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Online Anatomy Module 1

INTRO & TERMS CELL EPITHELIUM CONNECTIVE TISSUE MUSCLE NERVOUS SYSTEM AXIAL SKELETON APPENDICULAR SKELETON MUSCLES EMBRYOLOGY

SOFT CONNECTIVE TISSUES

The ‘soft’ distinction being made here is between cartilage and bone as firm connective tissues and the softer ones, such as fatty tissue, ligament, dermis of skin, etc.

Articular cartilage Marrow Dermis Hypodermis Bone Ligament & Tendon Text reading in Marieb is pp. 79-82 Joint capsule Muscle Periosteum

SMALL-GUT CONNECTIVE TISSUE ROLES

VILLI covered with simple columnar epithelium on a core of very loose-textured CT Extensive area of fairly loose textured CT holding the lining to the muscle of the wall Another layer of connective tissue outside and assisting the muscle by carrying vessels, nerves, and just holding things together

transport

GUT VILLUS

Simple Columnar Epithelium

absorbing ENTEROCYTES mucus-secreting

GOBLET CELLS BASAL LAMINA VILLUS CORE of: loose connective tissue C T cells lymphatic capillary capillaries

CONNECTIVE TISSUE ROLES I Connect/Support Transport/Nourish

EPITHELIUM

}

Connective tissue VESSEL The connective tissue under an epithelium is termed the LAMINA PROPRIA (adjacent layer). Where it is more intermingled with epithelial cells, as in a gland, it becomes the STROMA.

THE CELL: Some basics IV

Cells do not operate in isolation. They have surroundings and attachments - to other cells and materials outside them Surface specializations of the plasmalemma to interact with tube content Cell-cell attachments more specializations of the plasmalemma or ‘cell membrane’ Attachments to materials outside the cell in the EXTRA CELLULAR MATRIX

THE CELL: Some basics V

The cells shown here form a single layer. It holds this form in part by the cells’ fastening at the base to a sticky porous membrane named a BASAL LAMINA or a BASEMENT MEMBRANE

Basement membrane

Basement membrane itself attaches to connective tssue below it

THE CELL: Some basics VI

Cell are soft and squishy. Think jellyfish - it needs water to support it. To holds us together & for life on land and the ability to move and manipulate things, we need a strong , in place rigid, extracellular matrix.

Cells of the soft connective tissues , cartilage, and bone make materials that interact outside the cells to provide strength and support via EXTRA-CELLULAR MATRIX (ECM)

CONNECTIVE TISSUE MATERIALS Cells of the soft connective tissues make materials that interact outside the cells to provide strength and support

One very special product is the basement membrane to support epithelial cells

The bulk of the connective-tissue matrix comprises:

bound

water, meaning that it does not slosh as you move molecules to bind the water and hold other components together long fibers to give strength and elasticity to the tissue other sticky molecules - glycoproteins - to hold the fibers in place

CONNECTIVE TISSUE MATERIALS: Details

bound

water molecules to bind the water - PROTEOGLYCANS long fibers - COLLAGEN (strength) & ELASTIC other sticky molecules - GLYCOPROTEINS

MORE CONNECTIVE TISSUE ROLES

While the matrix properties allow the tissue to support & connect , other things are going on.

The matrix offers an ideal place for microorganisms to grow, so that connective tissues have a range of defensive cells and are a battle-ground of great medical significance The matrix stores a number of useful materials, including ones to help control defensive reactions and adjacent tissues. And a special cell - the fat cell/ adipocyte - stores fats/lipids for energy & growth Connective tissue readily repair themselves & react to damage to other tissues

CONNECTIVE TISSUE ROLES Connect/Support Transport/Nourish Defend Storage Control Repair

EPITHELIUM

}

Connective tissue VESSEL

CONNECTIVE TISSUE COMPONENTS

signals

Synthetic cells

for structural macromolecules, e.g. for building

fibers

collagen elastic

Defensive cells

Cells lie in, attach to, & are supported by the EXTRACELLULAR MATRIX (ECM) of fibers & ‘ground substances’

DEFENSIVE CONNECTIVE TISSUE CELLS

The matrix offers an ideal place for microorganisms to grow (food, warmth) so connective tissues have a range of defensive cells, and are a battle-ground of great medical significance

