Tob Flashcards
What is the value of histology?
Final proof of a disease- most doctors won’t decide on treatment without a histopathological diagnosis. Defines the extent of a disease
Why do shrinkage artefacts form?
In the dehydration process the dehydrating agents (ethyl alcohol) cause artifactual tears or splits to form along lines of weakness in the tissue - this unnatural space, shrinkage artefact, is visible under the microscope
How does formaldehyde and glutaraldehyde fix a biopsy?
Preserves cellular proteins by cross linking macromolecules. Aldehydes form covalent bonds with the amine groups on the proteins and thus cross link adjacent proteins, arresting biological activity and making cells more susceptible to staining
List the 11 steps of tissue processing
Biopsy, fixation, dehydrating, clearing, embedding, sectioning, rehydrating, staining, dehydrating, mounting, microscopy
What is meant by the process of biopsy?
The removal of a piece of tissue from an organ or part of the body for microscopic examination
Name 2 fixatives
Formaldehyde and glutaraldehyde
Name a dehydrating agent
Ethyl alcohol
Name 2 clearing agents
Xylene or toluene
How is a sample embedded in wax?
Paraffin wax at 56 degrees Celsius
Define a tissue
Collection of cells working together to perform a particular function
What does haematoxylin stain?
Acids blue
Nucleoli/ chromatin
What does eosin stain?
Bases pink
Cytoplasmic proteins
Extra cellular substances/ fibres
What does periodic acid schiff (PAS) stain?
Stains carbohydrates and glycoproteins magenta
Mucus secreting goblet cells
Basement membrane
What is used to mount a sample?
Dpx drying (xylene based medium)
What is gram staining used for?
To stain bacteria
What is the process of gram staining?
Add crystal violet complex (+) which binds to negatively charged structures Add iodine (-) which binds to the crystal violet and stains it purple Methanol is added to extract the complex from within the cell
Gram positive- has a thick peptidoglycan wall and so complex is not extracted by methanol and the structure stains purple still
Gram negative- has little or no peptidoglycan wall and so complex is extracted by methanol and the structure stains red
Why can’t mycobacterium be stained by gram staining?
Have no peptidoglycan cell wall
What bacteria are mycobacterium?
Tb and leprosy
What staining technique can be used for mycobacterium and what stain does it use?
Acid fast technique using a Z-N stain
What bacteria are gram positive?
Cocci and clostridium
What bacteria are gram negative?
Neisseria and everything else except mycobacterium and chlamydia
What is the value of histological staining?
To enable the visibility of components of a cell through a microscope
What is phase contrast microscopy?
Uses the interference effects of two combining light waves
What are the advantages of using phase contrast microscopy?
It enhances the images of unstained cells
What is dark field microscopy?
It excludes unscattered beams (light or electron) from the image
Used to detect malaria or syphilis
What are the advantages of using dark field microscopy?
Can look at live and unstained samples
What is confocal light microscopy?
Tissue is labelled with one or more fluorescent probes
What are the advantages of confocal light microscopy?
Eliminates the out of focus flare
3d from a series of 2d images
Imaging of living specimens
Allows thick samples to be used
What is fluorescent microscopy?
Targets molecule of interest with a fluorescently labelled monochromal antibody
What are the advantages of fluorescent microscopy?
Uses multiple fluorescent stains on one specimen to identify different parts of a sample
What is histology?
Study of structures of tissues using specialised staining techniques combined with light or electron microscopy
Define the limit of resolution
The minimum distance at which two objects can be distinguished
Lor is directly proportional to the wavelength
What is the difference between light and electron microscopy?
Light uses visible light, whereas electron uses electrons
Light- wavelength = 0.4-0.7 micrometers and Lor= about 0.2 micrometers
Electron- wavelength depends on accelerating voltage used (e.g. At 100000V wavelength= 0.004 nm
Tem- Lor= 2nm
Sem- Lor= 10nm
Explain why electron microscopes are capable of a finer resolution than light microscopes
Visible light wavelength= 0.4-0.7 micrometers; Lor= 0.2 micrometers
Electron at 100000V acceleration wavelength= 0.004nm; Lor= 0.002nm
Electron microscopes have a smaller wavelength and thus a smaller lor than light microscopes
Structure and function of cell membrane (bilipid)
Phospholipid bilayer with intrinsic proteins (carriers) and extrinsic proteins (with glycoprotein receptors) = fluid mosaic model
Allows free transport of lipid soluble substances across membrane; proteins facilitate movement of water soluble substances across
Structure and function of plasma membrane (plasmalemma)
Surrounds cells
Selective permeability, signal transduction, intracellular adhesion and recognition, transport into and out (endo and exo cytosis)
Structure and function of glycocalyx
Cell coat made up of oligosaccharide and polysaccharide side chains on outside of plasma membrane
Side chains give the cells specificity
Structure and function of nucleus
Nucleus, nuclear envelope, nucleolus, mostly consists of chromatin (unstructured form of cells DNA that will organise to form chromosomes during mitosis) -heterochromatin and euchromatin
Stores cells DNA and coordinates cells activities (metabolism, growth, protein synthesis and mitosis)
Structure and function of nuclear envelope
Double layered membrane that separates the contents of the nucleus from the cellular cytoplasm. Envelopes has lots of holes called nuclear pores that allow specific types and sizes of molecules to pass through. Also has an attached network of tubules - ER
Structure and function of nucleolus
Found within the nucleus
Synthesises protein producing macro molecular structures called ribosomes
Structure and function of ribosomes
Found free in cytoplasm or attached to ER
Humans 80S (60 and 40) and Bacteria 70S (50 and 30)
Two subunits small and large
Complex of rRNA and many proteins that act as a mini protein factory
Synthesised by the nucleolus
Sites of translation- protein synthesis
Structure and function of RER
Ribosomes attached (ribosome only binds to the ER once it begins to synthesise a protein destined for the secretory pathway MGD- i.e. to be secreted, vesicles, or for the membrane); membrane of RER is continuous with outer layer of nuclear envelope
Produces lysosomal enzymes with a mannose 6 phosphate marker added in the cis Golgi network
Secreted proteins- constitutively (collagen) or regulated (insulin)
N linked glycosylation
Structure and function of SER
Not associated with ribosomes; cisternae not as flattened as RER; less extensive; scattered around cytoplasm
Liver and mammary gland- lipid synthesis and intracellular transport
Ovaries, testes, adrenal glands- steroidogenesis
Structure and function of Golgi apparatus
Golgi consists of stacks if cisternae
Vesicles bud off from the RER and fuse with cis face of Golgi
Golgi bodies have a polarity such that proteins migrate from the convex to the concave (cis to trans) face of the stack
Functions to modify, sort, concentrate and package proteins synthesised in RER
O linked glycosylation
Vesicles containing different protein leave the maturing, trans face of the golgi and are destined for lysosome assembly, membrane or secretion
Secretory vesicles often condense (secretory granules) and release their contents at the cell surface by exocytosis
Structure and function of lysosomes
Contain acid hydrolases at pH 5; Lysosomal membrane proteins are highly glycosylated for protection from these enzymes; no genome of their own; dense, spherical or oval (primary)
Primary lysosomes fuse with membrane bounded vesicles (phagosomes or endosomes) with autophagosomes (defunct organelles encircles by ER) or with excess secretory product to form secondary lysosomes (digestive vacuoles= phagolysosome)
Degrade the contents of vacuoles
Lysosomes that have digested their contents but contain indigestible remnants are called residual bodies
What are residual bodies?
Lysosomes which have degraded their content but still contain indigestible material
Structure and function of peroxisomes
Major site of oxygen utilisation and hydrogen peroxide production (catalase uses the hydrogen peroxide (ie. with ROS- HP is oxidised into water and oxygen AND in alcohol metab- alcohol –> acetaldehyde))
Roughly spherical containing granular matrix, bound by single membrane; Self replicating but no genome of their own so proteins must be imported; present in all cells (ESP. Kidney tubules and liver parenchymal cells) which detoxify toxic molecules that enter the blood stream
Detoxification reactions
Structure and function of mitochondria
Double membrane- inner membrane folded to form cristae (usually lamellar but are tubular in cells engaged in steroid synthesis- ovaries, testes, adrenals)
Matrix contains enzymes of krebs and fatty acid cycles, DNA, RNA, ribosomes and calcium granules (ca signals to regulate mitochondrial function and acts to stimulate ATP synthesis)
Mitochondria can divide and have their own genetic info; dna, ribosomes and division is similar to bacteria; maternal lineage inheritance
Found in large numbers in liver and skeletal muscles; not found in rbc’s or terminal keratinocytes
Generation of energy rich ATP molecules by oxidative phosphorylation (main substrates are glucose and fatty acids)
Structure and function of cytoskeleton
Micro filaments, intermediate filaments and micro tubules
Produced by cells; responsible for maintaining/ changing cell shape
Structural support for plasma membrane and cell organelles
Means of movement for organelles, plasma membrane and other cytosol constituents
Locomotor mechanisms for ameboid movements (e.g. Lymphocytes) and for cilia and flagella
Contractability in cells of specialised tissues (e.g. Muscle)
SMLC (structure, movement, locomotor, contractability)
Structure and function of micro filaments
5nm diameter Two strings of actin twisted together Associated with ATP (contractile) Can assemble or dissociate (dynamic) E.g. Core of actin filaments allows intestinal micro villi to maintain their shape
Structure and function of intermediate filaments
SUPPORT
Not dynamic
10-12 nm in diameter
Common in nerve and neurological cells
Also common in epithelial cells that are made of cytokeratin
Form tough supporting mesh work in the cytoplasm and are anchored to plasma membrane at strong intracellular junctions (desmosomes)
Structure and function of Microtubules
MOVEMENT OF STRUCTURES WITHIN CELLS
13 alpha and beta sub units polymerise to form the wall of the hollow micro tubules - Originate from the centrosome/centriole (tubular units are added or subtracted)
Found at sites where structures in cells are moved (e.g. Elongated cellular processes such as nerve fibres, mitotic spindle and cores of cilia (9+2) and flagella)
Attachment proteins (dyenin and kinesin) can attach to organelles and move them along the micro tubules (classic e.g. movement of chromosomes along the mitotic spindle)
What are heterochromatin and euchromatin?
The DNA in the nucleus exist in two forms that reflect the level of activity of a cell. Heterochromatin appears as small, darkly staining, irregular particles scattered throughout the nucleus or accumulated adjacent to the nuclear envelope. Euchromatin is prevalent in cells that are active in the transcription of many of their genes while heterochromatin is most abundant in cells that are less active or not active.
Heterochromatin: darker, more sparsely distributed, present in cells that are inactive in the transcription of genes
Euchromatin: lighter, more evenly distributed, present in cells that are active in the transcription of their genes
Define epithelia
Sheets of contiguous cells that cover the external surface of the body and line internal surfaces, with varying embryonic origin
Name the three layers of the trilaminar embryonic disc
Ectoderm
Mesoderm
Endoderm
What epithelia cells are derived from the ectoderm?
Epidermis of the skin
Corneal epithelium of the eye
(EXTERIOR SURFACES)
What epithelia cells are derived from the mesoderm?
Epithelia of the urogenital tract (exception)
Blood and lymph vessel lining- endothelium
Pericardial and pleural sac lining
Peritoneal lining
(INTERIOR SPACES NOT OPENING TO THE EXTERIOR)
What epithelia cells are derived from the endoderm?
Epithelia of respiratory tract
Epithelia of GI tract
Epithelia of liver
Epithelia of many glands- thyroid, salivary, thymus
(INTERIOR SPACES OPENING TO THE EXTERIOR)
Where is basement membrane located?
Located between the epithelia cells and the lamina propria (subtending connective tissue)
What is the basement membrane?
Thin, flexible, acellular layer beneath the epithelial cells
What is the structure of the basement membrane?
It consists of a basal lamina, which is laid down by epithelial cells and therefore lies closest to them.
Its thickness can be increased by a variably thick layer of reticular fibrils (type III collagen) elaborated by lamina propria (subtending connective tissue)
What is the function of the basement membrane?
Serves as a strong flexible layer to which epithelial cells adhere
Serves as a molecular and cellular filter
The degree to which malignant cells penetrate the basement membrane is highly relevant to prognosis
What is the clinical relevance of the basement membrane?
If malignant cells penetrate the basement membrane = poorer prognosis
How are epithelia cells classified?
Simple- single layer thick
Compound/ stratified- more than one layer thick
Squamous, cuboidal, columnar, pseudostratified, transitional
What are the functions of simple squamous epithelia and where are they found?
