Semester 1 Flashcards
0
Q
Define tissue
A
A collection of cells specialised to perform a particular function
1
Q
What is histology?
A
The study of the structure of tissues by means of special staining techniques combined with light and electron microscopy
2
Q
What are the different types of tissue?
A
- Epithelial
- Connective
- Muscle
- Nervous
3
Q
In metres, how big is a millimetre?
A
10 ^ -3
4
Q
In metres, how big is a micrometre?
A
10 ^ -6
5
Q
In metres, how big is a nanometre?
A
10 ^ -9
6
Q
How big are most human cells?
A
10 - 20 um in diameter
7
Q
How big are red blood cells?
A
7.2 um diameter
8
Q
What is a biopsy?
A
The removal of a small piece of tissue from an organ or part of the body for microscopic examination
9
Q
What are the different types of biopsy and give an example of what they are each used for?
A
- 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)
10
Q
What chemicals can be used for fixation?
A
Glutaraldehyde, formaldehyde or alcohol
11
Q
What are the most commonly used stains?
A
Haematoxylin and eosin
12
Q
What is haematoxylin used to stain and what colour?
A
Acidic components of cells - purple/blue
13
Q
What is eosin used to stain and what colour?
A
Basic components of cells - pink
14
Q
Why are biopsies fixed?
A
To preserve the cellular structure
15
Q
What is Periodic Acid-Schiff (PAS)?
A
- Staining method
- Stains carbohydrates and glycoproteins magenta
16
Q
What is an artefact?
A
A structure seen in a tissue, under a microscope, that is not present in living tissue and occurs due to the preparation technique
17
Q
What is Weigert’s elastin?
A
A stain that stains elastic fibres silver
18
Q
What is Elastic Van Gieson?
A
A stain that stains:
- Collagen pink/red
- Elastin blue/black
- Muscle yellow
19
Q
How does phase contrast microscopy work?
A
- 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
20
Q
What is differential-interference-contrast-microscopy?
A
Similar to phase contrast microscopy
21
Q
What is confocal microscopy used for?
A
- 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
22
Q
How does confocal microscopy work?
A
- 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
23
Q
What is the process of staining and preserving biopsy for microscopy?
A
- 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
24
What is epithelia?
Sheets of contiguous cells, of varied embryonic origin, that cover the external surface of the body and line internal surfaces
25
Which exterior surface has epithelial linings?
Skin
26
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
27
What are the 3 germ layers of the embryo?
- Ectoderm
- Mesoderm
- Endoderm
28
Give an example of an epithelial derivative from an ectoderm layer
- Epithelium of skin
| - Corneal epithelium of eye
29
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
30
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
31
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
32
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
33
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
34
What is the role of the endothelium?
- Exchange gases and nutrients
- Allow certain blood cells to enter the tissues
- Regulate platelet coagulation
35
What is the mesothelium?
When simple stratified epithelium lines the pleural sac, the pericardial sac and the peritoneum
36
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
37
What are the functions of simple squamous epithelium?
- Lubrication
- Gas exchange
- Barrier
- Active transport by pinocytosis
38
Where can simple cuboidal epithelium be found?
- thyroid follicles
- small ducts of many exocrine glands
- kidney tubules
- surface of ovary
39
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
40
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
41
What are the functions of simple columnar epithelium?
- Absorption (nutrients and fluids)
- Secretion (enzyme and mucus)
- Lubrication
- Transport
- Some are ciliated
- Some have microvilli
42
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
43
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
44
What are the functions of pseudostratified epithelium?
- secretion and conduit
- absorption
- mucus secretion
- particle trapping and removal
- lining
- sensory reception
45
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
46
What are the functions of stratified squamous non-keratinized epithelium?
- Protection against abrasion
| - Reduces water loss but remains moist
47
Where can stratified squamous keratinized epithelium be found?
- Surface of skin
| - Limited distribution in oral cavity
48
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
49
Where can transitional epithelium be found?
- Renal calyces
- Ureters
- Bladder
- Urethra
50
What are the functions of transitional epithelium?
- Distensibility
| - Protection of underlying tissue from toxic chemicals
51
What are microvilli?
Apical extensions which greatly increase the surface area for selective absorption of intestinal contents
52
How is the shape of microvilli maintained?
Actin filaments
53
What are stereocilia?
Very long microvilli which may have an absorptive function
54
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
55
What is a gland?
An epithelial cell or collection of cells specialised for secretion
56
How can glands be classified?
- Destination of secretion
- Structure of the gland
- Nature of the secretion
- Method of discharge
57
How can glands be classified by destination?
- Exocrine: glands with ducts
| - Endocrine: 'ductless glands' which secrete into the bloodstream
58
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
59
How can glands be classified by nature of secretion?
- Mucous glands
| - Serous glands
60
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
61
What are serous glands?
- Glands whose secretions (often enzymes) are watery and free of mucus
- They are eosinophilic (pink) in H & E sections
62
How can glands be classified by method of secretions?
- Merocrine
- Apocrine
- Holocrine
63
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
64
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
65
What kind of secretion do apocrine sweat glands use?
Merocrine secretion
66
How can luminal contents move towards the duct?
Myoepithelial cells contract in order to facilitate the transport towards the duct
67
What is holocrine secretion?
- Disintegration of the cell
- Release of contents
- Discharge of whole cell
68
What is endocytosis?
- Engulfing material initially outside the cell
| - Opposite of exocytosis
69
What is transepithelial transport?
- Material endocytosis at one surface
- Transport vesicles shuttles across cytoplasm
- Material exocytosis at opposite surface
70
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
71
Where does glycosylation take place?
In the cisternae of the Golgi apparatus
72
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
73
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
74
How can secretion be controlled?
- Nervous
- Endocrine
- Neuro-endocrine
- Negative feedback chemical mechanism
75
What are the 3 major salivary glands?
Parotid
Submandibular
Sublingual
76
What is the duodenum?
The first part of the small intestine
77
What is the endocrine function of the pancreas?
Manufacture and secretion of insulin and glucagon (in the islets of Langerhans)
78
What is the exocrine function of the pancreas?
Production of digestive enzymes, releasing them into the duodenum
79
Where can the thyroid gland be found?
In the neck, in front of the trachea
80
What are the small cells in the thyroid called?
Thyroid follicles
81
What is the role of the parathyroid?
Secretes parathyroid hormone
| - This allows us to control calcium levels in the blood
82
Where is the parathyroid found?
Behind the thyroid gland
83
Why are branching sugars good?
They offer complex shapes for specific interactions in the glycocalyx
84
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
85
Where can mucous membranes be found?
Lining certain internal tubes which open to the exterior
| - E.g. the respiratory tract and the urinary tract
86
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
87
What are serous membranes?
Thin, 2-part membranes which line certain closed body cavities
88
Where can serous membranes be found?
The peritoneum
The pleural sacs
The pericardial sac
89
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)
90
Name the different parts of a serous membrane
- Parietal serosa (outer membrane)
- Air (in the middle)
- Visceral serosa (inner membrane)
91
What are the 4 layers of the gut wall?
- The mucosa (innermost)
- The submucosa
- The external muscle layers (muscularis externa)
- The serosa (outermost)
92
What does the mucosa of the gut wall consist of?
- Muscularis mucosae
- Lamina propria
- Epithelium
93
What does the submucosa contain?
- Connective tissue
- Nerves
- Bearing glands
- Arteries
- Veins
94
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
95
What does the oesophageal mucosa consist of?
- Epithelium (stratified squamous non-keratinized) to withstand abrasion
- Lamina propria
- Muscularis mucosae
96
What is the adventitia?
The thin, outermost layer of connective tissue
97
What are rugae?
Folds of gastric mucosa forming longitudinal ridges in empty stomach
98
What happens to tracheal cartilage as you get older?
The C-shaped cartilage rings begin to transform to bone
99
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
100
Why are macrophages found on the alveolar surface?
To phagocytose unwanted particles (e.g. microbes and dust)
101
Why are bladder epithelium impermeable to urine?
- Thick plasma membrane
| - Intercellular tight junctions
102
Define the limit of resolution
- The minimum distance at which 2 objects can be distinguished
- The limit of resolution is proportional to wavelength
103
What are the theoretical limits of resolution?
0. 2 um for light microscope
| 0. 002 nm for electron microscope
104
Are phospholipid molecules amphipathic?
Yes - they are both water-loving and water-hating
105
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
106
What is the glycocalyx?
The cell coat
| - It is made up of oligosaccharide and polysaccharide side chains on the outside of the plasma membrane
107
What are the functions of the plasma membrane?
- Selective permeability
- Transport of materials along cell surface
- Endocytosis
- Exocytosis
- Intercellular adhesion
- Intercellular recognition
- Signal transduction
108
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
109
Where can peroxisomes be found?
In liver and kidney cells
110
What do peroxisomes do?
They detoxify (oxidise) a number of molecules including alcohol, phenols, formic acid and formaldehyde
111
What does the mitochondrial matrix contain?
100s of enzymes and mitochondrial DNA genome
112
What does the mitochondrial inner membrane contain?
Enzymes for oxidation reactions of respiratory chain
113
How are mitochondria replicated?
They can divide like a whole cell would
| - They contain their own genetic information
114
What is the primary function of mitochondria?
Generation of potential energy (ATP) by oxidative phosphorylation
115
What is the cytoskeleton made of?
A network of actin filaments
116
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
117
What are microtubules?
Long hollow cylinders made of the protein tubulim
| - Found at sites where structures are moved
118
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
119
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
120
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
121
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
122
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
123
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)
124
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
125
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
126
What are differences in individuals' microbiomes linked to?
