Semester 1 Flashcards
Define tissue
A collection of cells specialised to perform a particular function
What is histology?
The study of the structure of tissues by means of special staining techniques combined with light and electron microscopy
What are the different types of tissue?
- Epithelial
- Connective
- Muscle
- Nervous
In metres, how big is a millimetre?
10 ^ -3
In metres, how big is a micrometre?
10 ^ -6
In metres, how big is a nanometre?
10 ^ -9
How big are most human cells?
10 - 20 um in diameter
How big are red blood cells?
7.2 um diameter
What is a biopsy?
The removal of a small piece of tissue from an organ or part of the body for microscopic examination
What are the different types of biopsy and give an example of what they are each used for?
- Smear (cervix or buccal cavity)
- Curretage (endometrial lining of uterus)
- Needle (brain, breast, liver, kidney)
- Direct incision (skin, mouth, larynx)
- Endoscopic (lung, intestine, bladder)
- Transvascular (heart, liver)
What chemicals can be used for fixation?
Glutaraldehyde, formaldehyde or alcohol
What are the most commonly used stains?
Haematoxylin and eosin
What is haematoxylin used to stain and what colour?
Acidic components of cells - purple/blue
What is eosin used to stain and what colour?
Basic components of cells - pink
Why are biopsies fixed?
To preserve the cellular structure
What is Periodic Acid-Schiff (PAS)?
- Staining method
- Stains carbohydrates and glycoproteins magenta
What is an artefact?
A structure seen in a tissue, under a microscope, that is not present in living tissue and occurs due to the preparation technique
What is Weigert’s elastin?
A stain that stains elastic fibres silver
What is Elastic Van Gieson?
A stain that stains:
- Collagen pink/red
- Elastin blue/black
- Muscle yellow
How does phase contrast microscopy work?
- Uses light waves and interference effects (these are produced when 2 sets of waves collide)
- A stained cell allows some light to pass through, but reduces the wave height
- This altered wave interferes with the other waves, causing the light to dim
What is differential-interference-contrast-microscopy?
Similar to phase contrast microscopy
What is confocal microscopy used for?
- To image tissues which have been labelled with 1 or more fluorescent probes
- Has facilitated the imaging of living specimens
- Has enabled the electronically automated construction of 3D images from a series of 2D images taken at successive depths
How does confocal microscopy work?
- Uses a light microscope
- The fluorescence in the image away from the region of interest interferes with resolution of structures in focus
- It eliminates the ‘out of focus’ flare from thick fluorescently labelled specimens
- The illumination can be achieved by scanning 1 or more focused beams of light (usually from a laser) across a specimen
- Images produced in this way are called optical sections
- The tissue is sectioned by light rather than by physical means
What is the process of staining and preserving biopsy for microscopy?
- Remove water from fixed biopsy so sample doesn’t go off
- Add ethanol to clear sample of bacteria, etc.
- Add xylene/toluene to remove the ethanol, since ethanol does not mix well with wax
- Embed and impregnate biopsy in wax
- Slice thinly using a microtome arm to section
- Rehydrate sample (stain is water soluble)
- Stain to highlight particular structures
- Dehydrate again so that the sample doesn’t go off
- Mount by adding DPX and a coverslip so that sample is ready for microscopy
What is epithelia?
Sheets of contiguous cells, of varied embryonic origin, that cover the external surface of the body and line internal surfaces
Which exterior surface has epithelial linings?
Skin
Which interior spaces have epithelial linings?
- With opening to exterior: gastrointestinal tract, respiratory tract, genitourinary tract
- With no opening to exterior: pericardial sac, pleural sacs, peritoneum, blood vessels, lymphatic vessels
What are the 3 germ layers of the embryo?
- Ectoderm
- Mesoderm
- Endoderm
Give an example of an epithelial derivative from an ectoderm layer
- Epithelium of skin
- Corneal epithelium of eye
Give an example of an epithelial derivative from a mesoderm layer
- Epithelium of urogenital tract
- Blood and lymphatic vessel lining
- Pericardial and pleural sac lining
- Peritoneal lining
Give an example of an epithelial derivative from an endoderm layer
- Epithelia of respiratory tract
- Epithelia of GI tract
- Epithelium of liver
- Epithelium of many glands: thyroid, thymus, salivary
What is the basement membrane?
- A thin, flexible, acellular layer which lies between epithelial cells and the subtending connective tissue
- Consists of a basal lamina which is laid down by the epithelial cells and therefore lies closest to them
- Its thickness can be augmented by a variably thick layer of reticular fibrils elaborated by the subtending connective tissue
- Serves as a strong, flexible layer to which epithelial cells adhere
- Serves as a cellular and molecular filter
What are the different types of epithelia?
Simple (1 cell layer thick):
- squamous: flat cells, nucleus creates bump
- cuboidal: as high as it is wide, involved in secretion
- columnar: taller than they are wide, involved in absorption
- pseudostratified: look stratified but aren’t (nuclei all at different levels)
Stratified (more than 1 cell layer thick):
- squamous
- cuboidal
- columnar
- transitional: changes shape from columnar/cuboidal to flattened
Why is the degree to which malignant cells penetrate the basement membrane important?