Lubrication (pericardium, pleura)
Gas exchange (pulmonary alveoli)
Active transport (via pinocytosis in endo/mesothelium)
Barrier (bowmans capsule)
Glomerulus Bowmans capsule Alveoli Mesothelium (pericardium, peritoneum, pleural Endothelium (blood vessel lining)
What are endothelium and mesothelium
Endothelium- lining of blood vessels
Mesothelium- lining of body cavities (pericardium, pleura, peritoneum)
How does the structure of simple squamous epithelia help its function?
Thin so minimises diffusion distances
Flexibility
What are the functions of simple cuboidal epithelia and where are they found?
Hormonal Mobilisation & Secretion & Storage (thyroid)
Absorption- exocrine glands and kidney tubules
Secretion
Kidney tubules
Thyroid gland
Small ducts of exocrine glands m
How does the structure of simple cuboidal epithelia help its function?
Absorption and secretion roles
What are the functions of simple columnar epithelia and where are they found?
Absorption
Lubrication
Secretion
Gall bladder Large ducts of exocrine glands Oviducts Small intestine Stomach Salivary gland (parotid)
How does the structure of simple columnar epithelia help its function?
MICRO VILLI AND CILIA
Absorbing function
Have micro villi which increase their surface area (small intestine)
Have cilia to help move substances along it’s surface (Fallopian tubes)
Also contain interspersed glands
What are the functions of pseudostratified epithelia and where are they found?
Secretion Conduit Absorption Mucus secretion Particle trapping S
Bronchus
Lungs
Trachea
Epididymis
How does the structure of pseudostratified epithelia help its function?
CILIA AND STEREOCILIA
Appear to be more that one cell thick, but all cells do touch the basement membrane
Cells are interspersed with mucus secreting goblet cells
Cells generally have cilia which facilitate movement of other substances across surface (trachea)
Cells can also have stereocilia assisting with reabsorption (epididymis)
What are the functions of non keratinised stratified squamous epithelia and where are they found?
Abrasion
Water loss prevention
Vagina
Oesophagus
Mouth (epiglottis- also have pseudostratified)
How does the structure of non keratinised stratified squamous epithelia help its function
Many layers means that water loss is prevented and that abrasion can be prevented
What are the functions of keratinised stratified squamous epithelia and where are they found?
Protection
Protection against UV
Protection against microbes
Prevention of water loss
Skin
Oral cavity
How does the structure of keratinised stratified squamous epithelia help its function?
Keratin layer helps with prevention of water loss and protection (link to SKIN- epidermis:HGPB (keratinocytes)/ dermis/ hypodermis)
Many layers is helpful with protection
What are the functions of stratified cuboidal epithelia and where are they found?
Secretion
Lining of sweat glands
Glandular ducts
How does the structure of stratified cuboidal epithelia help its function?
Cuboidal shape- secretion and absorption
???
What are the functions of stratified columnar epithelia and where are they found?
Secretion
Pharynx
Epiglottis
Large exocrine glands
Male urethra
How does the structure of stratified columnar epithelia help its function?
Columnar shape- absorption and secretion
???
What are the functions of transitional epithelia and where are they found?
Distension
Resistant to toxicity
Renal calyx
Urether
Bladder
Ureter
How does the structure of transitional epithelia help its function?
Can stretch/ distend to fill areas (bladder) and allow liquids through (ureter)
How is epithelia structure linked to function?
Simple Squamous = their thinness and smooth surface means fluids can move across them with less friction (not the case with stratified)
Cuboidal = usually secrete or absorb
Columnar = long and have long nuclei; contain sensory receptors; usually secrete or absorb
Pseudostratified = have cilia (hair like projections) move things when necessary
Transitional = have bulging apical surface of cells- which can distend
Simple= thin allowing diffusion across
Stratified= usually outer layer is squamous but in a few cases it is columnar or cuboidal; many layers provide better protection as they can resist mechanical stress and dehydration
How is the renewal rate for epithelial cells determined?
Depends on location and function of the epithelial cells
Always occurs at a constant rate (unless injury leads to acceleration)
Can be high!
Some epithelia aren’t removed but proliferation can be triggered to replace damaged/lost cells
What can cause the renewal rate for epithelial cells to increase?
Injury
What is the renewal rate for the epidermis (epithelium of the skin)?
28 days from cell division at the basal layer (through differentiation, migration to the exterior, keratinisation and death) to finally being sloughed off at the surface
What is the renewal rate of the small intestine epithelia?
4-6 days- replaced from the base of the crypts
What are the different types of surface specialisation found on epithelia cells?
Microvilli
Cilia
Stereocilia
What do microvilli look like? Structure related to function?
Brush border- Apical extensions of cell membrane that greatly increase the surface area for selective absorption of intestinal contents (found on simple columnar epithelial cells of small intestine)
What do stereocilia look like? Structure related to function?
Very long microvilli, extend from the surface of the ductus deferens of the epididymis (part of the male reproductive system) - may have an reabsorptive function (found on the pseudostratified columnar epithelia of the epididymis)
What do cilia look like? Structure related to function?
Extensions from cells that beat in coordinated waves to provide movement of material along the cell surface
Elongated, motile, plasmalemma covered extensions of cytoplasm
Each one arises from a centriole (contains microtubules: tubulin)
9 pairs of microtubules outside and 2 pairs of microtubules in the middle (found in the pseudostratified epithelia of trachea and simple columnar epithelia of Fallopian tubes)
How can you differentiate between cilia, sterocilia and microvilli?
9+2 structure of cilia differentiates it from microvilli
Cilia are cytoplasmic extensions whereas microvilli are extensions of apical cell membrane
Stereocilia are in fact not cilia but elongated microvilli (so also do not have 9+2 structure)
When looking at a slide of stratified epithelial cells, which layer of cells determines the classification?
The most superficial layer
Which layer of cells in a stratified structure is in contact with the basement membrane?
ONLY the basal layer
What is a mucous membrane?
Made up of surface epithelia, basal lamina, lamina propria and muscularis mucosa (only in alimentary)
Lines cavities in contact with the outside - trachea, nasal cavity, respiratory, alimentary, urinary tract
SECRETES THICK AND STICKY MUCUS which traps bacteria/ microbes preventing them from entering into the system
Endodermal origin
What is a serous membrane?
Made up of lining epithelium (mesothelium thus simple squamous), basal lamina and lamina propria
Lines closed cavities within the body- pericardial sac, peritoneum, pleural cavity
SECRETES SURFACTANT FLUID- thin, smooth and shiny- which lubricates surfaces and reduces friction
Mesodermal origin
Internal surface of the alimentary tract
Mucosa- surface epithelia, basement membrane (separates ec and ct), lamina propria (supporting ct- lymph node and blood vessels), muscularis mucosa (controls localised movements of mucosa e.g. movement of cilia)
Sub mucosa- layer of connective tissue lying below mucosa bearing glands, arteries, veins and nerves
Muscularis propria/ externa- larger muscular group; smooth muscle (longitudinal, transverse, circular, oblique); control movements of entire structure (e.g. Peristaltic movements of GI tract)
Serosa- external mesothelial lining (simple squamous)/ Adventitia/ rugae/ plicae circulares
Where is the muscularis mucosa found?
In the mucosa layer of the internal surface of the ALIMENTARY TRACT ONLY
Internal surface of gut wall
Mucosa (simple columnar ec), sub mucosa, muscularis externa (outer longitudinal and inner circular), serosa, mesentery (double layer of peritoneum that suspends the jejunum and ileum from the posterior wall of the abdomen)
Internal surface of oesophagus
Mucosa, submucosa (contains mucus secreting glands), muscularis externa (outer longitudinal and inner circular), Adventitia (thin outermost layer of connective tissue)
Internal surface of stomach
Mucosa (secretes acid, gastrin and digestive enzymes; simple columnar ec), submucosa, muscularis externa (oblique, circular and longitudinal- moves food along in peristalsis), rugae (folds of gastric mucosa- forms ridges in empty stomach)
Internal surface of the jejunum
Mucosa (simple columnar epithelium), submucosa, muscularis externa (outer longitudinal and inner circular), plicae circulares (circular folds of mucosa and submucosa that project into the gut lumen)
Internal surface of large intestine
Mucosa (crypts of lieberkuhn- peyers patch- lymphoid tissue) (simple columnar ec), submucosa, muscularis externa
Internal surface of the respiratory tract
Mucosa- epithelial cell, basal lamina, lamina propria (NO MUSCULARIS MUCOSA)
Sub mucosa
Internal surface of tracheal wall
Mucosa (ciliated pseudostratified columnar ec) Submucosa Cartilage ring (c shaped) Fibroelastic membrane (contains tracheal muscle)
Internal surface of bronchus
Mucosa (ciliates pseudostratified columnar ec) Sub mucosa (sero mucous glands) Cartilage (crescent shaped and near to artery and veins)
Internal surface of bronchioles
Mucosa (ciliated simple columnar)
Clara cells (secrete surfactant)
Alveoli nearby
NO CARTILAGE- held open by elastic fibres in alveoli
Internal surface of alveoli
Type 1 cells - squamous 90% - gas exchange in capillaries
Type 2 cells - cuboidal 10% - produce surfactant
Macrophages - phagocytise particles
Surrounded by basket work of capillaries and elastic fibres
Gas exchange occurs across blood brain barrier
Internal surface of urinary tract
Mucosa- epithelial cell, basal lamina, lamina propria (NO MUSCULARIS MUCOSA)
NO SUBMUCOSA
Muscularis externa
Internal surface of ureter
Mucosa (transitional ec)
Muscularis externa (circular)
Adventitia
Internal surface of bladder
Mucosa (transitional ec)
Muscularis externa (circular, oblique and longitudinal)
Adventitia
Internal surface of urethra
Mucosa (transitional ec)/ penile urethra= stratified columnar ec Muscularis externa (inner circular and outer longitudinal ) Adventitia
Define a gland
An epithelial cell or an aggregate of cells specialised for secretion
How can glands be classified?
By destination of secretion-
exocrine (secrete through ducts directly onto target)
endocrine (secrete into bloodstream- ductless)
By structure of gland-
Unicellular (e.g. goblet cell) or multicellular (e.g submandibular)
Acinar (bulbed glands with myoepithelial lining for contraction
e.g. Sebaceous, mammary gland) or tubular (e.g. Intestinal
glands, merocrine sweat glands, gastric glands, mucous
glands of oesophagus, mucous glands, testes)
Coiled (e.g. merocrine sweat gland) or branched (e.g. Gastric
glands, mucous glands of oesophagus, sebaceous glands)
Simple (e.g. intestinal glands merocrine sweat glands,
sebaceous glands, gastric glands, mucous glands of
oesophagus) or compound (e.g. mucous glands, testes,
mammary glands, salivary glands, pancreas)
Main, interlobular, intralobular and intercalated
By nature of secretion-
Mucous gland- brunners gland
Serous gland- parotid gland, pancreas
Seromucous gland- submandibular (mostly serous) and
sublingual (mostly mucous)
By method of discharge-
Merocrine (sweat glands)
Apocrine (mammary gland)
Holocrine (sebaceous gland)
What does exocrine mean?
Gland secretes directly into target through ducts
What does endocrine mean?
Ductless
Gland secretes into bloodstream
What does acinar mean?
Describes structure of gland
Small sac or cavity surrounded by secretory cells of a gland
Bulbed glands with myoepithelial lining for contraction
What does tubular mean?
Describes structure of gland
Contains tubules- small cylindrical hollow structures
What does simple mean (wrt glands)?
Single duct and thus exocrine
What does compound mean (wrt glands)?
Many branched ducts (branches are branched)
What defines a mucous gland?
Nature of secretion
Secretes mucus rich in mucins (highly glycosylated proteins)
Stain poorly in H&E sections- appear light
E.g. Brunners gland
What defines a serous gland?
Nature of secretion
Secretions often watery and enzyme rich (free of mucus)
Eosinophilic- appear pink (darker) in H&E sections
E.g. Parotid gland
What defines seromucous glands?
Mixed serous and mucous glands
Submandibular and sublingual glands
What is a serous demilune?