- Health (tissue differentiation)
| - Diseases such as obesity, diabetes and psoriasis
127
What does the Gram stain allow us to do?
To detect and begin to classify most bacteria
128
What do acid fast stains allow us to do?
Detect the bacterial causes of tuberculosis and leprosy
129
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
130
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
131
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
132
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
133
What is the clinical importance of cell walls?
- Detection and diagnosis via Gram and Acid fact stains
- Endotoxin effects
- Target for antibiotics
134
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)
135
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
```
136
What are the requirements for growth?
- Specific energy source
- Specific building blocks
- Specific atmosphere
137
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
138
What causes infection?
- Pathogenic microbes
- Viruses
- Prions
- Bacteria
- Protozoa
- Fungi
- Helminths
(- Archaea: not yet sure, but likely to)
139
Why do particular individuals get particular infections?
- Encounter
- Virulence vs. host resistance
- Innate and adaptive immunity
140
What influences the outcome of infection?
- Encounter dose and route
- Virulence vs. host resistance
- Innate and adaptive immunity
- Timely diagnosis and treatment
141
What are the major groups of prokaryotes and eukaryotes?
```
P = bacteria, archaea
E = fungi, protozoa
```
142
How many chromosomes do prokaryotes and eukaryotes have?
```
P = 1
E = many
```
143
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
144
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)
145
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
146
What is a capsid?
A virus' protein outer coat
- It is composed of individual subunits called capsomers
- 2 basic capsid structures: icosahedral, helical
147
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
148
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
149
What is the host range of a virus?
The spectrum of host cells that the virus can successfully infect and replicate in
150
What is a permissive cell?
A host cell that can become infected by the virus
151
How can you classify viruses?
- By nucleic acid type
| - By whether or not they have an envelope
152
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
153
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
154
How is damage in infection usually caused?
Due to ineffective host responses rather than direct toxicity of the microbe
155
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
156
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)
157
What is morphogenesis?
The development of form and structure
158
What is cell differentiation?
Where a cell becomes specialised to perform a function
159
How does 1 cell become a multicellular body?
- Growth
- Morphogenesis
- Differentiation
160
What are the 3 stages of human development before birth?
- Pre-embryonic (2 weeks)
- Embryonic (3rd to 8th week)
- Fetal (rest of weeks)
161
How is the pregnancy due date calculated?
- From days of last menstrual period
| - So may potentially add an extra 2 weeks on
162
What happens in the pre-embryonic period?
- Cleavage (mitotic cell division): formation of morula
- Compaction: formation of blastocyst
- Implantation begins
163
How does fertilisation occur?
- Oocyte is released from the ovary
- Travels along the Fallopian tube
- Fertilised by sperm in the ampulla
164
What is a fertilised oocyte called?
Zygote
165
Where is the ideal site for the implantation of a zygote?
The posterior uterine wall
166
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)
167
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
168
What does totipotent mean?
The capacity to become any cell type
169
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
170
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
171
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
172
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
173
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
174
What does pluripotent mean?
The capacity to become one of many cell types
175
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
176
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
177
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
178
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
179
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
180
What conditions are linked to implantation defects?
- Inter uterine growth restriction
- Pre-eclampsia
- Ectopic pregnany
- Placenta praevia
181
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
182
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
183
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)
184
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)
185
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
186
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
187
How does the chorionic cavity form?
Spaces within the extra embryonic mesoderm merge to form it
188
What is metaplasia?
The capacity to change from 1 type of epithelium to another
| - Usually caused by disease
189
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
190
What are the 2 layers in the skin?
Epidermis and dermis
191
What layers are there in the dermis?
Papillary region
| Reticular layer
192
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
193
What are the functions of the skin?
- Protection
- Prevention of fluid loss
- Temperature regulation
- Excretion
- Absorption
- Regeneration
- Sensation
- Psychosexual communication
194
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
195
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)
196
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
197
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
198
What fibres can be found in the extracellular matrix?
- Collagen
- Reticulin
- Elastic
199
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
200
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
201
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)
202
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
203
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
204
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
205
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
206
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)
207
What do smooth muscle cells produce
- Elastin
- Collagen
- Matrix
208
What is the difference between dense irregular connective tissue and loose tissue?
Dense irregular connective tissue is:
- Thicker
- More abundant collagen
- Fewer fibroblasts
209
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
210
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
211
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
212
Describe collagen bundle structure
- Densely packed in parallel arrangement
- Undulate
- Arranged in fascicles
- Seperated by loose connective tissue
213
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
214
What does mast cell cytoplasm contain?
Abundant granules, which contain:
- Heparin (anticoagulant)
- Histamine (increases blood vessel wall permeability)
- Substances that attract eosinophils and neutrophils
215
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
216
What does brown adipose tissue contain?
- An abundance of mitochondria
| - Multiple, separate lipid droplets
217
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
218
What is the role of adipose tissue?
- Contains fat, a fuel reserve
- Role in thermal regulation
- Role in shock absorption
219
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
220
What is alopecia areata?
Partial or complete hair loss
| - Autoimmune attack against hair follicles
221
Why does wrinkling occur?
Because of the gradual breakdown of collagen
| - UV light can speed this process up
222
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)
223
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
224
What happens in the prickle cell layer?
- Terminal differentiation begins
| - Keratinocytes lose their ability to divide
225
What do keratinocytes do?
- Synthesise keratins
- These contribute to the strength of the epidermis
- Keratins are also the main constituents of hair and nail
226
What joins prickle cells?
Prickle-like desmosomes (intercellular junctions)
227
What happens in the granular layer?
- Keratinocytes lose their plasma membrane
| - Keratinocytes begin differentiating into corneocytes, the main cells of the stratum corneum
228
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
229
What is the stratum corneum made up of?
Laters of flattened corneocytes
230
What is the role of the stratum corneum?
- Major role in skin barrier function
- Forms a chemo-barrier
- It has a water-barrier function
231
What is the transit time of a keratinocyte from basal layer to stratum corneum?
30-40 days
232
What other cells are there in the epidermis?
- Melanocytes
| - Langerhans cells
233
What are melanocytes?
- Dendritic cells of neural crest origin
- Occur at intervals along the basal layer of the epidermis
- Also found in hair follicles
- Difficult to see histologically without special stains
- Produce melanin, the main pigment that gives the skin its colour
- Melanin is 'fed out' to surrounding keratinocytes through dendrites
- Produce more melanin, but are not increased in number in black or tanned skin
234
What are Langerhans cells?
- Dendritic cells of bone marrow origin
- Scattered throughout the prickle cell layer
- Difficult to see histologically without special stains
- Highly specialised capacity to present antigens to T lymphocytes
- Mediate immune reactions
- Responsible for cutaneous delayed-type hypersensitivity reactions
235
What happens to mature melanosomes?
They are transferred to neighbouring keratinocytes
- By pigment donation
- Involves phagocytosis of the tops of the dendritic processes
236
What is psoriasis?
Abnormal epidermal growth and
- A very common skin disease (affects 2% of the population)
- Runs in families
- Associated with extreme proliferation of the epidermal basal layer, causing gross thickening of the prickle cell layer and production of excessive stratum corneum cells
237
What mediates allergic contact dermatitis?
Langerhans cells
238
What is malignant melanoma?
Malignant growth of melanocytes
- An aggressive malignant tumour
- Common primary site is the skin
- Penetrating nodular melanomas may have a poor prognosis
- Common moles are benign growths of melanocytes
239
What is vitiligo?
Autoimmune destruction of melanocytes
- Usually in symmetrical, localised areas of skin
- Causes well-demarcated depigmentation
240
What are keloids?
The product of grossly excessive scar tissue production following wounding
241
What is a tissue mast cell?
- Cells that are distributed around dermal blood vessels
- Contains numerous cytoplasmic granules
- These granules contain histamine
- Histamine can be released during type 1 immediate hypersensitivity (allergic) reactions
242
What is the result of histamine release?
- Increased vascular permeability
- Leakage of plasma into extravascular sites, causing local oedema
- In the skin, this can cause urticaria and angio-oedema
243
What skin appendages are there?
- Hair follicles
- Sebaceous glands
- Sweat glands (eccrine, apocrine)
- Nails
244
What is acne?
A skin disease that affects sebaceous glands
Caused by:
- abnormal differentiation of sebaceous gland ducts which become obstructed
- increased sebum production
- infection with normally harmless skin bacteria
245
What is hyperhidrosis?
Increased sweating
- Cause is usually unknown
- May affect only the palms and soles
- Embarrassing wet hands
- Wet, malodorous feet
246
What are apocrine sweat glands?
- Large sweat glands
- Most abundant in axillae, genital and submammary areas
- Have no function of value
- Produce an odourless, protein-rich, apocrine secretion
- Digestion of this by cutaneous microbes produce body odour
247
What is the barrier function of the skin?
- The outer epidermis (stratum corneum) forms a major barrier
- It prevents percutaneous absorption of exogenous substances
- It must be overcome during percutaneous absorption of drugs
- May be seriously disrupted by many diseases (e.g. psoriasis)
248
What problems can occur due to extensive psoriasis?
Disrupted skin barrier so poor barrier function
- Loss of fluid
- Loss of protein
- Loss of other nutrients
- Loss of heat
- Excessive absorption of potentially harmful exogenous agents
249
What is vascular thermoregulation?
- Dilation of skin blood vessels leads to heat loss
| - Constriction of skin blood vessels leads to pallor and heat conservation
250
What happens if vascular thermoregulation fails?
Heat loss
| - Patients are often shivery and may become hypothermic
251
What is thermoregulatory eccrine sweating?
Evaporation of eccrine sweat causes cooling
252
What is psychosexual communication?
