Cell biology & histology. Study of cells: –Microscopes to study cells –Various “stains” to see organelles etc. –Various ways to look at proteins, signal.

Cell biology & histology

• Study of cells: – Microscopes to study cells– Various “stains” to see organelles etc.– Various ways to look at proteins, signal

transduction (second messengers) etc.• Antibody (bind directly to proteins)

• Chemicals sometimes bind to certain proteins

Histology

• The important thing about microscopes is NOT the magnification per se BUT resolution– The ability to see structures is more important

than the capability to magnify

Histology

Histology

• Various types of microscopes:– Light microscope

Light microscopes

Light microscope Fluorescent microscope

Histology

• Various types of microscopes:– Electron microscopes:

• Transmission electron microscope (TEM)

– “ultrathin” sections (angstrom thick…

• Scanning electron microscope (SEM)

Intestinal tissue (epithelial/absorptive/columnar)

Light microscope (40X)

TEM (1200X)

SEM (2000X)

• Organs are made of various tissues, each tissues are made of various cells that carry out a particular function

• 4 primary classes of tissues1. Epithelial tissue2. Connective tissue3. Nervous tissue4. Musculature (muscle tissue)

Tissue histology

Epithelial tissues

– Characteristics:– Located on a surface, inside or outside (epidermis) of

the body

- “flat sheet” of tightly packed cells – 1-cell layer or multi-cell layer

– NO room for blood vessels (nutrients, oxygen arrive via diffusion)

– Attached to connective tissue by the basement membrane

– Cell polarity basal and apical surfaces (the 2 sides look different and have different roles)

Epithelial tissue

Apical surface

Basal surface

Basement membrane

Connective tissue

Epithelial tissue

– “Basement membrane” = the connective area between the epithelial “sheet” and the connective tissue below the “sheet”

– Usually too thin to see on a microscope

– Often made from various proteins

– Collagen, adhesive glycoproteins (laminin, fibronectin) and Heparan sulfate (huge protein that prevents blood clots)

– 2 types of epithelial tissue1. “Simple” epithelial tissue

– 1 cell thick “sheet” of epithelial tissue– “simple squamous”– “simple cuboidal”– “simple columnar”– Usually have mucus-secreting cells (“goblet

cells”) to protect the surface with mucus

2. “Stratified” epithelial tissue– Multi-cell thick sheet of epithelial tissue– “stratified squamous”– “stratified cuboidal”– “stratified columnar”

Epithelial tissue

Epithelial tissue

Simple cuboidal epithelial tissue

Cube-shaped cells

Single-cell thickness

Simple columnar epithelial tissue

Long & narrow cells,

Single-cell thickness

– Epithelial tissue usually has a certain rate of cell turnover – Single layer epithelia are fragile and found lining

organs inside the body (blood vessels, alveoli, intestine…)

– Multilayer epithelia are tougher, regenerate easily because of the presence of stem cells. Found lining body exterior or cavities where friction is present (skin, esophagus, rectum, mouth)

Epithelial tissue

Pseudostratified ciliated epithelium

Note how some of the cells do not reach the

surface. This is why this is

called pseudostratified.

Only found in the trachea.

Stratified squamous epithelial tissue (Keratinized)

Keratinized stratified squamous

epithelia

(Layer of keratinized dead squamous cells)

Note: layer of cuboidal cells

(keratinocytes) at the base of the

living epithelial cells

“solid” to prevent water loss and infiltration by bacteria

Stratified squamous epithelial tissue (non-keratinized)

Multi-cell thick

epithelium

Note: layer of cuboidal cells at the base of

the living epithelial cells

Usually found in epithelia

that is normally moist

Stratified cuboidal epithelial tissue

Multi-cell thick

epithelium. Often found in sweat glands.

Epithelial tissue

– Secrete products (Insulin, sweat, breast milk etc.)