When the seromucous cell undergoes artefactual distortion due to dehydration in preparation- so appear as serous half moons as serous (darker) portion of cell is pushed to sides to form a half moon shape
Describe merocrine secretion
Exocytosis of small membrane bound vesicle, commonly proteins from the cell
Membrane bound vesicle approaches cell surface and fuses with plasma membrane
Contents of vesicle are in continuity with the extra cellular space
Plasma membrane is very slightly larger
Membrane retrieved stabilising cell surface area
Sweat glands, salivary glands, pancreas
Describe apocrine secretion
Involves process of exocytosis of a free structure from the cell
Non membrane bound structure approaches cell surface
Makes contact and pushes up apical membrane
Thin layer of apical cytoplasm drapes around droplet
Membrane surrounding the droplet pinches off from cell
Plasma membrane is very slightly smaller
Membrane added to regain original surface area
Mammary glands
Describe holocrine secretion
Entire cell disintegrates to release its contents
Disintegration of entire cell
Release of contents
Discharge of whole cell
Sebaceous glands
List the exocrine glands you need to be able to identify
Goblet cells in jejunum and colon Parotid glands Submandibular lands Liver (exo and endo) Pancreas acinar (has exo and endo)
What is the location and function of myoepithelial cells in glands?
In lining of acinar glands- assist with secretion
E.g. In mammary glands- (compound acinar)
List the endocrine glands you need to be able to identify
Thyroid gland
Parathyroid gland
Adrenal gland
Pancreas- islet of lagerhans (exo and endo)
Describe endocytosis
Process of engulfing material initially outside the cell
Opposite of exocytosis (merocrine)
What is transepithelial transport?
Coupling of endocytosis and exocytosis (merocrine)
When a molecule is too large to penetrate membranes it can be shunted across from one component of the body to another.
- material is endocytosed at one surface of the cell
- transport vesicle shuttles it across the cytoplasm
- material/vesicle is then exocytosed at the opposite surface
E.g calcium transport across epithelial cells in the gut- 3 ways: with ATP, transcellular transport or endo/exo with a CaBP complex
What is the importance of glycosylation of newly synthesised proteins in the Golgi apparatus?
O linked glycosylation occurs in Golgi (where sugars are added to hydroxyl group of serine or threonine) [REMEMBER: N linked glycosylation occurs in ER where sugars are built up on the dolichol phosphate carrier molecule on the membrane and then transferred to the amide group of an asparagine]
Branching sugars offer complex shapes for interactions in the glycocalyx
Enzymatic destruction if this layer alters specificity based properties of cells:
-adhesion to substrates and neighbouring cells
-communication with neighbouring cells
-contact inhibition of movement and division
-mobility of cells
Sugars make the molecules more specific- so secretions can communicate effectively with outside world
What are some simple mechanisms of control of secretion from glands?
Nervous- SNS stimulates adrenal medulla to secrete adrenaline
Endocrine- ACTH stimulates adrenal cortex (zona fasisculata) to secrete cortisol
Neuroendocrine- nervous cells and CRH of hypothalamus control ACTH secretion from Anterior pituitary
Negative feedback- inhibitory effect if high T3 and T4 hormones on TsH synthesis by anterior pituitary/ cortisol on ACTH/ calcium on PTH
(Metabolism)
Define connective tissue
Tissue of mesodermal origin with three basic components- cells, extra cellular fibres and ground substance
What are the functions of connective tissue?
Structure- ligaments and tendons Infection defence Cushioning and support- submucosa Attachment and binding Diffusion medium- blood Injury repair- fractures (cartilage--> bone)
What are some examples of connective tissue?
Submucosa- alimentary canal (dense irregular or loose)
Ligaments and tendons- tensile strength (dense regular)
Dura mater, periosteum (covers outer surface of bone), perichondrium (surrounds cartilage of developing bone)- (dense irregular)
What CT are found in cartilage, bone, muscle and nerves?
Epimysium/ epineurium
Perichondrium/ periosteum/ perimysium/ perineurium Endosteum/ endomysium/ endoneurium
What are the common cells found in connective tissue and what are their functions?
Fibroblast- synthesis of collagen, elastic, reticular fibres and most of the ground substance (depends on Vit C to function)
Adipocytes- responsible for storage and metabolism of fats; may form small clusters in loose CT; protects, insulates and cushions organs of the body
Macrophages- derived from monocytes in bone marrow; migrate to connective tissue and function in ingesting (phagocytosing) foreign particulate matter
Mast cells- secrete histamine in allergic reactions or asthma
Myofibroblasts- fibroblasts with additional contractile function
Chondrocytes- inactive cartilage synthesising (chondroblast) cells
Osteocytes- inactive bone synthesising (osteoblast) cells
Plasma cells- secrete antibodies in infection
Fibrocytes- inactive fibre synthesising (fibroblasts) cells
What do fibroblasts depend on to function?
Vitamin C
What do fibroblasts, adipocytes, mast cells, chondroblasts, osteoblasts etc look like?
Google it/ ppt
What three fibres are found in connective tissue?
Collagen, reticular, elastin
What makes up the extra cellular matrix of connective tissue?
Ground substance and collagen, elastic and reticular fibres that lie within it and extra cellular fluid
Describe the structure and function of collagen
Bundles of non elastic fibres of varied thickness
Most abundant protein (25-30% of all protein)
Composed of 3 alpha chains of tropocollagen (varies with type of collagen e.g. Type 1 = 2 alpha and 1 beta)
Every 3rd amino acid is glycine (smallest amino acid- folds into the inside of the triple helix of 3 chains) gly-x-y
X and y are most commonly proline- (helix breaker prevents individual chains from forming individual helices) and hydroxyproline/ hydroxylysine- (can form hydrogen bonds which hold the three chains together and maintain the stability of the tropocollagen molecule) and lysine
Requires vitamin c to hydroxylate lysine and proline
Constitutively secreted protein
Synthesis occurs on RER of fibroblast cells
(MGD collagen formation link)
Where is type 1 collagen found?
Skin dermis
Where is type 2 collagen found?
Ears- hyaline and elastic cartilage
Where is type 3 collagen found?
Reticular fibres- intestine, skin, uterus, basement membrane
Where is type 4 collagen found?
Lens of the eye
Where is type 5 collagen found?
Placenta
What are some special names for macrophage cells?
Kupffer cells found in the liver
Microglia found in the CNS
Osteoclasts found in the bone
Where are reticular fibres found?
Lymph nodes
Where are elastic fibres found?
Lungs
What is the ground substance?
Gel like matrix in which the fibres and cells are embedded- through which extracellular fluid diffuses
What is the structure and function of the ground substance in connective tissues?
Viscous- lubricant and barrier to invaders
Composed of glycosamionglycans (GAGs) (hexosamine and hexuronic acid), hyaluronic acid, proteoglycans and glycoproteins
In the ground substance each hyaluronic acid molecule has many proteoglycan molecules branching off it
Each individual proteoglycan molecule has many GAGs branching off it
GAGs are negatively charged and so attract water molecules keeping the ground substance hydrated
=hyaluronate proteoglycan aggregate
Describe the four broad classifications of connective tissue
Embryonic- mesenchyme and mucus
Supporting- bone and cartilage
Proper- loose, dense regular, dense and reticular
Specialised- adipose, lymphatic and haemopoetic tissue, blood, cartilage and bone
Describe mesenchyme connective tissue
Embryonic ct
Cells are spindle shaped with large nuclei
ECM contains reticular fibres
Describe mucus connective tissue
Embryonic ct Whaton's jelly Fibroblast cells with oval nuclei ECM contains collagen bundles arranged irregularly LOOSE Umbilical cord
Describe loose connective tissue
Made up of loosely packed fibres and cells separated by amorphous ground substance
Cells include fibroblasts, macrophages, mast cells, fat cells, plasma cells
ECM consists of collagen and elastic fibres and watery ground substance
Support and frame work of internal structures
Forms walls and rods that make up the framework inside organs and adipose tissue- adipose, blood, areolar ct, reticular tissue
Describe adipose tissue
Loose ct
Adipose cells occur singly or in groups between collagen fibres
When they make up most of the cells in a tissue the tissue is termed adipose tissue
Nuclei are often compressed against cell membrane
Describe reticular tissue
Loose ct
Made up of lots of type 3 collagen and form framework of lymphoid tissues and liver
Describe reticular connective tissue
Type of loose ct
Cells consist of reticular cells, large ovals nuclei, lymphocytes, macrophages
ECM consists of reticular fibres
Found in liver kidney spleen lymph nodes and bone marrow
What is areolar ct?
A type of loose ct
Found in sub mucosa, deep under the skin, beneath ecs of mucous membranes, below mesothelium and peritoneum, associated with Adventitia of blood vessels, surrounding parenchyma of glands
Contains fibroblasts, macrophages, mast cells, abundant collagen fibres and less abundant elastic fibres
Describe dense connective tissue
Closely packed fibres with proportionally fewer cells and less ground substance
Achieve mechanical support and transmit forces
Describe dense regular connective tissue
Where fibres are arranged in parallel to provide maximum tensile strength
Cells include flattened fibroblasts in parallel rows
ECM consists of parallel rows of densely packed collagen
Describe two examples of dense regular connective tissue
Ligaments- collagen fibres interspersed with fibroblasts
Tendon- collagen fibres interspersed with flattened fibroblasts- fascicles (bundles of collagen and fibroblasts) are separated by endotendineum (loose ct) and held together by peritendineum
Fibrous sheath surrounds whole tendon
Describe dense irregular connective tissue?
Interwoven bundles of collagen which criss cross each other in many directions- counteracts multi directional forces to which the tissues are subjected
Cells include fibroblasts and macrophages
ECM consists of thick wavy bundles of collagen fibres as well as elastic and reticular fibres
What are the specialised connective tissues?
Blood Adipose tissue Cartilage Bone Lymphatic tissue Haemopoetic tissue
List some loose connective tissues
Adipose tissue
Blood
List some dense regular connective tissues
Tendons
Ligaments
List some dense irregular connective tissue
Dermis, periosteum, perichondrium, dura mater
List where reticular connective tissues can be found
Structural framework of: Liver Kidney Spleen Lymph nodes Bone marrow
What 6 diseases are related to connective tissue?
Systematic sclerosis Keloid Vitamin C deficiency Marfan's syndrome Ethlers Danlos disease Edema
What is systematic sclerosis?
Ct
Organs have excessive accumulation of collagen (fibrosis)
Occurs in skin, digestive tract, muscles and kidneys
=hardening and functional impairment
What is a keloid?
Ct
Scar of skin cause by abnormal amounts of collagen
What is vitamin C deficiency?
Ct
Scurvy
Fibroblasts unable to function leading to defective collagen synthesis and degeneration of connective tissue
Enzyme prolyl hydroxylase (relies on vitamin C and Fe2+ for functioning) cannot function - cant hydroxylate proline residues in collagen - so lack of H bonds means tropocollagen triple helices are weak
Periodontal ligament (with normal high collagen turnover) is affected in scurvy- loosening of teeth in sockets and eventual loss and bleeding gums
What is Marfan’s syndrome?
Ct
Defect in gene coding for fibrillin (found in elastic fibres)
Elastic fibres underdeveloped
Bulges form in artery walls, causing a smaller lumen and increasing blood pressure
As a result large elastic arteries (such as aorta) rupture
Tall
Arachnodactyly
Frequent joint dislocation
What is skin?
Continuous external surface which covers the outside of the body
Has keratinised stratified squamous epithelia (made up of mainly keratinocytes and their products)
Arranged in layers of connective tissue over the epidermis, dermis and hypodermis
What causes skin to vary?
Colour Hair Thickness Laxity/ wrinkling Oiliness
How does skin vary with colour?
Ethnicity
Site- lips areolae
UV exposure
How does skin vary with hair?
Site of hair- e.g little hair found in palmar surfaces of hands and feet but found on plantar surfaces
Gender- more profuse body and facial hair in men
Age- baldness in men and greeting in both sexes
Ethnicity- colour and character
How does skin vary with thickness?
Site- scalp vs ball of foot vs eyelid
How does skin vary with oiliness?
Puberty and site
How can variations in skin influence the susceptibility to and/or manifestations of skin disease?
Vitiligo (depigmentation of skin) much less of a problem in fair skinned individuals as its barely visible
Alopecia areata/ totalis - autoimmune response leading to hair loss
Fair skinned people are more susceptible to UV induced acute sunburn, freckling, ageing and skin cancer- especially thouse with red hair and blue eyes
Acne is common through puberty
What are the three layers that make up the skin?
Epidermis dermis and hypodermis
What are the four layers that make up the epidermis of the skin?
Horny layer (stratum corneum) Granular layer (stratum granulosum) Prickle cell layer (stratum spinosum) Basal layer (stratum basale)
What does the horny layer of skin consist of?
Layers of flattened corneocytes (dead keratinocytes) and keratin
What does the granular layer of skin consist of?