The skin itself and its appendages are manipulated in many ways as a means of communication and expression
253
What is dense connective tissue?
- Connective tissue that has closely packed fibres
- Cells are proportionally fewer in number than in loose connective tissue
- Provides mechanical support for various structures
- Sometimes transmit forces used in muscular movements
- The arrangement of collagenous fibres is either regular or irregular
- Found in tendons, ligaments, aponeuroses, fascia...
254
What is dense irregular connective tissue?
- Contains interwoven bundles of collagen
- These crisscross each other in many directions
- This helps them to counteract the multi-directional forces to which the tissue is subjected
- E.g. forms the capsules, large septa and trabecular of many organs, the deep fascia of muscles, the dermis of the skin,...
255
What is dense regular connective tissue?
- Contains fibre bundles orientated in parallel
- This provides maximum tensile strength for the transmission of opposing forces
- Found in tendons, ligaments, aponeuroses,...
256
What is the difference in structure between ligaments and tendons?
- Both are composed of collagen fibres, interspersed with fibroblasts
- The elements are less regularly arranged in ligaments
257
What is areolar connective tissue?
- Formed by the differentiation of cells from the mesenchyme
- It is a loosely arranged fibro-elastic connective tissue with an extensive distribution
- It occur just deep to the skin
- Also lies below the mesothelial lining of the peritoneum, is associated with the adventitia of blood vessels and surrounds the parenchyma of glands
- Forms a layer beneath the epithelia of mucous membranes where it is called the submucosa
- Contains both fibroblasts and macrophages, as well as occasional mast cells
- Collagen fibres are the most abundant of the 3 fibre types, - Elastin fibres are also present (form a continuous fine branching network)
- Very few reticular fibres present
258
What is adipose tissue?
A tissue in which the majority of cells are adipose cells
259
Why are adipose cells unstained in normally processed slides?
The fat has dissolved out by xylene during the processing of the tissue
- But their thin nuclei compressed against the cell membrane can usually be seen
260
What is found in the dermis?
- Fibroblasts and extracellular matrix
- Blood vessels
- Lymphatic vessels
- Mast cells
- Nerves
261
What is cartilage?
An avascular tissue
- Consists of an extensive an extradcellular matrix
- Chondrocytes lie in this matrix
262
What do chondrocytes do?
They produce and maintain the extracellular matrix
263
Describe the extracellular matrix?
- Solid
- Firm
- Pliable so resilient to the repeated application of pressure
264
What can be found in the extracellular matrix?
Hyaluronic acid
265
What is the role of hyaluronic acid in the extracellular matrix?
Assists in the resilience to the repeated application of pressure
266
Why can substances readily diffuse between the chondrocytes and surrounding blood vessels?
There is a large ratio of glycosaminoglycans (GAGs) to type II collagen in the cartilage matrix which permits diffusion
267
What are the 3 types of cartilage?
- Hyaline
- Elastic
- Fibrocartilage
268
What is the structure of hyaline cartilage?
- Has a matrix containing proteoglycans, hyaluronic acid and type II collagen
- The hyaluronate proteoglycan aggregates are bound to the fine collagen matrix fibres
- The extra cellular matrix is highly hydrated
- This, and the transient movement of water within the matrix permits resilience to varying pressure loads
- Chondrocytes are present singly or, if recently divided, as small clusters called isogenous groups
269
What is the structure of elastic cartilage?
- Has a matrix like that of hyaline cartilage (proteoglycans, hyaluronic acid, type II collagen)
- But with the addition of many elastic fibres and elastic lamellae
- Perichondrium above it
270
What is the structure of fibrocartilage?
- Has abundant type I collagen
- Has the matrix material of hyaline cartilage (proteoglycans, hyaluronic acid, type II collagen)
- Contains chondrocytes and fibroblasts
- Has relatively few chondrocytes
- Has dense regular connective tissue
- No surrounding perichondrium
271
What cell types are present in hyaline cartilage?
Chondrocytes only
272
What is the fetal role of hyaline cartilage?
- In early fetal development it is the precursor model of those bones which develop by endochondrial ossification
- It is mineralised to form bone
- As long bones develop some hyaline cartilage remains at the articulating surface
273
Where can hyaline cartilage be found?
- At articulating surfaces
- In parts of the rib cage
- Nose
- Trachea, bronchi and larynx
274
What is perichondrium?
A dense connective tissue
- It covers the margin of hyaline cartilage
- Contains many elongate, fibroblast-like cells
- These can develop into flat, newly formed chondroblasts and thereafter chondrocytes
275
How does cartilage grow?
As a result of chondrocytes and the secretion of matrix
| - Appositonal growth (from the periphery)
276
What happens to chondrocytes deeper in the cartilage?
May divide and give rise to isogenous groups
277
How can interstitial growth occur?
When isogenous groups deep in the cartilage deposits further matrix, interstitial growth occurs
- The cells of the isogenous group separate as they lay down further matrix
278
What is the effect of pressure loads on the chondrocytes?
When applied to cartilage, they create mechanical, electrical and chemical signals that direct the synthetic activity of thin chondrocytes
279
What surrounds a chondrocyte?
A lacuna
280
Where is perichondrium found in developing tarsal bones?
- At non-articulating surfaces
- Contributing to developing joint capsule
- Not at articulating surfaces
281
Structure of a long bone
- Spongy or cancellous bone in centre, to give more flexibility
- Compact bone on the outside
- Hyaline cartilage lines the articulating surface of the bond (not lined by perichondrium)l which is very smooth
- Also forms the epiphyseal growth plate
- There is an irregular boundary between the articulating cartilage and the underlying bone
282
What are the roles of elastic cartilage?
- The cartilage has elasticity
- Resilient
- Doesn't calcify with ageing
283
Where can elastic cartilage be found?
- The external ear
- The external acoustic meatus
- The epiglottis
- The Eustachian tube
284
What is the role of fibrocartilage?
- Acts as a shock absorber
- Resists shearing forces
- Resists compression
- Durable
- Tensile strength
285
Where can fibrocartilage be found?
In areas of directional stress
- Intervertebral discs
- Articular discs of the sternoclavicular
- Temporomandibular joints
- Menisci of the knee joint
- Pubic symphysis
286
How are chondrocytes found in the fibrocartilage of an intervertebral disc?
- They are rounded
- Tend to be arranged in rows
- Or as isogenous groups
A relatively small number of elongated fibroblast nuclei are also evident
287
Describe cancellous/spongy bone
- It forms a network of fine bony columns or plates
- This combines strength with lightness
- Porous
- The spaces are filled by bone marrow and yellow marrow
- Highly vascular
- Has a 3D network of irregular trabeculae, with a system of intercommunicating spaces
288
What does compact bone form?
The external surfaces of bones
289
What do Haversian and Volkmann's canals do?
They carry blood vessels, lymph vessels and nerves
290
Differences between immature and mature bone
Imm: has osteocytes which are fairly randomly arranged and large
Mat: has osteocytes arranged. The concentric lamellae of osteons
291
In mature bone, where are resorption canals found?
Parallel to the osteons' long axes
292
What is special about osteocytes?
- Have very slender cytoplasmic processes
- These reach out to those of adjacent osteocytes, via canaliculi
- These processes connect via gap junctions such that nutrients can be passed between osteocytes
- The canaliculi are believed to connect with the Central Haversian canal
293
What is the structure of the trabeculae of spongy bone?
- Internal histological structure is similar to that of compact bone
- Consists of numerous osteocytes embedded within irregular lamellae of bone
- Osteoblasts and osteoclasts on their surface act to remodel them
- No Haversian or Volkmann's canals
- They can be interconnecting
- Adipose and haemopoietic cells lie in the cavities
294
How does an osteon form?
- Osteoblasts deposit new osteoid
- This forms a circular layer around the osteoblasts
- Layers of osteoids form osteons
- Osteoclasts can then be found surrounding an osteon
295
What does cartilage do?
- Provides support for some soft tissues in the body
| - Forms a smooth sliding surface in moveable joints
296
What are the functions of bones?
- Supports the body
- Protects internal organs
- Serves as a reservoir of inorganic substances (e.g. Calcium and phosphorus)
297
What do bones consist of?
- Cells (osteoblasts, osteocytes, osteoclasts, etc.)
- Collagenous fibres (type I)
- A hard, calcified matrix
- Water
- Non-collagen proteins
- Mineral (calcium hydroxyapatite crystals)
298
What is the periosteum?
A tough vascular fibrous layer
- Surrounds bones
- Attached to the bone by collagen fibres called Sharpey's fibres
- Consists of 2 layers
- The outer is dense collagenous connective tissue with blood vessels, nerves and a few fibroblasts
- The inner layer is more loosely arranged, less vascular and provides the Sharpey's fibres
- The inner layer also contains fusiform osteogenic (bone forming) cells next to the bone
299
What is the endosteum?
A thin cellular layer
| - Lines the marrow cavity
300
What is special about bone?
It is the only solid tissue in the body that can replace itself
- When a bone is fractured, it heals with bone
- Other solid tissues heal with fibrous tissues that leaves a scar
301
How does bone remodelling occur?
A cutting cone bores a tunnel through the bone by the action of osteoclasts, which release H+ ions and lysosomal enzymes
- Occurs in response to stress and strain
302
How does bone resist fracture?
- It has great tensile and compressive strength
- It also had a degree of flexibility
- Lamellae are thought to be able to slip, relative to each other, before excessive load causes fracture
303
How does fracture repair occur?
- Bone breaks
- Bone matrix is destroyed and the bone cells adjoining the fracture will die
- Inflammatory cells invade and form a pre-callus. This contains a blood clot (haematoma) and fibrous tissue
- An osteocallus of primary bone is made
- This is then calcified to secondary bone
- The bone is pulled and persuaded to match the contours of the surrounding bone (mainly via tendons) and eventually forms mature bone
- Bone heals without forming a scar
304
Why are bone banks used?