– Characterized as:– Exocrine (outside secreting)– Endocrine (inside secreting, think

“import”)– Have NO ducts

– Usually close to a blood vessel (often surrounded by capillary bed)

– Secrete HORMONES INTO BLOOD

Specialized epithelia: Glands

Exocrine glands

– Characteristics (outside secreting…think “export”, NOT into the blood)

- Usually empties onto the surface through a duct or “tube” of cells (sweat, milk)

- Duct can empty into another tissue (liver, pancreas intestine)

– Oddities:– Some organs can have BOTH exocrine and

endocrine glands– Liver secretes bile into the tube of the intestine

in order to rid the body of bilirubin (the broken iron/hemoglobin in red blood cells)

– Liver also secreted various proteins and hormones into the blood

– Pancreas secretes digestive enzymes and bicarbonate into the tube of the intestine to digest dietary nutrients

– Pancreas also secretes insulin into the blood

Glands

- Individual secretory cells, usually dispersed in epithelial tissue

- The tissue itself doesn’t secrete anything, but these cells are part of the tissue

- Examples:– “Goblet cells” secrete mucus

– Usually within airway epithelium, throughout the intestinal tract

– Intestinal tract also has other unicellular glands– Enteroendocrine cells (single hormone cells)– G-cells (important for acid control in the stomach)– Parietal cells (secrete acid into the stomach)

Unicellular glands

Goblet cell

Glands

– Composed of several lobes surrounded by a capsule

– Blood vessels, neural connections run through the septa

– Within each lobe smaller network of “lobules”

– Actual synthesis and secretion within the gland is carried out by specialized cells: parenchymal cells

– Normally cuboidal or columnar

Figure 5.29a

Connective tissue

Connective tissue: Roles

– Connects and binds organs and tissues together– Helps to protect organs and tissues– Supports organs and tissue structures– Important for movement– Serves as storage center– Important for heat (temperature homeostasis)– Vital for transport of various nutrients,

hormones, water etc. throughout the body

Connective tissue: Basic structures3 basic components:

- Cells: - Fibroblasts (synthesize fibers and ground substance)- Macrophages (fight off bacteria, phagocytize damaged cells..

- Mast cells: rich in histamine and heparin

- Fibers- Collagen: thickest, strongest and most abundant- Elastin: thinner than collagen, able to stretch without breaking and can recoil- Reticulin: thin, forms a mesh sieves for retaining bacteria, cancer cells

- Ground substance- Gelatinous substance containing various proteins. The type and amount of

proteins, the presence of salts give rise to various types of tissue* “soft jelly”: aerolar, reticular and adipose tissue* “hard jelly”: cartilage* “mineralized jelly”: bone

* Fibers + ground substance = matrix

– Fibrous connective tissues– Connect and bind organs together (loose or areolar connective

tissue dense connective tissue, tendon, ligament, adipose tissue)

– Variable amount of gelatinous ground substance, variable amounts and types of fibers

– Supportive connective tissues: – Support and protect (cartilage and bone)– Specialized ground substance (chondroitin for cartilage,

mineralized for bones)

– Fluid connective tissues– Blood: plasma is the ground substance

Connective tissue: Organization

Loose connective tissue

-Sometimes called “areolar connective tissue”.

- “Soft gelatinous ground substance, moderate amount of fibers.

-Under microscope, appears to have ‘air” or space between the many fibers

- Found under the skin, between organs, blood vessels

- Adipose tissue is a specialized tissue (fibroblast adipocyte)

- Almost EVERY epithelial tissue will rest on a form of areolar tissue “bed”

- Open structure allows leukocytes to easily enter and move

Adipose tissue- Adipose cells (fat cells, a connective tissue cell type) dominate

- Normally 70-120 M long, but in obese patients, can be up to 5X longer!

- Body’s primary energy reserve (fat/triglyceride storage)

- Good thermal insulatorGenerally white (recall brown fat in infants…for heat

production)

– “Reticular tissue”: sponge-like / meshwork

– Found in lymph nodes, spleen, thymus, bone marrow

Reticular Connective tissue

Dense Connective tissue

• Collagen fibers are densely packed• Minimal amount of ground substance• Fibroblasts mostly

• Organized into regular and Irregular dense connective tissue

Dense irregular connective tissue:

-

Dense regular connective tissue- Tendon, ligaments:

collagen fibers are tightly packed in parallel

- Vocal cords: Elastin fibers in addition to collagen

- Sheets of yellow elastic tissue: Line the larger arteries to permit expansion and contraction during heart pumping

– Thick bundles of collagen, randomly placed

• Permits tissue to handle unpredictable stresses

• Most of the dermis (skin) is connected to “dense irregular connective tissue”

Dense Irregular Connective tissue

Dense irregular connective tissue vs. areolar connective tissue

Dense irregular fibrous connective tissue

Note smaller “spaces”

Areolar fibrous connective tissue

Note larger “spaces”

– Cartilage: supportive connective tissue– Extracellular matrix is rubbery and flexible– Starts as chondroblast cells that secrete

extracellular matrix (rich in chondroitin sulfate)

– Matrix surrounds the chrondroblast until it forms a complete “shell” (shell = lacunae)