Highly relevant to prognosis - if it has penetrated, prognosis is not good
What is the role of the endothelium?
- Exchange gases and nutrients
- Allow certain blood cells to enter the tissues
- Regulate platelet coagulation
What is the mesothelium?
When simple stratified epithelium lines the pleural sac, the pericardial sac and the peritoneum
Where can simple squamous epithelium be found?
- Bowman’s capsule
- Loop of Henle
- Inner and Middle ear
- Respiratory epithelium
- Lining of body cavities
- Lining of blood and lymph vessels
What are the functions of simple squamous epithelium?
- Lubrication
- Gas exchange
- Barrier
- Active transport by pinocytosis
Where can simple cuboidal epithelium be found?
- thyroid follicles
- small ducts of many exocrine glands
- kidney tubules
- surface of ovary
What are the functions of simple cuboidal epithelium?
- absorption and conduit
- absorption and secretion
- barrier/covering
- hormone synthesis, storage and mobilisation
- synthesis thyroxine, store it in colloid and transport it to the bloodstream
- partly determine urine volume and concentration by reabsorbing urea and water
Where can simple columnar epithelium be found?
- Stomach lining and gastric glands
- Small intestine and colon
- Gall bladder
- Large ducts of some exocrine glands
- Oviducts
- Uterus
- Ductuli efferent of testis
What are the functions of simple columnar epithelium?
- Absorption (nutrients and fluids)
- Secretion (enzyme and mucus)
- Lubrication
- Transport
- Some are ciliated
- Some have microvilli
What is the role of occludin?
- Binds adjacent plasma membranes tightly together in the apical portions of some epithelia
- Membrane proteins cannot bypass these ‘zonula occludens’
- This enables the cell to restrict certain proteins to its apical (free) surface and segregate others to its lateral and basal surfaces
Where can pseudostratified epithelium be found?
- lining of nasal cavity, trachea and bronchi
- epididymis and ductus deferens
- auditory tube and part of tympanic cavity
- lacrimal sac
- large excretory ducts
What are the functions of pseudostratified epithelium?
- secretion and conduit
- absorption
- mucus secretion
- particle trapping and removal
- lining
- sensory reception
Where can stratified squamous non-keratinized epithelium be found?
- Oral cavity
- Oesophagus
- Larynx
- Vagina
- Part of anal canal
- Surface of cornea
- Inner surface of eyelid
What are the functions of stratified squamous non-keratinized epithelium?
- Protection against abrasion
- Reduces water loss but remains moist
Where can stratified squamous keratinized epithelium be found?
- Surface of skin
- Limited distribution in oral cavity
What are the functions of stratified squamous keratinized epithelium?
- Protection against abrasion and physical trauma
- Prevents water loss
- Prevents ingress of microbes
- Shields against UV light damage
Where can transitional epithelium be found?
- Renal calyces
- Ureters
- Bladder
- Urethra
What are the functions of transitional epithelium?
- Distensibility
- Protection of underlying tissue from toxic chemicals
What are microvilli?
Apical extensions which greatly increase the surface area for selective absorption of intestinal contents
How is the shape of microvilli maintained?
Actin filaments
What are stereocilia?
Very long microvilli which may have an absorptive function
What does cell renewal depend on?
- The rate depends on the location and function
- Different for each epithelial type
- The time frame for each type of epithelium is constant unless damage leads to acceleration
- Some cease to be renewed once they reach adulthood
What is a gland?
An epithelial cell or collection of cells specialised for secretion
How can glands be classified?
- Destination of secretion
- Structure of the gland
- Nature of the secretion
- Method of discharge
How can glands be classified by destination?
- Exocrine: glands with ducts
- Endocrine: ‘ductless glands’ which secrete into the bloodstream
How can glands be classified by structure?
Secretory part:
- Unicellular/multicellular
- Acinar (alveolar)/tubular
- Coiled/branched
Duct system:
- Simple gland (single duct)
- Compound gland (branched ducts)
Branching ducts
- Main > interlobular > intralobular > intercalary
How can glands be classified by nature of secretion?
- Mucous glands
- Serous glands
What are mucous glands?
- Glands whose secretions contain mucus and are rich in mucins (highly glycosylated polypeptides)
- The cells stain poorly in H & E sections
What are serous glands?
- Glands whose secretions (often enzymes) are watery and free of mucus
- They are eosinophilic (pink) in H & E sections
How can glands be classified by method of secretions?
- Merocrine
- Apocrine
- Holocrine
What is merocrine secretion?
Exocytosis:
- Membrane bound component approaches cell surface
- Its bounding membrane fuses with the plasma membrane
- Its contents are in continuity with the extracellular space
- Plasma membrane transiently larger
- Contents released
- Membrane retrieved, stabilising cell surface area
What is apocrine secretion?