If a fracture involves loss of bone fragments, then bony union and callus formation is not possible
- So bone fragments are frozen and used by orthopaedic surgeons
305
What does autograft mean?
The donor is the recipient
| - most successful in bone banks
306
What does homograft mean?
The donor is a different human
307
What does heterograft mean?
The donor is of a different species
| - This is the least successful in bone banks
308
What is the perichondrium?
A connective tissue sheath that covers most cartilage
- It is vascular
- It's vessels supply nutrients to the cartilage cells (chondrocytes)
309
How are chondroblasts formed?
By the development of chondrogenic cells
310
What cartilage covers bone ends?
Hyaline articular cartilage
- This is not covered by perichondrium
- It is avascular, but is nourished by the synovial fluid
- Cells near the surface tend to be more flattened, with their longer axes parallel to the articular surface
- As they get further from the surface, the cartilage cells become larger and more rounded
- The surface cells are chondrocytes involved in cell division
- In the deeper layers, mature chondrocytes are mainly involved in the synthesis of the matrix
311
Difference between Haversian and Volkmann's canals?
H: for communication of osteons with the marrow cavity and periosteum, parallel to the lamellae
V: for communication with other osteons, cuts through the lamellae
312
Describe the structure of compact bone
- Appears as a solid continuous mass
- The great majority of the lamellae are concentrically arranged
- Between the lamellae are cells
- These cells are called osteoblasts when they are active and bone-forming
- They are called osteocytes when they are mature or resting
313
What happens during the embryonic period (weeks 3 to 8)?
- Period of greatest change
- All major structures and systems are formed
- The most perilous for the developing child
314
What are the 2 crucial processes that occur around days 13-14 of development?
- The embryo is converted from a bilaminar to a trilaminar disc (gastrulation)
- It also becomes bilaterally symmetrical, with well defined anterior and posterior ends, and a midline
These processes end the pre-embryonic phase
315
What does gastrulation do, other than producing the trilaminar disc?
It sets the axes observed in the adult:
- Anterior/posterior
- Dorsal/ventral
- Right/left
316
How does gastrulation begin?
- The primitive streak appears
| - By cellular rearrangement
317
What is associated with the primitive streak?
- The primitive node (located at the centre of the node)
| - The primitive pit (located at the cranial end of the streak)
318
What does the primitive streak indicate?
The future posterior end
319
What is the primitive streak and what does it do?
- A narrow groove with bulging edges
- A slot through which cells, originally part of the ectoderm, lose their epithelial characteristics and migrate into the potential space between the ectoderm and the endoderm
- They spread out to the borders of the embryonic disc
- Thus, a middle layer the mesoderm, forms
- It regresses as gastrulation proceeds
- Leads to cellular rearrangement
320
In which direction does development proceed?
In a cranial to caudal direction
321
How does the cellular rearrangement in gastrulation occur?
By migration and invagination
- The epiblast cells migrate towards the centre of the bilaminar disc
- They pile up around the groove
- They then push themselves (invaginate) into the epiblast layer
- The hypoblast is displaced (it regresses because it has done its job)
- This produces the 3 germ layers: ectoderm, mesoderm, endoderm
322
What are the 2 exceptions in the embryo, where mesoderm does not spread between the ectoderm and endoderm?
- The future mouth
| - The future anus
323
What is the notochord?
- A solid rod of cells running in the midline, which do not spread out
- It is the basis for the axial skeleton (the axial skeleton forms around it)
- They have an important signalling role
- But it regresses
324
What do dorsal and ventral mean?
```
Dorsal = back
Ventral = front
```
325
What do rostral/cephalic and caudal mean?
```
Rostral/cephalic = anterior (head end)
Caudal = posterior (tail end)
```
326
When does gastrulation occur?
In the 3rd week of development, marking the start of the embryonic period
327
What is derived from the ectoderm?
Organs and structures that maintain contact with the outside world
- E.g. nervous system, epidermis
328
What is derived from the mesoderm?
Supporting tissues
| - E.g. muscle, cartilage, vascular system (including heart and vessels), connective tissue, urinary system
329
What is derived from the endoderm?
Internal structures
| - E.g. epithelial lining of GI tract, respiratory tract, parenchyma of glands
330
How are 'left-sided' signals produced?
- By the action of ciliated cells at the node
| - This causes left-ward flow of signalling molecules
331
What is situs invertus?
Complete mirror image viscera
- I.e. everything is on the opposite side!
- No associated morbidity
- Problems occur if there is both normal and mirror-image deposition
332
What are monozygotic twins?
A single fertilised oocyte that gives rise to 2 identical twins
333
What are dizygotic twins?
2 fertilised oocytes
334
How does monozygotic twinning occur?
- Embryo splits after first cleavage, producing 2 embryos, each with its own placenta
OR
- Inner cell mass is duplicated, producing 2 embryos, sharing a placenta (rarer, can lead to conjoined twins as is later)
335
What is teratogenesis?
The process through which normal embryonic development is disrupted
- Weeks 3 to 8 are the most sensitive to teratogenic insult
336
What are teratogenic agents?
Chemical and infectious agents known to cause developmental defects
337
What do osteoblasts do?
- Secrete matrix
- Facilitate mineralisation
- Form osteons by producing circular layers of matrix
338
What do osteoclasts do?
- Break down matrix
| - Release minerals
339
What is the composition of bone?
- 65% mineral (calcium hydroxyapatite crystals)
- 23% collagen (type I)
- 10% water
- 2% non-collagen proteins
340
What is endochondral ossification?
- The replacement of a pre-existing hyaline cartilage template by bone
- The way in which most of the bones of the body develop
- The hyaline cartilage is mineralised to form bone
341
What are growth plates?
- Made of hyaline cartilage
- Where growth occurs
- Found in growing bones
- Disappears when growth stops
342
How does long bone develop?
By endochondral ossification
- Initial cartilage model in embryo (much smaller than final bone)
- The collar of periosteal bone appears in the shaft
- In the foetus, the central cartilage calcifies. Nutrient artery penetrates, supplying bone-depositing osteogenic cells
- Postnatal: medulla becomes cancellous bone and cartilage forms epiphyseal growth plates (epiphyses). These develop secondary centres of ossification
- Prepubertal: Epiphyses ossify and growth plates continue to move apart, lengthening bone
- Mature adult: The epiphyseal growth plates are replaced by bone. Hyaline articular cartilage persists
343
What is hyaline articular cartilage?
It is the cartilage that is found at the end of bones
| - It is found in movable joints
344
How does a long bone elongate?
By endochondral ossification:
- Chondrocytes in the hyaline cartilage divide to form columns and enlarge
- They begin to secrete matrix
- They secrete matrix until they have enlarged too much (they become surrounded by their own matrix)
- They then begin to degenerate
- The matrix calcifies
- The calcified matrix is in direct contact with the marrow cavity
- Small blood vessels and connective tissue invade the region occupied by the dying chondrocytes, leaving the calcified cartilage as spicules between them
- Bone is laid down on these cartilage spicules
345
If cartilage is avascular, how does it receive substances?
Nutrients and gases reach the chondrocytes by leaving the blood vessels of the perichondrium and diffusing through the extracellular material
346
What is the structure of flat/irregular bones?
- Spongy bone is found in the centre
- Compact bone forms the plates of flat bones
- The plates are separated by spongy bone
347
What happens in bone marrow?
Active blood cell formation (haemopoiesis)
348
What is found in yellow marrow?
Adipose tissue
349
What is compact bone for?
Mechanical strength and protection
350
How is cartilage tearing or damage repaired?
By deposition of fibrous scar tissue
351
What is a benign tumour called in cartilage?
A chondroma
352
What is a benign tumour called in bone?
An osteoma
353
What is a malignant tumour called in cartilage?
A chondrosarcoma
354
What is a malignant tumour called in bone?
An osteogenic sarcoma
355
What is ossification?
The process of bone formation
| - It involves the replacement of existing connective tissue by bone in an orderly process of growth and differentiation
356
What do osteocytes do?
They maintain the bone
| - It secretes nutrients into the matrix
357
What develops by intramembranous ossification?
Flat bones
- E.g. skull bones, maxilla, mandible, pelvis, clavicle
Contributes to the thickening of long bones
358
In intramembranous ossification, what do bones develop from?
Mesenchymal tissue
359
What are the effects of growth hormone on bone?
Before puberty:
- Excessive GH can cause gigantism through promotion of epiphyseal growth plate activity
- Insufficient GH can affect epiphyseal cartilage and cause pituitary dwarfism
In an adult:
- Excessive GH cannot cause gigantism because there are no longer any epiphyseal plates
- It may, however, cause increase in bone width by promoting periosteal growth (resulting in acromegaly)
360
What is osteogenesis imperfecta?
- A rare genetic disorder
- It is an autosomal dominant disorder
- Affects the synthesis of type I collagen during ossification
- Makes the bones brittle and prone to fractures
- There are 4 different types
- Severely affected individuals may die before birth from multiple fractures
- Less severely affected children grow up with a variety of disabilities and deformities
- The bones become thin and bowed
- Can also have hearing impairment and dental abnormalities
361
What are the effects of sex hormones on bone?
Influence the development of ossification centres
- Androgens (male) and oestrogens (female) are hormones that are present in each sex
- They induce secondary sexual characteristics and give rise to the pubertal growth spurt
- Precocious sexual maturity retards bone growth due to premature closure (fusion) of epiphyses
- But if the sex hormone is deficient, epiphyseal plates may persist later into life than they normally would, leading to prolonged bone growth and tall stature
362
What is osteoporosis?
