Teamwork The human body contains about 100 trillion cells. However, no one cell can carry out all the necessary bodily functions by itself. So, cells aggregate and form TISSUES Tissue  Collection of cells with a similar structure and function. The study of tissues is known as histology

Tissues There are 4 primary tissue types in the human body: Epithelial (covering/lining) Connective (support) Muscle (movement) Nervous (control) These tissues differ in the types and functions of their cells, and the products of those cells and the relative distribution of the two. Which picture on this slide corresponds to which tissue?

Epithelial Tissue Covers the surface of the body, lines the body cavities, forms the external and internal linings of most organs, and constitutes the bulk of most glands. Functions include: 1. Protection 4. Absorption 2. Secretion 5. Filtration 3. Sensory reception It’s found all over the place! On the right we have a section of skin. Where would the bulk of the epithelial tissue be found?

Characteristics of Epithelia Composed almost entirely of sheets of close-packed cells – very little extracellular material. Look at the cartoon below (it represents the epithelium that lines much of your respiratory tract) . Do you see much space between these cells? Now look at the actual slide and notice the same thing. Epithelial cells are often strongly connected to adjacent cells via tight junctions and desmosomes:

Tight junctions are protein complexes that completely encircle a cell and thus connect it to all its neighboring cells and makes it impossible for anything to pass btwn them. Common in lining of the stomach & intestines. (Why here?) Desmosomes – “spot weld” that holds cells together and enables a tissue to resist mechanical stress. Common in the epidermis and cervix. (Why these 2 areas?)

Characteristics of Epithelia Polarity Different areas of epithelial cells have different structures. (If they have different structures, they can have different ___________) The area of an epithelial cell adjacent to the exterior or to a body cavity is the apical side and the opposite area is the basal side. In the picture at the top right, what is present in the basal portion of the cell that’s not in the apical portion? Always supported by a layer of connective tissue. It’s known as the basement membrane and is labeled by arrows in the pictures at the right.

More Characteristics of Epithelia No blood vessels – it’s avascular. Can you pierce your skin with a needle without bleeding? Has the capacity to regenerate. Why is this a good thing? Considering the locations of epithelial tissue, is it likely to get damaged?

We classify epithelia based on the number of cell layers present and the shape of the cells in the apical layer. If there is only one layer of cells, the epithelium is simple. If there is more than one layer, the epithelium is stratified. There are 3 cell shapes: Squamous = flat, scale-like Cuboidal = cube-shaped Columnar = column-shaped

Epithelia Types You can see that we’ve got at least 6: Simple squamous Simple cuboidal Simple columnar Stratified squamous Stratified cuboidal Stratified columnar There are actually 2 other ones that are special – transitional epithelium and pseudostratified columnar epithelium.

Simple Squamous Epithelium Microscopic Appearance: Single layer of flattened cells, shaped like fried eggs with bulge where nucleus is located. Nucleus is flattened in the plane of the cell. Cytoplasm may be very thin and tough to see. In surface view, cells have angular contours and nuclei appear round. Above, the roundish structure is a ball of capillaries found in the kidneys known as a glomerulus. The blue arrow indicates the simple squamous epithelium surrounding it.

Simple Squamous Epithelium Locations: Air sacs (alveoli) of lungs Glomerular capsules of kidneys Some kidney tubules Lining of heart and all blood vessels Here it’s called the endothelium Serous membranes External lining of visceral organs Here it’s called the mesothelium

Endothelium The blue arrow points directly at the nucleus of an endothelial cell. What type of cell does the yellow arrow indicate?

Simple Squamous Epithelium Functions: Thinness allows material to rapidly diffuse or be transported through the epithelial layer. Example  Gases diffuse across the thin air sac epithelium in the lungs. Blood traveling to the lungs is high in CO2 and low in O2. After gas exchange in the lungs, the blood leaving is high in O2 and low in CO2 Why is thinness an asset in this situation? In pneumonia, a build-up of mucus can increase the distance that the gases must move. Does this make it easier or harder “to breathe?”

Simple Squamous Epithelium More Functions Blood is filtered through the epithelium of the kidney capillaries. This begins the process of removing waste products from the blood and modifying its ionic content. Secretion of a lubricating fluid by the epithelium making up the serous membranes (we’ll talk about them soon).

