’s immune system is often unable to halt its progress.
A number of cancers have been identified through their tumor antigens,11 including malignant melanoma and bone cancer. Individuals with such types of cancer typically produce antibodies against those specific tumor antigens. Nevertheless, the body’s immune system is more capable of destroying cancerous cells early on in some types of cancers such as corneal carcinoma (cancerous tumor development in the uterus from parts of the developing embryo).
Figure 2-14 Cancer cells.
Blood tests can determine the presence of tumor antigens. Antigens are also commonly defined as tumor markers. Measuring tumor markers is a way to screen individuals with no previous symptoms of cancer, and are often capable of aiding in diagnosis and evaluating treatment responses.
■How do Cells Function?
Cells have the ability to move things from one point to another. One major function of cells is the ability to engage in transportation of vital components necessary for cellular health and wellness. Two specific types of transportation are common to all cellular function:
•Active transport
•Passive transport
Figure 2-15 Passive and active transport.
Active transport is defined as something that occurs when the cell must utilize energy for transportation. This involves literal movement of molecules across a cellular membrane.
Because the inside and outside of cells are composed of different substances, cells are often required to work very hard and use energy to maintain adequate balances of molecules and ions inside and out.
One of the most common forms of active transportation occurs across the cellular membrane. Literally thousands of proteins are embedded into the lipid bilayer of the cell. These proteins are likened to workhorses and are positioned in such a way that one portion of such proteins remains on the inside and the other portion of the protein protrudes to the outside of the cellular membrane. Only when the bilayer is crossed are the proteins capable of moving ions and molecules into or outside of the cell.
However, these proteins, often called membrane proteins, are not created equal. For example, one proteins may only be able to move glucose, while another is responsible for the movement of calcium. Hundreds of membrane proteins are found in the body, each charged with a specific function.
When pressure or concentration differs between the inside and outside of the cell (especially in the case of neurons), the proteins are working “against” concentrated gradients. This is typical when an ion wants to move from an area of lower concentrations to an area of higher concentrations. In this situation, membrane proteins must consistently push ions into or out of the cell in order to prepare the neuron membrane to transmit an electrical impulse.
Passive transportation is another cellular function. While active transport relies on energy, passive transport is achieved through several different methods:
•Osmosis
•Filtration
•Diffusion
Osmosis is defined as a process by which molecules pass from semi-permeable membranes with less concentrated solutions into an area of higher concentration. This results in equalization of concentration on both sides (inside and outside) of the membrane.
Figure 2-16 Osmosis and reverse osmosis.
Osmosis is primarily defined as a water-based movement. The balance of ions inside and outside of the cell needs to be the same. If ions are not balanced, water molecules want to enter, which can cause swelling and literally explode or pop the cell.
Diffusion defines a process where molecules move from an area of higher concentration to lower concentration. Think of the unloading of passengers from a train. A high volume of passengers surge from the train car and disperse throughout the train station, decreasing the volume of passengers in the train.
Filtration is another method of passive transport. Most of us are familiar with filters, which function in a physical capacity. Filtration, pressure and other forces such as gravity can propel movement. One example is cardiovascular function, where the heart’s pumping capacity effectively regulates blood pressure as it flows through blood vessels.
As we have seen, cells and cell structures share a number of similarities, and the same applies to the longevity of a cell. We conclude this overview of cytology with an explanation that defines the two main types of ‘death’ experienced by cells.
Cellular necrosis and apoptosis
Necrosis defines cellular death caused by unexpected damage to the cell that can be caused by a number of sources:
•Exposure to toxic chemicals
•Trauma
•Blocked blood flow
•Radiation
In such cases, the cell literally ruptures or pops like an overfilled water balloon, allowing the interior components of the cell to disperse into the cellular environment. Once there, the remnants are consumed by phagocytes.
Figure 2-17 Cellular necrosis
Apoptosis is ‘normal’ cellular death; think of it as an aging cell that eventually wears out. The cell begins to lose its structural shape and further breaks down into smaller bodies.
Some studies have explored the potential of some vaccines to trigger apoptosis in mouse livers.12 Studies attempting to determine whether some cytotoxic anti-cancer agents actually trigger and influence apoptosis have been performed since 2000,13 resulting in improved cancer treatments.
The National Cancer Institute has developed apoptosis inducers,14 which actually cause cancer cells to succumb to apoptosis. Cancer cells have the unique ability to resist apoptosis, but angiogenesis inhibitors and delivery of monoclonal antibodies15 that dispense toxic molecules into cancer cells has shown positive progress in the treatment of different types of cancers today.
Apoptosis is often called a programmed cellular death and is natural. Apoptosis does not cause a cell to ‘burst’ as with necrosis, but rather allows the cell to be consumed and eventually removed.
■Conclusion
Cells are incredibly complex; responsible for hundreds of functions in the human body. Cells are the foundation of any structure in the body and vary in size, shape, and function. Each performs a specific job in the human body.
Cytology provides a fascinating glimpse into the smallest units of life; without which there would be no life. Cells provide the foundation of all living things, from simple amoebas to people, animals, and plants. It is estimated that the human body contains multiple trillions of cells, all with predestined functions and activities that sustain life for decades.
Case Study Conclusion
Dr. Sanderson has sent Erica’s biopsy to the pathology lab. He is aware that melanoma is rated as the fifth most common cancer for men and the seventh most common malignancy found in women.16 The American Cancer Society estimates approximately 87,000 new cases of melanoma will be diagnosed in 2017.17 He hopes that Erica has come to him early enough to enjoy many years to come. He received the biopsy results and his suspicions of a cutaneous melanoma were verified. He had been careful to note the classification and thickness of the suspected cutaneous melanoma (T1, less than or equal to 1.0, and without ulceration and mitosis less than 1/millimeter2.)