- The most common bone condition affecting the elderly
- There is a loss of bone matrix, a loss of structural density and demineralisation
- It increases the risk of fractures, especially in the spine, hip and wrist
- Can be easily detected by scanning for bone mineral density
- Main risk factor is age (as bones weaken with age)
- Women are also at a higher risk than men (hormones from the gonads act on osteoblasts and osteoclasts, but oestrogen has less of an effect than testosterone and its secretion is stopped after menopause, so bones are weaker)
- Other risk factors include low calcium intake, immobility, genetic factors and smoking
363
What is achondroplasia?
- One of the most common forms of short limb dwarfism
- Caused by an autosomal dominant point mutation in the fibroblast growth factor receptor-3-gene
- FGFR3 plays a role in bone development and maintenance
- The mutation causes a gain in function of the FGFR3 gene, resulting in:
- - Decreased endochondral ossification
- - Inhibited proliferation of chondrocytes in growth plate cartilage
- - Decreased cellular hypertrophy
- - Decreased cartilage matrix production
- As a result, the limbs are very short
- The shortening is most prominent in the proximal segment (upper arms and legs)
- The trunk is of normal length
- The vault of the skull is enlarged
- The face is small, with the bridge of the nose often flattened
- More than 80% of people with achondroplasia are born to parents without the condition (result of a new mutation)
364
Why is vitamin D important in normal bone development?
- 2 different types: some is dietary but most is synthesised in the skin by the action of UV light
- Both are hydroxylated in the liver and then the kidney
- This produces active 1,25-dihyroxyvitamion D3
- This increases calcium absorption by the small bowel and promotes mineralisation of bone
365
What is myalgia?
Muscle pain
366
What is myasthenia?
Weakness of the muscles
367
What is myocardium?
Muscular component of the heart
368
What is myopathy?
Any disease of the muscles
369
What is myoclonus?
A sudden spasm of the muscles
370
What is the sarcolemma?
The outer membrane of a muscle cell
371
What is the sarcoplasm?
The cytoplasm of a muscle cell
372
What is the sarcoplasmic reticulum?
The smooth endoplasmic reticulum of a muscle cell
373
What are the 3 types of muscles?
```
Striated:
- Skeletal
- Cardiac
Non-striated:
- Smooth
```
374
What are the major characteristics of muscle?
- Tissue responsible for internal and external movements
- Exhibits functions of contractility and conductivity
- Exhibits elongated cells (fibres) in axis of contraction
375
Describe some features of skeletal muscle
- Cell length = 1mm - 20cm
- Cell diameter = 10-100um
- Long parallel cylinders of muscle fibres
- The fibres are tapered/rounded at their ends
- The fibres are shorter than the length of the muscle
- Striated
- Multinucleated
- Controlled by somatic motor neurones
- Under voluntary control
- Rapid and forceful
- Skeletal muscle fibres differ in their diameter and natural colour (there are narrower red, wider white and intermediate skeletal muscle fibres)
- It has a triad (1 T tubule associated with 2 terminal cisternae)
376
Describe some features of cardiac muscle
- Cell length: 50-100um
- Cell diameter: 10-20um
- Short branched cylinders of muscle fibres
- Striated
- Single central nucleus
- Junctions join cells end to end
- Intercalated discs (where cells meet; have low electrical resistance)
- Controlled by involuntary autonomic modulation, with intrinsic rhythm
- Lifelong variable rhythm
- Action potentials are generated in the sinoatrial node, pass to the atrioventricular node and from there to the ventricles
- These impulses are carried by Purkinje fibres
- Has a diad (1 T tubule associated with 1 terminal cisternae)
- Instead of forming myofilaments, actin and myosin form continuous masses in the cytoplasm
377
Describe some features of smooth muscle
- Cell length: 20-200um
- Cell diameter: 5-10um
- Spindle shaped, tapering ends
- Single central nucleus
- No striations
- Involuntary autonomic control
- Stimulated by intrinsic activity and local stimuli
- Slow, sustained contraction
- No T tubules
- Contraction still relies on actin-myosin interactions
- Contraction requires less ATP
- Can be stretched
- Form sheets, bundles or layers
- Thick and thin filaments are arranged diagonally within the cell, spiralling down the long axis
- Cells contract in a twisting way
- Intermediate filaments attach to dense bodies scattered throughout the sarcoplasm and occasionally anchor to the sarcolemma
378
What are some differences between red and white skeletal muscle fibres?
- Red has slow contraction and has lots of myoglobin and mitochondria
- White has fast contraction and easily fatigued
379
What does the power output from skeletal muscle depend on?
The number of muscle fibres, not growth in their length
380
How does exercise increase muscle volume?
- Hypertrophy: growth of fibres, causing the cells to swell
- Not through division of muscle cells
- Increased number of myofibrils in each muscle fibre
381
How are muscle fibres organised?
- Packed with parallel columns of myofibrils
- Organelles are ordered in rows
- Lipid droplets and glycogen provide energy
382
How is skeletal muscle organised?
- Skeletal muscle is wrapped by epimysium (thick CT)
- It is composed of fascicles
- These are wrapped by perimysium (thin CT)
- Fascicles are composed of muscle fibres (cells)
- The muscle fibres are wrapped by endomysium
- Muscle cells are composed of myofibrils
- Myofibrils are composed of myofilaments
383
What does the perimysium carry?
Nerves and blood vessels
384
What is a muscle fibre?
A striated muscle cell
385
What is the structure of a sarcomere?
- The Z lines define the edges of the sarcomere
- Just inside the Z lines are the I bands (only contain actin)
- Next to the I bands is the A band
- The A band contains the M line and H zone (H zone only contains myosin without any myosin heads)
386
What happens to a sarcomere when it is contracted (vs relaxed)?
- A band stays the same
- H band gets shorter
- I band gets shorter
- Z lines get closer
387
What does the endomysium contain?
Capillaries and venules
388
In I band, what does the I stand for?
Isotropic
389
What does the A in A band stand for?
Anisotropic
390
Is actin the thick or thin filament?
Thin
| - Myosin is the thick filament
391
How is actin found in skeletal muscle?
- The actin filament forms a helix
- Tropomyosin filaments coil around the actin helix, reinforcing it
- A troponin complex is attached to each tropomyosin molecule
392
Why is troponin a useful diagnostic tool?
- Can be used as a clinical marker for cardiac ischaemia
- Released from ischaemic cardiac muscle within an hour
- The smallest changed in troponin levels in the blood are indicative of cardiac muscle damage
- Quantity of troponin is not necessarily proportional to the degree of damage
393
What is the structure of an individual myosin molecule?
- A rod-like structure from which 2 heads protrude
394
Why is calcium needed for muscular contraction?
- The troponin complexes on tropomyosin block the myosin binding sites
- When calcium binds to TnC (troponin C), a conformational change moves tropomyosin away from the binding sites
- This allows myosin heads to bind to actin
- Contraction can then begin
395
What is the sliding filament model?
A model for muscular contraction
- Myosin cross bridge attaches to the actin myofilament
- This releases ADP and Pi
- The myosin head then pivots and bends, pulling the actin filament towards the M line
- When a new ATP molecule attaches to the myosin head, the cross bridge detaches
- As ATP splits into ADP and Pi, the myosin head returns to its original position
- Contraction can then reoccur
396
How is contraction initiated?
- It is activated through nerves entering the epimysium
- These attach to muscle at a motor end plate
- When the impulse reaches the neuromuscular junction, it causes voltage gated Ca ion channels to open
- Ca+ then floods in
- This causes the vesicles of acetylcholine to move to and fuse with the pre-synaptic membrane
- Acetylcholine is then released by exocytosis
- It diffuses across the synaptic cleft
- Binds to specific receptor sites on Na ion channels, causing them to open
- Na+ floods into the muscle, causing depolarisation
- This depolarisation travels along the sarcolemma and down the T tubules
- Causes the sarcoplasmic reticulum to release Ca+ ions
- These are then used by the muscle cell for contraction
- Once contraction has finished, acetylcholine is broken down by acetylcholinerase
397
What is the function of a gap junction in cardiac muscle?
Used for electric coupling
398
What is the function of a adherens-type junction in cardiac muscle?
To anchor cells and provide anchorage for actin filaments
399
What are Purkinje fibres?
- Large cells
- Have abundant glycogen
- Sparse myofilaments
- Extensive gap junction sites
400
What can smooth muscle form?
Contractile walls of passageways or cavities
- Walls of respiratory passages from the trachea to the alveolar ducts
- Wall of ducts and glands, urinary and genital ducts
- Walls of arteries, veins and large lymphatics
- Muscles of iris in eye
- Arrector pili
- Contractile part of wall of GI tract from mid-oesophagus to anus
401
What are myoepithelial cells?
Stellate cells forming a basket work around the secretory units of some exocrine glands
- Their contraction assists secretion into secretory ducts
402
How can modified smooth muscle cells occur?
- Singly, as myoepithelial cells
| - As myofibroblast cells
403
Where can myofibroblast cells be found and what do they do?
- At sites of wound healing
| - They produce collage nous matrix but also contract
404
What is the nature of repair in muscle cells?
- Skeletal muscle: cells cannot divide but the tissue can regenerate by mitotic activity of satellite cells (hyperplasia). Satellite cells can also fuse with existing muscle cells to increase mass
- Cardiac muscle: incapable of regeneration. Following damage, fibroblasts invade, divide and lay down scar tissue
- Smooth muscle cells: retain their mitotic activity and can form new smooth muscle cells
405
What is the function of epimysium/perimysium/endomysium?
