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