- Non-membrane bounded structure approaches cell surface
- Makes contact and pushes up apical membrane
- Thin layer of apical cytoplasm drapes around droplet
- Membrane surrounding droplet pinches off from cell
- Plasma membrane transiently smaller
- Membrane added to regain original area
What kind of secretion do apocrine sweat glands use?
Merocrine secretion
How can luminal contents move towards the duct?
Myoepithelial cells contract in order to facilitate the transport towards the duct
What is holocrine secretion?
- Disintegration of the cell
- Release of contents
- Discharge of whole cell
What is endocytosis?
- Engulfing material initially outside the cell
- Opposite of exocytosis
What is transepithelial transport?
- Material endocytosis at one surface
- Transport vesicles shuttles across cytoplasm
- Material exocytosis at opposite surface
What is the structure of the Golgi apparatus?
- Stack of disc-shaped cisternae
- 1 side of discs are flattened; other concave
- Discs have swellings at their edges
- Distal swellings pinch off as migratory Golgi vacuoles
Where does glycosylation take place?
In the cisternae of the Golgi apparatus
What is the function of the Golgi apparatus?
- Sorting into different compartments
- Packaging through condensation of contents
- Adding sugars to proteins and lipids, in specific orders (glycosylation)
- Transport of resultant vesicles
What are the destinations of the Golgi products?
- Majority extruded in secretory vesicles
- Some retained for use in the cells
- Some enter the plasma membrane
How can secretion be controlled?
- Nervous
- Endocrine
- Neuro-endocrine
- Negative feedback chemical mechanism
What are the 3 major salivary glands?
Parotid
Submandibular
Sublingual
What is the duodenum?
The first part of the small intestine
What is the endocrine function of the pancreas?
Manufacture and secretion of insulin and glucagon (in the islets of Langerhans)
What is the exocrine function of the pancreas?
Production of digestive enzymes, releasing them into the duodenum
Where can the thyroid gland be found?
In the neck, in front of the trachea
What are the small cells in the thyroid called?
Thyroid follicles
What is the role of the parathyroid?
Secretes parathyroid hormone
- This allows us to control calcium levels in the blood
Where is the parathyroid found?
Behind the thyroid gland
Why are branching sugars good?
They offer complex shapes for specific interactions in the glycocalyx
What are some specificity based properties of cells?
- Adhesion to substrates and neighbouring cells
- Mobility of cells
- Communication with neighbouring cells
- Contact inhibition of movement and division
Where can mucous membranes be found?
Lining certain internal tubes which open to the exterior
- E.g. the respiratory tract and the urinary tract
What does a mucous membrane consist of?
- An epithelium lining the lumen of a tube
- The basement membrane
- An adjacent layer of connective tissue (the lamina propria)
- A third layer consisting of smooth muscle cells (the muscularis mucosa) in the alimentary tract
What are serous membranes?
Thin, 2-part membranes which line certain closed body cavities
Where can serous membranes be found?
The peritoneum
The pleural sacs
The pericardial sac
What does a serous membrane consist of?
- A simple squamous epithelium (mesothelium) which secretes a watery lubricating fluid
- A thin layer of connective tissue which attaches the epithelium to adjacent tissues (also carries blood vessels and nerves)
Name the different parts of a serous membrane
- Parietal serosa (outer membrane)
- Air (in the middle)
- Visceral serosa (inner membrane)
What are the 4 layers of the gut wall?
- The mucosa (innermost)
- The submucosa
- The external muscle layers (muscularis externa)
- The serosa (outermost)
What does the mucosa of the gut wall consist of?
- Muscularis mucosae
- Lamina propria
- Epithelium
What does the submucosa contain?
- Connective tissue
- Nerves
- Bearing glands
- Arteries
- Veins
What is the muscularis externa?
2 layers of smooth muscle:
- Outer longitudinal layer
- Inner circular layer
It creates successive peristaltic waves to move luminal contents along the gut
What does the oesophageal mucosa consist of?
- Epithelium (stratified squamous non-keratinized) to withstand abrasion
- Lamina propria
- Muscularis mucosae
What is the adventitia?
The thin, outermost layer of connective tissue
What are rugae?
Folds of gastric mucosa forming longitudinal ridges in empty stomach
What happens to tracheal cartilage as you get older?
The C-shaped cartilage rings begin to transform to bone
What are the different types of cells in the alveoli?
Type I cells: squamous epithelial cells, cover 90% of surface area, permit gas exchange with capillaries
Type II cells: cuboidal epithelial cells, cover 10% of surface area, produce surfactant
Why are macrophages found on the alveolar surface?
To phagocytose unwanted particles (e.g. microbes and dust)
Why are bladder epithelium impermeable to urine?
- Thick plasma membrane
- Intercellular tight junctions
Define the limit of resolution
- The minimum distance at which 2 objects can be distinguished
- The limit of resolution is proportional to wavelength
What are the theoretical limits of resolution?
- 2 um for light microscope
0. 002 nm for electron microscope
Are phospholipid molecules amphipathic?
Yes - they are both water-loving and water-hating
What is the phospholipid bilayer?
- A membrane which forms a relatively impermeable barrier to most water-soluble molecules
- The protein molecules ‘dissolved’ in the lipid bilayer mediate most of the other functions of the membrane
What is the glycocalyx?
The cell coat
- It is made up of oligosaccharide and polysaccharide side chains on the outside of the plasma membrane
What are the functions of the plasma membrane?
- Selective permeability
- Transport of materials along cell surface
- Endocytosis
- Exocytosis
- Intercellular adhesion
- Intercellular recognition
- Signal transduction
Describe lysosomes
- Molecules that are generated by the Golgi apparatus
- Contain many hydrolytic enzymes (acid hydrolyses) at pH 5
- Lysosomal membrane proteins are highly glycosylated for protection from these enzymes
- They fuse with material requiring digestion
- Highly diverse in shape: usually dense, spherical or oval
- They are identified by enzyme content
- Primary lysosomes fuse with endocytosed, membrane-bound vesicles, with autophagosomes, or with excess secretory product to form secondary lysosomes in which the contents are digested
- Lysosomes which have digested their contents but contain indigestible remnants are called residual bodies
Where can peroxisomes be found?
In liver and kidney cells
What do peroxisomes do?
They detoxify (oxidise) a number of molecules including alcohol, phenols, formic acid and formaldehyde
What does the mitochondrial matrix contain?
100s of enzymes and mitochondrial DNA genome
What does the mitochondrial inner membrane contain?
Enzymes for oxidation reactions of respiratory chain
How are mitochondria replicated?
They can divide like a whole cell would
- They contain their own genetic information
What is the primary function of mitochondria?
Generation of potential energy (ATP) by oxidative phosphorylation
What is the cytoskeleton made of?
A network of actin filaments
What are intermediate filaments?
- Filaments that are bigger than actin filaments
- They are common in nerve, neuroglial and epithelial cells
- Form tough supporting meshwork in cytoplasm
- Also found just beneath inner nuclear membrane forming the nuclear lamina
- Not dynamic
- 10-12nm diameter
- Made of cytokeratin in epithelial cells
What are microtubules?
Long hollow cylinders made of the protein tubulim
- Found at sites where structures are moved
Describe the nucleus
- Contains DNA, nucleoproteins and RNA
- T.E.M. reveals electron-dense heterochromatin and electron-lucent euchromatin
- Inactive cells have small nuclei containing condensed heterochromatin; actively transcribing cells have relatively large nuclei, containing dispersed nuclei material (euchromatin)
- Not present in erythrocytes, stratum corneum cells and lens fibre cells
Describe the nucleolus
- One or more electron dense structures within nucleus
- More prominent inactive cells
- Sites of ribosomal RNA synthesis for ribosome assembly
- Ribosomal subunits are exported from the nucleus for ribosome activity
- Nucleoli disappear during cell division
Describe the nuclear envelope
- A double layer of membranes boding the nucleus
- A type of specialised endoplasmic reticulum
- The perinuclear cistern between the inner and outer nuclear membranes is continuous with that of the er
- Contains nuclear pores
Describe the endoplasmic reticulum
- Interconnecting membranes, vesicles and cisternae
- Known as rough ER when ribosomes are attached to its outer surface
- Rough ER is extensive in cells actively synthesising protein
- The ribosomes generate proteins which associate with the RER and are destined for the cell exterior (by exocytosis), for lysosomes or for cell membrane incorporation
- Known as smooth ER when not associated with ribosomes
- Cisternae not as flattened as RER and normally less extensive
- Functions primarily in lipid biosynthesis and intracellular transport
Describe peroxisomes
- Roughly spherical, containing granular matrix, bound by single membrane
- Self-replicating but no genome of their own
- Present in all cells, especially in kidney tubules and liver parenchymal cells which detoxify toxic molecules that enter the bloodstream
- Major sites of oxygen utilisation and H2O2 production
- Catalase utilises the H2O2 generated to oxidise other substrates including phenols, formic acid, formaldehyde and alcohol
Describe mitochondria
- Variable shape (often spherical to elongated oval)
- Double membrane with inner membrane thrown into distinct folds called cristae which are usually lamellar
- Primary function = generation of energy-rich ATP molecules by oxidative phosphorylation
- ATP molecules store energy needed by the cell
- Main substrates are glucose and fatty acids
- Large numbers in liver and skeletal muscle cells
- Inner space contains enzymes of Krebs and fatty acid cycles, DNA, RNA, ribosomes and calcium granules
- Can divide
- DNA, ribosomes and division similar to bacteria
- Female lineage (inherit all mitochondria from mother)
Describe the cytoskeleton
- All cells possess a cytoskeleton which is responsible for maintaining and/or changing cell shape
- Provides structural support for plasma membrane and cell organelles
- Provides means of movement for organelles, plasma membrane and other cytosol constituents
- Provides locomotor mechanisms for amoeboid movements and for cilia and flagella
- Provides contractility in cells of specialised tissues
- 3 main types = microfilaments, intermediate filaments and microtubules
Why can you not see the bacteria at the stomach’s epithelial surface?
- They stain poorly with H&E
- The tissue preparation deliberately removed most of them
- Insufficient magnification
- Routine histology often ignores or deliberately removes the microbial cells normally present on and in the human body
What are differences in individuals’ microbiomes linked to?
- Health (tissue differentiation)
- Diseases such as obesity, diabetes and psoriasis
What does the Gram stain allow us to do?
To detect and begin to classify most bacteria
What do acid fast stains allow us to do?
Detect the bacterial causes of tuberculosis and leprosy
How does the Gram stain work?
- Positively charged crystal violet binds to negatively charged cell components
- Iodine forms large molecular complexes with crystal violet
- Acetone or methanol extract the complexes through the Gram-negative but not through the Gram-positive bacterial cell wall
- A red dye is used to stain the now unstained Gram-negative cells
- The difference in extraction reveals a fundamental and medically important feature in bacteria
What are the differences between molecules with a Gram positive and a Gram negative stain?
Gram positive = cytoplasmic membrane + peptidoglycan
Gram negative = cytoplasmic membrane + outer membrane
What is the structure of bacteria?
- Shape = cocci (spherical), rods/bacilli (elongated), coccobacilli (partway between)
- Variations = curved, spiral, filamentous
- Internal structures = spores, inclusion granules
- External structures = fimbraie/pili, flagellae, capsule
- The cell envelope
Which cell envelope types are not visualised with Gram stain?
- Mycobacteria: shows up with Acid Fast Stain
- Mycoplasmas: no peptidoglycan
- Chlamydia, treponemes, rickettsia: too small
What is the clinical importance of cell walls?
- Detection and diagnosis via Gram and Acid fact stains
- Endotoxin effects
- Target for antibiotics
What are the different ways in which you can grow bacteria?
- Broth turbidity (leave in sterile environment)
- Colonies (streak - usually arise from a single cell)
- Biofilms (many all over body, often get colonised by bacteria)
What is the clinical importance of bacterial growth?
Broth turbidity: - Sensitive detection - Fluid filled cavities Colonies: - Easy identification and counting Biofilms: - Medical devices Speed: - Rate at which disease develops - Time to diagnosis
What are the requirements for growth?
- Specific energy source
- Specific building blocks
- Specific atmosphere
What is infection?
The establishment of an organism in or on a host associated with its multiplication and damage to, or dysfunction of, the host, specifically related to that organism or its products
What causes infection?
- Pathogenic microbes
- Viruses
- Prions
- Bacteria
- Protozoa
- Fungi
- Helminths
(- Archaea: not yet sure, but likely to)
Why do particular individuals get particular infections?
- Encounter
- Virulence vs. host resistance
- Innate and adaptive immunity
What influences the outcome of infection?
- Encounter dose and route
- Virulence vs. host resistance
- Innate and adaptive immunity
- Timely diagnosis and treatment
What are the major groups of prokaryotes and eukaryotes?
P = bacteria, archaea E = fungi, protozoa
How many chromosomes do prokaryotes and eukaryotes have?
P = 1 E = many
What is a virus?
- Non-living organism
- Submicroscopic
- Obligate intracellular parasites
- Have no genes that encode the proteins that function as the metabolic machinery for energy generation
- Have no genes that encode the proteins that function as the metabolic machinery for protein synthesis
- May or may not contain the genes that encode enzymes involved in nucleic acid synthesis
- Have RNA or DNA, not both
- Have no small ions or polysaccharides
- May or may not contain lipids
What is the basic structure of a virus?
Contains a nucleic acid core surrounded by a protein capsid
The capsid of some viruses is surrounded by an envelope
Nucleic acid (RNA or DNA):
- Single or double stranded
- Linear, circular or nicked
- Unsegmented or segmented
- If single stranded RNA, may be of the + or - sense (can serve as mRNA if it is + RNA, and can be directly translated into protein)
How are viruses usually diagnosed?
- Can be detected by genome directed nucleic acid amplification, culturing in cell cultures or identification of virus particles/antigens in tissue specimens
- Can also be recognised by detecting the specific virus-directed immune response
What is a capsid?
A virus’ protein outer coat
- It is composed of individual subunits called capsomers
- 2 basic capsid structures: icosahedral, helical
What is the function of the capsid?
- Protects the delicate inner nucleic acid from harsh environmental conditions
- May be involved in attachment to host cells
What is required for a virus to successfully infect and replicate in a host cell?
- Cell must contain the specific receptor that the virus binds to when initiating an infection
- The part of the virus that binds to the receptor is called the ligand
- The ligand is on the capsid of naked viruses and on the envelope of enveloped viruses
- The cell must also have the cellular machinery that the virus needs for replication
What is the host range of a virus?
The spectrum of host cells that the virus can successfully infect and replicate in
What is a permissive cell?
A host cell that can become infected by the virus
How can you classify viruses?
- By nucleic acid type
- By whether or not they have an envelope
What are the effects of a virus on a cell?
- Death of the cell
- Inclusion bodies are produced at the site of active virus synthesis
- Syncytia formation (giant, multinucleate cells formed by the fusion of plasma membranes)
- Chromosomal damage
- Inhibition of host cell protein, RNA or DNA synthesis
- Cancer
- Translate their RNA/DNA within the host cell to produce viral proteins (these can then be released during cell lysis or budding)
Many enveloped viruses produce no direct light microscope observable cytopathic effects
How can a virus cause cancer?
- If the virus integrates all or part of its genome into the host cell DNA
- Only RNA viruses that are retroviruses can cause cancer - by turning on, or bringing in, oncogenes
- Many DNA viruses can cause cancer, but they usually do it in a non-permissive cell
- They usually inactivate tumor-supressor proteins that normally act to keep the cell from going through the cell cycle
How is damage in infection usually caused?
Due to ineffective host responses rather than direct toxicity of the microbe
How are viruses absorbed into host cells?
- By first binding to receptors on the host cell
- The virus then enters the particles by receptor-mediated endocytosis
- Or by crossing the host cell membrane via coated pits or fusion with the host cell membrane
Describe viral infection
- Can be acute, subacute, chronic or latent
- Can be acquired from other humans or from the environment
- Characterised by an incubation period in which virus replication eventually leads to damage or dysfunction that is symptomatic
- Can spread via nerves to the nervous system and via the blood to many organs
- Many viruses spread by multiple pathways
- Is curtailed within the host primarily through cell-mediated immunity (cells of immune system recognise infected cells and destroy them)
What is morphogenesis?
The development of form and structure
What is cell differentiation?
Where a cell becomes specialised to perform a function
How does 1 cell become a multicellular body?
- Growth
- Morphogenesis
- Differentiation
What are the 3 stages of human development before birth?
- Pre-embryonic (2 weeks)
- Embryonic (3rd to 8th week)
- Fetal (rest of weeks)
How is the pregnancy due date calculated?
- From days of last menstrual period
- So may potentially add an extra 2 weeks on
What happens in the pre-embryonic period?
- Cleavage (mitotic cell division): formation of morula
- Compaction: formation of blastocyst
- Implantation begins
How does fertilisation occur?
- Oocyte is released from the ovary
- Travels along the Fallopian tube
- Fertilised by sperm in the ampulla
What is a fertilised oocyte called?
Zygote
Where is the ideal site for the implantation of a zygote?
The posterior uterine wall
How does cleavage occur?
- Begins 30 hours after fertilisation
- Results in 2 identical blastomeres of equal size
- Zona pellucid forms (a thick glycoprotein shell)
- This prevents polyspermy (fertilisation by multiple sperm)
What happens during the 1st week after the zygote has formed?
- A morula (multicellular ball) forms
- Each cell is totipotent at this stage
- Compaction
- Hatching
What does totipotent mean?
The capacity to become any cell type
What is in vitro fertilisation?
- An assisted reproductive technique
- Oocytes are fertilised in vitro and then allowed to divide to the 4- or 8- cell stage
- The morula is then transferred into the uterus
In IVF, why are the fertilised oocytes allowed to divide?
- Not all oocytes will progress to this stage
- Allowing cleavage to occur will help to see whether pregnancy is viable
What is PGD?
- Pre-implantation Genetic Diagnosis
- A cell can be safely removed from the morula and tested for serious heritable conditions prior to transfer of the embryo into the mother
What is compaction?
- Formation of the first cavity, which then gets larger and larger
- This is called the blastocyst cavity
- The inner cell mass is called the embryoblast and will eventually form the embryo
- The outer cell mass is called the trophoplasy and will produce the placenta
- Occurs during week 1
During compaction, how does the cavity form and why?
- The morula became so packed with cells that they could no longer receive nutrients, so a cavity forms to allow then to gain some
- Cells secrete tiny amounts of fluid which can coalesce
- This pushes the morula cells to the side, creating a fluid-filled cavity
What does pluripotent mean?
The capacity to become one of many cell types
What is hatching?
- Blastocyst hatches from the zone pellucida, since the risk of polyspermy has receded
- It is no longer constrained, so is free to enlarge
- It can now interact with the uterine surface to implant
- Occurs during the first week
What happens to the majority of cells at the end of the first week?
- They form the fetal membranes and placenta (99/107)
- The others will make the embryo
What happens during week 2 of the zygote?
Differentiation:
- 2 distinct cellular layers emerge from the outer cell mass: the synctiotrophoblast and the cytotrophoblast
- The inner cell mass becomes the bilaminar disk (the epiblast and the hypoblast)
- The outer cell mass forms the amniotic sac whereas the inner cell mass forms the embryo
What has happened by the end of the 2nd week?
- The conceptus has implanted
- The embryo and its 2 cavities (amniotic sac and yolk sac) will be suspended by a connected stalk within a supporting sac (chorionic cavity)
- The connected stalk is a column of mesoderm and is the future umbilical cord
How does implantation occur?
- The blastocyst makes contact with the uterine wall and releases enzymes which allow it to become embedded
- This is invasive, so can cause bleeding
- The fibrin plug forms after implantation
- It is interstitial
- It establishes maternal blood flow within the placenta
- This changes the embryo support from histiotrophic to haemotrophic
- The embryo no longer has to rely on simple diffusion
- It establishes the basic structural unit of materno-fetal exchange
What conditions are linked to implantation defects?
- Inter uterine growth restriction
- Pre-eclampsia
- Ectopic pregnany
- Placenta praevia
What is an ectopic pregnancy?
- Implantation at site other than uterine body (most commonly the Fallopian tube)
- Can be peritoneal or ovarian
- Can very quickly become life-threatening emergency
What is placenta praevia?
- Implantation in the lower uterine segment
- The placenta can grow across and cover the reproductive tract
- Can cause haemorrhage in pregnancy
- Requires C-section delivery
What different cavities/sacs form during pregnancy?
- Blastoceole (1st cavity, formed as a result of compaction)
- Amniotic sac (formed from spaces within the epiblast)
- Primitive yolk sac (a.k.a. exocoelomic cavity, formed by hypoblast lining blastoceole)
- Secondary yolk sac (a.k.a. definitive yolk sac, formed from primitive yolk sac)
- Extraembryonic coelum (a.k.a. chorionic cavity, formed from spaces within extra embryonic reticulum and mesoderm)
How are the amniotic sac and the primitive yolk sac formed?
- There is an amniotic cavity between the cytotrophoblast and the epiblast
- The epiblast and hypoblast are pushed further away from the cytotrophoblast as they extent, increasing the amniotic cavity
- This produces the primitive yolk sac (it is the space between the hypoblast and the cytotrophoblast)
How does uteroplacental circulation begin?
- The synctiotrophoblast rapidly develops and forms lacunae
- It invades maternal sinusoids
- The lacunae become continuous with sinusoids
- This allows blood to flow
How does the secondary yolk sac form?
- The primitive yolk sac membrane is pushed away from the cytotrophoblast layer by an acellular extra embryonic reticulum
- The reticulum layer is converted to extra embryonic mesoderm by cell migration
- The secondary yolk sac can then pinch off from the primitive yolk sac
How does the chorionic cavity form?
Spaces within the extra embryonic mesoderm merge to form it
What is metaplasia?
The capacity to change from 1 type of epithelium to another
- Usually caused by disease
What is neoplasia?
- In disease, changes may occur in epithelia giving rise to a tumour (a carcinoma)
- The cells in benign tumours resemble those of their tissue of origin, but those in malignant tumours have altered or abnormal cell structure and also invade adjacent tissues
What are the 2 layers in the skin?
Epidermis and dermis
What layers are there in the dermis?
Papillary region
Reticular layer
What is special about the shape of the dermis?
It has finger-like projections (folds) which reach up into the epidermis, stabilising it and preventing it from shearing off
What are the functions of the skin?
- Protection
- Prevention of fluid loss
- Temperature regulation
- Excretion
- Absorption
- Regeneration
- Sensation
- Psychosexual communication
What is connective tissue?
- A tissue that forms a huge continuum throughout the body, linking together muscle, nerve and epithelial tissue in a structural way
- This also provides support in metabolic and physiological ways
What connective tissue types are there?
- Blood, a liquid tissue with its gas transport and immune defence functions
- Cartilage
- Bone (both have solid skeletal functions)
What is the function of connective tissue?
- Provide substance and form to the body and organs
- Provide a medium for diffusion of nutrients and wastes
- Attach muscle to bone and bone to bone
- Provide a cushion between tissues and organs
- Defend against infection (a place where many immune cells reside)
- Aid in injury repair
What are the components of connective tissue?
- Cells (undifferentiated mesenchymal cells, fibroblasts, adipocytes, macrophages, mast cells, plasma cells and blood cells)
- Extracellular matrix: this contains the ground substance and fibres
What fibres can be found in the extracellular matrix?
- Collagen
- Reticulin
- Elastic
What does the ground substance contain?
- Protein
- Glycoprotein
- Glycosaminoglycans (GAGs)
- Lipid
- Water
(The high density of negative charges on the GAGs attracts water, forming a hydrated gel)
Also contains the cells, fibres and blood vessels
In what way do connective tissues differ from each other?
- The type of cells they contain
- The abundance/density of their cells
- The constitution of their extra cellular matrix in terms of ground substance composition and fibre type/abundance/arrangement
How can connective tissue be classified?
Embryonic connective tissue:
- Mesenchyme
- Mucous connective tissue
Regular connective tissue
- Loose (or areolar) connective tissue
- Dense connective tissue (irregular or regular): this connects the epithelial tissue of the skin to the underlying tissue
Specialised connective tissue:
- Adipose tissue
- Blood
- Cartilage
- Bone
- Lymphatic tissue
- Haemopoietic tissue (bone marrow)
What is mesenchymal tissue?
- Made from the mesodermal cells of the middle embryonic germ layer and a few ectodermal cells
- Multipotent progenitor cells
- The cells are morphologically similar but will give rise to cells that differentiate into a variety of different cell types
- Mesenchymal cells persist in the adult and can give rise to new connective tissue cells when healing is required
What are fibroblasts?
- Cells which secrete procallagen
- This assembles collagen fibrils
- They synthesise and secrete both ground substance and the fibres that lie within the ground substance
- Very important in wound healing
- The fibroblasts are intimately associated with the collagen fibrils
- Spindle-shaped cells
What is collagen?
- The commonest protein in our body
- The thin fibres can aggregate to form collagen bundles
- There are at least 28 identified types of collagen
- Fibrillar collagen: I-III
- Amorphous collagen: IV-VI
- Type I: most widely distributed type, fibrils aggregate into fibres and fibre bundles, has periodic banding, each fibril is composed of staggered collagen molecules, each collagen molecule is composed of a triple helix of a chains
- Type II: fibrils do not form fibres
- Type III: fibrils form fibres around muscle and nerve cells and within lymphatic tissues and organs. Called reticulin
- Can be remodelled by specific collagenases
What is elastin?
- The primary component of elastic fibres
- It enfolds itself and is surrounded by micro fibrils called fibrillin
- It occurs in most connective tissues but to widely varying degrees
At which sites are elastic fibres important?
- The dermis
- Artery walls
- Those sites bearing elastic cartilage
- Consists of the tunica intima (in distinct endothelial cells), the tunica media (elastin lamellae) and the tunica adventitia (collagen)
What do smooth muscle cells produce
- Elastin
- Collagen
- Matrix
What is the difference between dense irregular connective tissue and loose tissue?
Dense irregular connective tissue is:
- Thicker
- More abundant collagen
- Fewer fibroblasts
What connective tissue is in the dermis and why?
Dense irregular tissue
- The irregularity helps the skin to resist forces in multiple directions to prevent tearing
- Elastic fibres allow a degree of stretch and a restoration to the original shape after the skin is bent or folded
What is a capsule?
Connective tissue that surrounds a gland
- Can very from loose to dense, irregular connective tissue
- Depends on location
- They protect the tissues they surround
How do tendons connect muscles to bones?
- The collagen bundles lie in a parallel, densely packed formation in line with the tensile force exerted by the muscle
- Rows of flattened fibroblasts lie between the collagen bundles
Describe collagen bundle structure
- Densely packed in parallel arrangement
- Undulate
- Arranged in fascicles
- Seperated by loose connective tissue
What are macrophages?
- Phagocytic
- Can degrade foreign organisms and cell debris
- Professional antigen presenting cells
- Derived from blood monocytes
- Move into loose connective tissue, especially when there is local inflammation
What does mast cell cytoplasm contain?
Abundant granules, which contain:
- Heparin (anticoagulant)
- Histamine (increases blood vessel wall permeability)
- Substances that attract eosinophils and neutrophils
What does white adipose tissue contain?
- Multiple lipid droplets which fuse to form a single large droplet
- This large droplet displaces all other cell contents to the cell periphery
What does brown adipose tissue contain?
- An abundance of mitochondria
- Multiple, separate lipid droplets
What is the structure of an adipose cell?
- Almost completely filled by a single fat droplet
- The cytoplasm is displaced to the rim of the cell and the nucleus to one side
What is the role of adipose tissue?
- Contains fat, a fuel reserve
- Role in thermal regulation
- Role in shock absorption
What variations in macroscopic structure of human skin are there?
Colour:
- Ethnicity
- Site
- Ultraviolet
Hair:
- Site (hairy vs hair-free areas)
- Sex (facial and more profuse body hair growth in men)
- Age (baldness in men; greying in both sexes)
- Ethnicity (colour, character)
Laxity/wrinkling:
- Site
- Age/ultraviolet
What is alopecia areata?
Partial or complete hair loss
- Autoimmune attack against hair follicles
Why does wrinkling occur?
Because of the gradual breakdown of collagen
- UV light can speed this process up
What are the 4 layers in the epidermis?
- Stratum corneum (horny layer)
- Granular layer (stratum granulosum)
- Prickle cell layer (stratum spinosum)
- Basal layer (stratum basale)
What happens in the basal layer?
- Keratinocyte mitosis (cell division) occurs mainly in the basal layer
- The daughter keratinocytes then move upwards to form the prickle cell layer
What happens in the prickle cell layer?
- Terminal differentiation begins
- Keratinocytes lose their ability to divide
What do keratinocytes do?
- Synthesise keratins
- These contribute to the strength of the epidermis
- Keratins are also the main constituents of hair and nail
What joins prickle cells?
Prickle-like desmosomes (intercellular junctions)
What happens in the granular layer?
- Keratinocytes lose their plasma membrane
- Keratinocytes begin differentiating into corneocytes, the main cells of the stratum corneum
What does the granular layer contain?
Keratohyalin granules, which are aggregations of:
- Keratins
- Other fibrous proteins
- Enzymes which degrade the phospholipid bilayer (phospholipase)
- Enzymes which cross link proteins