Contains keratohyalin granules which consist of keratins, other fibrous cross link proteins (such as filaggrin- which aggregates keratins; and involucrin- which forms a major part of corneocytes envelope) and enzymes which degrade phospholipid bilayer (phospholipases)
What does the prickle cell layer of skin consist of?
Prickle cells joined by prickle like desmosomes (intracellular junctions) Langerhans cells (dendritic cells with a bone marrow origin; scattered in prickle cell layer; mediate immune reactions and present antigens to T lymphocytes)
What does the basal layer of skin consist of?
Melanocytes (dendritic cells with a neural crest origin; intervals along basal layer; produce melanin- pigment that gives skin it’s colour*) difficult to see without special stains
Site of keratinocyte mitosis
*darker skin= more melanin production NOT more melanocytes
What is the dermo-epidermal junction?
Epidermal basement membrane below the basal layer of the epidermis- best seen with a PAS stain
Why is the dermo epidermal junction best seen with a PAS stain?
Stains carbohydrates and glycoproteins magenta
It’s a basement membrane containing carbohydrates and glycoproteins
Why is the dermo-epidermal junction/ epidermal basement membrane important in prognosis?
Retention of malignant melanocytes above the membrane is associated with a good prognosis in melanoma
If malignant melanocytes break through membrane= poorer prognosis
What are langerhans cells and where are they found?
Langerhans cells (dendritic cells with a bone marrow origin; scattered in prickle cell layer; mediate immune reactions and present antigens to T lymphocytes)
What are melanocytes and where are they found?
Melanocytes (dendritic cells with a neural crest origin; intervals along basal layer; produce melanin- pigment that gives skin it’s colour*) difficult to see without special stains
*darker skin= more melanin production NOT more melanocytes
Describe the process of keratinocyte differentiation in the epidermis
Basal layer- keratinocytes undergo mitosis and cell division
Prickle cell layer- keratinocytes undergo terminal differentiation/ lose ability to divide/ actively produce proteins (keratins= heterodimeric fibrous proteins which contribute to epidermis strength)
Granular layer- keratinocytes lose their plasma membranes and begin differentiating into corneocytes
Horny layer- cells lyse to release keratin
What is the transit time of s keratinocyte from the basal layer to the horny layer?
30-40 days
What type of connective tissue is the dermis?
Dense irregular connective tissue
What does the dermis consist of?
Highly vascularised- lots of blood and lymph vessels - so it can supply the avascularised epidermis
Deeper the dermis the larger the blood vessels –> birth marks
Fibroblasts- spindle shaped cells which make the ECM- collagen and elastic fibres –> keloid
Mast cells- distributed around blood vessels; contains cytoplasmic histamine granules –> local oedema/ urticaria and angio-oedema in skin
Nerves- sensory- important in transmitting skin sensation
What are birthmarks?
Malformations of blood vessels in the dermis
Name 4 skin appendages
Hair
Sebaceous glands
Sweat glands
Nails
How are hair follicles connected to sebaceous glands?
Sebaceous glands are branched acinar exocrine glands, which have a duct that communicates with the hair follicles. Sebaceous glands operate by holocrine secretion
What type of gland are sebaceous glands?
Branched
Acinar
Exocrine
Holocrine
Where are sebaceous glands located in the skin?
Dermis, with a duct going into a hair follicle
Where are hair follicles located in the skin?
epidermis
Where are sweat glands located in the skin?
Epidermis and Dermis
What are eccrine sweat glands?
Major sweat glands of the body
Found in most of the skin
Produce clear odourless merocrine secretion (water and NaCl- reabsorbed to reduce salt loss)
Active in thermoregulation
Controlled by hypothalamus
Consist of an intraepidermal spiral duct, straight dermal portion and a coiled acinar potion in dermis
What are apocrine sweat glands?
Large sweat glands
Abundant in Axillae, genital and submammary areas
No function of value
Produce odourless, protein rich, apocrine secretion- digestion by cutaneous microbes produces body odour
Duct joins onto a hair follicle duct
What type of connective tissue is the hypodermis?
Loose connective tissue composed mainly of adipose tissue
What is Ethlers Danlos disease?
Ct
Deficiency in collagen type III and hence reticular fibre
Causes ruptures in tissues with a high reticullin content ( structural framework of liver kidney spleen bone marrow and lymph nodes)
What is subcutaneous fat?
Found beneath the skin mainly in the hypodermis
Composed of adipocytes, grouped in lobules surrounded by connective tissue- adipocytes tissue= loose connective tissue
What is oedema?
Ct
Mast cells release histamine granules
Increases permeability of capillaries
Promotes flow of blood out of blood stream and into tissue spaces
Results in excess accumulation of EC fluid and thus gross swelling
Especially apparent in loose ct
What are some examples of dense irregular connective tissue?
Dermis of skin, large septa (walls) and trabecular (rods) of many organs, periosteum, perichondrium and dura mater
Describe the structure and function of reticular fibres
Thin branching carbohydrate coated fibres composed of type III collagen
Form delicate network around smooth muscle cells, certain epithelial cells , blood vessels, adipocytes and nerve fibres (seban)
Make a structural framework around certain organs such as the liver, spleen, bone marrow and lymphoid organs
(When stained with silver- appear brown with light microscope due to carbohydrate coat)
Describe the structure and function of elastic fibres
Elastin surrounded by microfibrillous component consisting of fibrillin
Similar to collagen but contains same amount of hydroxyproline but different amount of hydroxylysine- so thinner
Elasticity of elastin is because of high lysine content- 4 lysine amino acids from different chains form covalent cross links with one another- highly deformable and can stretch as tensile forces are applied
What are the main functions of skin?
Barrier
Sensation
Thermoregulation
Psychosexual communication
How does skin act as a barrier?
Horny layer of epidermis forms a major barrier preventing percutaneous absorption of exogenous substrates
Studied in detail as horny layer barrier must be overcome during percutaneous absorption of drugs
Horny late barrier can be disrupted by many diseases- psoriasis
How does skin function with sensation?
Sensory nerves in dermis
Leprosy
Diabetic sensory neuropathy
Both diseases of peripheral nerves
How does the skin function with thermoregulation?
Vascular thermoregulation (dilation leads to heat loss and constriction leads to pallor and heat conservation) Thermoregulation eccrine sweating (evaporation of eccrine sweat causes cooling) Both maintain body temperature
How does skin function with psychosexual communication?
Skin and its appearance are manipulated in a many ways as a means of communication and expression (tattoos and piercings)
What 5 diseases are associated to skin diseases?
Psoriasis Malignant melanoma Vitiligo Alopecia (areata or totalis) Acne
What is psoriasis?
Disorder of epidermal growth and differentiation
There is extreme proliferation of the basal layer
The prickle cell layer thickens
The horny layer is excessively produced
Leads to excessive scaling of skin surface
What is malignant melanoma?
Aggressive tumour of melanocytes in basal layer
Can break through the epidermal basement membrane /dermo-epidermal junction= poor prognosis
ABCDE mole classification
What is vitiligo?
Autoimmune disease
Immune system attacks melanocytes usually in symmetrical localised areas of skin
Causing well demarcated pigmentation
(cause is unknown- could be that process is under neural control as melanocytes are embryonic ally derived from the neural crest)
What is alopecia areata?
Autoimmune attack against hair follicles
What is acne?
Sebaceous glands produce excessive amounts of sebum (e.g. during puberty)
Duct between sebaceous glands and hair follicles becomes obstructed
Normally harmless bacteria on skin surface, can infect a blocked follicle- causing pus filled papules/ cysts
What is vellus hair?
Short, fine, light coloured and barely noticeable hair that develops on most of a persons body during childhood
What are terminal hairs?
Thick, long and dark compared with vellus hair
During puberty the increase in androgen hormones causes vellus hair to be replaced by terminal hair in certain parts of the body
Define cartilage
Specialised avascular connective tissue with a mesenchymal origin (from mesoderm)
What does cartilage generally consist of?
Cells: chondrocytes (produce and maintain ECM) , chondroblasts (spindle shaped- can become fibroelastic and crowd perichondrium; produce and maintain ECM), fibroblasts (cells that produce fibres in perichondrium)
ECM: type 2 collagen, hyaluronic acid, proteoglycan monomers, GAGs
Remember perichondrium is dense irregular connective tissue
How is the ECM of cartilage adapted to its function?
Negatively charged GAGs attract water- so keep gel hydrated
High GAGs : collagen (II) ratio per its the ready diffusion of substances between chondrocytes and blood vessels surrounding the cartilage
Large amounts if hyaluronic acid makes ECM solid, firm and pliable- so resistant to repeated application of pressure
What is the perichondrium?
Dense irregular connective tissue that surrounds the cartilage
What are the 3 main types of cartilage?
Hyaline, elastic and fibrocartilage
What is the function of hyaline cartilage?
Support and movement
Where is hyaline cartilage found?
Respiratory pathways, ends of long bones (articulating surfaces), epiphyseal plate, anterior ends of ribs, foetal skeleton
Whatis the structural composition of elastic cartilage?
Cells: chondrocytes
ECM: pgm, ha, GAGs, collagen (II) AND ELASTIN
Perichondrium present
What is the function of elastic cartilage?
Support and shape
Where is elastic cartilage found?
Pinna of ear, epiglottis, eustacian tube
What is the structural composition of fibrocartilage?
Cells: chondrocytes AND FIBROBLASTS
ECM: pgm, ha, GAGs, collagen (II) and collagen (I)
Perichondrium NOT PRESENT
What is the function of fibrocartilage?
Shock absorber
Where is fibrocartilage found?
Intervertebral discs, knee meniscus, pubic symphysis, portions of tendons
Which cartilages can calcify in old age/ disease?
Hyaline cartilage can calcify
What is the relevance of cartilage in osteoarthritis?
Joint pain occurs due to erosion at the hyaline cartilage articulating surfaces on ends of bone
What is cauliflower ear?
Perichondrium haematoma which causes necrosis and fibrosis of cartilage
What is an embryo’s skeleton made of?
In 5th week of development- Hyaline cartilage
until it is replaced with bone
What remnants of the cartilage in the embryo exist in humans?
Epiphyseal growth plates and articulating surface cartilage- which eventually is converted to bone
What is the clinical relevance of hyaline cartilage?
Can calcify/ossify in old age and disease.
Susceptible to degenerative ageing process- normal but accelerates in ageing via calcification of matrix due to increase in number and size if chondrocytes and cell death.
Joint pain can be the result of articular cartilage erosion on the ends of bones (osteoarthritis)
Rheumatoid arthritis occurs when secondary destruction of articular cartilage occurs by granulating synovial membrane tissue
What is the clinical relevance of elastic tissue?
Does not calcify/ ossify in old age
What is the clinical relevance of fibrocartilage?
Rupture of annulus fibrosus (invertebral disc capsule) leads to slipped disc
Tearing of menisci
What are the two stages of cartilage growth?
Appositional growth
Interstitial growth
What is appositional growth?
Fibroblast cells of perichondrium give rise to flat newly formed chondroblasts which secrete ECM and round up to develop onto chondrocytes
Cartilage grows from the periphery- wide ways
At the edge of cartilage mass- appositional growth adds various protuberances that will eventually be replaced by bone to create the final shape
Mainly in mature cartilage
What is interstitial growth?
Chondrocytes deeper in the cartilage divide and give rise to isogenous groups which deposit further matrix
These cells separate as they lay down further matrix
Cartilage grows long ways
In middle of cartilage mass- interstitial grown increases its overall size
Mainly in immature cartilage
What is the structural composition of hyaline cartilage?
Cells: chondrocytes
ECM: pgm, ha, GAGs, collagen (II)
Perichondrium present (except on articulating surfaces)
Amongst the isogenous groups of chondrocytes what is the interterritorial and territorial matrix?
Interterritorial matrix is the lighter stained areas
Territorial matrix is the darker stained areas that contain more highly sulphated substances in ground substance - generally closer to isogenous groups
What cells do not contain mitochondria?
Red blood cells
What cells don’t have a nucleus?
Red blood cells
What are the characteristic features of bone in the body?
Hardest bone in the body
Vascularised- supplied with blood and lymph vessels and nerves (so sensitive to pain- esp. in periosteum)
Dynamic- can withstand compression, stress and deformation
Type of connective tissue- so contains characteristic cells, fibres and ground substance
What are the 4 general functions of all bone?
Support
Protection
Mineral storage (calcium and phosphate)
Haemopoeisis- formation of blood cells (bone contains the bone marrow- site of haemopoiesis)
Is bone vascularised? How does this affect it?
Yes- helps with repair
Is cartilage vascularised? How does this affect it?
No- so difficult to repair
What two forms can bone have?