– Cell inside lacunae = “chondrocyte”

– Usually no vasculature (blood vessels) in cartilage

– Nutrient delivery, waste removal require diffusion through the extracellular matrix

Connective tissue

– Cartilage: supportive connective tissue– 3 types of cartilage:

– Hyaline cartilage: clear, glossy looking (from the fine mesh of collagen fibers)

– Usually at joints– Acts as a lubricant in the joint

– Elastic cartilage: in your ear & nose– Flexible, elastic support structural tissue

– Fibrocartilage: coarse (can see collagen fibers)

– Between vertebrate– In meniscus (disc in your knee)– Where tendon enters bone

Connective tissue

– Cartilage: – Both hyaline cartilage and elastic

cartilage are often “sheathed” in “irregular fibrous connective tissue”

– Called “perichondrium”

– At each joint, there are usually “spare” chondroblasts that serve to help maintain the cartilage over life

Supportive Connective tissue

Hyaline cartilage (connective tissue)

Note the clear extracellular matrix

Elastic cartilage (connective tissue)

Note the fibrous extracellular matrix

Fibrocartilage (connective tissue)

Note the parallel fibers of the extracellular matrix and no perichondrum

– Bone: – Has 2 meanings:

– Organ: femur, mandible– Not just a “bone” but also a source of stem cells in

the marrow that are important for blood cells

– Osseous tissue: the mass of bone – 2 types:– Spongy bone is at the “head” of the long bones

(head of the femur etc.)

– Compact/dense bone: more dense, calcified bone with NO visible spaces

– The general external surface of bone

– Normally covered by a fibrous tissue = periosteum

Supportive Connective tissue

Spongy (cancellous) bone

• Located in flat, irregular bones, long bone extremities (epiphysis)

• Structure: irregular lattice of bone

• Spaces within the lattice filled with red bone marrow

• The arched structure of the lattice gives it lightness and strentgh

Compact boneLocated on external aspects of all bones

Its thickness depends on the bone

Structure: Arranged into cylinders, the osteons, organized around a canal (“haversian” / “osteonic canals

- Blood vessels, nerves etc. run through the canal

The matrix of bone is deposited like a tree trunk (in rings called lamellae)

Mature bone cells (osteocytes) live between each lamellae / ring,.. Each lamellae is connected by a “canal” (canaliculi) that allows osteocytes to communicate with each other

Bone structure: Osteon

Fluid Connective tissue

– Blood: – Transports cells,

nutrients, waste between organs/tissues

– 2 components– Ground substance =

plasma

– Formed elements = cells & cell fragments

Formed elements of blood:– Red blood cells (erythrocytes): largest

population– No nuclei

– Transport O2 to tissue, remove CO2 from tissue

– Leukocytes: white blood cells– Most move in and out of organs / tissues, between

blood and lymph

– Despite movement, majority of their lives are spend in some region of connective tissue

– Platelets: cell fragments

Blood

Nervous tissue

– Excitatory tissue– Neurons: the actual “excitable” cells

that control, signal and sense

– Neuroglia (glial cells): more numerous than neurons

– Serve to protect, support and nourish the neuron cells

Nervous tissue

Nervous tissue– Excitatory tissue

– Neurons: the actual “excitable” cells that control, signal and sense

– Cell body = soma

– Numerous small extensions = dendrites

– Single long extension = axon

– Some neurons can extend from the brain to your foot!

Muscle tissue

– Excitatory tissue (like nervous tissue)

– Elongated cells that are specialized in contracting

– Prime goal is to exert external force on another tissue

• Three types of muscles:– Skeletal muscle– Cardiac muscle– Visceral muscle

Muscle tissue

Muscle tissueSkeletal muscle:

- Long, multinucleated cells (syncitium)

- Usually attached to bone- EXCEPT tongue, upper

esophagus, anus-Described as “striated and

voluntary”- Striated = you can see

lines or striations (actin / myosin cytoskeleton arranged in lines)

- Voluntary = under conscious control

Striated muscle tissue

Note the multi-nuclear cells and

striations

Muscle tissueCardiac muscle:

- ONLY in heart

- Striated, but cells are shorter than skeletal muscle

- Cells also only have 1 nucleus

- Joined end-to-end by “intercalated discs”

- Permit electrical connections between each muscle cell to aid in coordinating contraction

- Called “involuntary” because not under conscious control

Muscle tissueSmooth muscle:

- Lacks striations (actin cytoskeleton isn’t as dense or linear)