To protect, strengthen and bind muscle fibres into fascicles and bind bundles together
406
What is the deep fascia?
- Layers of dense connective tissue
- Associated with muscles
- Surrounds adjacent muscles
- Extends in between adjacent muscles and binds them into functional groups
- Large blood vessels, nerves and small amounts of fat are also found in it
407
What is muscle atrophy?
The wasting of muscle tissue due to lack of use
- Can occur after prolonged immobilisation of joints
- Can occur in the aged
- Can occur due to loss of nerve supply following injury or disease
- Destruction > replacement
408
How does skeletal muscle respond to injury?
- The connective tissue in the endomysium and perimysium divides
- It differentiates into myoblasts
- These fuse to form new muscle fibres
409
How frequently does remodelling of muscles occur?
- Continually
| - Replacement of contractile proteins in 2 weeks
410
What happens to skeletal muscles when exercise is increased?
Metabolic adaptation:
- Sarcoplasmic reticulum swells
- Increased volume of mitochondria
- Increased Z band width
- Increased ATPase
- Increased density of T tubules systems
- Increase in number of contractile proteins
411
What is the difference in adaptations between high-resistance and endurance exercise?
H-R: Stimulates contractile protein synthesis, increases muscle mass and strength (may lead to hypertrophy)
E: No hypertrophy, stimulates synthesis of mitochondrial proteins, vascular changes allowing for greater oxygen utilisation, shift to oxidative metabolism
412
How can muscle length increase?
```
By sustained stretching
- Addition of sarcomeres
- Changes in neurology (pain, stretch receptors and stretch reflex)
- Viscoelastic properties
Muscle length reduces if immobilised
```
413
How can myasthenia gravia be treated?
- Acetylcholinerase inhibitors
- Immune suppressants
- Plasmapheresis (removal of harmful antibodies from patients serum)
- Thymectomy (operation to remove the thymus, as the thymus gland is large and abnormal in MG; may cause tumours)
414
What are the symptoms of myasthenia gravis?
- Profound weakness
- Weakness increases with exercise
- Fatigability
- Sudden falling (not enough acetylcholine receptors occupied to keep the muscle contracted)
- Drooping under eyelids causing double vision
- Symptoms are affected by general state of health, fatigue and emotion
415
What is serum?
The blood plasma without the fibrinogens
416
What are muscular dystrophies?
- Genetic disorders
| - Progressive muscle weakness and wasting
417
What is Duchenne muscular dystrophy?
Complete absence of dystrophin
- Dystrophin connects actin filaments to sarcolemma
- Symptoms = fatigue, difficulty walking, learning disorders, Gower's sign
- Muscle fibres tear themselves apart on contraction
- Calcium enters cell causing cell death
- Pseudohypertrophy (swelling) before fat and connective tissue replace muscle fibres
- Can test for creatine kinase in the blood (as muscle is damaged)
- Treatment = steroids
418
What is Beckers muscular dystrophy?
Altered, truncated dystrophin
| - Less severe form of Duchenne muscular dystrophy
419
What is Limb-girdle muscular dystrophy?
Deficiency of sarcoglycans
420
What is congenital mersosin deficient muscular dystrophy?
50% deficiency of merosin
421
What is Gower's sign?
The use of hands to push on legs in order to stand up
| - "walk" hands up body
422
What are the origins of skeletal muscle problems?
- Neurological
- Metabolic
- Immunological
- Neuromuscular junction
- Muscle tissue itself (proteins, ion channels, inflammation)
423
What are the 3 main parts of the nervous system?
- Brain
- Spinal cord
- Nerves
424
What nerves are associated with the brain and how many are there?
Cranial nerves
| - There are 12 pairs
425
What nerves are associated with the spinal cord and how many are there?
Segmental or spinal nerves
| - 31 pairs
426
What are the functional units of hate nervous system?
Made from billions/trillions of neuronal cells
427
What are the 2 types of nerve cells?
Glia (90%): divisible into microglia and macroglia, also called neuroglia
Neurones (10%)
428
What are the different types of macroglia?
- Astrocytes
- Oligodendrocytes
- Schwann cells
429
What do microglia do?
- Act as immune cells of the CNS
- Act as phagocytes
- Usually not seen except in inflammatory insult (infection/damage) to CNS
430
What are ependymal cells?
A type of neuroglia that forms the epithelial lining of the ventricles and the central canal of the spinal cord
- They have cilia, which beat in a coordinated pattern to influence the direction of flow of cerebrospinal fluid
431
Which neuroglia are found in the peripheral nervous system (PNS)?
- Schwann cells
- Satellite cells (physical support of neurones)
- Microglia
432
Which neuroglia are found in the central nervous system (CNS)?
- Astrocytes
- Oligodendrocytes
- Ependymal cells
- Microglia
433
What are the main features of a neurone?
- The cell body
| - The axon
434
What is the cell body?
- The engine of the neurone
- Vary in shape
- Vary in size (4-120um diameter)
- Contains a nucleus, Nissl substance (for protein synthesis) and a Golgi apparatus
- In some neurones, cell bodies have appendages called dendrites
435
What is grey matter made up of?
Collections of cell bodies
- Nerve nuclei are a typical example of grey matter
- Found in the CNS
436
What is white matter made up of?
Collections of axons
| - A peripheral nerve is a typical example of white matter in the PNS
437
In the PNS, what are ganglia?
Collections of nerve cell bodies
| - Ganglia means swelling
438
What are the components of an axon?
- Axonal membrane
- Myelin sheath
- Node of ranvier
- Axonal terminal
- Initial segment
439
How can axons differ from each other?
- Variable in thickness (the thinner they are, the less myelination they need)
- Variable in length
440
What is a node of ranvier?
A separation between 2 successive Schwann cells
- It is made up of an unmyelinated axonal segment
- It is approximately 1um in length
441
What is the anatomy of a peripheral nerve?
- Axons are surrounded by endoneurium
- Axons are grouped together to form fascicles
- Fascicles are surrounded by perineurium
- Fascicles are grouped together to form the peripheral nerve
- The adjacent fascicles are attached to each other by interfascicular bands
- The nerve is surrounded by epineurium
442
How does a neurone react to its axon being severed?
- The proximal segment of the axon soon seals up the damage to prevent leakage of cell contents
- Its cell body suddenly puffs up with increased contents and the nucleus is displaced from its central position to peripheral margins
- This is called a nerve stump and the process is chromatolysis
- The distal segment is cut off from nutritional support of the cell body
- The distal segment of the axon soon dies
- It then undergoes Wallerian degeneration
443
How is the peripheral nervous system subdivided?
Into the autonomic system and the somatic system
444
What does the central nervous system consist of?
The brain and the spinal cord
445
How can the autonomic nervous system be subdivided?
Into the sympathetic and parasympathetic systems
446
When does loss of myelin sheath occur?
In certain disorders of the CNS
- E.g. Multiple sclerosis
- It is a defect
- The loss of myelin is selective and patchy in its occurrence
- Axonal destruction and overgrowth of glial tissue also occurs
447
What do macroglia do?
Astrocytes
- Support cellular matrix of the nervous system
- Give shape to the brain and spinal cord
- Act as phagocytes
- Breakdown of glucose to lactate for neuronal nourishment
- Comprise the blood brain barrier
- Assist in the transfer of nutrients and waste products between the neurone and the blood
Oligodenderocytes:
- Myelinate CNS axons
- They produce and secrete the myelin
Schwann cells
- Myelinate PNS axons
448
What nerves are found in the PNS?
- Cranial
- Spinal
- Autonomic
449
What does the dorsal nerve root do?
It carries sensory fibres impulses to the grey matter
| - It extends outside of the spinal cord
450
What is the central canal?
- Canal found in the centre of the spinal cord
- It contains cerebrospinal fluid
- It disappears at puberty
451
What is Nissl substance?
- Aggregates of rough endoplasmic reticulum
| - Found in the cell bodies of neurones
452
What does the epineurium contain?
- Blood vessels
- Lymphatics
- Fat cells
- Sometimes nerve fibres
453
What are dendrites?
- Multiple elongated processes
- They are specialised for receiving stimuli from the environment or other neurones
- They conduct these stimuli towards the cell body
454
What does the cell body of a neurone do?
Maintains the cell
455
What are multipolar neurones?
Cells that have more than 2 processes (2+ dendrites, 1 axon)
456
What are bipolar neurones?
Cells with 2 processes (1 dendrite, 1 axon)
457
What are pseudo-unipolar neurones?
Neurones that have a single stem from the cell body which is formed by the fusion of the first part of the dendrite and axon
458
What do neuroglial cells do?
- They are highly branded cells
- They occupy the spaces between neurones
- They provide both structural and metabolic support for the neurones
459
Where do ventral roots terminate and what axons are they made from?
- They terminate in muscles
- Made from efferent axons
(further away from spinal cord than dorsal roots)
460
What happens at the ganglia and neuroeffector junctions?
Chemical transmission
| - Involves the neurotransmitters acetylcholine and noradrenaline
461
What is involved in a sympathetic or parasympathetic neurone?
- Pre-ganglionic neurone
- Ganglion
- Post-ganglionic neurone
462
In a sympathetic nerve, is the pre-ganglionic neurone short or long?
- Pre = short
| - Post = long
463
In a parasympathetic nerve, is the pre-ganglionic neurone short or long?
- Pre = long
| - Post = short
464
How does communication between pre- and post-ganglionic sympathetic and parasympathetic neurones occur?
Via nicotinic receptors
| - It is cholinergenic
465
How can communication at the neuro-effector junction occur?
- Can be exclusively cholinergenic (parasympathetic)
| - Or predominantly noradrenergic
466
What is an afferent neurone?