Spongy/ cancellous bone
Compact/ dense bone
What is the general arrangement of these two forms of bone?
Spongy is normally surrounded by compact
What is the arrangement of compact/ dense bone?
Concentric lamellae with central vertical Haversian canals (bearing blood and lymph vessels and nerves) which communicate via horizontal Volkmann’s canals} collectively all known as an osteon/ haversian system
What is a Haversian canal?
Vertical canals found in the centre of an osteon of compact bone bearing blood vessels, lymph vessels and nerves
What is a Volkmann’s canal?
Horizontal canals which connect Haversian canals in different osteons
Bear blood, lymph vessels and nerves
What is an osteon?
An entire Haversian system consisting of a Haversian canal (containing blood, lymph vessels and nerves) surrounded by concentric lamellae of bone
What is interstitial lamellae?
Adjoining lamellae found between osteons (so not in concentric circles)
Usually the remnants of remodelled bone
What is the arrangement of spongy/cancellous bone?
Mesh work of trabeculae (thin bits of bone) filled in with marrow
What is bone marrow?
Flexible tissue in interior of bones
Red bone marrow- red blood cell synthesis
Yellow bone marrow- contains adipose tissue
Marrow is confined within a thin cellular layer- endosteum
Site of B cell production and haemopoisis
What is endosteum?
Thin cellular layer of connective tissue that lines the trabeculae of spongy bone and confines the loose bone marrow
What is periosteum?
Double layer of connective tissue that covers the external surface of an entire bone
What does bone consist of?
Cells- osteoblasts, osteoclasts and osteocytes
ECM- fibres and ground substance- rigid calcified matrix (65% inorganic calcium phosphate and calcium carbonate salts= hydroxyapatite crystals ; 35% osteoid- organic collagen, non collagenous proteins and water)
Cells embedded in a calcified matrix- matrix consists of collagen and hydroxyapatite crystals
What are osteocytes?
Bone cells- found in lacunae cavities; maintain bone; formed when osteoblasts that release their matrix are entombed to form osteocytes
What are osteoblasts?
Builder bone cells
Synthesise the osteoid matrix (Organic portion of ECM )
When stimulated by PTH Secrete cytokines- stimulate differentiation of osteoblasts into osteoclast and hence stimulate osteoclast activity (METABOLISM)
Can differentiate into other bone cells –> osteocytes and osteoclastsc
What are osteoclasts?
Claw away at bone
Large multinucleated cells from monocytes that digest bone
When stimulated by PTH and cytokines produced by osteoblasts- will reabsorb bone- releasing calcium into blood
What gives bone its hardness and rigidity?
Inorganic calcium and phosphate salts and collagen
What gives bone it’s flexibility?
Collagen
How are calcium and phosphate stores in the matrix regulated?
Calcium and phosphate stores in the matrix are either stored in the bone or released into the blood to maintain constant levels of calcium and phosphate in the blood plasma
Parathyroid hormone- released when blood calcium concentration is lower than normal- stimulates osteoclast activity- increases bone reabsorption
Calcitonin- released when blood calcium concentration is higher than normal- inhibits osteoclast activity- decreases bone reabsorption
What are some functions of calcium which deem it necessary for blood calcium concentrations to be controlled?
Sickle contraction
Blood coagulation
Cell membrane permeability
Nerve impulse transmission (parathyroid)
What are the 5 main types of Bone in the human body?
Long bones, short bones, flat bones, irregular bones, sesmoid bones
What are the characteristic features of long bone?
Longer than it is wide
Compact bone surrounds central spongy bone
Both ends have Growth plates- epiphysis
Both ends have hyaline cartilage- acts as protection and support
What is the function of long bone? Where is long bone found?
Provide shape for our bodies, help in movement with muscles
Femur Humerus Tibia Metacarpals (lower bone of fingers) Metatarsals (lower bones of toes) Phalanges
What are the characteristic features of short bone?
As wide as they are long
Thin layer of compact bone surrounds spongy bone (containing lots of bone marrow)
What is the function of short bone? Where is short bone found?
Provide support and stability with little movement
Carpals (wrist)
Tarsals (ankle)
What are the characteristic features of flat bone?
Strong flat plates of bone
Anterior and posterior surfaces composed of compact bone which consists of spongy bone in the centre (and varying amounts of bone marrow)
What is the function of flat bone? Where is flat bone found?
Protection for vital body organs, base for muscular attachment
Scapula (shoulder blades) Sternum (breast bone) Cranium (skull) Coxae (hip bones) Pelvis Ribs
What are the characteristic features of irregular bone?
Non uniform shape- fit into no other category
Primarily consist of thin layer of compact bone surrounding spongy bone
What is the function of irregular bone? Where is irregular bone found?
No universal functions
Vertebrae
Sacrum
Mandible (lower jaw)
What are the characteristic features of sesmoid bones?
Short or irregular bones embedded in a tendon where it passes over a joint
What is the function of sesmoid bone? Where is sesmoid bone found?
Serves to protect the tendon
Patella (kneecap)- which lies in the patella/quadriceps tendon
What is an osteoid matrix?
Part of the ECM of bone which consists of the ORGANIC substances (collagen and non collagenous proteins)
What is a ligament?
Fibrous connective tissue that connects bones to other bones
What is a tendon?
Fibrous connective tissue that connects muscle to bones
What is the end of long bone called?
Epiphysis
What is the long part of the long bone called?
Diaphysis
What is the cone shaped region of long bone called, which changes shape as we grow?
Metaphysis
What is needed for calcification if matrix?
Matrix vesicles (alkaline phosphatase and other enzymes)
Which enzyme is a clinical marker of bone damage?
Alkaline phosphatase
What is the name of the squamous cells on the bone surface waiting to become active?
Inactive osteoblasts
What are the cytoplasmic processes of osteocytes?
Communication
Metabolic exchange
GAP junctions
What are the spaces which contain cell bodies (osteocytes) called?
Lacunae
What are caniculae?
Extensions of cytoplasm of osteocytes
What cells can revert back to osteoblasts?
Osteocytes
What are the spaces where osteoclasts are found called?
Resorption bays and canals
What are hydroxyapatite crystals called?
Plates along collagen fibres which are surrounded by a hydration shell (fluid bound to crystals of calcium phosphate and calcium carbonate)
What is the significance of layered arrangement in compact bone?
Efficiency (transfer of metabolites and waste)
Strength of bone in multiple directions (from alternating angles good for tension and torsion)
What type of bone is embryonic and in fracture repair and lacks organisation?
Woven
Compared to compact bone, woven bone has ________ mineral content and ________ cell concentration?
Less
Greater
What are the two layers of the periosteum?
Outer fibrous layer- dense irregular ct
Inner osetogenic layer- contains osteoprogenitor cells which can differentiate into osteoblast
What is the primary microstructure of bone?
Woven/immature bone- first bone to appear in embryonic development and repair; later replaced by mature bone
Collagen fibres arranged in random, interwoven fashion
More cells and less minerals
What is the secondary microstructure of bone?
Compact/ mature bone- compact dense cortical bone- osteons and interstitial lamellae
Spongy bone- mesh work of bone plates or trabeculae- spaces filled with marrow
What is remodelling? Explain the remodelling process of bone
Skeleton is a metabolically active organ that undergoes continuous remodelling throughout life to compensate for changes on forces being placed on it Haversian system (osteon) is remodelled by the bone remodelling unit which has two components: the resorption cavity (cutting cone) and lamellar formation (closing zone)
A resorption cavity is formed as osteoclasts enter the Haversian canal and begin resorbing bone. Osteoclastic activity is followed by an invasion by capillaries, osteoprogenitor cells and osteoblasts
Once the osteoclastsc activity ceases, the osteoprogenitor cells divide, forming osteoblasts, which lay down osteoid matrix which becomes calcified and thus manufacture lamellae of bone until a new osteon is completed.
What is the purpose of remodelling?
Serves to adjust bone architecture to meet changing mechanical needs
Helps repair micro damages in bone matrix preventing the accumulation of old bone
Maintains plasma calcium homeostasis
How is bone repaired following a fracture?
Haematoma formation- blood escapes from ruptured blood vessels in bone and periosteum and forms a haematoma- bone cells at fracture edge die (no blood supply), phagocytic cells and osteoclasts remove dead and damage tissue, macrophages remove blood clot- inflammation and swelling
Fibrocartilaginous callus- new blood vessels infiltrate, pro callus of granulation tissue, fibroblasts produce collagen fibres that span the break, fibroblasts differentiate into chondroblasts which increases hyaline cartilage formation = fibrocartilaginous callus; osteoblasts invade fracture site and begin bone reconstruction
Bony callus- new bone trabeculae form by : endochondral ossification (cartilage–> spongy bone) and intramembranous ossification (mesenchymal connective tissue –> spongy bone)
Remodelling- bony spongy callus is remodelled into compact bone; bulging material on sides of fractured bone is removed by osteoclast action
What is the process of endochondral ossification?
Process of bone formation by which cartilage is replaced by calcified bone matrix–> bone
[Endochondral- means within cartilage- so from centre (diaphysis) outwards (to epiphysis)]
The cartilage model- in the embryo, chondrocytes lay down hyaline cartilage which is the cartilage model for future bones; as cartilage calcifies, chondrocytes die off
Bone collar- osteoblasts, derived from the newly formed periosteum, secrete organic bone matrix (collagen) and matrix undergoes calcification (calcium/phosphate); this results in a bone collar which covers the diaphysis; bone collar is compact bone which thickens over time
Primary ossification centre- blood vessels bring osteoblasts to interior and they begin to lay down spongy bone (= primary ossification centre- first centre for bone formation)
Medullary cavity and secondary ossification centres- spongy bone of diaphysis centre is absorbed by osteoclasts and cavity created becomes the medullary cavity; shortly after birth secondary ossification sites form in the epiphysis; spongy bone formation persists in the epiphysis; [cartilage remains present at epiphyseal growth plate and articulate cartilage at needs of long bones]
Epiphyseal growth plate- band of cartilage (epiphyseal growth plate(0) remains between primary ossification centre and secondary ossification centres- limbs continue to increase in length so long as growth plates are present
What is the basic outline of Endochondral ossification?
Hyaline cartilage forms cartilage model for future bones in embryo
Chondrocytes in the shaft absorb the surrounding matrix and die, leaving empty lacunae
Primitive mesenchymal cells, from the perichondrium, invade the lacunae and differentiate into osteoblasts
Osteoblasts form organic bone matrix which becomes calcified to form a sleeve of compact bone around diaphysis
Blood vessels from the perichondrium invade the diaphysis (forming primary ossification centre) and bring osteoblasts to centre of diaphysis, so spongy bone forms within diaphysis
Spongy bone of diaphysis centre is reabsorbed by osteoclasts forming the medullary cavity (where red and yellow bone marrow is stored); secondary ossification centre form in epiphysis and spongy bone formation persists there
Some cartilage remains in the form of epiphyseal growth plates (between epiphysis and diaphysis) and articulating cartilage over the epiphysis (where no perichondrium is present)
Epiphyseal growth plate (continual growth) - chondrocytes proliferate and lengthen the bone; they then mature and die to be replaced by osteoblasts which ossify the region
What are the two processes of bone formation?
Endochondral ossification
Intramembranous ossification
What does Endochondral ossification form?
Long bones of tibia (e.g.)humerus and femur
Forms majority if bones of the body
What does intramembranous ossification form?
Flat bones of skull
What is the process of intramembranous ossification?
Process of bone formation in which bone forms between sheets of fibrous connective tissue
Primitive mesenchymal cells derived from connective tissue cells become osteoblasts located in ossification centres; osteoblasts secrete organic matrix of bone (collagen); calcification occurs when calcium salts are added to the organic matrix- results in the formation of spongy bone trabeculae (containing red bone marrow)
Periosteum forms outside the spongy bone, and osteoblasts derived from the periosteum carry out further ossification
Trabeculae undergo remodelling to form a compact bone collar which surrounds the inside of spongy bone
What is red bone marrow important for?
Red blood cell synthesis
What is yellow bone marrow important for?
Contains adipose tissue
What is the medullary cavity?
Central cavity of bone shafts where red and yellow bone marrow is stored
Lined with endosteum
Can be considered to be any area within a long bone that contains bone marrow- so cavity and endosteum is present between trabeculae and in central cavity
Which ossification lengthens and thickens long bones?
Endochondral ossification
Which ossification mostly thickens flat bone and sometimes long bones?
Intramembranous ossification
In Endochondral ossification how does growth in diameter occur?
