ToB Flashcards

1
Q

State the relationship between

  • meters
  • millimetres
  • micrometres
  • nanometres
  • angstroms
A

Metre = m

Millimetre = 10 to the -3 m

Micrometre = 10 to the -6 m

Nanometre = 10 to the -9 m

Angstrom = 10 to the -10 m

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2
Q

State the meaning of the term tissue.

A

A collection of cells specialised to perform a particular function.

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3
Q

What to aggregations of tissues constitute?

A

Organs.

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4
Q

Define histology.

A

The study of the structure of tissues by means of special staining techniques combined with light and electron microscopy.

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5
Q

Why is histology valuable in diagnosis?

A

In many diseases such as Crohn’s, treatment is not given until the histopathologists have given a diagnosis. A biopsy and histology is the final proof for many diseases, like lung/breast cancer.

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6
Q

Define the term biopsy.

A

The removal of a small piece of tissue from an organ or part of the body for microscopic examination.

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7
Q

Describe a smear and give an example of a tissue that can be sampled by this method.

A

Collecting cells by spontaneous/ mechanical exfoliation, and smear on the slide.

Example tissue: cervix, buccal cavity.

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8
Q

Describe a curettage and give an example of a tissue that can be sampled by this method.

A

Removal of tissue by scooping/ scraping.

Example of tissue: endometrial lining of the uterus.

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9
Q

Describe a needle biopsy and give an example of a tissue that can be sampled by this method.

A

Put needle into tissue to gather cells.

Example of tissues: brain, breast, liver, kidney, muscle.

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10
Q

Describe a direct incision biopsy and give an example of a tissue that can be sampled by this method.

A

Cut directly into the tissue of interest and remove the tissue.

Example of tissue: skin, mouth, larynx.

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11
Q

Describe an endoscopic biopsy and give an example of a tissue that can be sampled by this method.

A

Removal of tissue via instruments through an endoscope.

Example of tissue: lung, intestine, bladder.

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12
Q

Why does tissue in a slide need to be fixed?

What does it do the proteins?

A

To confer stability; unfixed tissues are subject to putrefaction and attack by autolytic enzymes.

It makes proteins insoluble. Macromolecular cross linkage.

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13
Q

Name two common fixatives.

A

Formaldehyde and glutaraldehyde.

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14
Q

Describe how tissue processing can lead to the formation shrinkage artefacts.

A

During slide preparation the tissue is dehydrated then rehydrated, which can lead to abnormalities in the final slide.

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15
Q

Describe the 5 steps of tissue preparation for microscopy.

A
  1. FIXATION: add formaldehyde/glutaraldehyde, cross linking adjacent proteins, arresting biological activity.
  2. DEHYDRATION AND CLEARING: Ethyl alcohol replaces water, cleared with xylene/toluene to make miscible with wax.
  3. WAX EMBEDDING: wax impregnation at 56C, solidifies so it can be sectioned.
  4. STAINING: xylene clears wax, hydrated with descending % of alcohol, as most stains are water soluble. Dyes selectively stain components based on chemical nature.
  5. MOUNTING: Slides are dehydrated, placed in xylene, mounted on xylene based medium, coverslip placed on top.
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16
Q

What does H&E stand for?

A

Haemotoxylin and Eosin

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17
Q

What does PAS stand for?

A

Periodic Acid-Schiff

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18
Q

What does haemotoxylin stain in cells, and what colour does it stain them?

A

It stains ACIDIC compoonents of cells, PURPLE/BLUE.

  • Nucleolus (RNA)
  • Chromatin (DNA)
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19
Q

What does eosin stain in cells, and what colour does it stain them?

A

It stains BASIC components of cells, PINK.

  • Most cytoplasmic proteins
  • Extracellular fibres
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20
Q

What does Periodic Acid-Schiff stain, and what colour does it stain them?

A

It stains CARBOHYDRATES and GLYCOPROTEINS.

MAGENTA

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21
Q

What is PHASE CONTRAST microscopy?

Advantages?

A

Using the interference effects of two combining light waves.

Advantage: It enhances the image of unstained cells.

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22
Q

What is DARK FIELD microscopy?

Advantages?

A

Exclude unscattered beam (light/electron) from the image.

Advantages: can use live and unstained samples.

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23
Q

What is FLUORESCENCE microscopy?

Advantages?

A

Targets molecule of interest with fluorescence.

Advantage: can use multiple fluorescent stains on one specimen.

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24
Q

What is CONFOCAL microscopy?