MACROPHAGE (M

F

) eats dead & bad stuff; coordinates defense PLASMA CELL (from B Lymphocyte) makes & secretes antibodies (Igs) MAST CELL triggers defensive reaction/ inflammation

(degranulates)

MACROPHAGE (M

F

) PLASMA CELL

Golgi Cartwheel nucleus much GER

[Peripheral clumps of heterochromatin]

lysosomes

MAST CELL

Big granules

MACROPHAGE M

f

POD

Macrophage can:

attach to fibers;

release & crawl around;

extend projections - podia; recognize bad things; wrap its podia around them; eat the stuff (phagocytosis); digest it with lysosomes

Collagen fiber

MACROPHAGE M

F

FOCAL ADHESION - attachment

lysosome -POD Actin monomers & filaments in controlled flux

for crawling, podia-extension, & phagocytosis

MACROPHAGE /M

F

receptors

Pathway for phagocytosis & lysosomal digestion

lysosome POD Membrane

scavenger receptors

to recognize targets

CONTEXT FOR MAST CELL ACTIONS

Invader

EPITHELIUM

VESSEL

Defensive white blood cells & chemicals in vessel need to get out to counteract the invader }

CT MAST CELL

Triggered by invader Releases granules Granule agents act on vessels & white blood cells to encourage exit

MAST CELL

MAST-CELL ACTIVATION

IgE antibody molecules Fc e Receptor for a region of the Ig molecule

Invader

IgE binding triggers degranulation

IgE binding triggers degranulation

MAST-CELL ACTIONS I

Granules contain many agents (& proteoglycans), e.g.

HISTAMINE to increase permeability & loosen wall MAST CELL of Vessel CHEMOKINES to attract leukocytes out into CT

MAST-CELL ACTIONS II

Heparin & proteoglycans influence signaling MAST CELL Chemokine receptors White blood cell Vessel Defensive blood chemicals, e.g., Complement

CONNECTIVE-TISSUE CELLS: TWO MORE TYPES MACROPHAGE (M

F

)

lysosomes

PLASMA CELL

Golgi

MAST CELL FIBROBLAST Fibroblast is an elongated cell amidst the fibers etc it has made

Cartwheel nucleus much GER

[Peripheral clumps of heterochromatin] Big granules ADIPOCYTE Adipocyte/ fat cell grows to be very large, with a thin shell of cytoplasm around a huge fat droplet

fat droplet

Collagen I trimer Three intertwined helices

COLLAGEN - Molecule to Fiber

Last of the spinning. Hereafter, strength comes from cross-linking & glueing “Glueing” & control of fibril & fiber width are done by high-# collagens, glycoproteins, and proteoglycans Assembly of trimers end-to-end, side-by-side, but staggered to build a cross-banded fibril Further glueing of fibrils to make a FIBER

CONNECTIVE TISSUES

ROLES CELLS EC MATRIX WORKING CONTEXTS

TYPES

CONNECTIVE-TISSUE CELLS MACROPHAGE (M

F

) FIBROBLAST

lysosomes

PLASMA CELL

Golgi Cartwheel nucleus much GER

[Peripheral clumps of heterochromatin] ADIPOCYTE

One huge fat droplet

MAST CELL

Big granules

ROLES OF CONNECTIVE-TISSUE CELLS FIBROBLAST makes ECM; destroys ECM MACROPHAGE (M

F

) eats dead & bad stuff; coordinates defense PLASMA CELL (from B Lymphocyte) makes & secretes antibodies (Igs) MAST CELL triggers defensive reaction/ inflammation

(degranulates)

ADIPOCYTE stores & releases ‘energy’ (& brown adipocytes can make heat)

ROLES OF CONNECTIVE-TISSUE CELLS FIBROBLAST MACROPHAGE (M

F

) PLASMA CELL) MAST CELL ADIPOCYTE

CONNECTIVE TISSUE COMPONENTS: Cells & ECM Fibroblast Osteoblast Chondroblast

synthetic

Structural & other ECM molecules Macrophage Plasma cell Lymphocyte Mast cell

defensive

Fat cell or Adipocyte

storage

What are these?