Deposition of bone at periphery of shaft
In Endochondral ossification how does growth in length occur?
At cartilaginous epiphyseal growth plates in orderly series of zones (growth outwards from primary ossification centre)
What is osteogenesis imperfecta?
AD
Mutations in gene for type I collagen results in abnormal collagen type I synthesis by osteoblasts and fibroblasts–> bone fragility
Skeleton and joint fractures, deformities in ears, ligaments, weak teeth, yellow sclerae, inflexible skin, bowing and thinning of bones
Less severe cases are not apparent at birth- leads to fragility in bones and multiple fractures of long bones and bone deformities (caused by fracture healing with poor alignment and weak callus)
Where is type 1 collagen found?
Major collagen of connective tissue- found in skin, bones and tendons
Why does osteogenesis imperfecta have a legal importance?
Possible confusion with multiple fractures caused by deliberate injury and physical abuse
What is rickets?
Deficiency of vitamin D in CHILDREN (normally obtained in diet and synthesis in skin by UV action)
Low vitamin D means long term serum Ca concentration is low (due to decreased uptake of Ca from gut) which means decreased calcification of osteoid and hence weaker bones
Soft bones, malformations, distortion of skull bone, enlargement of costochondral junctions in ribs=rickety rosary
What is osteomalacia?
Deficiency of vitamin D in ADULTS (normally obtained in diet and synthesis in skin by UV action)
Low vitamin D means long term serum Ca concentration is low (due to decreased uptake of Ca from gut), which means decreased calcification of osteoid and hence weaker bones
Trabeculae of bone have an abnormally large amount of non-calcified osteoid covering their trabecular surface- hence weakened by insufficient mineralisation- more prone to fracture FEMORAL NECK, PUBIC RAMUS, SPINE, RIBS
More commonly seen in Muslims and elderly
What is osteoporosis?
Metabolic bone disease in which mineralised bone is decreased in mass to the point that it no longer provides adequate mechanical support
Bone density is reduced to a point where it’s a risk of fractures
The collagen framework and deposited minerals are broken down much faster than they are formed:
-bone resorption> bone formation
-osteoclast activity> osteoblast activity
Medullary canals in centres of bone become enlarged and gaps develop in lamellae making bone fragile
Type 1 post menopausal women- decrease in oestrogen results in increase in osteoclast number
Type 2 elderly of both sexes- decreased osteoblast function (so osteoclast function remains the same)
Can be treated with bisphosphonate- inhibits osteoclast activity
What is achrondroplasia?
Autosomal dominant point mutation in FIBROBLAST GROWTH FACTOR RECEPTOR-3 FGFR-3 causes a gain in function of FGFR-3 gene = failure of proliferation at epiphyseal growth plates= impairs lengthening of long bones
This results in a decrease in Endochondral ossification (impairs longitudinal growth of long bones), inhibited proliferation of chondrocytes in epiphyseal growth plate (=thin epiphyseal growth plates and premature fusion of the epiphysis with the diaphysis), decreased cellular hypertrophy, decreased cartilage matrix production
Short limb dwarfism (mostly proximal segment), trunk of normal length, vault of skull enlarged, small face, bridge of nose flattened (due to decrease in Endochondral ossification)
80% of the time caused by new mutation
Two parents with achondroplasia- 25% homo and die; 50% hetero and achondroplasia; 25% normal
What are the risk factors of osteoporosis?
Genetic (peak bone mass is higher in blacks)
Insufficient calcium intake (for pmw- 800mg/day)
Insufficient calcium absorption and vitamin D (decreased renal activation of vitamin D with age may be a factor in population such as Muslim (cover up) and elderly (stay indoors))
Exercise (immobilisation of bone- bed rest- leads to accelerated bone loss)
Cigarette smoking (in women- linked to increase in incidence of op)
Explain the importance of vitamin D in normal bone development
Vitamin D is obtained from diet and synthesised in skin by action of UV light
Vitamin D undergoes hydroxylation in liver and then in the kidney forming active calcitriol 1,25 dihydroxyvitamin D
Calcitriol stimulates absorption of calcium and phosphate by small intestine
Therefore high vit D results in a high plasma Ca concentration and so there is increased calcification of osteoid and bones are made stronger (vice versa)
What is the effect of growth hormone on bone development before puberty?
Excessive GH = gigantism due to promotion of epiphyseal growth plate activity
Insufficient GH = pituitary dwarfism- affects epiphyseal growth plates
What is the effect of thyroid hormone on bone development?
Neonatal congenital hypothyroidism- readily reserved by thyroxine administration (T4/T3)
If untreated thyroid hormone deficiency can lead to infant with permanent neurological damage (CRETINISM) and other abnormalities like a short stature
What is the effect of growth hormone on bone development in an adult?
Excessive GH= cannot cause gigantism- no longer any epiphyseal growth plates; causes increase in bone width ACROMEGALY by promoting periosteum growth
What is the effect of sex hormones on bone development?
Influence the development of ossification centres
Androgens/oestrogen - give rise to pubertal growth spurt
Precocious sexual maturity (brought about by a sex hormone producing tumour) retards bone growth because of premature closure of epiphysis
Deficiency- epiphyseal plates may persist into later life, leading to prolonged bone growth and tall stature
What are some differences between rickets and osteomalacia?
Rickets- children, soft bones
Osteomalacia- adults, increased coating of trabecular bone in non calcified osteoid- weakened bones more prone to fractures
What is haemopoiesis?
Formation of blood cells
Where does haemopoiesis occur?
Bone marrow Spleen Thymus Lymph nodes Lymph follicles Liver
Outline the process of haemopoiesis
1-Proliferation: starting with a stem cell, the cell divides into 2, one to replace the original stem cell (self renewal) and one that differentiates
2- Early blood cells are held in the bone marrow by adhesion molecules (collagen and fibronectin)- adhesion molecule receptors down regulate during maturation- leading to mature blood cells in circulation
3- Differentiation: haemopoetic progenitor will first differentiate to form either a myeloid blast (RBC, WBC, platelets) or a lymphoid blast (immunoresponse cells); The progenitor cells will differentiate into a certain cell type under the influence of particular cytokines
Know flow chart
What cytokines result in the formation of rbc’s?
Erythropoietin
What cytokines result in the formation of lymphocytes?
IL’s and TNF’s
What cytokines result in the formation of platelets/ thrombocytes?
Thrombopoeitin
What cytokines result in the formation of granulocytes?
Granulocyte- colony stimulating factor
Where are white blood cells formed?
Bone marrow
Where do white blood cells often mature?
Thymus or bone marrow or elsewhere
Name 5 WBCs that circulate in the blood and lymphatic system
Neutrophils Eosinophils Basophils Monocytes Lymphocytes
Neutrophils
Multi lobed nucleus
Granulocyte (pale cytoplasm)
FUNCTION
Migrate out of circulation to site of infection
Phagocytosis
Increased production by G-CSF
Eosinophils
Bi lobed nucleus
Granulocyte (red granules containing phospholipids and enzymes)
FUNCTION
Migrate to epithelial surfaces (lungs gut skin)
Capable of phagocytosis (of antigen antibody complex)
Increase in number in allergic reactions
Release cytotoxic particles to damage larger particle
Basophils
Bi or tri lobed
Granulocyte (dark blue granules contain heparin, serotonin and histamine) like MAST cells
FUNCTION
Migrate to site of damage
Mediate acute inflammatory reactions/allergic reactions
Histamine= vasodilation and leakage of fluid into tissue
Heparin= prevents blood clotting
Monocytes
Kidney shaped nucleus
NO GRANULES
Grey cytoplasm
FUNCTION
Migrate to become MACROPHAGES in many organs of the body
Capable of phagocytosis and interact with T cells
Respond to antigenic and inflammatory stimuli
Lymphocyte
Deep staining, large round nuclei
Small cells
Little cytoplasm
Nuclear chromatin- stains as light (euchromatin) and dark (heterochromatin) patches
FUNCTION
B - humoral immunity- stimulated by antigens, transform into plasma cells (when they interact with T cells) or memory cells (when within the lymph nodes), plasma cells secrete immunoglobulins (antibodies)
T - mature in thymus gland, express CD4 on surface (helper cells- increase T and B cells and activate macrophages from monocytes), can express CD8 on surface (killer cells- cytotoxic activity inducing apoptosis), permit transformation of B cells into plasma cells
Erythrocytes structure
Biconcave disc (facilitates passage through narrow capillaries)
Haemoglobin- 4 globulin chains (2 alpha and 2 beta); Each molecule carries a haem
Membrane has many glycoproteins- give it shape and specificity
8 micrometer diameter
What is the average diameter of a typical human cell?
10-20 micrometers
Erythrocytes function
Carries oxygen to tissues and carbon dioxide to lungs
Reticular cells structure
Synthesise reticular fibres and surround them with cytoplasm
Reticular cell function
Direct the T and B lymphocytes to specific regions within the lymphatic tissues
Platelets structure
2-3 micrometer diameter
Small round blue particles
Produced by megakaryocytes in the bone marrow
Complex surface membrane- phospholipid surface for clotting factor and platelet adhesion, via glycoproteins receptors
Cytoplasm contains alpha and dense granules
Alpha granules contain glycoproteins, fibrinogen and von Willebrand’s factor
Dense bodies contains serotonin, ADP, catecholamines and Ca2+ for platelet aggregation
Describe Red blood cell synthesis (erythropoeisis)
Reduced partial pressure of oxygen is detected in the interstitial peri tubular cells in the kidney
This results in an increased production of the erythropoietin hormone which stimulates maturation and release of red cells from bone marrow
Haemoglobin increases, partial pressure of oxygen rises and thus EPO production falls
Describe the two main pathways by which red blood cells are supplied with energy
2 main metabolic pathways-
Emblem Meyerhof pathway (glucose –> lactate and ATP is generated)
Hexose monophosphate pathway (G-6-P metabolised and NADPH is generated)
What is the survival rate of a rbc?
20 days
What is the survival rate for and platelet?
10 days
What is the survival rate for WBCs?
1 day- years varies widely
What is the minimum diameter of RBCs in capillaries?
3.5 micrometers
Platelet aggregation?
Ofhigh we’d
What are the three histological forms of muscle?
Skeletal muscle striated
Cardiac muscle striated
Smooth muscle non striated
What is the banding of skeletal muscle?
MHAZI
M line is in the H zone which is in the A band (dark)
Z line is in the I band (light)
What are the main filaments found in muscle?
Actin and myosin (present in all 3 types, only visible in skeletal and cardiac)
What filaments are present in the A band?
Actin and myosin, myosin (H zone), actin and myosin
What filaments are in the I band?
Actin- backbone along Z line
What is the sarcomere?
Distance between adjacent Z lines which are formed by the joining points of actin
What is the arrangement of an actin molecule?
Actin filaments are double helical strands of globular protein subunits
Can be isolated free in solution from G form (individual globular proteins) - under correct physiological conditions can polymerise into F form (long chain)
Tropomyosin, a thinner filamentous polymer, lies in the actin groove
Troponin is distributed along the thin filaments attached to tropomyosin at 40nm intervals
Each troponin is a Ca2+ receptor
Together, troponin and tropomyosin control the interaction of actin and myosin
What is the arrangement of a myosin filament?
> 150nm long and 10nm thick
Light meromyosin tail and heavy meromyosin globular head
Heavy meromyosin has the ability to bind actin and split ATP (forming bridges between thick and thin filaments)
What is the structure of a Myofibril?
Made up of smaller units- myofilaments (thin actin and thick myosin)
Present in a 2a:1m ratio
1000 myofilaments per Myofibril
What muscles are voluntary?
Skeletal
What muscles are involuntary?
Cardiac and smooth
What are two functions of muscle?