Simple Cuboidal Epithelium Microscopic Appearance: Single layer of square or round cells. Centrally-placed spherical nuclei. Apical layer often has microvilli. Microvilli are small extensions of the cell membrane that increase the surface area of the cell. You usually want a cell to have more surface area when it is involved with secretion or absorption. WHY? Above, we have a longitudinal section of a kidney tubule. Notice the almost square-shaped cells . One cell is highlighted for you in red.

Simple Cuboidal Epithelium Locations: Liver Pancreas Thyroid, salivary, and most other glands Most kidney tubules Bronchioles (small tubes within the lungs) Cross-Section of a kidney tubule

Simple Cuboidal Epithelium Functions: Absorption Kidney tubules Microvilli often present to increase the available surface area Liver Secretion Pancreas Thyroid, salivary, and most other glands Cross-section of the thyroid gland

Simple Columnar Epithelium Microscopic Appearance: Single layer of tall, narrow cells. Oval or sausage-shaped nuclei, vertically-oriented, usually located in the basal half of the cell. Secretory vesicles sometimes visible in apical portion of the cell. Microvilli occasionally present. Cilia occasionally present. Cilia are hair-like extensions of the cell membrane that can move and sweep material across the cell surface Goblet cells often interspersed. Secrete a lubricating mucus

Simple Columnar Epithelium Locations: Inner lining of stomach, intestines, and rectum. Inner lining of gallbladder Inner lining of uterus and uterine tubes Simple columnar epithelium lining the lumen of the gallbladder.

Simple Columnar Epithelium Functions: Absorption and secretion Columnar cells in small intestine have microvilli to increase the available surface area for the absorption of nutrients. Movement of egg and embryo in uterine tube. Hence the presence of cilia. Secretion of mucus. Lots of goblet cells in the large intestine so as to lubricate it and ease the passage of feces.

Stratified Squamous Epithelium Microscopic Appearance: Multiple cell layers with cells becoming flatter and flatter toward surface. In keratinized stratified squamous epithelium, the apical layers are layers of dead cells lacking nuclei and packed with the tough protein keratin. Nonkeratinized stratified squamous epithelium lacks the layers of dead cells at the surface. This is keratinized stratified squamous epithelium from the sole of the foot. It extends the length of the blue line on the left. Notice the multiple layers of clear, dead, enucleated cells.

Stratified Squamous Epithelium Location of keratinized version: Epidermis. Palms and soles of feet are typically heavily keratinized. Locations of non-keratinized version: Lining of oral cavity and surface of tongue Lining of esophagus Lining of vagina and anal canal Non-keratinized stratified squamous epithelium What do the regions that contain the non-keratinized version have in common?

Which of these is keratinized and which is non-keratinized stratified squamous epithelium?

Stratified Squamous Epithelium Functions: Protection! Keratinized version (a.k.a. dry epithelium) protects against mechanical abrasion, water loss, and pathogen entry. Keratin is very strong, waterproof, and is bacteriostatic (prevents bacteria from reproducing). Non-keratinized version (a.k.a., wet epithelium) also protects from mechanical abrasion. Eating food, swallowing, sexual intercourse, birth, defecation.

Stratified Cuboidal Epithelium Microscopic Appearance: 2 or more layers of cells. Surface layers are square or round (cuboidal). Locations: Some sweat gland ducts. Ovarian follicle Cells that surround the developing egg

Stratified Cuboidal Epithelium To the left, we have an oocyte (egg cell) surrounded by stratified cuboidal epithelium. The oocyte is circled in blue Functions: Contributes to sweat secretion. Secretion of ovarian hormones (e.g., estrogens)

Stratified Columnar Epithelium Microscopic Appearance: 2 or more layers of cells. Surface cells tall and narrow with basally located nuclei. Locations: Rare. Small portions of anal canal, pharynx, epiglottis, and male urethra. Sometimes seen in large ducts of sweat and salivary glands. Functions: Often seen where 2 other tissue types meet Structural integrity of gland ducts

Pseudostratified Columnar Epithelium Microscopic Appearance: Looks multi-layered, but it’s NOT! All cells touch the basement membrane. In stratified epithelia, only the bottom cell layer touches the basement membrane. Cells are of varying heights which gives the appearance of stratification. Nuclei are at several levels. Often has goblet cells interspersed. Cells often have cilia.