CONNECTIVE TISSUE COMPONENTS: Cells & ECM Fibroblast

synthetic

Structural & other ECM molecules

Fibroblasts rework the matrix that they have formed by carefully breaking it down, while synthesizing new materials to adapt to greater or otherwise changed loads Collagen FIBERS Reticular Elastic BINDERS & CONTROLLERS: Sticky glycoproteins Water-binding proteoglycans Destructive enzymes Enzyme inhibitors Signaling Molecules

CONNECTIVE TISSUE ‘GROUND SUBSTANCE’ Fibroblast

Structural & other ECM molecules

‘Ground substance’ is the old-fashioned name for the non-fiber extracellular part of connective tissue

Collagen FIBERS Reticular Elastic BINDERS & CONTROLLERS: Sticky glycoproteins Water-binding proteoglycans Destructive enzymes Enzyme inhibitors Signaling Molecules

CONNECTIVE T. COMPONENTS: Reticular fibers Collagen Fibroblast

synthetic

Structural & other ECM molecules

FIBERS Reticular Elastic Reticular fibers are a delicate version of collagen fibers, used so as to support cells, but not interfere with blood-cell interactions, e.g., in liver Reticular fibers

HEPATOCYTES

blood vessel blood

Endothelial cells lining vessel

TYPES OF CONNECTIVE TISSUE

Around the body different combinations of these cells, fibers, and other ECM materials are needed The starting embryonic tissue is mesenchyme - jelly like, with a few thin fibers and unspecialized mesenchymal cells As the mesenchymal cells become fibroblasts, these can make the tissue, by fiber packing, loose or dense The fibroblasts may align the fibers parallel to make a regular tissue ,or arrange them in different orientations - an irregular tissue Elsewhere, mesenchymal cells may become fat cells making an adipose tissue The tissue requirements also vary when the tissue is somatic (in body wall or limb) rather than visceral

TYPES OF CONNECTIVE TISSUE

SOMATIC VISCERAL

Loose irregular

Dense irregular Reticular Adipose Elastic Dense regular

Loose irregular

Dense irregular Reticular Adipose Elastic In the beginning was Mesenchyme

MESENCHYME

signals

Mesenchymal cells, mostly synthetic

for structural macromolecules, e.g. for building

fibers immature collagen

Much ground substance e.g., hyaluronan (a GAG)

Mesenchymal cells - precursors/ progenitors of some differentiated CT cells, e.g., fibroblasts

Mesenchyme takes up & commits space to be a future connective tissue, and has modest jelly like mechanical properties of its own

CONNECTIVE TISSUES: Contexts

Tube Man Head -

modification of body wall + brain & special senses + start of two tubes

Soma -

body wall & the limbs

- - - V i s c e r a

tubes, modified tubes, & accessory organs

o Al

re

cvl - u

Worm Woman

diaphragm

Bone SOMATIC STRUCTURES Articular cartilage Dermis Marrow Hypodermis Ligament & Tendon Joint capsule Muscle Periosteum

SOMATIC CONNECTIVE TISSUES: Dense regular Ligament

&

Tendon

dense regular

Muscle

DENSE REGULAR CONNECTIVE TISSUE

Bundles of

{

thick collagen I fibers

{

Elongated fibroblasts Looser vascular CT between the bundles

DENSE REGULAR CONNECTIVE TISSUE: Tendon

Bundles of

{

thick collagen I fibers

{

Elongated fibroblasts - tenocytes Looser vascular CT between the bundles -

endotendinuem

If the tissue is in a tendon, some special names (not to be learned) are used

SOMATIC CONNECTIVE TISSUES: Reticular & Adipose Marrow

reticular

Hypodermis

adipose

Muscle

WHITE ADIPOSE TISSUE

Capillary

Adipocyte

Reticular fibers Fat cell

CONNECTIVE TISSUE - Mechanical functions The stringy strength of collagen allows a variety of mechanical actions

Supporting - ligament Binding - ligament Restraining - ligament Directing - tendon Separating - fascia For firmer support something has to be added to the collagen to make cartilage or bone The large soft cells of adipose tissue can be confined in sheets of collagenous tissue for