- Involuntary (not under conscious control)

- Fusiform (thick in the middle, thinner at the ends)

- Location: around the eye, throughout the intestinal tract, respiratory system, urinary tract

– Membrane in this context does not refer to “cell membrane” but TISSUE MEMBRANE

– Various tissues are arranged into membanes throughout the body

– Cutaneous membrane: skin

– Mucus membrane: external openings

– Serous membrane: lining certain organs

– Endothelium: line the blood vessel system

– Synovial membrane: holds synovial fluid (joint lubricant)

Membranes

– Cutaneous membrane:– Stratified squamous epithelium resting on a bed

of connective tissue– Dry surface: dead cells that prevent invading

organisms from penetrating into the body

– Mucus membrane:– Usually line the entrances to the body (oral,

anal, reproductive, cardiovascular)– Usually 3 layers of tissue types:

– Epithelium– Areolar connective tissue– Muscularis (muscle tissue)

Membranes

– Serous membrane:– Simple squamous epithelial tissue

(mesothelium) on a THIN layer of areolar connective tissue

– Produces watery fluid (serous fluid) similar to blood plasma (BUT NOT BLOOD PLASMA)

– Lines the inside of some body cavities (peritoneum, pericardium, pleura)

Membranes

Membranes– Endothelium:

- Simple squamous epithelial tissue on a thin layer of areolar connective tissue that all rests on an elastic connective tissue sheet

- All 3-layers = “tunica interna” when rolled up as a blood vessel

- All 3-layers = “endocardium” when lining the heart

– Synovial membrane:– Highly specialized epithelial tissue supported by

areolar connective tissue– secretes and retains synovial fluid to lubricate joints

Membranes

– All tissues originate from one of the 3 primary tissue “layers” forming during fetal development– Ectoderm: Outer layer that will eventually develop

into the epidermis and nervous system

– Endoderm: Inner layer that will develop into the gastrointestinal and cardiovascular system

– Mesoderm: lies between the ecto- and endoderm layers

Origin of tissues:Embryonic tissue

• Growth of tissue can be through two mechanisms

– Hyperplasia: increase cell number– Hypertrophy: increase cell size

– A neoplasia refers to tumor development: abnormal, nonfunctional tissue growth

Tissue growth

• Some tissues are able to grow AND develop– Change from 1 tissue type to another– Embryonic tissue can grow and develop into a

fetus, and eventually in infant– Metaplasia: when tissue changes from one form to

another– Esophageal reflux disease: constant acid reflux can cause

esophagus to undergo metaplasia from stratified squamous epithelium to columnar epithelium (Barrett’s esophagus…a pre-carcinomic risk)

Tissue growth

Stem cells- Stem cells: undifferentiated

cells that can divide to give rise to a specialized cell type (can give rise to tissue)

- Totipotent stem cells: can become anything involved in fetal development

- Pluripotent stem cells: Can develop into any embryonic cell (but not into accessory organ types like placenta or umbilicus)

- Adult stem cells:

• Adult stem cell– Small number in the infant/adult

– Divides by mitosis to produce 1 original stem cell and 1 daughter cell that can develop

• Development can be “multipotent”…can develop into 2 or 3 different cell types (but NOT just any type of cell)

– Present in the bone marrow (blood cell production) and intestinal tract (4 types of cells in the intestinal epithelium)

• Development can be limited to “unipotent”…only 1 cell type is possible

– Sperm, egg, keratinocytes in epithelium

Tissue growth

• Repair of tissue can be carried out by 2 mechanisms– Regeneration: replacement of dead/damaged cells with

cells of the same type• Restores function to the organ

• Liver is able to do this quite well

– Fibrosis: replacement of dead/damaged cells with scar tissue

• Scar tissue = collagen + fibroblasts

• Will hold organ / tissue together, but does not restore function

• Healing damaged muscle, skin etc.

Tissue repair

Tissue repair• Presence of

granualtions =

• Tissues usually can die by a number of different mechanisms

– Atrophy: shrinkage due to loss of size or cell number

• Senile atrophy: loss due to normal aging

• Disuse atrophy: lack of use of the organ / tissue

– Necrosis: premature, pathological cell death• Cells die by lysis

• Often after trauma, infection

Tissue death

Tissue death • Gangrene: necrosis by certain

strain of bacteria

• Infarction: sudden death of tissue (heart attack)

• Decubis ulcer: “bed sore”…constant pressure on a point that results in cutting off blood supply to the area and subsequent tissue necrosis