Anatomy and Physiology

A system always involves____

Multiple elements that are connected in specific ways.

A system always displays ____

Novel properties that none of the parts possess.

Intelligence of a biological system is embedded in:

The design of the elements and the connections between the elements.

Anatomy

Structural connections

Physiology

Functional connections

Types of Proteins

• Enzymes

• Receptors

• Channels

• Transporters

• Motors

• Highways

• Adhesives

• Building blocks

Protein structure is sensitive to the physical and chemical factors in their environment including:

• Detergents

• pH

• Temperature

• Pressure

• Solutes

Homeostasis

A stable internal environment that supports the structure and function of proteins. Essential for survival.

Protein function depends entirely on ___

3-D structure

Thermoregulation

Maintaining homeostasis in body temperature

Heat receptor examples

TRPV1, TRPV2, TRPV3, TRPV4

Cold receptor examples

TRPA1, TRPM8, TRPC5

Mechanism of temperature receptor activation

Temperature changes alter ion channel structure => opening or closing

Effectors for changing temperatures

• Skeletal muscles

• Brown fat

• Blood vessels

• Sweat glands

Thermoregulatory center

In the hypothalamus

W neurons

• Stimulated by warm sensitive receptors

• Inhibited by cold sensitive receptors

• Stimulate W efferent neurons

• Inhibits C efferent neurons

I neurons

• Insensitive to temp

• Auto fire at a stable frequency (stabilizes the thermoregulatory network by providing steady background activity)

• Stimulates C efferent neurons

• Inhibits W efferent neurons

Number of steps in fever mechanism

6

Step 1 of Fever mechanism

Step 1: Trigger

• Exogenous pyrogens activate immune cells

Example of exogenous pyrogen

LPS

Example of immune cells (fever mechanism)

• Macrophages

• Dendritic cells

Step 2 of Fever mechanism

Step 2: Release of Endogenous Pyrogens

• Activates immune cells release cytokines

Example of cytokines (Fever mechanism)

• IL-1β

• IL-6

• TNF-α

Step 3 of Fever Mechanism

Step 3: Signal to the Hypothalamus

• Cytokines to to hypothalamus and stimulate expression of COX-2

Step 4 of Fever Mechanism

Step 4: Cox-2 converts arachidonic acid to prostaglandins especially prostaglandin E₂(PGE-2)

Step 5 of Fever mechanism

Step 5: PGE2 Action on the hypothalamus

• PGE2 binds to EP3 receptors on warm sensitive neurons in the hypothalamus

• Leading to reduced firing of warm sensitive neurons

Step 6 of Fever mechanism

Step 6: Physiological response (Set-point is raised)

• Vasoconstriction

• Shivering

• Behavioral changes

=> Fever develops

Positive feedback loop

Response to a stimulus amplifies the original stimulus, moving the system further from homeostasis

Examples of positive feedback loop

• Blood clotting

• Childbirth

• Lactation

Negative feedback loop

Response reduces or counteracts the original stimulus helping maintain homeostasis

Example of negative feedback loops

• Thermoregulation

• Blood glucose regulation

• Blood pressure regulation

• Thyroid hormone regulation

LECTURE 2- TISSUES EPITHELIUM

Four types of Human Tissues

Epithelial tissue: Forms boundaries

Muscle tissue: Enables contraction

Nervous tissue: Facilitates communication and control

Connective tissue: Provides connection and support

Epithelial tissue/Epithelium

A sheet of cells that covers a body surface or lines a body cavity

1 Cell Layer Epithelium

Simple Epithelium

More than 1 Cell Layer Epithelium

Stratified

Scalelike Cell shape

Squamous

Cubelike Cell shape

Cuboidal

Column-shaped Cell

Columnar

Structure supports___

Function

Simple squamous epithelia function

• For exchange of material by diffusion and filtration

• In sites where protection is not important

• Secretes lubricating substances in serosae

Simple squamous epithelia location

• Kidney glomeruli, air sacs of lungs (alveoli), lining of heart, blood vessels, lymphatic vessels, lining of ventral body cavity (serosae).

Simple cuboidal epithelia function

• Secretion and absorption

Simple cuboidal epithelia location

• Kidney tubules, ducts and secretory portions of small glands, ovary surface

Simple columnar epithelia function

• Absorption, secretion of mucus, enzymes, and other substance

• Ciliated type propels mucus (or reproductive cells) by ciliary action

Simple columnar epithelia location

• Non-ciliated type lines most of the digestive tract (stomach to anal canal), gallbladder, and excretory ducts of some glands

• Ciliated type lines small bronchi, uterine tubes and some regions of the uterus

Pseudostratified columnar epithelia function

• Secretion, particularly of mucus

• Propulsion of mucus by ciliary action

Pseudostratified columnar epithelia location

• Non-ciliated type in male’s sperm-carrying ducts and ducts of large glands

• Ciliated variety lines the trachea, most of the upper respiratory tract

Stratified squamous epithelia function

• Protects underlying tissues in areas subject to abrasion

Stratified squamous epithelia location

• Nonkeratinized type forms the moist linings of the esophagus, mouth, and vagina

• Keratinized variety forms the epidermis of the skin (a dry membrane)

Transitional epithelia function

• Stretches readily and permits distension of urinary organs by contained urine

Transitional epithelia location

• Lines the ureters, bladder, and part of the urethra

Common functions of epithelial tissue

1. Forms barriers

   • Skin

   • Endothelium of blood vessels

   • Blood brain barrier

2. Secretion

3. Absorption

4. Sensation

External boundaries

• Separate the body from external environment

Internal boundaries

• Separate one part of the body from another

Exocrine glands: secretory epithelium surrounds a ___

Duct, which empties their secretion out of the body

Exocrine gland secretion examples

• Sweat glands

• Salivary glands

• Sebaceous glands

• Lacrimal glands

• Mammary glands

• Exocrine pancreas

• Stomach and intestinal glands

Endocrine glands: are ____

• Ductless, they release their secretion (hormones) into the blood- circulatory system.