Pseudostratified Columnar Epithelium Locations: Respiratory tract from nasal cavity to bronchi. Ciliated Goblet cells Portions of male reproductive tract Non-ciliated Ciliated pseudostratified epithelium from the respiratory tract. Do you see how it appears that there are multiple layers. Do you see the cilia (indicated by the arrow)?

Pseudostratified Columnar Epithelium Functions: In the respiratory tract there are lots of mucus-secreting goblet cells. The mucus traps dust and bacteria Cilia “sweep” the bacteria-laden mucus up the respiratory tract towards the pharynx where it can be swallowed. Smoking paralyzes cilia – smokers have to cough violently to expel their mucus. Then they die!

Here, we have pathogens traveling down the pharynx trying to attack the surface cells. How can they be repelled???

The mucosal cells lining the trachea have released a flood of mucus, trapping the pathogens! Now what???

The cilia successfully sweep the pathogens up and away!

Transitional Epithelium Microscopic Appearance: Somewhat resembles stratified squamous epithelium, but the surface cells are rounded and often bulge above surface (dome-shaped). Typically 5-6 cell layers thick when relaxed and 2-3 cell layers thick when stretched. Cells may be flatter and thinner when epithelium is stretched. Some cells are binucleate, i.e., they have 2 nuclei.

Transitional Epithelia Locations: Predominant epithelium lining the urinary tract Found in part of the kidney, the ureters (tubes that connect the kidney to the urinary bladder), the urinary bladder, and part of the urethra. Functions: Stretches to allow filling of the urinary tract. Originally called “transitional” because it was thought to be an intermediate between stratified squamous and stratified columnar epithelium. This isn’t true but the name has persisted.

Easy Epithelium Review 

Glands Thyroid Gland: An endocrine gland A gland is a cell or an organ that secretes substances for use inside or outside the body. Glands are composed predominantly of epithelial tissue. Glands are broadly classified as: Endocrine Exocrine An exocrine gland Stomach: Both an exocrine and an endocrine gland

Exocrine Glands Typically secrete material into ducts that lead to the body surface or to one of the cavities that is continuous with the body surface, i.e., digestive, reproductive, respiratory tract. Exo = outside and crine = secrete. Can be multicellular or unicellular. Multicellular: Pancreas, stomach, sweat glands, salivary glands, mammary glands, sebaceous glands, etc. Unicellular: Goblet cells. The parotid gland (a salivary gland) Goblet Cell

Endocrine Glands Endo = within. Do not secrete material into ducts. Secrete chemical signals called hormones into the bloodstream where they travel through the body and affect other cells. Examples include: Thyroid, thymus, testes, ovaries, pituitary, pineal, adrenal, etc.

Exocrine Gland Structure Exocrine glands are either: Simple if their ducts do not branch. Compound if their ducts do branch. Exocrine glands are further classified by the shape of their secretory portion as: Tubular if the secretory portion is the same diameter as the duct. Alveolar if the secretory portion is like a round ball . Tubuloalveolar if it’s a combination of the 2. Compound Simple

Connective Tissue Most abundant, widely distributed, and histologically variable of the 4 primary tissue types. Consists of cells that are typically widely separated by lots of extracellular material – referred to as the extracellular matrix. In the diagram above, compare the density of cells in the epithelial layers and in the connective tissue layers. What’s the difference? Most cells are not in contact with each other but are distributed throughout the extracellular matrix.

Functions of Connective Tissue Binding of organs Support Physical protection Immune protection Movement Storage Heat production Transport What do you NOT see a lot of in this micrograph of connective tissue?

Categories of CT Loose Connective Tissue Fibrous connective tissue (a.k.a. connective tissue proper) Supporting connective tissue Fluid connective tissue Bone Blood

Fibrous Connective Tissue Most diverse type of CT. Contain extremely conspicuous fibers – hence the name, fibrous connective tissue. The illustration below shows a 3-D model of some typical CT fibers, typically made of multiple strong filamentous proteins twisted about one another. Fibrous CT consists of cells, fibers, and something called ground substance. Of these 3, which you do suppose is typically NOT that abundant?

Cells of Fibrous CT: Fibroblasts Macrophages Fibro = fat, blast = making Large, flat cells with tapered ends; produce fibers and ground substance. Inactive ones are known as fibrocytes. Macrophages Macro = large, phage = eating Large phagocytic cells that wander through connective tissue, where they engulf and destroy bacteria, other foreign particles, and dead or dying cells of our own body. They activate the immune system when they encounter foreign matter called antigens. Derived from white blood cells known as monocytes.