A neurone that carries signals from the periphery to the CNS
467
What is an efferent neurone?
A neurone that carries signals from the brain or spinal cord to the periphery
468
What is an effector?
A target organ through which the nervous system exerts its actions
469
Are the CNS and PNS dependent on each other?
No: they are independent of each other, although they are a continuum of the same cell
470
What characterises the CNS?
- Protected by the cranium and vertebral column
- Suspended in cerebrospinal fluid
- Responsible for the sophisticated functions of the nervous system
471
In the CNS, what are fibre tracts?
Collections of neuronal axons
472
In the PNS, what are nerves?
Collections of neuronal axons
473
How is grey matter and white matter arranged in the spinal cord?
- Grey matter is found centrally, having a butterfly shape
- It has dorsal horns (at the back of the brain) and ventral horns (at to front of the brain)
- White matter is found peripherally, on the outside, and fully surround the grey matter
474
What is a somatic efferent neurone?
A neurone that carries output from spinal or cranial locations to an effector organ
- It terminates directly on the effector organ
- The effector organ is a skeletal muscle, which is activated to carry out a specific task and is inactive the rest of the time
- They are underdeveloped at birth but are fully developed by puberty
475
What is the role of the autonomic nervous system?
- Subserves fundamental life-functions
- Maintains a constant internal environment in the body (homeostasis)
- Promotes excretory mechanisms of the body as and when necessary and appropriate
476
What are some features of the autonomic nervous system?
- Not under voluntary control
- Becomes active along with organogenesis
- Functions are non-stop throughout life
- Controls functions by changing the continuous output in 2 opposing systems
477
What is the general layout of an efferent autonomic nervous system pathway?
There are always 2 neurones arranged in a series
- 1 neurone is in the CNS (pre ganglionic, myelinated, known as white rami communicantes)
- 1 neurone is in the PNS (post ganglionic, somata located outside CNS, non-myelinated, known as grey rami communicantes) and terminates directly on the effector organ
478
What are the effector organs of the autonomic nervous system?
- Visceral organs
- Smooth muscle
- Secretory glands
479
How are most organs innervated?
By the autonomic nervous system
- Most receive dual innervation of the sympathetic and parasympathetic nervous systems
- Most of their effects are reciprocal
- The balance of their outputs determines the effect
480
What is the effect of over activity of the parasympathetic nervous system?
Results in dilated blood vessels over time, which can result in shortage of substrate to the brain
481
What are the effects of over-activity of the sympathetic nervous system?
Results in construction of blood vessels, which can result in profound problems
- E.g. Shortage of substrate to tissues of the body
482
When is the sympathetic nervous system expressed?
Predominantly in stressful situations
| - Known as the 'fight or flight' system
483
What effects can the sympathetic nervous system have?
- Expenditure of energy
- Diversion of blood to muscles and heart
- Increase in heart rate
- Increase in blood pressure
- Reduced blood flow to GI tract and skin
484
In order to increase the speed of conduction, should thick or thin axons be myelinated?
Thick: greater diffusion distance so myelination will increase speed
- The thin axons will already have a fast sped of conduction so don't need to be myelinated
485
Where are the cell bodies of the sympathetic nervous system found?
- In all 12 thoracic segments of the spinal cord
| - And in the first 2 lumbar segments
486
What neurotransmitters do sympathetic nerves use and what receptors do they have?
- Pre-ganglionic neurones are cholinergenic
- Post ganglionic neurones express nicotinic receptors and are noradrenergic (some are adrenergic: sweat glands and ejaculatory mechanisms)
- The effector organs express a variety of receptors
487
What are the effects of the parasympathetic system?
- Reduces heart rate and force of contraction of the heart
- Promotes digestion
- Promotes bodily functions (e.g. Emptying bladder)
- Promotes sleep
488
Where do parasympathetic messages flow from?
The brain and the spinal cord
- Cranial nerves in brain
- Sacral spinal cord
489
What neurotransmitters do parasympathetic nerves use and what receptors do they have?
- Pre-ganglionic neurones are cholinergic
- Post-ganglionic neurones express nicotinic receptors and are cholinergic
- Effector organs express muscarinic receptors
490
Are post-ganglionic neurones in the parasympathetic nervous system long or short? Where are they located?
- Short (pre-ganglionic neurones are long)
| - They are located within the walls of the effector organs
491
Are only myelinated neurones found in the ANS and SNS?
No:
- In the ANS there are both myelinated and unmyelinated neurones
- But in the SNS there are only myelinated neurones
492
Which neurotransmitter do excitatory neurones release?
Glutamate/aspartate
493
Which neurotransmitter do inhibitory neurones release?
Glycine/GABA (g-amino butyric acid)
494
What are pathogens?
Disease-causing organisms
| - E.g. Protozoa, bacteria, viruses, fungi, worms
495
What does the immune system detect, that causes them to acknowledge a pathogen?
The different amino acid sequences
496
What are the first barriers to infection in a human body?
Epithelia
- They function within seconds of pathogen contact
- They act as a mechanical, selective permeable barrier between the 'outside' and 'inside'
- Produce natural antibiotics
- They may possess motile cilia
- They are rapidly renewable
- Produce cytokines
- Produce chemokines
- May produce mucins
- Transport antibodies from 'inside' to 'outside'
497
How do we facilitate the clearance of pathogens from our epithelial surfaces?
- Rapid epithelial regeneration
- Blinking
- Flow of tears
- Ear wax
- Nasal hairs
- Coughing
- Sneezing
- Mucociliary escalator
- Vomiting
- Digestive enzymes
- Peristaltic gut movement
- Regular urine flow
498
What is the general scheme of an immune response?
- Pathogen with non-self proteins damages the epithelium to break through the epithelial barrier
- Epithelial cells 'activated' upon contact with microorganism
- Chemokines and cytokines are made by activated epithelial cell
- The endothelium can become permeabilised
- Cells and fluid may migrate into the tissue
- Opsonisation can then occur, causing phagocytosis
499
What is the effect of increased permeability in an immune response?
- It allows increased fluid leakage from blood vessels
- Extravasation of antibiotics and complement at the site of infection
- Migration of macrophages, neutrophils and lymphocytes into tissue is increased
- Microbicidal activity of macrophages and neutrophils is also increased
500
What is a complement?
The collective name of a set of soluble substances, synthesised by the liver, which can act in a cascading fashion to recruit immune cells, opsonise and directly kill bacteria
501
What are the 4 signs of inflammation? (What are there ancient names?)
- Heat (calor)
- Swelling (tumor)
- Redness (rubor)
- Pain (dolor)
502
What are the 2 types of immune response?
Innate and adaptive
503
What is an innate immune response?
- Inbuilt immunity to resist infection
- Native, natural immunity
- Oresent from birth
- Not specific for any particular microbial substance
- Not enhanced by second exposure
- Has no memory
- Uses cellular and humoral components
- Is poorly effective without adaptive immunity
- Involved in the triggering and amplification of adaptive immune responses
504
What are humoral components?
Dissolved substances
505
What is adaptive immunity?
- Immunity that is established to adapt to infection
- It is 'specific' or 'acquired' immunity
- It is learnt by experience
- Confers pathogen-specific immunity
- Enhanced by second exposure
- Has memory
- Uses cellular and humoral components
- Poorly effective without innate immunity
506
What cells are involved in innate immunity?
- Macrophage
- Monocyte
- Neutrophil
- PMN
- Eosinophil
- Basophil
- Mast cell
- Natural killer cells
507
What are phagocytes?
Cells that are able to engulf and destroy bacteria, extra cellular viruses and immune complexes
- Macrophages and neutrophils
508
What is phagocytosis?
Active engulfment of particles into a phagosome
509
What are neutrophils?
A type of white blood cell
- They are specialised for working under the anaerobic conditions that prevail in damaged tissues
- They are normally excluded from healthy tissues
- Their arrival is the first event of inflammatory response
- They contain granules which have different enzymes in them, including lysozymes
- They are unable to synthesise more granules after they have been activated
- Once the granules are used up the neutrophil dies
- They can sometimes release their lysosome contents on the outside of pathogens which are too big to digest
510
How do neutrophils cause phagocytosis?
- The neutrophil expresses receptors for many bacterial constituents
- When the bacteria bind, the neutrophil can engulf and digest it
511
What do macrophages do?
- Phagocytose microbial cells
- Phagocytose damaged or unwanted cells
- Release a variety of cytokines (important in innate and adaptive immunity)
- Macrophages are long-lived and continue to generate more lysosomes as needed
- Act as professional antigen presenting cells in the elopement of adaptive immunity
512
What is opsonisation?
The coating of a microorganism by antibodies or complement to render it recognisable as foreign by phagocytes, thus enhancing phagocytosis
513
What are natural killer cells?
- Non-T, non-B cells
- Non-classical antigen receptors
- Recognise and kill abnormal cells
- Directly induce apoptosis in virus-infected cells by pumping proteases through pores that they make in target cells
- Similar to cytotoxic T cells but has no specific T cell receptor
- Provides innate immunity against intracellular infections
- Provide an early response to a virus infection
514
What does the complement system do?
It marks pathogens for destruction by covalently binding to their surface
- Enhances the opsonising effects of antibodies
- Or it help recruit inflammatory cells
- Or it can enhance the direct killing of pathogens
- Can be used immediately after an infection begins
515
What do T and B lymphocytes do?
- T lymphocytes recognise and respond to antigens
| - B lymphocytes responsible for humoral immunity
516
What are antigens?
Molecules that elicit a specific immune response when introduced into the tissues of an animal
517
What are the 3 main ways in which antibodies protect the host from infection?
- Neutralisation (prevents bacterial adherence)
- Opsonisation (promotes phagocytosis)
- Complement activation (activates complement, which enhances opsonisation and lyses some bacteria)
518
What does the clonal distribution of antigen receptors mean?
Lymphocytes of a particular specificity will be too infrequent to mount an effective response
519
What is clonal selection?
The increase in clonal frequency of cells within a particular antigen specificity
520
What are the phases of an adaptive immune response?
- Recognition phase (clonal selection)
- Activation phase (clonal expansion
- Effector phase (differentiation to effector cells)
- Decline homeostasis (T and B cell apoptosis)
- Memory
521
What are the different T lymphocytes?
- T helper cells
| - Cytotoxic T lymphocytes
522
What do T helper cells do?
Permit the transformation of B cells to plasma cells
523
What do cytotoxic T lymphocytes do?
Recognise and kill virus-infected host cells
524
What are plasma cells and what do they do?
- Derivatives of B cells
| - Produce antibodies
525
What is neurulation?
Creation of the beginning of the nervous system
- The formation of the neural tube from the neural plate
- Notochord-driven induction of overlying ectoderm to form the nervous system
526
How does neurulation occur?
- The notochord signals cause overlying ectoderm (the neural plate) to thicken
- The edges elevate out of the plane of the disk and curl towards each other, creating the neural tube
527
What is the structure of mesoderm?
There is:
- Paraxial mesoderm (found on either side of the axis)
- Lateral plate mesoderm (split into somatic mesoderm - covers the amnion - and splanchnic mesoderm - covers the yolk sac -, which are separated by the intraembyronic cavity)
- Intermediate mesoderm (in the middle, between the paraxial and lateral plate mesoderm)
528
What happens after somites are formed?
Organised degeneration
- The ventral portion of the somite breaks down, leading to formation of the sclerotome (the tissue that forms hard tissue)
- The dorsal portion is further organised to form the combined dermomyotome
- The myotome proliferates and migrates, and the dermatome disperses
All the cells maintain their innervation, no matter where they migrate (supplied by a single spinal nerve)
529
What are the somite derivatives?
- Dermatome (the skin section - dermis)
- Myotome (the muscle section - muscle)
- Sclerotome (the hard tissue section - bones)
530
What does the intermediate mesoderm form?
The urogenital system
531
What does the lateral plate mesoderm form?
- Somatic: connective tissue of limbs
| - Splanchnic: smooth musculature, connective tissue and vasculature of gut
532
What does the embryonic folding achieve?
It draws together the margins of the disk
- It creates a ventral body wall
- It pulls the amniotic membrane around the disk
- It pulls the connecting stalk ventrally
- it also creates the primordial of the gut from the yolk sac
- It puts the heart and the primordium of the diaphragm into the right place
- It creates a new cavity within the embryo
533
How are platelets produced?
By megakaryocytes
- The cells increase in size and replicate their DNA
- Platelets 'bud' from the cytoplasm
- Platelet production is controlled by thrombopoietin
534
How long can red blood cells survive for?
120 days
535
What does the bone marrow produce?
- Red blood cells
- Platelets
- Most white blood cells
536
Where is the bone marrow found?
Infant: throughout the skeleton
Adult: pelvis, sternum, skull, ribs, vertebrae
537
What drives haemopoiesis?
Cytokines
| E.g. Erythropoietin (RBCs), thrombopoietin (platelets)
538
What is symbiosis?
Ad and Taya
539
What is the main composition of Tissue
Trick question! Once we've had sex the tissues change composition quite a lot
540
What are the functions of red blood cells?
- To deliver oxygen to the tissues
- Carry haemoglobin
- Maintain haemoglobin in its reduced state
- Maintain osmotic equilibrium
- Generate energy
541
Why is the biconcave flexible disc shape an advantage to RBCs?
It facilitates their passage through the microcirculation (diameters are less than half the diameter of an RBC)
542
What is the role of the globin chains in haemoglobin?
- Protect harm molecule from oxidation
- Confer solubility
- Permits variation in oxygen affinity
543
How can RBCs be metabolised?
By the Embden Meyerhof pathway
- Glucose is metabolised to lactate
- ATP is generated
By the hexose monophosphate pathway
- Glucose-6-phosphate is metabolised
- NADPH is generated
544
What are all products of haematopoiesis derived from?
Multipotent haematopoietic stem cell
545
How is the production of red blood cells regulated?
By negative feedback
- If the kidney senses hypoxia (anaemia) it increases erythropoietin production
- Erythropoietin increases the rate of red blood cell production and release from the bone marrow
546
Where are platelets stored?
In the spleen
547
What is the function of platelets?
- Adhesion to connective tissue (when there has been damage to a vessel wall)
- Aggregation with other platelets
- Phospholipid membrane to facilitate clotting (interact with clotting factors, such as factor VII, IX and X)
548
What is the function of neutrophils?
- To migrate out of the circulation to a site of infection (chemotaxis)
- Then destroy foreign material by phagocytosis
- Both chemotaxis and phagocytosis can be increased by cytokines
549
What is the structure of mature neutrophils?
- Multi-lobed nucleus
| - Small granules in the cytoplasm
550
What are leukocytes?
```
Nucleated cells which circulate in the blood
Includes:
- Neutrophils
- Eosinophils
- Basophils
- Monocytes
- Lymphocytes
```
551
What is the structure of eosinophils?
- Bilobed nucleus
| - Orange granules
552
What is the function of eosinophils?
- They are capable of phagocytosis
- Can also release cytotoxic enzymes to damage larger particles
- Migrate to epithelial surfaces
- Their numbers are increased in association with allergic reactions and atropy
553
What are basophils?
- Cells with many large, dark purple granules
| - They mediate acute inflammatory reactions
554
What is the structure of monocytes?
- Large cells
- Folded nucleus
- Grey/blue cytoplasm
- Occasional vacuoles
555
What is the function of monocytes?
- Can move out of the circulation after 20-40 hours
- Can then migrate to become macrophages in many other organs of the body
- Capable of chemotaxis (move towards areas of infection, inflammation or neoplasm)
- Also capable of phagocytosis
- Interact with T cells
556
What is the reticuloendothelial system?
Part of the immune system containing phagocytic cells
- Cells in this system identify and mount an appropriate immune response to foreign antigens
- Main organs = spleen, liver, lymph nodes
557
What is the structure of lymphocytes?
- Small cells
- Round nucleus
- Rim of pale blue cytoplasm
- 75% are T lymphocytes (processed by the thymus)
558
What can happen to B lymphocytes after antigen stimulation?
- Transformed into immunoblasts
| - Then transformed into plasma cells
559
What do plasma cells do?
Secrete immunoglobulins (antibody molecules)
- May interact with T cells, transforming to plasma blasts or memory cells, within lymph nodes
- Plasmablasts migrate to marrow and form plasma cells
560
What is the function of natural killer cells?
- Recognise self
- Killl non-self cell lines
- Kill cells by lysis
561
What is the structure of platelets?
- Small round blue particles
- Complex surface membrane
- Cytoplasm contains alpha granules and dense granules
562
What is the fate of the cells found in the following somite zones?
Dorsal, ventral, dorso-lateral, dorso-medial, ventro-lateral, ventro-medial
Dorsal: dermomyotome
Ventral: sclerotome
Dorso-lateral: ventral body wall muscles, limb muscles
Dorso-medial: back muscles
Ventro-lateral: vertebral arches, distal ribs
Ventro-medial: vertebral body, proximal ribs
563
What is dermatome?
- The part of the somite that gives rise to the dermis
| - A strip of skin supplied by a single spinal nerve
564
What is myotome?
- Gives rise to muscles
| - A muscle/group of muscles supplied by a single spinal nerve
565
What does the paraxial mesoderm form?
- Axial skeleton
- Dermis
- Muscles of body wall
- Some limb muscles
566
What is Marfan's syndrome?
- Autosomal dominant
- Misfolding of fibrillin leading to more elastic connective tissue
- Sufferers are abnormally tall, exhibit arachnodactyly, have frequent joint dislocation and can be at risk of catastrophic aortic rupture
567
What are the effects of botulinum poisoning?
Acetylcholine release is blocked by the botulinum toxin
| - No muscle contraction
568
What are the effects of organophosphate poisoning?
- Acetylcholinesterase is inhibited
| - So acetylcholine remains in the receptors and muscle stays contracted
569
What is malignant hyperthermia?
- Autosomal dominant disease
- Life-threatening reaction to general anaesthesia
- Leads to release of Ca+ from all sarcoplasmic reticulum
- Huge spike in oxidative phosphorylation in skeletal muscle
- Causes a huge temperature spike which overwhelms control mechanisms causing death
570
What is Ehlers-Danlos disease?
- A heterogenous group of 6 inherited disorders
- The collagen fibres lack adequate strengt
- Type 3 collagen deficiency leading to loss of structure
- Skin is hyper extensible, fragile and susceptible to injury
- Joints are hypermobile
- Wound healing is poor
- Patients have a predisposition to joint dislocation
- Collagen in internal organs is disrupted, so patients can suffer from rupture of the colon and large arteries
- Corneal rupture and retinal detachment can also be seen
571
Is the parotid saliva gland mucous, serous or mixed?
Entirely serous
572
Is the submandibular saliva gland mucous, serous or mixed?
Mixed
573
What is myasthenia gravis?
Autoimmune destruction of the end plate acetylcholine receptors
- Causes loss of junctional folds at end-plate and widening of the synaptic cleft
- Caused by antibodies directed against nAChR on post-synaptic membrane of skeletal muscle
- Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degradation
- Endplate potentials are reduced in amplitude, leading to muscle weakness and fatigue