Advantages?

A

Tissue labelles with one or more fluorescent probes.

Advantage: Eliminates ‘out of focus flare’, 3D imaging from a series of 2D images, imaging of living specimens.

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25
Define epithelia
Sheets of continguous cells, of varied embryonic origin, that cover the external surface of the body and line internal surfaces.
26
2 examples of an exterior surface with an epithelial lining. Which germ layer do they come from?
Skin Cornea of eye ECTODERM
27
3 examples of interior surfaces opening to the exterior that have epithelial linings. Which germ layer do they come from?
Gastrointestinal tract. ENDODERM Respiratory tract. ENDODERM Genitourinary tract. MESODERM
28
5 examples of interior spaces not opening to the exterior which have epithelial linings. Which germ layer do they come from?
Pericardial sac Pleural sac Peritoneum Blood vessels Lymphatic vessels All come from the MESODERM
29
What are the two main ways of classifying epithelium? (explain both)
SIMPLE: one cell layer thick STRATIFIED: more than one cell layer thick
30
What are the 4 types of simple epithelia?
Squamous Cuboidal Columnar Pseudostratified
31
What are the 5 types of stratified epithelia?
Squamous - keratinised Squamous - non keratinised Cuboidal Columnar Transitional
32
Name some locations and functions of simple squamous epithelia.
Locations: blood vessel lining (ENDOTHELIUM), lining of body cavities (MESOTHELIUM, pericardium, pleura, peritoneum), alveoli, Bowman's capsule, Loop of Henle. inner and middle ear. Functions: lubrication (viscera), gas exchange, barrier (Bowman's), active transport via pinocytosis (meso/endothelium).
33
Name some locations and functions of simple cuboidal epithelium.
Locations: Glands (thyroid follicles, small ducts of many exocrine glands), kidney tubules, germinal epithelium surface of ovary. Functions: absorption and conduit (exocrine glands), absorption and secretion (kidney tubules), barrier/covering (ovary), hormone synthesis, storage and mobilisation (thyroid).
34
Name some locations and functions of simple columnar epithelium. What feature might it have on its apical surface?
Locations: stomach lining and gastric pits, small intestine and colon, gallbladder, large ducts of some exocrine glands, uterus, oviducts, ductuli efferents of testis (epididymis) Functions: absorption, secretion, lubrication, transport. MICROVILLI
35
What is a zona occludens?
A tight junction
36
What does occludin do?
Binds adjacent plasma membranes together tightly, so membrane proteins can not bypass and are restricted to the apical surface, and segregate others to the lateral and basal surfaces.
37
Name some locations and functions of simple pseudostratified epithelia. What other features might they have?
Locations: URT (lining of nasal cavity, trachea and bronchi), epididymis and ductus deferens, auditory tube, tympanic cavity, lacrimal sac, large excretory ducts. Functions: secretion and conduit (URT, ductus deferens), absorption (epididymis), mucus secretion (URT), particle trapping and removal (URT). CILIA, MUCUS SECRETION
38
Name some locations and functions of stratified squamous keratinised epithelium.
Locations: surface of skin, limited distribution in oral cavity. Functions: prevents water loss, protection against abrasion and physical trauma, prevents ingress of microbes, shields against UV light damage.
39
Name some locations and functions of transitional stratified epithelium.
Locations: renal calcyes, ureters, urethra, bladder Functions: distensibility, protection of underlying tissue from toxic chemicals.
40
What and where is the basement membrane?
The thin, flexible, acellular layer which lies between the epithelial cells and the subtending connective tissue.
41
What lays down the basal lamina?
The epithelial cells
42
What is the structure of the basement membrane?
The basement membrane and various other layers. There is also a reticular fibre (type III collagen) layer, the thickness of which can be changed.
43
What is the function of the basement membrane?
A strong, flexible layer to which epithelial cells adhere. Also serves as a cellular and molecular filter.
44
How is the basement membrane related to prognosis of cancer?
The degree to which malignant cells penetrate the basement membrane is related to prognosis.
45
Cell renewal rate in epithelial tissues is normally constant. What can accelerate it?
Injury.
46
How long does it take from cell division in the basal layer of the epidermis to finally being sloughed off?
28 days.
47
How often are small intensinal epithelial cells replaced from the base of the crypts?
4-6 days
48
What are sterocilia? Where might they be found?
Very long microvilli, which may have an absorbative function. Ductus deferens and epididymis.
49