After discussing the results with Erica, he scheduled a procedure to remove the melanoma. He then recommended that she undergo annual skin examinations on a yearly basis and be proactive with her own monthly skin examinations. He also showed her how to perform a self-lymph node exam, recommended for patients with stage IA cutaneous melanoma, which was Dr. Sanderson’s determination. He also recommended she undergo physical examinations with special focus on her skin and lymph nodes every three to 12 months for the next five years and then on an annual basis as indicated. Routine imaging was not recommended.
He stressed to her the importance of these follow-ups to identify any recurrence early on, as patients diagnosed with any stage of melanoma have an up to 8% risk over lifetime of developing a secondary primary melanoma.
■Questions
1.What does selective permeability imply in regard to the plasma membrane?
A.It serves as an impassable protective barrier.
B.It allows movement of only lipids.
C.It allows certain substances to enter or leave the cell while preventing others from doing so.
D.It’s a membrane that is not composed of a phospholipid bilayer.
Answer: C. The cell membrane is permeable, which enables certain substances to enter or exit, depending on function.
Learning Objective: 1
2.Which organelle is responsible for the formation of the mitotic spindle and is also involved in mitosis as well as regulation of the cell cycle?
A.Mitochondria
B.Centrosomes
C.Cytoskeleton
D.Peroxisomes
Answer: B. Centrosomes are involved in several vital functions of the many organelles in the cell found inside the cellular matrix. The centrosomal matrix organizes development of the mitotic spindle and microtubule generation in cell division.
Learning Objective: 2
3.Which type of transport is the most common and how does it work?
A.Active. Active transport processes cannot cross the cellular membrane.
B.Passive. Passive transport implies a process where molecules move from areas of high molecule concentration to areas of lower concentrations.
C.Active. Describing a unique process where one-half of a protein molecule is embedded into the inside of a molecule and the other half protrudes to the outside of the cell membrane.
D.Passive. Describes a situation where ion molecules move from areas of low concentration to areas of high concentration.
Answer: C. Active transport is the most common form of transport and defines the movement of molecules across the cell membrane facilitated by the energy supplied by ATP. This energy is needed for transportation.
Learning Objective: 3
4.Which type of cancers are most commonly diagnosed in younger people than older people?
A.Sarcomas
B.Carcinomas
C.Non-Hodgkin’s lymphoma
d.Bone cancer
Answer: C. Carcinomas such as skin cancer, lung cancer, and colon cancer are more prevalently diagnosed in younger individuals than older. In some cases, these types of cancers may be a result of lifestyle (smoking, diet, drug use, overexposure to sunlight, environmental factors, etc.)
Learning Objective: 5
■References
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| 2. | Elaine Marieb and Katja Hoehn. Human Anatomy & Physiology. 10th ed. (San Francisco: Pearson, 2016), 62. | ||
| 3. | Singer SJ, Nicolson GL. “The fluid mosaic model of the structure of cell membranes.” Science. 1972 Feb 18;175(4023):720–31. Accessed April 2017. Available from: https://www.ncbi.nlm.nih.gov/pubmed/4333397 | ||
| 4. | Timothy Paustian. “Inclusions and other internal structures.” University of Wisconsin-Madison, accessed April 2017. Available from: http://lecturer.ukdw.ac.id/dhira/BacterialStructure/Inclusions.html | ||
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| 8. | Scitable [Internet]. Nature Education. “Cell Signaling”, accessed April 2017. Available from: https://www.nature.com/scitable/topicpage/cell-signaling-14047077 | ||
| 9. | Elaine Marieb and Katja Hoehn. Human Anatomy & Physiology. 10th ed. (San Francisco: Pearson, 2016), 644 | ||
| 10. | CDC.gov [Internet] Schultz, M. Rudolf Virchow. “Emerging Infection Diseases.” www.cdc.gov/eid. Vol. 14. No. 9, Sept. 2008. Accessed April 2017. Available from: https://wwwnc.cdc.gov/eid/article/14/9/pdfs/08-6672.pdf | ||
| 11. | Science Daily [Internet] “Immunotherapy for cancer: New method identifies target antigens by mass spectrometry”. Science News: University of Munich. Dec. 15, 2016. Accessed April 2017. Available from: https://www.sciencedaily.com/releases/2016/12/161215143317.htm. | ||
| 12. | PubMed. US National Library of Medicine National Institutes of Health [Internet] Hamza H, Cao J, Li C, Zhu M, Zhao S. “Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells.” Apoptosis 2012 May;17(5):516-27. doi: 10.1007/s10495-011-0690-1. Accessed April 2017. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22249285 | ||
| 13. | PubMed. US National Library of Medicine National Institutes of Health [Internet] Lowe SW, Lin AW. “Apoptosis in cancer.” Carcinogenesis 2000 Mar;21(3):485–95. Accessed April 2017. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10688869 | ||
| 14. | National cancer Institute [Internet] “Targeted Cancer Therapies”. Accessed April 2017. Available from: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet | ||
| 15. | Ibid. | ||
| 16. | American Cancer Society [Internet]”Cancer facts and figures 2013”. American Cancer Society. Accessed April 2017. Available from: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2013.html | ||
| 17. | American Cancer Society [Internet] “Cancer Facts & Figures 2017”. Accessed April 2017. Available from: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf |
