Introduction: It is within the cell where the functions of the body occur. We are going to look at structure, function and reproduction of cells in this chapter.
Animal cells differ from plant cells in that animal cells do not have cell walls. This allows much material to easily diffuse across the plasma membranes into the cytosol of the cell where the materials can be stored as inclusion bodies or can be utilized in the organelles of the cell.

The PLASMA MEMBRANE is a very thin barrier that separates the internal components of a cell from the external environment. The membrane is composed of lipids (phospholipids, glycolipids, and cholesterol), proteins (mostly glycoproteins) that form channels through which materials pass. Proteins also act as transporters and serve as receptors, enzymes, cytoskeleton anchor, and cell identity markers. The membrane functions in cellular communication, as an electrochemical gradient which is important for proper function of the cells. In selective permeability certain substances are allowed to pass through while others are restricted. Permeability depends on size of the molecule, lipid solubility, electric charge, and the presence of transporters and channels.

The Cell can be divided into two parts, the CYTOSOL or Intracellular Fluid and the ORGANELLES. The cytosol is a semi-fluid portion of the cytoplasm in which organelles and inclusions are suspended. The function of the cytosol is to provide a place where metabolic reactions occur. The organelles are specialized structures in the found in the cytosol. The most important organelle is the Nucleus. It controls cellular activities, contains the genetic material of the cell, which is seen as chromosomes during cellular division, and is separated from the cytoplasm by a nuclear membrane. Within the nucleus are nucleoli which are the site of assembly of ribosomes. Ribosomes have a role in protein synthesis. They are either free floating in the cytosol or attached to the endoplasmic reticulum. The Endoplasmic Reticulum is a network of membrane-enclosed channels continuous with the nuclear membrane. Its function is to transport substances, store newly synthesized molecules, detoxify chemicals, and release calcium ions involved in muscle contractions. Another structure is the Golgi Complex which processes, sorts, and delivers proteins and lipids to the plasma membrane, lysosomes and secretory vesicles. Lysosomes contain digestive enzymes that dissolve cellular contents and extracellular materials. Mitochondria generate ATP (energy source of the cell). The Cytoskeleton provides structure for the cell. Some cells contain Flagella and Cilia which are external appendages use for locomotion. Finally, the Centrosome serves as mitotic spindles in dividing cells.

CELL JUNCTIONS are points of contact between adjacent plasma membranes. One type is a tight junction that forms fluid tight seals between cells. These are common in epithelial cells that line the GI tract and the urinary bladder. Another type is anchoring junctions that fasten cells to one another or to extracellular material. They are found in tissues subjected to friction and stretching (muscle tissue of the heart). Lastly are communicating junctions which permit electrical or chemical signals to pass from cell to cell. These are found in heart muscle and smooth muscle of the GI tract.

MOVEMENT OF MATERIALS ACROSS PLASMA MEMBRANES
The most important thing to remember about movement across membranes is that passive processes don’t use energy whereas active processes do. Examples of passive processes include simple diffusion (particles move from an area of high concentration to a lower concentration to reach a point of equilibrium). This is seen in gas exchange in tissues and lung. A second type is osmosis or the movement of a solvent through a selectively permeable membrane. Here osmotic pressure, or the pressure needed to stop the flow of water across the membrane, depends on the permeability of the membrane and the tonicity of the solutions involved (hypotonic, isotonic, or hypertonic). Osmosis always involves water. Filtration occurs when water and some dissolved substances move across a membrane due to gravity or hydrostatic water pressure. It always moves from higher levels of pressure to lower levels. In facilitated diffusion certain molecules are helped across a membrane by a transporter that moves the molecules from a higher concentration gradient to a lower concentration. Facilitated diffusion depends on difference in concentrations, number of transporters available, and how quickly the transporter and the substance combine.

Active Processes use energy from spitting ATP. Active transport can be either primary active transport in which ATP directly moves a substance across the membrane or secondary active transport in which energy stored in ion differences drives the substance across the membrane. Another active process is Bulk transport. Examples of this mechanism include endocytosis (brining substances into a cell), phagocytosis (engulf a substance and bringing that substance into the cell), pinocytosis (engulf tiny droplet of extracellular fluid), receptor-mediated endocytosis (takes in specific substances), and exocytosis (discharges substances from cell).

The process of NORMAL CELL DIVISION is a means by which cells replicate themselves. It consists of a nuclear division (mitosis) and a cytoplasmic division (cytokinesis). Somatic Cell Division results in an increase of body cells. Parent cells and daughter cells both contain the diploid (2n) number of chromosomes. Interphase is the time period between cell divisions during which replication of DNA occurs and the original DNA molecule becomes two DNA molecules. Some terms of mitotic cell division you should become familiar with are:

• prophase: chromatin material shortens and condenses

• metaphase: centromeres of the chromatid spindles line up at the exact center of the mitotic spindle

• anaphase: centromeres divide and chromosomes move to opposite ends of the cell

• teleophase: nuclear envelope reappears and encloses chromosomes which resume chromatin form, nucleoli reappear, and mitotic spindle disappears

• cytokinesis: division of the parent cell’s cytoplasm and organelles, cleavage appears to separate cytoplasm into usually two equal portions

The length of the cell cycle varies with location, temperature.

Meiosis or Reproductive Cell Division is a process that produces a haploid number of chromosomes and consists of two nuclear divisions called reduction division and equatorial division. In meiosis the homologous chromosomes undergo synapsis (chromosomes become arranged in homologous pairs) and crossing-over to result in two diploid daughter cells. Then the two haploid daughter cells undergo mitosis (equatorial division). The entire process results in four haploid daughter cells.

ABNORMAL CELL DIVISION: CANCER
Cancer is uncontrolled cell growth resulting in a tumor or neoplasm. A growth than spreads (metastasis) is a malignant tumor. Non-spreading growth is called a benign tumor. Cancer cells compete for nutrients and space. They crowd out normal tissue until that normal tissue dies. Some causes of cancer are carcinogens, which are found in the environment (such as chemicals or radiation) and viruses. The treatment of cancer employs a variety of methods depending on type of cancer. Some methods include surgical removal, chemotherapy, radiation, immunotherapy to get rid of the cancer. Bone marrow transplants may be used in certain types of cancer to regenerate blood cells.

CELLULAR METABOLISM

Anabolism is the chemical reactions that combine simple substances into more complex molecules (requires energy). For example, glycogenesis is the storage of glucose as glycogen in the liver and skeletal muscles;  in glycogenolysis, glycogen is converted to glucose and released from the liver; in gluconeogenesis protein or triglyceride molecules are converted into glucose; and in lipogenesis glucose or amino acids are converted into lipids.

Catabolism is the chemical reactions that breaks down complex molecules into simpler ones (releases energy). During gycolysis, glucose breaks down into 2 molecules of pyruvic acid. In lipolysis, lipids break down into glycerol and fatty acids.

Metabolic reactions require energy to start. Enzymes make cellular reactions happen faster. Enzymes are usually proteins that promote specific reactions. They are required in very small quantities and are not consumed in the reaction process. Because they react on a specific substrate they are often referred to as the "lock-and-key effect. Enzymes are usually named according to their substrate with an -ase at the end.

Metabolic processes in cellular metabolism occur in three interconnected series of reactions: glycolysis, the citric acid cycle, and the electron transport chain. What is important about these reactions is that they produce the energy needed by in cellular respiration. The energy derived from this series yields thirty-eight ATPs.

GENE ACTION: The function of cell is to make proteins and the instructions on how to make the proteins is found on the genes. The process is pretty simple. In transcription genetic information encoded in a region of the DNA helix is copied (transcribed) onto messenger RNA (mRNA). The next step is translation, a process by which the mRNA specifies the amino acid sequence of a protein in the ribosome. The result is an amino acid. Combinations of amino acids make different proteins. In summary, DNA → RNA → protein. (THIS IS GOSPEL – KNOW IT!)

Some more notes on NUCLEIC ACIDS AND PROTEIN SYNTHESIS
The total amount of DNA in a cell is called its genome. DNA is the blueprint that tells the cell through RNA what proteins to make. DNA is composed of two strands of nucleotides which contain Nitrogenous Bases [purines (adenine & guanine) and pyrimidines (cytosine & thymine)]. Base pairing rules dictate that they always, always pair up as A-T or C-G only. Also included in DNA is a sugar, deoxyribose and a phosphate, HPO4. The structure forms a double alpha helix (a twisted ladder formation). Sections of DNA are the genes (a certain segment of DNA that contains the necessary code to make a protein or RNA molecule). These sections maintain the genetic code during reproduction, yet provide variability due to crossing over during meiosis. DNA replication is the production of identical strands of DNA. This must occur prior to cell reproduction. Semiconservative replication means that each “old strand” of DNA serves as a template upon which the “new strand” is synthesized. The double strands separate to form two templates.

DNA relationship to proteins
The protein’s primary structure, that is the order and type of amino acids in the chain determine its shape and function. The proteins that are produced determine phenotype or the expression of a gene. And DNA is the blueprint that tells the cell how to and which kinds of proteins to make.

RNA Code
RNA is composed of single strands of nucleotides which contain Nitrogenous bases [purines (adenine & guanine) and pyrimidines (cytosine and uracil)]. RNA also contains a sugar, ribose, a HPO4. There are three types of RNA, messenger RNA (mRNA) which is produced from DNA patterns in transcription. The master DNA code is first copied onto mRNA through transcription. Transfer RNA (tRNA) is also produced from DNA patterns. Sixty-four varieties of codons are determined by anti-codons (nucleotide triplets) and amino acid binding sites. 61/64 types represent some type of amino acid, other types are either start or stop codons. Each variety of tRNA converts the master code on mRNA into a specific amino acid. Ribosomal RNA (rRNA) forms the major part of the ribosome and participates in protein synthesis. Link for a comparison of DNA and RNA molecules.

Review of Steps in Protein Synthesis Sequence

1. DNA unzips

2. Transcription produces mRNA using the DNA code by complimentary base pairing mRNA attaches to ribosome

3. tRNA anticodons attach to complimentary codons of mRNA amino acids join to produce protein

4. Translation: production of a protein from a mRNA strand
   a.    All elements needed to synthesize a protein are brought together on the ribosome.

Mutation Mechanisms or Nucleic acids gone bad
A Mutation is a permanent change in the DNA that may be passed along from generation to generation. The wild type (strain) of the organism exhibits, non-mutated characteristics. A mutant strain can show variance in morphology, nutritional characteristics, genetic control mechanisms, resistance to chemicals, temperature preference, and any type of enzymatic function.

Causes of mutation can be spontaneous where there is a random change in DNA. This arises from mistakes in DNA replication. Mutations can be induced due to chemical or physical factors. Many chemical mutations are also carcinogenic and can result in cell death. The categories of mutations are as follows:

1. Point mutations change the nature of one gene. These can be either frameshift (deletion or insertion of a base pair) or substitution in which the wrong base pair is put in place of correct bp producing error in base pairing, thus a change in the codon.

2. Inversion is the change in one or two codons (adjacent base pairs change position). These can be silent (no change in amino acid) if the same bp are exchanged or missense which can have consequences of none to severe. This is due to a faulty, nonfunctional protein, a different, but functional protein, or there can be no significant alteration in protein function.

3. Some mutation result in nonsense or STOP codon. The protein stops being produced. If large mutations in which whole chromosomes are lost or large genetic sequences are inserted, the cell or organism often will not survive. Thus major mutations alter the number of genes present.

TISSUE LEVEL OF ORGANIZATION

TYPES OF TISSUES AND THEIR ORIGINS
A tissue is a group of similar cells that usually have the same embryological origin and are specialized for a particular function. In a tissue surrounding the cells is fluid called extracellular fluid. There are two types of extracellular fluid: interstitial fluid and plasma. Plasma is found in the blood stream and serves as a transport medium for the blood cells. In addition plasma carries nutrients, proteins, electrolytes, gases and wastes.

• Epithelial tissue is a specific type of tissue that covers body surfaces, lines hollow organs, body cavities, and ducts; forms glands.

• Connective tissue: protects and supports the body and its organs; binds organs together; stores energy reserves as fat; provides immunity.

• Muscle tissue: excitable cells responsible for movement and generation of force.

• Nervous tissue: excitable cells that initiate and transmit action potentials that help coordinate body activities.

EPITHELIAL TISSUE
Epithelial tissue is composed mostly of cells with little extracellular material and these cells are closely packed together and are arranged in continuous sheets in one or multiple layers. The apical surface is exposed to body cavity, lining of an internal organ or the exterior of the body and a basal surface which is attached to the basement membrane (two layers: basal and reticular lamina). Numerous cell junctions are present to secure cells to each other. Epithelial tissue is avascular (not supplied by blood vessels). It gets nutrients and removes wastes by diffusion. Epithelial tissue can be renewed easily and has a nerve supply. The functions of epithelial tissue include protection, filtration, lubrication, secretion, digestion, absorption, transportation, excretion, sensory reception, and reproduction. Arrangement of cells can be simple (one layer), stratified (cells stacked), or pseudostratified . The shapes can be squamous (flattened and scalelike), cuboidal (cube shaped), columnar (tall and cylindrical), or transitional.

Each type found has a different function. For example, simple squamous epithelium functions in filtration and diffusion. Simple cuboidal epithelium and non-ciliated simple columnar epithelium function in secretion and absorption. Ciliated columnar epithelium move fluids or particles along passageways by ciliary action. Stratified squamous and cuboidal epitheliums provide protection. Whereas stratified columnar epithelium provides both protection and secretion. Transitional epithelium permits distention. Pseudostratified columnar epithelium allows secretion and movement of mucous by ciliary action. The most widespread epithelium in the body is stratified squamous epithelium.

Glandular Epithelium
Exocrine glands secrete their products into ducts and are either unicellular or multicellular. Functional types include holocrine glands (oil gland of the skin), merocrine gland which discharge product by exocytosis, and apocrine glands (mammary glands).

The endocrine glands are ductless, secrete products into extracellular fluid and into blood.

CONNECTIVE TISSUE
Connective tissue is the most abundant body tissue in the body. It consists of widely separated cells, ground substance and fibers which form a matrix. It does not occur on free surfaces. Except for cartilage and tendons, it has a nerve supply and usually has a good blood supply.

Types of connective tissue cells found in the body include fibroblasts which secrete the molecules that form the matrix, macrophages which are derived from a monocyte and used to phagocytize other dead cells, plasma cells which make and secrete antibodies, mast cells which produce histamine, adipocytes (fat cells) and leukocytes (white blood cells). Connective tissue serves to connect different tissues together. Other functions include physical protection, immune protection, movement, heat production, and transport.

The connective tissue matrix is comprised of ground substance and fibers. The fibers in the matrix provide the support and strength for tissues. Types of fibers include collagen fibers, elastic fibers, reticular fibers.

Types of Mature Connective Tissue:

1. loose connective tissue: fibers loosely woven

2. dense connective tissue: contains more fibers and less cells than loose connective tissue

3. areolar connective tissue: widely distributed in the body, combined with adipose tissue, it forms the subcutaneous layer

4. reticular connective tissue: helps to bind together the cells of smooth muscle

5. adipose tissue, composed of adipocytes which store fats

6. dense regular connective tissue: provides strong attachment between various structures (tendons and ligaments)

7. dense irregular connective tissue: provides strength (fasciae)

8. elastic connective tissue: allows stretching off various organs (lungs)

Cartilage
Hyaline cartilage is the most abundant type of cartilage in the body. In muscle tissue it is the gristle. It affords flexibility and support, reduces friction and absorbs shock. Fibrocartilage provides support and fusion. Elastic cartilage gives support, yet maintains shape (epiglottis).

Bone tissue (osseous), blood (vascular tissue), muscular, and nervous tissue will be covered at a later time.

INTEGUMENTARY SYSTEM

SKIN
Skin is an organ because it consists of different tissues that are joined to perform specific activities. It covers about 2 sq. meters and weighs 10-11 lb. The range in thickness is from 0.5 to 4.0 mm depending on its location.

The anatomy of skin includes three layers; the epidermis is the most outer layer, a thinner portion that is composed of epithelium. Next is the dermis, the inner, thicker portion that is composed of connective tissue. Beneath the dermis is a subcutaneous layer which is composed of superficial fascia (hypodermis).

 

The epidermis is composed of stratified squamous epithelium. Cell types found in the epidermis and their function are: the keratinocytes that produce keratin which waterproofs the skin, the melanocytes that produce the pigment melanin which absorbs UV light, the Langerhans cell that arise in the bone marrow and migrate to the epidermis and help with immunity, and Merkel cells that are thought to function in the sensation of touch.