What is the average size of a human cell?
10 to 20 micrometers
50
What makes us the epithelial basement membrane?
Basal lamina (lamina lucida and densa) and lamina reticularis
51
What are microvilli?
Extensions of the cell membrane, core of which is a cluster of actin fialmenets embedded in villin
52
What is metaplasia? Give an example
Transforming to another cell type Stratified squamous epithelium is replaced by simple columnar epithelium with goblet cells
53
What does the basement membrane do?
Molecular filter Regulates cell migration Epithelial regeneration Cell to cell interactions
54
What is a zonula occludens?
A tight junction between cells that makes it virtually impermeable to fluid
55
What is a gap junction?
Permits cells to communicate Can be closed Directly connects cytoplasm Analagous to plasmodesmata in plants
56
What is a desmosome? What is a hemidesmosome?
Desmosome: macula adherens, anchoring junction for cell to cell adhesion. Lateral, help to resist shearing forces in simple and stratified squamous epithelium Hemidesmosome: mediate adherence to the basal lamina.
57
How are most glands formed? What are the secreting cells of a gland called?
By epithelial downgrowths into surrounding connective tissue Parenchyma
58
Define a gland.
An epithelial cell or collection of cells that are specialised for secretion
59
How are glands classified by destination?
Exocrine: a gland with ducts that open into the lumen of an organ or onto the surface of the skin Endocrine: a gland that secretes directly into the bloodstream or lymphatic system, ductless. Arranged as cords, follicles or clusters around a profuse blood supply for transport
60
How are glands classified by structure?
Unicellular, such as goblet cells, release secretion onto surface epithelium Multicellular: duct system, extends from surface to underlying connective tissue Uncoiled, coiled Simple, complex Unbranched, branched
61
What is a mixed gland? Give an example
A gland with both endocrine and exocrine components Pancreas Exocrine secretes enzymes through ducts to the duodenum, D2. Acinar cells Endocrine, Islets of Langerhans, Insulin and Glucagon to the blood
62
What is a goblet cell? What does it secrete? What type of epithelium is it?
Unicellular gland Secretes mucin which combines with water to form mucus Mucus onto the apical surface to lubricate respiratory tract, intestines etc Simple columnar eputhlium
63
What is an acinus? Give an example of an organ in which acini are found in
Swelling of secretory glands at the end of a tube The pancreas is multi acinar
64
What types of simple glands are there? Give examples
Simple tubular: intestinal cells Simple coiled: merocrine sweat glands Simple branched tubular: gastric glands, mucous glands of oesophagus, tongue, duodenum Simple branched acinar: sebaceoud glands. Simple acinar is only a developmental stage Acinar is aka alveolar
65
What typre of compound glands are there? Give examples
Compund tubular: mucous glands in mouth, bulbourethral glands in males, testes in the seminiferous tubule Compound acinar: mammary glands Compound tubuloacinar: salivary, pancreas, glands of respiratory tract
66
How are glands classified by their method of secretion? Give examples
Merocrine: exocytosis, most glands. Salivary glands, pancrease Holocrine: disintegration of the entire cell, sebaceous gland disintegrate to fill hair follicle with sebum Apocrine: Non membrane bounded lipid secretion, mammary glands, myoepithelial cells assist
67
How are glands classified by their nature of secretion? How effectively are they stained by H and E?
Mucous: contain mucus and are high in mucins, which are highly glycosylated polypeptides. They stain poorly with H and E. Serous: often contain enzymes, are watery and free of mucus. Stain pink with H and E, so are eosinophilic.
68
Describe the process of merocrine secretion
Membrane bound vesicle approaches cell surface Fuses with plasma membrane Contents of vesicle released into extracellular space Plasma membrane is transiently larger Membrane is retrieved which stabilises the cell surface area
69
Describe apocrine secretion
Non membrane bound lipid particle approaches the cell surface Fuses with the plasma membrane, pushes up apical membrane Thin layer of apical cytoplsam drapes around the droplet, surrounding droplet pinches off the cell Plasma membrane transiently smaller Membrane added to regain cell surface area
70
Describe holocrine secretion
Disintegration of entire cell Release of contents Discharge of the whole cell
71
What is endocytosis?
Engulfing of material initially outside of the cell Opposite of exocytosis Coupled wtuih exocytosis in transepithelial transport
72
What is transepithelial transport?