Cells of Fibrous CT Leukocytes Plasma Cells Leuko = white, cyte = cell White blood cells that crawl out of the bloodstream and spend the majority of their time in the CT. Many are phagocytes that wander in search of pathogens. Plasma Cells Certain white blood cells differentiate into plasma cells when they detect foreign agents. Plasma cells produce and secrete antibodies (proteins that bind to foreign molecules (antigens), thus inactivating them or marking them for future destruction.

Cells of Fibrous CT Mast Cells Adipocytes Often found in CT adjacent to blood vessels. Secrete a chemical called heparin which is an anti-coagulant and a chemical called histamine which is a vasodilator. Adipocytes Adipo = fat Appear in small clusters in some fibroconnective tissues. If they dominate an area, we call that area adipose tissue. Contain huge droplets of lipids for storage.

Fibers in Fibrous Connective Tissue: Collagenous Fibers Reticular Fibers Elastic Fibers Collagen Fibers as seen with a scanning electron microscope

Collagenous Fibers Interwoven strands of the protein collagen. Close-up of a single fiber Interwoven strands of the protein collagen. The most abundant protein in the human body. Thick fibers with great tensile strength – i.e., it’s tough to pull them apart. In fresh tissue, they have a white appearance, so they are sometimes called white fibers. In stained slides, they are often pink and they usually appear quite wavy. Tendons, ligaments, and the deep layer of the skin (the dermis) are made primarily of collagenous fibers. Multiple fibers arranged in the extracellular matrix

Reticular Fibers A thinner collagen fiber coated with glycoproteins. Stained black in the adjacent micrograph of the liver. These fibers can branch extensively and form networks or frameworks for certain organs.

Elastic Fibers Made primarily of a protein called elastin, whose coiled structure allows it to stretch and snap back like a rubber band. Account for the ability of the lungs, arteries, and skin to spring back after they are stretched. Fresh elastic fibers are yellowish and thus often called yellow fibers. In this slide, “A” is an elastic fiber – what do you suppose “B” is?

Ground Substance Gelatinous material that occupies the space between the cells and the fibers in connective tissues. Imagine some lime Jell-o that a not-so-bright chef decided to make with carrots and grapes. The carrots are like fibers, the grapes like cells, and the Jell-o itself is the ground substance/

Types of Fibrous Connective Tissue 2 types based on the relative abundance of fibers. Loose Connective Tissue Lots of ground substance and cells. Fewer fibers. Leaves lots of empty space in tissue sections. Dense Connective Tissue Fibers occupy the most space. Much lower number of cells and less ground substance. Appears closely packed in tissue sections.

Types of Loose CT 1 Areolar CT Reticular Tissue Adipose Tissue 2 3

Areolar CT Microscopic Appearance: Loose arrangement of collagenous and elastic fibers. Some reticular fibers. (All 3 fiber types.) Scattered Cells. All 6 types can be present. Abundant ground substance. Numerous blood vessels. (Highly vascular.)

Areolar CT Locations: Underlying nearly all epithelia. Surrounding blood vessels, nerves, trachea, and esophagus. Between muscles. Within mesenteries, and the visceral layers of the pericardium and the pleura.

Areolar CT Functions: Loosely binds epithelia to deeper tissues. Allows passage of nerves and blood vessels through other tissues. Provides an arena for immune defense. Blood vessels provide nutrients and waste removal for overlying epithelia.

Reticular Tissue Microscopic Appearance: Locations: Loose network of reticular fibers and a type of fibroblast known as the reticular cell. Infiltrated with numerous white blood cells. Often appears dark purple or black. Locations: Lymph nodes, spleen, thymus, and bone marrow.

Reticular Tissue Functions: The branching network of reticular fibers will form a scaffold-like framework for lymphatic organs. Spleen, thymus, and lymph nodes. Such a framework is known as a stroma. The functional tissue of these organs is known as the parenchyma.

Adipose Tissue Microscopic Appearance: Dominated by adipocytes – large, empty-looking cells with thin margins. Nucleus usually pressed against the cell membrane – signet ring appearance. Often pale. Blood vessels often present.

Adipose Tissue Locations: Subcutaneous fat beneath skin. Breast. Heart surface. Cushioning organs Kidneys Eyes

Adipose Tissue Functions: Energy storage. Thermal insulation. Shock absorption Protective cushioning for some organs.

Types of Dense CT 1 Dense regular Dense irregular 2

Dense Regular CT Microscopic Appearance: Densely packed, parallel, often wavy collagenous fibers. Slender fibroblast nuclei compressed between bundles of collagenous fibers. Scanty open space (little ground substance) Scarcity of blood vessels.

Dense Regular Connective Tissue Locations: Tendons. Ligaments. NOTE the waviness of the fibers. What function could this structural aspect provide?

Dense Regular CT Functions: Ligaments bind bone tightly to other bones. Resist stress. Tendons attach skeletal muscles to bone and transfer muscular tension to bones.

Dense Irregular CT Microscopic Appearance: Densely packed, collagenous fibers running in random directions. Compare this to dense regular CT. Scanty open space (ground substance). Few visible cells. Scarcity of blood vessels.

Dense Irregular CT Locations: Deeper portion of dermis of skin. Capsules around visceral organs such as the liver, spleen, and kidneys. Fibrous sheaths around cartilages and bones.

Dense Irregular CT Functions: Provides a durable, hard to tear structure that can withstand stresses placed in unpredictable directions. Why aren’t tendons and ligaments made of this stuff?

Supporting Connective Tissue They provide the majority of the structural support of the human body. 2 types: Cartilage Bone. 1 2

Cartilage Supportive CT with a flexible, rubbery matrix. Cells called chondroblasts secrete the matrix and surround themselves in it until they become trapped in little cavities known as lacunae (lacuna is Latin for “lake”). Once enclosed in lacunae, cells are called chondrocytes.

Cartilage Cartilage is avascular and chondrocytes depend on the diffusion of nutrients through the stiff, viscous matrix. Thus their metabolism and rate of division (a.k.a. mitosis) is low and healing of torn cartilage is a long process. It’s avascular b/c chondrocytes produce a chemical called antiangiogenesis factor that, like its name suggests, prevents the growth of blood vessels. Based on this, why do you suppose shark cartilage has been touted as a possible aid in the fight against cancer? Cartilage matrix collagenous fibers that range in thickness from invisibly fine to conspicuously coarse.

Cartilage 3 3 types (classified based on fiber differences): 2 1 Hyaline Cartilage Elastic Cartilage Fibrocartilage. 2 1

Hyaline Cartilage Microscopic Appearance: Clear, glassy matrix, often stained light blue or pink. Hyalos is Greek for glass. Fine, dispersed collagenous fibers, not usually visible. Chondrocytes often in small clusters of 3-4 cells within a single lacuna (known as cell nests or isogenous groups). Covered by a perichondrium – a fibrous sheath made of dense irregular connective tissue.

Close-up of Hyaline Cartilage. Notice the 2 cells in the single lacuna Locations: Forms the majority of the fetal skeleton. Forms boxlike structure around larynx and supportive rings around trachea and bronchi. Attaches ribs to the sternum. Forms a thin articular cartilage over the ends of bones at moveable joints. Close-up of Hyaline Cartilage. Notice the 2 cells in the single lacuna

Hyaline Cartilage Functions: Eases joint movements. Keeps airways patent. Moves vocal cords. Precursor of bone in the fetal skeleton. Structural attachment.

Elastic Cartilage Microscopic Appearance: Locations: Elastic fibers form web-like mesh amid lacunae. Always covered by a perichondrium. Locations: External ear. Epiglottis – flap of tissue that covers the tracheas when you swallow to prevent food/liquid from going down the “wrong pipe.” Eustachian tube – connects the ear to the nasopharynx.

Elastic Cartilage Functions: Provides flexible, elastic support. What happens when you bend and release your ear? A – Chondrocyte B – Matrix w/ black elastic fibers C -Lacuna

Fibrocartilage Microscopic Appearance: Parallel collagenous fibers similar to those of tendon. Rows of chondrocytes in lacunae between collagenous fibers. Chondrocytes are fewer and smaller and are not in isogenous groups. Never has a perichondrium.

Fibrocartilage Locations: Functions: Pubic symphysis – the anterior joint between the 2 halves of the pelvic girdle. Intervertebral discs that separate the bones of the spinal column. Menisci (shock-absorbing pads of cartilage) in the knee joint. At points where tendons insert on bones near articular hyaline cartilage. Functions: Resists compression and absorbs shock in some joints. Often a transitional structure between dense connective tissue and hyaline cartilage. For example, at some tendon-bone junctions.

More Connective Tissues Bone is the other supporting connective tissue. It will be discussed in detail later. Blood is a fluid connective tissue that you’ll examine in A&P II.

Muscle and Nervous Tissue Consists of 2 cell types: Neurons and glia. Detects stimuli, integrates information, and transmits signals. Muscular tissue 3 types: skeletal, cardiac, and smooth. Specialized to contract and exert forces on other tissues. Major function is the creation of movement.

Body Membranes The majority of the body’s structures are lined by epithelial membranes. Such structures include: body cavities, tracts, external surfaces of organs, and the external surface of the body itself. An epithelial membrane is defined as: A continuous multicellular sheet composed of at least 2 primary tissue types: An epithelium bound to an underlying layer of fibrous connective tissue.

Epithelial Membranes Cutaneous membrane Mucous membranes Serosa covering the heart Cutaneous membrane Mucous membranes Serous membranes Mucosa lining the duodenum (1st part of the small intestine

Cutaneous Membrane Skin! It’s an organ system consisting of a keratinized squamous epithelium (epidermis) firmly attached to a thick layer of dense irregular connective tissue (dermis). Unlike other epithelial membranes, it is exposed to the air and is a dry membrane.

Mucous Membranes (a.k.a. Mucosae) Line passageways (body cavities) that open to the external environment. Digestive, respiratory, urinary, and reproductive tracts. Wet membranes that are bathed by their own secretions or, in the case of the urinary tract, urine. Mucosae have 2 or occasionally 3 layers: Lining epithelium (simple columnar or nonkeratinized stratified squamous) is adjacent to the lumen and above the: Layer of areolar CT called the lamina propria which is sometimes above a: Layer of smooth muscle called the muscularis mucosae.

Mucous Membranes Have absorptive, secretory & protective functions. Often covered with mucus secreted by goblet cells, multicellular mucous glands, or both. Mucus is often involved in trapping foreign particles (including bacteria) or providing lubrication. The presence of mucus does not define a mucous membrane however – e.g., the mucous membrane lining the urinary tract lacks mucus. Cells modified for absorption are present in the small intestine Cells modified for protection are present mainly at those positions of the tracts closest to the exterior. Normal stomach mucosa

Serous Membranes (a.k.a. Serosae) Moist membranes found in closed ventral body cavities – not open to the exterior. Line the insides of the peritoneal, pleural, and pericardial cavities; and line the outer surfaces of some of the viscera. Consist of a simple squamous epithelium lying upon a thin layer of areolar CT. Secrete a thin, watery fluid that arises from the blood. It’s called serous fluid.

Serosae Provide an efficient means of lubricating cavity walls and organ exteriors so as to reduce the friction associated with movement. Why is this essential? The serosa lining the pleural cavity and the lung exterior are the parietal and visceral pleurae, respectively. Those of the heart are the parietal and visceral pericardium and those of the abdomen are the parietal and visceral peritoneum.

Tissue Repair 2 possibilities: Regeneration  Replacement of dead or damaged cells by the same type of cells as before. Most skin injuries heal by regeneration. The liver also regenerates quite well. Fibrosis  Replacement of damaged tissue with scar tissue, composed mainly of collagen produced by fibroblasts. Helps hold an organ together but does not restore normal function. Examples include severe cuts and burns, the healing of muscle injuries, and scarring of the lungs in tuberculosis.

Stages of Healing a Wound to the Skin Severed blood vessels bleed into the cut. Mast cells and cells damaged by the cut release histamine which dilates blood vessels, increases blood flow to the area, and makes capillaries more permeable. Blood plasma seeps into the wound carrying antibodies, clotting proteins, and blood cells.

A blood clot forms, loosely knitting the edges of the cut together and interfering with the spread of pathogens. Scab forms and seals the wound and blocks infection. Beneath it, macrophages begin to clean up tissue debris. New capillaries sprout from nearby vessels and grow into the wound. The deeper portions of the clot become infiltrated by capillaries and fibroblasts and transform into a soft mass called granulation tissue. Macrophages remove the blood clot while fibroblasts secrete collagenous fibers to replace it.

Stages of Healing a Wound to the Skin Surface epithelial cells around the wound multiply and migrate into the wounded area beneath the scab. The scab loosens and eventually falls off, and the epithelium grows thicker. Thus, the epithelium regenerates while the underlying connective tissue undergoes fibrosis.