Padding - fat pad

SOMATIC CONNECTIVE TISSUES: Dense irregular

The collagen fibers are arranged in various directions for different pulls on the tissue Dermis

dense irregular

Joint capsule

dense irregular

Muscle Periosteum

dense irregular

SOMATIC CONNECTIVE TISSUES: Loose irregular

marks

loose irregular

filling in between more solid structures & allowing them freedom of movement Muscle

TYPES OF CONNECTIVE TISSUE

SOMATIC

Loose irregular (Areolar)

between more solid structures Dense irregular joint capsule, periosteum, dermis Dense regular tendon, ligament Adipose hypodermis Elastic elastic ligament (inconspicuous in man)

SOMATIC CONNECTIVE TISSUES

Articular cartilage (

hyaline)

Bone

Marrow

reticular loose irregular

Dermis

dense irregular

Hypodermis

adipose

Ligament

&

Tendon

dense regular

Joint capsule

dense irregular

Muscle Periosteum

dense irregular

TYPES OF CONNECTIVE TISSUE

VISCERAL

Loose irregular

Dense irregular Reticular Adipose Elastic In the beginning was Mesenchyme

Tube Man Al

re

cvl

Worm Woman

Liver

processes blood drained from the GI tract - - - - u diaphragm

Al re cvl

Liver

processes blood drained from the GI tract - - - - u diaphragm

Visceral Connective Tissue 1 -

Reticular

e.g., in liver, spleen, kidney

Reticular fibers

HEPATOCYTES

Macrophage

blood vessel

Endothelial cells lining vessel

Reticular fibers + Macrophages = Reticular tissue

TYPICAL TUBULAR ORGAN Visceral Connective Tissue 2 -

Loose irregular

main working tissue Epithelium

inner service tissue Connective tissue

lumen

loose irregular ct with vessels & nerves

motility tissue Muscle

outer service tissue Connective tissue

VISCERAL CONNECTIVE TISSUE TYPES ESOPHAGUS

lumen

re

AORTA

Elastic

Lamina propria

Loose irregular

Adventitia LIVER

Reticular - - - Al cvl - u diaphragm

Kidney

CAPSULE

Dense irregular

MESENTERY

Adipose

TYPES OF CONNECTIVE TISSUE Loose irregular

lamina propria, tunica adventitia

Dense irregular

organ capsules

Reticular

liver, spleen

Adipose

mesentery, pericardium

VISCERAL Elastic

lung, elastic arteries

have collagen fibers for strength, but need much elasticity

CONNECTIVE TISSUE COMPONENTS: Cells & ECM Fibroblast Osteoblast Chondroblast

synthetic

Macrophage Plasma cell Lymphocyte Mast cell

defensive

Structural & other molecules

Fat cell or Adipocyte

storage

Collagen FIBERS Reticular Elastic BINDERS & CONTROLLERS: Sticky glycoproteins Water-binding proteoglycans Destructive enzymes inhibitors Enzyme Signaling Molecules

CONNECTIVE TISSUE ROLES Connect/Support

COMPARTMENTS

Transport/Nourish

LUMINAL

Defend

}

(EPITHELIAL)

}

INTERSTITIAL connective tissue

Storage

VASCULAR

Control

nervous, paracrine (local), biochemical

Repair

EXTRACELLULAR MATRIX ECM

What cells produce and organize

outside

theselves allows them to construct huge organisms, with complex repertoires of movements & behaviors, and multiple physiologies based on separate compartments

Tight junctions

} LUMINAL } (EPITHELIAL) } INTERSTITIAL connective tissue VASCULAR

EXTRACELLULAR MATRIX ECM 2

Cells create and achieve control over their environment by synthesizing combinations of types of macromolecule which interact outside the cells

Learn the requirement, not the particular molecules meeting it

Over water (why you don’t slosh as you walk)

Hyaluronan Large proteoglycans

Why you can swallow, wink, spit, etc Creation of barriers - Basal laminae - Connective tissue ground substance

Mucin glycoproteins ( epithelial products ) Laminin, Collagen IV Perlecan (a heparan sulfate proteoglycan) Fibronectin Tenascin