Endocrine glands example

• Pituitary gland

• Adrenal gland

• Thyroid gland

Key characteristics of Epithelial tissues

• Polarity: apical and basal

• Specialized junctions

• Supported by connective tissue: basement membrane (an acellular material secreted partly by the epithelial cells and connective tissue cells)

• Avascular but innervated: depend on diffusion of nutrients from underlying connective tissue. (The epidermis is Aneural)

• Regeneration: epithelial cells can easily divide to regenerate the tissue

Cell junction types

• Tight Junctions

• Adherens junctions

• Desmosomes

• Hemidesmosomes

• Gap junctions

Tight junctions Function

Seal space between cells to prevent paracellular leakage

Tight junctions key proteins

Claudins, occludins

Tight junctions typical distributions in epithelium

• Apical region of absorptive epithelia to maintain polarity

• E.g. intestinal lining, kidney tubules

Adherens junctions Function

Mechanical link between actin cytoskeletons of adjacent cells. Belt like

Adherens junctions key proteins

Cadherins (E cadherins), catenins

Adherens junctions typical distribution in epithelium

Just below tight junctions in most simple epithelia to maintain tissue integrity

eg. intestinal epithelium

Desmosomes function

Strong spot-like adhesion, resist mechanical stress. Spot adhesion.

Desmosomes key protein

Desmoglein, desmocollin (cadherins)

Desmosomes typical distribution in epithelium

Abundant in stratified squamous epithelium

Hemidesmosomes function

Anchor basal surface of epithelial cells to basement membrane

Hemidesmosomes key protein

Integrins, BP180, BP230

Hemidesmosomes typical distribution in epithelium

Basal surface of epidermis and other epithelia under mechanical stress

Gap junctions function

Direct communication via ion and small molecule exchange

Gap junctions key proteins

Connexins

Gap junctions typical distribution in epithelium

Found in epithelia that coordinate activity

• E.g. ciliated epithelium of respiratory tract, secretory epithelium of glands.

Cell polarity

A structural and functional asymmetry exists within the cell.

Three surfaces of a cell

• Apical surfaces: faces the lumen of external space

• Lateral surface

• Basal surface: adheres to basement membrane (layers of extracellular matrix)

Epithelial tissue in the small intestine have specialized protein transporter that _____

Recognize and absorb various nutrients.

Apical-Basal Polarity

Protein machinery is localized to different surfaces, ensuring the proper execution of specific functions.

Villi+Microvilli increase the surface area by ___ x compared to a smooth tube

600

Epithelial tissue in the gastric gland have specialized protein tools for _____

generating acids and secretion.

To ensure the proper execution of specific function, there is Apical-basal polarity.

(4 steps) Secretion of HCl by parietal cells of gastric gland

1. The enzyme carbonic anhydrase catalyzes the formation of carbonic acid (H₂CO₃) from CO2 and H2O. They H2CO3 dissociates and HCO3- (bicarbonate ion), and H+

2. The protons are actively (using ATP) pumped into the stomach lumen

3. HCO3- transported to blood in exchange for Cl- from the blood. This is called Chloride Shift.

4. Cl- is then transported into the lumen via a Cl- channel.

Endothelium main functions

• Regulates vascular tone by releasing signaling molecules.

• Involved in angiogenesis (formation of new blood vessels)

• Facilitates immune cell trafficking

• Regulate blood clotting

• In capillaries, its a selective barrier between blood and tissues

Three types of capillaries

1. Continuous capillaries

2. Fenestrated capillaries

3. Sinusoidal capillaries

Continuous capillaries characteristics

• Have tight junctions, forming barrier as in the blood brain barrier (BBB)

• E.g. in the brain, lungs

Fenestrated capillaries characteristics

• Have small pores within endothelial cells to allow greater permeability.

• E.g. in kidneys, intestines

Sinusoidal capillaries characteristics

• Have large gaps between cells to allow the passage of larger molecules like proteins and cells

• E.g. in liver, spleen

Layers of the epidermis

1. Stratum corneum

2. Stratum lucidum (thick skin only)

3. Stratum granulosum

4. Stratum spinosum

5. Stratum basale

Stratum corneum

• 20-30 layers of dead keratinocytes, shedding

Stratum lucidum

• In response to mechanical stress (friction, pressure), keratinocytes are genetically programmed to pass through an extra transitional stage

• Packed with eleidin, a clear, lipid-rich form of keratin derived from keratohyalin granules

Stratum granulosum

• Accumulate lamellar granules & keratohyalin granules (makes skin waterproof)

• Apoptosis occurs, cells become flat and die

Stratum spinosum

• Start to produce keratin and release glycolipids (makes skin water proof)

• Desmosomes (“spines”) connect cells tightly

• Provide protection against penetration by irritants and pathogens and loss of water

Stratum basale

• Mitotic division, stem cells

CONNECTIVE TISSUE

Lecture 3

Two main parts of connective tissue

• Cells

• Matrix (abundant)

Two main parts of connective tissue matrix

• Fibers

• Ground substance

Three main types of connective tissue fibers

• Collagen fiber (collagen proteins)- resist stretch

• Elastic fiber (elastin + fibrillin proteins)- stretch and recoil

• Reticular fiber (collagen proteins)- delicate mesh

Two main types of connective tissue ground substance

• Polysaccharide- negatively charged so fills space with H2O

• Proteoglycans- provides cushioning