Contractility and conductivity
Describe the sliding filament mechanism **
When a muscle is innervated, an influx of Na and outflux of K causes a depolarisation of muscle cytosol which spreads to the T tubules
This causes the voltage sensor proteins of the T tubule membrane to change their conformation affecting the associated sarcoplasmic reticulum
Ca2+ is released from the sarcoplasmic reticulum from adjacent terminal cisternae
Ca2+ binds to the troponin c sub unit of troponin, which results in a conformational change which moves tropomyosin away from the actin binding sites
This displacement allows myosin heads to bind to actin and contraction begins:
-ATP attached to myosin head is hydrolysed, allowing the myosin head to move to approximate the active site of the actin molecule. ADP and Pi remain attached to the myosin head
- Pi is released from the myosin head, in the presence of calcium, causing the myosin head to bind with the actin filament
-ADP molecule is released from the myosin head, causing the myosin head to alter its conformation, moving the actin filament towards the centre of the sarcomere (POWER STROKE)
-A new ATP molecule attaches to the globular head of the myosin causing it to detach from that active site of the actin molecule and to return to its normal position
- Cycle repeats itself 200-300 times for complete contraction of the sarcomere- myosin binds to another active site further along the actin filament
Describe the mechanism of innervation of muscle and excitation contraction coupling
Arrival of ap at presynaptic neuron terminal causes an influx of Ca2+ ions from ECF to ICF
Influx of Ca2+ ions causes acetyl choline (ACh) containing vesicles to migrate to the neurons membrane, bind and release ACh into the synaptic cleft
ACh diffuses across the synaptic cleft and binds to nicotinic ACh receptors bound to the motor end plate
Receptors are ligand gated ion channels and when they bind ACh the channels open allowing an influx of Na and out flux of K to and from the muscle cytosol= depolarisation of the sarcomere
Depolarisation spreads to t tubules, voltage sensor proteins of the t tubule membrane change their conformation which affects the associated sarcoplasmic reticulum
Ca2+ is released from adjacent terminal cisternae
ca2+ binds to troponin c subunit of troponin
Contraction cycle is initiated and Ca2+ is returned to the terminal cisternae of the sarcoplasmic reticulum
What happens to the banding when contraction occurs?
H zone and I band shorten
Sarcomere shortens
A band is unaffected
What is the clinical importance of troponin c?
In cardiac muscle act as a marker for cardiac ischaemia
Released from heart muscle within an hour
Measured from 1 - 20 hours
Smallest change in troponin c is indicative of damage (not proportional)
What is rigor mortis?
In death when no ATP is being formed, no ATP is available to bind to myosin filaments, causing them to detach from the actin filament. As a result myosin remains bound to actin and muscle remains contracted = hardness of death
What is the structure of an entire organ of skeletal muscle?
Muscle= bundle of fascicles
Fascicles = bundle of fibres
Fibre= bundle of myofibrils
Myofibril- bundles of myofilaments (actin and myosin)
Epimysium- surrounds entire muscle
Perimysium- surrounds individual muscle fascicles
Endomysium- surrounds individual muscle fibres
Explain the muscle continuity of (skeletal) muscle fibres, muscle sheath, tendon and bone
Uegcyugecwyegcuygc
Skeletal muscle fibres connect with tendon collagen bundles at myotendinous junctions
Sarcolemma always lies between collagen bundles and muscle fibre myofilaments
Epimysium, perimysium and endomysium (bearing capillaries and nerves) become connective tissue joining the muscle to the tendon to the bone
What will the transverse section of the I band look like?
Thin dots = ony actin present
What does the transverse section of the h band look like?
Thick dots= only myosin present
What does a transverse section of the M line look like?
Thick dots with lines joining all dots
What does a transverse section of the A band look like?
Thick and thin dots = overlap of actin and myosin
What are t tubules and how are they associated with sarcoplasmic reticulum in a) skeletal muscle, b) cardiac muscle and c) smooth muscle?
T(ransverse) tubules are deep invaginations of the sacrolemma (plasma membrane) of the muscle
Run perpendicular to myofilaments
a) In skeletal muscle- T tubules located at junction overlap between A and I bands; present with a pair of terminal cisternae (bulbous large areas of sarcoplasmic reticulum) = triad
b) In cardiac muscle- T tubules located at Z line; present with a single terminal cisterna = diad
c) In smooth muscle- t tubules are not present
Where do t tubules interact with the myofilaments in a) skeletal muscle and b) cardiac muscle?
a) skeletal muscle - junction overlap between A and I bands
b) cardiac muscle - Z line
What are some key structural features of skeletal muscle?
Striated
No branching, parallel myofibrils
Distinct myofibrils
Multiple peripheral nuclei
T tubules in line with junctions between A and I bands
T tubules present as a triad with two adjoining terminal cisternae
What is the derivation if skeletal muscle?
Mesodermal (paraxial)
What is the nature of the repair of skeletal muscle?
Cells cannot divide but tissues can regenerate by mitotic activity of satellite cells so that hyperplasia (increase in cell number) follows muscle injury
Satellite cells can also fuse with existing skeletal muscle sells to increase mass (skeletal muscle hypertrophy- swelling)
Gross damage is repaired by connective tissue which leaves a scar
If the nerve or blood supply is interrupted muscle fibres degenerate and are replaced by fibrous tissue
What two types of skeletal muscle are there?
Red- Low intensity high endurance exercise Smaller rich in myoglobin, vascularisation and oxidative enzymes Poor in ATPase Numerous mitochondria Fewer neuromuscular junctions Slow, repetitive and weaker contraction Slowly fatigue = limb muscle of animals, postural muscles of back, breast muscle of migrating birds
White- High intensity low endurance exercise Larger Poor in myoglobin, vascularisation and oxidative enzymes Rich in ATPase Fewer mitochondria More neuromuscular junctions Faster, stronger contraction Rapidly fatigue = extra ocular muscles, muscles controlling fingers, breast muscle of domestic hens
What are some key structural features of cardiac muscle?
Striated
Branching, unparallel myofibrils
Indistinct myofibrils
1 or 2 central nuclei
T tubules in line with junctions between Z lines
T tubules present as a diad with a single adjoining terminal cisternae
What is the derivation of cardiac muscle?
Mesodermal (paraxial)
What is the nature of repair of cardiac muscle?
Incapable of regeneration
Following damage fibroblasts invade, divide and lay down scar tissue
What are extrinsic muscles?
Skeletal muscle attached to bones and cartilage- allows change in POSITION (of e.g. Tongue)
What are intrinsic muscles?
Skeletal muscle not attached to bone- allows a change in SHAPE (of e.g. Tongue)
What initiates contraction to occur in the heart?
Action potential is generated in the SAN, passed to the AVN and from there they are carried by specialised myocardial cells (bundle of His), of which the distal conducting cells are the PURKINJE FIBRES, to the ventricular muscle- causing simultaneous contraction of the ventricles
What are the PURKINJE fibres?
Distal conducting myocardial cells at the base of the ventricles Large cells with: Abundant glycogen Sparse myofilaments Extensive gap junction sites
Why are PURKINJE fibres used for ventricular contraction instead of cardiac fibres?
PURKINJE fibres conduct ap’s more rapidly at 3-4m/s compared to 0.5m/s for cardiac fibres
This rapid conduction enables ventricles to contract in a synchronous manner
What are some key structural features of smooth muscle?
Spindle shaped fusiform cells with a central nucleus
Not striated (no sarcomere)
No T tubules
Actin and myosin filaments arranged diagonally within the cell, spiralling down the long axis so the smooth muscle contracts in a twisting way
What is the derivation of smooth muscle?
Mesoderm/ ectoderm (paraxial)
What is the nature of repair of the smooth muscle?
Cells retain their mitotic activity and can form new smooth muscle cells
Ability is particularly evident in pregnant uterus where muscle wall becomes thicker by hypertrophy (swelling) and by hyperplasia (mitotis) of individual cells
What types of smooth muscle are there?
Circular - appears fusiform/ spindle shaped in transverse cut; inner wall of muscularis externa in gut
Longitudinal- appears circular in transverse cut; outer wall of muscularis externa in gut
What is the arrangement of actin and myosin in smooth muscle?
Arranged diagonally within the cell
Form sheets bundles or layers containing thousands of cells
What is the arrangement of actin and myosin in skeletal muscle?
A and I bands
What is the arrangement of actin and myosin in cardiac muscle?
A and I bands
What initiates smooth muscle cell contraction?
Responds to stimuli in the form of nerve signals, hormones, drugs, or local concentrations of blood gases
Wha are two types of modified smooth muscle cells?
Myoepithelial cells- form a basketwork around exocrine glands (sweat,salivary and mammary); contraction assists with secretion
Myofibroblasts- at sites of wound healing; produce collagenous matrix but also contract
Describe the remodelling process of muscle?
Change in number of proteins ; replacement of contractile proteins occurs in 2 weeks
Continuous
What is atrophy?
When destruction of protein > replacement of protein
Muscle wasting
Loss of protein (actin and myosin) causes fibre diameter to decrease (number of fibres remains the same)
What is hypertrophy?
When destruction of protein < replacement of protein
Muscle increases in size
Gain of proteins (actin and myosin) causes fibre diameter to increase (number of fibres remains the same)
What are some causes of atrophy?
Disuse- muscle fibres shrink when there is not frequent movement against resistance
Age- muscle fibres shrink after the age of 30 (50% loss by 80)
Denervation- muscle fibre shrinks as it no longer receives contractile signals that are required to maintain the normal size (causes weakness, flaccidity, twitching) ; muscle fibres are replaced with fibrous and fatty tissue
What is myasthenia gravis?
Autoimmune destruction of end plate ACh receptors so ACh cannot bind and is continuously broken down by acetylcholinesterase
Loss of junctions, folds at end plate
Widening of synaptic cleft
CRISIS when it affects respiratory muscles
Symptoms- fatigability, sudden falling due to reduced ACh release; drooping eyelids; double vision, effected by general state of health and emotion
Treatment- acetylcholinesterase inhibitors (neostigimine, physostigimine; placing ice on eyelids decreasing acetylcholinesterase activity
What is botulism?
Toxins block ACh release
Botox cosmetic treatment- removes wrinkles
What was botulin previously used for?
Originally used as a medicine to stop twitching in the eyes
What is duchenne muscular dystrophy?
Complete absence of dystrophin
Consequences of protein abnormality:
- muscle fibres tear themselves apart on contraction
-Enzyme creatine (phospho) kinase liberated into serum
-Calcium enters cell causing death of cell
-Pseudohypertrophy (swelling) before fat and connective tissue replaces muscle fibres
Symptoms- gowers sign (crouching to get up); contractures (imbalance between agonist and antagonist muscles)
What is organophosphate poisoning?
Irreversibly inhibits acetyl cholinesterase
So ACh remains in the receptors and muscle stays contracted
What is malignant hyperthermia?
Rare AD disorder
Life threatening reaction to certain drugs (volatile anaesthetic agents and neuromuscular blocking agent succinylcholine) used for general anaesthesia
Succinylcholine inhibits action of ACh acting non competitively on nicotinic receptors
Succinylcholine is degraded by butyrylcholinesterase much more slowly than the degradation of ACh by acetylcholinesterase
In susceptible individual these drugs can induce a drastic and uncontrolled increase in skeletal muscle oxidative metabolism, quickly overwhelming the body’s capacity to supply oxygen and remove carbon dioxide and thus regulate body metabolism
Eventually leads to circulatory collapse and death if not quickly treated
Malignant hyperthermia us treated by the correction of hyperthermia, acidosis, dysfunction, discontinuation if triggering agents and administration of DANTROLENE
DANTROLENE is a muscle relaxant which works by preventing the release of calcium
What does the CNS consist of?
The brain and the spinal cord
What are the membranous coverings of the brain and spinal cord in the CNS?
MENINGES Skull/ spinal vertebrae Dura mater Arachnoid mater Pia mater Brain / spinal cord
(Outside inwards)
What are collectively known as the leptomeninges?
Arachnoid mater and pia mater
What is the space between The arachnoid and pia mater known as?
Sub arachnoid space
What does the sub arachnoid space consist of?
Highly vascularised plane
Contains cerebrospinal fluid
How does the sub arachnoid space form?
By the failure of the arachnoid mater to follow the furrows of the brain
By the failure of the arachnoid mater to adhere to the pia mater (as a result of the dilated blood vessels of the brain)
What is the function of CSF?
Major fluid of brain
Supplies nutrients and oxygen to CNS neurones
Carries away metabolites of CNS
Exerts hydrostatic pressure= CNS pressure
What is the effect of having too much CSF?
Clinical implications- intracranial hypertension
What is the equivalent fluid to CSF in the PNS?
Endoneurial fluid- surround the individual nerve fibres
What epithelia are found on the meninges?
Stratified squamous
Wich layer of the meninges forms the boundary between the PNS and CNS?
Pia mater
How are neurones arranged in the spinal cord (CNS)?
Grey matter (collection of cell bodies) White matter (collection of nerve fibres)
Butterfly shaped grey matter surrounded by white matter
Smaller wings = dorsal (where afferent sensory neurones enter)
Larger wings = ventral (where efferent motor neurones leave)
How are neurones arranged in the brain (CNS)?
Grey matter (collection of cell bodies) White matter (collection of nerve fibres)
Secondary migration of grey matter has occurred resulting in the grey matter (cerebrum and cerebellum) forming a convoluted outer layer = cortex
Grey matter can also exist as deeply placed collections of cell bodies= nuclei
White matter is present as fibre tracts
What gives white matter its white appearance?