Attachment & support

Collagen fibrils & fibers (I & III) + associated molecules

BASAL LAMINA CONSTRUCTION a sticky hedge

Learn the requirement, not the particular molecules meeting it

Epithelial-cell attachments to laminin Interwoven networks of LAMININ attached by Nidogen/Entactin &

COLLAGEN IV

Basal-lamina Proteoglycan molecules attached to the lattice , e.g., Perlecan

Generally

LAMININ ‘IN’ ending - glycoprotein

PERLECAN ‘AN’

ending - proteoglycan

Heparin - a glycosaminoglycan - is an exception

EXTRACELLULAR MATRIX ECM 3

Cells create and achieve control over their environment by synthesizing combinations of types of macromolecule which interact outside the cells Elastic recovery of shape & elastic storage of the work of the heart & respiratory muscles Elastic fibers & laminae

Elastin & fibrillin

Resilient firmness in joint, airway, & fetal-skeletal cartilages

Cartilage collagens II & IX aggregated proteoglycans link proteins & hyaluronan cartilage glycoproteins

Resilient hardness of bone

Collagens I & XII bone proteoglycans bone glycoproteins mineral crystals

Again, learn the requirement, not the particular molecules meeting it

EXTRACELLULAR MOLECULAR INTERACTIONS 1

Further assembly

of the molecules to make larger & eventually ‘visible’ structures, such as fibrils

Modification

of the molecules, e.g., cross-linking, to make them resistant to digestion

Deliberate breakdown

of the molecules by the forming cells for turnover and renewal, by proteases & other enzymes Controlled breakdown, with more synthesis & assembly, provides for remodeling & adaptation of ECM, e.g., to a heavier load in tendon or cartilage Some of these enzymes, e.g. collagenase, include a zinc atom & require Ca 2+ to work - hence

Matrix Metalloproteinases

, e.g. MMP-3

Some of these enzymes, e.g. collagenase, include a zinc atom & require Ca 2+ to work - hence Matrix Metalloproteinases, e.g. MMP-3 The

inhibitors

of these enzymes go under the abbreviation

TIMPs

- Tissue Inhibitors of MMPs; & are also made by fibroblasts & other matrix-influencing cells

ECM MOLECULAR INTERACTIONS - Pathology 1

Unintended degradation

by enzymes released from cells, e.g., leukocytes, engaged in defensive reactions. ECM is the

battleground

for defenses initially targeted at microorganisms.

“--itises”

occur throughout the body, & are real hazards to comfort & life, e.g., endocarditis weakens & distorts heart valves & thus can kill

ECM MOLECULAR INTERACTIONS - Pathology 2

Unwanted degradation

by bystander inclusion in cytokine signaling pathways of defensive cells

IL-1

M

F

Lymphocytes

of inner joint synovium

IL-1

Articular chondrocytes

Joint cartilage cells also respond to the signal: enzymes enzyme inhibitors proteoglycans =

an inappropriate response causing cartilage matrix destruction - ARTHRITIS

IL-1 Interleukin-1 a typical cytokine

ECM MOLECULAR INTERACTIONS - Pathology 3

Unwanted degradation

by: microbes trying to colonize, e.g., using bacterial hyaluronidase to liquify ground substance metastasizing cancer cells breaking through basal laminae & connective tissues to get into the blood or lymph streams

Unwanted synthesis

the formation of excess collagen, clogging organs with delicate blood-cell relations. Cytokines released by activated macrophages trigger synthesis in fibroblasts, causing

cirrhosis

in the liver and

fibrosis

in kidney, lung, marrow, etc

Bad assembly

- genetically defective fibrillin makes an inadequate scaffold for elastin deposition weak aorta, slack connective tissues, etc, of Marfan’s syndrome

This balance is significant

matrix cells

Thus, loose connective tissues have less matrix materials (except for water) and more cells than dense ones, because the looser textured matrix is more favorable to the growth of microorganisms, and hence needs more defensive cells: dense tendon needs far fewer.

Adipose tissue is mostly the very large fat cells

.

WHERE AM I?

ORIENTATION

Online Anatomy Module 1

You are at the End

CELL EPITHELIUM CONNECTIVE TISSUE MUSCLE NERVOUS SYSTEM AXIAL SKELETON APPENDICULAR SKELETON MUSCLES EMBRYOLOGY Caution how you exit.

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