The layers of the epidermis from deepest to most superficial are:

• stratum basale: single layer of cuboidal to columnar cells which are stem cells (that produce the keratinocytes),  melanocytes, and tactile cells.

• stratum spinosum: layer contains 8 -10 rows of many-sided keratinocytes

• stratum granulosum: 2-5 layers of keratinocytes that develop keratohyalin (precursor of keratin) which functions in waterproofing the skin

• stratum lucium: normally seen only in thick skin

• stratum corneum: uppermost 25-30 layers of cells completely filled with keratin; keratinization occurs in cellular development as the cells are pushed towards the surface.

The dermis is composed of connective tissue containing collagen and elastic fibers. The papillary region, the outer 1/5, has a surface area that is increased by projections called dermal papillae (ridges, that when formed cause the epidermal layer to develop finger prints) which are filled with capillaries and tactile receptors. The reticular region, or inner portion consists of dense irregular connective tissue containing collagen, adipose tissue, hair follicles, sebaceous (oil) glands, nerves and sudoriferous (sweat) glands. Beneath the dermis is the subcutaneous layer (hypodermis). This layer binds the skin to underlying tissue, pads the body, and serves as an energy reserve.

Skin color is due to melanin, carotene (yellow), and hemoglobin (red). All races have about the same number of melanocytes, it’s the amount of melanin produced that determines the skin color. UV light stimulates melanin production.

EPIDERMAL DERIVATIVES (ACCESSORY ORGANS OF THE SKIN)
Hair
The primary function of hair is protection. It decreases heat loss and protects us from large foreign particles being inhaled and getting into our eyes and ears. The anatomy consists of a shaft above the surface, a root that penetrates the dermis and subcutaneous layer, and a hair follicle. Sebaceous (oil) glands, arrector pili muscles, hair root plexus are also associated with hair. Hair color is primarily due to melanin.
Nails
Nails are hard, keritinized epidermal cells over the dorsal surface of the terminal portions of fingers and toes. Parts of a nail are the body free edge, root, lunula, eponychium (cuticle) and the nail matrix. The function is protection and to help us grasp small objects.
Glands
Sebaceous (oil) glands are usually connected to hair follicles, produce sebrum which moistens hair and waterproofs skin. An infection of sebaceous glands leads to boils or pimples. Sudoriferous (sweat) glands are basically of two types: apocrine which are found in the skin of the axilla, the pubic region and areolae and are stimulated during emotional stress or sexual excitement and merocrine (eccrine) sweat glands which cover most of the body. The ducts terminate at a pore on the surface of the epidermis. The function is to produce perspiration and remove small amounts of waste. Ceruminous glands are modified sudoriferous glands that secrete cerumen (ear wax) which helps prevent foreign particles from entering the ear. Mammary glands produce milk in lactating females after childbirth.

SKIN AND HOMEOSTASIS
The major function of the skin is the maintenance of normal body temperature (thermoregulation). Heat is lost or given off by radiation, conduction, convection, and evaporation. If body temperature is high, stimuli are sent to the brain which responds by sending stimuli back to the skin to produce sweat and for the blood vessels to vasodilate. As sweat evaporates, large amounts of heat energy leave the body.

Skin Wound Healing
Epidermal wounds are repaired by enlargement and migration of basal cells, contact inhibition, and division of migrating and stationary basal cells. In deep wound healing there is an inflammatory phase where blood clot unites the wound edges, epithelial cells migrate across the wound, and vasodilatation delivers phagocytes. In the migratory phase, epithelial cells beneath the scab bridge the wound, fibroblasts develop scar tissue and damaged blood vessels repair themselves. The proliferative phase continues more of the above. In the maturation phase, the scab sloughs off, blood vessels are repaired. Finally in fibrosis there is the process of scar tissue formation.

DISORDERS
Skin Cancer is usually a result of excessive sun exposure. Basal cell carcinoma is the most common and rarely metastasizes. Squamous cell carcinoma has a variable tendency to metastasize and develops from preexisting lesions on sun exposed skins. Malignant melanomas arise from melanocytes, readily metastasize, and can cause death within months especially if not treated. It is mostly seen in young women. Predisposing factors include skin type (fair skin more susceptible), amount of skin exposure, family history, age and immunologic status.