Presence of lots of myelin (on nerve fibres)
What cells are found surrounding all axons of the CNS?
Oligodendrocytes
How do oligodendrocytes form myelin sheath around axons in the CNS?
Oligodendrocytes wind themselves around the axon, wrapping it in concentric layers of its own plasma membrane (myelin)
250 axons per oligodendrocyte cell
How many pairs of cranial nerves are there?
12 (10 of which are present in the PNS as 1st and 2nd cranial nerves are actually part of the CNS)
How many pairs of spinal nerves are there?
31 (all in PNS)
What does the PNS consist of?
All the afferent (sensory) and efferent (motor) (to the CNS) nerves
What are the membranous connective tissue coverings of the nerves in the PNS?
Epineurium- surrounds entire nerve (bundle of nerve fascicles)
Perineurium- surrounds nerve fascicles (bundle of nerve fibres)
Endoneurium- surrounds individual nerve fibres (one axon)
What is the function of the connective tissue sheaths that surround nerves?
Blood- supply nutrients and oxygen, and remove metabolites of PNS
What is the structure of a sensory neurone?
Pseudo unipolar
Myelinated
Where do sensory neurones enter the spinal cord?
Dorsal root
What is the structure of a motor neurone?
Multipolar
Somatic- myelinated and autonomic- unmyelinated
How do motor neurones leave the spinal cord?
Ventral root
What is the structure of inter neurones?
Multipolar
Smallest neurones
Held solely within brain and spinal cord substance
What is the structure of the cerebrospinal ganglia of the sensory neurones in the PNS?
Round large ovoid nuclei
Conspicuous nucleoli
Each ganglia cell is surrounded by a single layer of satellite support cells
Cell bodies are grouped at the periphery of the ganglia
Myelinated fibres grouped in middle of ganglia
What are ganglia and where are they found?
Ganglia are collections of cell bodies surrounded by connective tissue capsules
Found in PNS
There are two types- sensory (cerebrospinal) ganglia (fusiform swellings of each dorsal root of spinal nerves) and motor autonomic ganglia (found in two parallel chains (sympathetic chain of ganglia), along anterior surface of vertebrae OR as poorly encapsulated structures near or within the target organs (parasympathetic ganglia)
There is no such thing as motor somatic ganglia as motor somatic neurones consist of only one axon (with no ganglia)
What is the structure of the autonomic ganglia found in the motor neurones of the PNS?
No peripheral arrangement of cell bodies Small ganglion cells Unmyelinated axons Ill defined layer of satellite cells Eccentric cell body nuclei
What is the general structure of a neurone in the CNS and PNS?
Dendrites- receive stimuli from sensory organs or other neurones (from the environment) and conduct nerve impulse towards cell body; specialisations of cell body
Cell body- involved in maintenance of cell; has a light nucleus, darker nucleoli, Nissl substance (aggregation of RER-involved in protein synthesis and is basophilic due to high conc of rRNA)
Axon- exists as a single process; conducts nerve impulses always from cell body to other neurones or target organs
What is the neurone, nerve cell and nerve fibre?
Neurone is collectively the dendrites, cell body and axon
Nerve cell is sometimes used to refer to cell bodies and attached dendrites, or can be interchanged with the use of neurones
Nerve fibres refers to the axons
What are the three basic neurone types?
Multipolar- multiple dendrites and 1 axon (many processes)
Bipolar- 1 dendrite and 1 axon (2 processes)
Pseudo unipolar- 1 axon (fusion of dendrite and axon) (1 process)
Where are multipolar neurones found?
Motor neurones
Where are bipolar neurones found?
Largely in the retina of the eye
Where are pseudo unipolar neurones found?
Sensory neurones
What is myelin sheath?
Where Schwann cells or oligodendrocyte cells wrap their membrane (containing myelin) in concentric layers around the axon
At regular intervals along the axon
What is a node of Ranvier?
The gaps between the discontinuous myelin sheath along an axon
What is the initial segment of a myelinated neurone?
The initial node of Ranvier before the first myelin sheath
What is the internodal membrane of a myelinated axon?
Region of axon underneath the myelin sheath
What is the relevance of a high lipid content of the myelin sheath?
Cannot conduct electricity resulting in saltatory conduction
Dissolved by xylene and alcohol in tissue processing
What is saltatory conduction?
Propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials without the need to increase the diameter of the axon
How is the speed of an action potential along an axon increased?
Myelinated axons- presence of myelination= quicker transmission Schwann cells wrap around the axons, insulating them and their lipid content means they can’t conduct electricity; electricity can nkt be conducted at nodes of ranvier; so action potential jumps from node of Ranvier to the next in saltatory conduction
Diameter of axon- larger the axon diameter= quicker transmission
Temperature
Describe the structure of the cell body
Light nucleus, dark nucleolus
Golgi apparatus- packages neurotransmitters into vesicles
Nissl substance- RER aggregates- where protein synthesis occurs; basophilic due to high rRNA content
Dendrites
Dendrite spines- associated with learning experience (more you learn the more dendritic spines you have)
Cell membrane- bilipid layer; separates inside from outside, selectively permeable to certain ions (ionic conc grad across cm/ ions are charged/ electrochemical gradient across cm; neurone is electrically charged)
Ion channels in cell membrane- membranes have many pores which form ion channels for specific ions; voltage gated channels opens and close by changes in voltage across the membrane; other channels open and close in response to neurotransmitters/ ligands
Axon (axial hillock and axon terminal)
Describe the axon
Summaries all the input
Initiates the all or nothing action potential
Conducts ap’s away from cell bodies towards terminals
Depolarisation of terminal leads to secretion of neurotransmitter
Communicates with follower cells
Varies in thickness and length
Can be myelinated or unmyelinated
May divide into twig like branches (terminal arborations) at terminal site of axon, which in turn may have swellings known as boutons terminaux (synaptic knob)
What is the relevance of multiple sclerosis and demyelination?
Nerve impulse has to travel further due to demyelination as saltatory conduction is inhibited; therefore the response is much slower
Myelin sheath (oligodendrocytes and schwann cells) is destructively removed from the axon and replaced by scar tissue
Conduction velocity slows down as saltatory conduction is impaired
Scar tissue cannot permit conduction and therefore the axon is useless
How much of the CNS and PNS is made up of neurones and how much of glial cells?
10% neurone
90% glial cells
What are glial cells?
Cells that support and insulate neurones in the CNS and PNS
What is temporal summation?
Inputs summated with respect to their time of arrival on the cell body/ dendrites - high frequency over short period of time
What is spatial summation?
Inputs summated with respect to their relative spatial location n the cell body/ dendrites- lots of input from different sources/ presynaptic knobs
How does communication between neurones occur?
Depolarisation leads to secretion of chemical messengers called neurotransmitters
What are excitatory neurones and what do they release?
Excitatory neurones (causes its follower cell to be depolarised) release glutamate / aspartate neurotransmitter
What are inhibitory neurones?
Inhibitory neurones (causes its follower cell to be hyper polarised) Release glycine/ GABA (gamma amino butyric acid)
What is the motor neurone system made up of?
Somatic (voluntary) and autonomic (involuntary) nervous systems
What is grey matter?
Collection of cell bodies (nerve cells)
What is white matter?
Collection of neuronal axons (nerve fibres)
How is the somatic system arranged?
Consists of 1 neurone carrying the output from the CNS
The neurone terminates directly on the effector organ (SKELETAL MUSCLE)
The efferents are underdeveloped at birth and fully developed at puberty
What are the effector organs for the somatic nervous system?
Skeletal muscle
How is the autonomic nervous system arranged?
Pathways consists of 2 neurones
1 neurone (pre-ganglionic) has cell body in CNS and 1 neurone (post-ganglionic) has cell body in PNS
Cell body in PNS is either in the sympathetic chain (ganglions) or near the effector organ (parasympathetic ganglion)
What are the effector organs of the autonomic nervous system?
Cardiac muscle
Smooth muscle
Secretory glands
What are the functions of the autonomic nervous system?
Part of peripheral nervous system that regulates the functions of our internal viscera/organs
Maintains homeostasis
Becomes active along with organogenesis
Promotes excretory mechanisms
What does the autonomic nervous system consist of?
Sympathetic and parasympathetic nervous system
What is the sympathetic nervous system involved in?
Stimulating effector organs
Fight or flight response
What is the parasympathetic nervous system involved in?
Inhibiting effector organs
Relaxation- rest or digest
Describe the pathway by which the sympathetic nervous system distributes its fibres to the effector organ
Thoraco lumbar outflow (nerve fibres have cell bodies in all 12 thoracic sections and first 2 lumbar sections)
Short pre-ganglionic neurone
Sympathetic chain- may synapse at: (1) same level of origin (paravertebral origin); (2) different level of origin (up or down sympathetic chain); (3) nowhere in sympathetic chain
Long post-ganglionic neurone
Describe the pathway by which the parasympathetic nervous system distributes its fibres to the effector organ
Cranial sacro outflow (nerve fibres have cell bodies in oculomotor, facial, glossopharangeal, vagus cranial section and S2,3,4 of the sacral section)
Long pre-ganglionic neurone
Short post-ganglionic neurone
What synapses and receptors are present in the sympathetic nervous system?
Sympathetic
Pre-ganglionic neurone are cholinergic
Post ganglionic neurones express nicotinic receptors and are noradrenergic
Effector muscle expresses alpha and beta adrenoreceptors
What synapses and receptors are present in the sympathetic nervous system?
Parasympathetic
Pre-ganglionic neurone are cholinergic
Post ganglionic neurones express nicotinic receptors and are cholinergic
Effector muscle expresses muscarinic receptors
What are some of the functions of the sympathetic nervous system?
Fight/flight/ fright response Diversion of blood to muscles and heart Increase in heart rate Increase in blood pressure Reduced blood flow to GIT and skin Hyperventilation
What are some of the functions of the parasympathetic nervous system?
Relaxation
Reduced heart rate a d force of contraction
Promotes digestion
Promotes bodily functions such as bladder emptying
Promotes sleep
What are the 6 main glial cells and their functions?
Astrocytes- assist in transfer of nutrients and waste across the blood brain barrier (CNS)
Oligodendrocytes- myelination up to 250 axons/cell (CNS)
Microglia- immune and inflammatory functions (CNS and PNS)
Ependyma- line ventricles and central canal of spinal for circulation of CSF) (CNS)
Schwann cell- myelination 1 axon/ cell (PNS)
Satellite- physical support of peripheral neurones (afferent and efferent) and ganglia (PNS)
What cells are found surrounding all axons of the PNS?
Schwann cells
How do Schwann cells form myelin sheath around axons in the PNS?
Schwann cells wind themselves around the axon, wrapping it in concentric layers of its own plasma membrane (myelin)
1 axons per schwann cell
Why is it normally difficult to see myelin sheath under a microscope?
Myelin membrane of Schwann/oligodendrocyte cells which wraps itself around the axon contains lipid (being a membrane) which is dissolved by lipid solvents such as xylene and alcohol in the tissue processing. Hence this causes the breakdown of the myelin sheath so it can’t be seen under a microscope
What fixative can be used to preserve the lipid in myelin sheath
Osmium tetraoxide - so myelin sheath stains an intense black
What is the pathology of muscular dystrophy?
Genetic faults causes the absence or reduced synthesis of specific proteins which anchor the actin filaments to the sarcolemma (membrane) such that in their absence the muscle fibre cells may tear themselves apart when contracting
What is Barrett oesophagus?
Stratified squamous –> simple columnar in oesophagus as a result of acid reflux from the stomach
What type of gland is intestinal gland?
Simple tubular
What type of gland is the merocrine sweat gland?
Simple coiled tubular
What type of gland is the sebaceous gland?
Simple branched acinar
What type of gland are the gastric glands, mucous glands of oesophagus, tongue and duodenum?
Simple branched tubular
What type of glands are the mammary glands?
Compound acinar
What type of glands are the mucous glands?
Compound tubular
What type of glands are the salivary glands?
Compound tubuloacinar
What is the function of the gall bladder?
To extract water and electrolytes from bile produced by liver, thus reducing its volume
What is the function of the parotid salivary gland?
Removes sodium ions rendering saliva hypotonic
Describe the epididymis
Pseudostratified epithelium
StereoCiliated
Principal cells- (ecs) absorb fluid, secrete substances which promotes sperm maturation, phagocytose residual bodies and degenerate sperm
Basal cells- (beneath ecs)- stem cells of epithelia