When a molecule is too large to penetrate membranes it can be shunted across from one bodily compartment to another Material is endocytosed at one surface Transport vesicle shuttles it across the cytoplasm Vesicle and material is exocytosed at the oppostie surface
73
Describe the structure of the Golgi apparatus
Stack of disc shaped cisternae One side is flate, the other side is concave Discs have swellings at their edges where vesicles bud off: migratory Golgi vacuoles Cis face to trans face
74
What is the function of the golgi apparatus?
Sorting into different compartments Packaging through condensation of contents Adding sugars to proteins and lipids: GLYCOSYLATION, in the cisternae, vesicles move to the flat face Transport
75
What are the destinations of products from the golgi apparatus?
Majority extruded in secretory vesicles Some retained for use in the cell e.g lysosomes Some eneter the plasma membrane , glycocalyx Or are secreted
76
How does glycosylation in the golgi apparatus increase specificity? What happens if enzymes destory the glycocalyx ?
SUGARS MAKE MOLECULES MORE SPECIFIC Branching sugars offer complex shapes for specific interations in the glycocalyx Destruction of the glycocalyx by enzymes alters specificity of cells: adhesions to substrates and neighbouring cells, communication with neighbouring cells, contact inhibition of movement and division, mobility of cells
77
Name 4 types of control of secretion? Examples
Nervous: sympathetic netvous stimulate of the adrenal medulla leads to the release of adrenaline Endocrine: ACTH stimulate release of cortisol from the cortex of the adrenal glands, zona fasciculata Neuroendocrine: Nervous cells of the hypothalamus control the release of ACTH by CRH Negative feedback chemical mechanism: inhibitory effect of high t3/4 on TRH and TSH
78
What are the 3 major salivary glands? What is the nature of secretion from each?
Parotid: serous Sub-mandibular: mixed, mucous and serous Sub-lingual: more mucous but mixed
79
Classify the following glands as exocrine or endocrine Goblet cells in jejunum/colon, Pancreas, Thyroid Gland, Parotid glands, Parathyroid glands, Adrenal glands, Sub mandibular glands
Exocrine: Goblet cells, Parotid glands, Sub mandibular glands Endocrine: Thyroid, Parathyroid, Adrenals Mixed: Pancreas
80
What is a serous demilune?
Artefactual structure squeezed out by conventional fixation Salivary glands A gland with this structure produces both serous and mucous secretions, mixed Mucosal and serosal cells actually aligned in the acinus
81
What type of epithelium is found in the thyroid gland?
Simple cuboidal epithelium
82
What surfaces do mucosal membranes line? Examples What cells do they have?
Certain internal tubes which open to the exterior Alimentary tracts Respiratory tract Mucus secreting cells to varying degrees
83
What is the structure of a mucous membrane? Constitution
Epithelium (type depending on site) lining the lumen of a tube An adjacent layer of connective tissue, the LAMINA PROPRIA In the alimentary tract, there is a layer of smooth muscle, MUSCULARIS MUCOSAE
84
What are serous membranes? What do they envelope? Examples
Serous membranes are two part membranes that line certain closed body cavities (do not open to exterior) They envelope the viscera/organs Examples Peritoneum envelopes the abdominal organs Pericardium envelopes the heat Pleural sac envelopes the lungs
85
What is secreted by serosal membranes? What is the function of this? What are the two layers of a serosal membrane called?
Secretes lubricating fluid Promotes relatively friction free movement of structures that they surround Visceral (inside) and parietal (outside)
86
What does a serosal membrane consist of?
Simple squamous epithelium MESOTHELIUM which secretes a watery lubricating fluid A thin layer of connective tiossue which attaches to epithelium of adjacent epithelium, and carries blood vessels and nerves
87
What is the gut mesentry?
Double layer of peritoneal membrane which supports the small intestine
88
Describe the layer structure of the alimentary tract
Mucosa: epithelium, basement membrane, lamina propria (aggregrates of lymphocytes, Peyers patches, loose connective tissue), muscularis mucosae Submucosa: connective tissue layer, arteries, veins, nerves Muscularis externae: circular muscle inside, longitudinal muscle outside, peristaltic waves Serosa: mesothelium if peritoneal OR Adventitia: loose connective tissue if retroperitoneal (behind)
89
Describe the layer structure of the oesophagus
Epithelium: stratified squamous non-keratinised Lamina propria: loose connective tissue with blood and lymph vessels, some smooth muscle and immune cells Muscualris mucosae: smooth muscle thin layer Submucose: subtending layer of connective tissue with mucus secreting glands Muscularis externa: circular and longitudinal smooth muscle, peristalsis Adventitia: thin outermost layer of connective tissue
90
Describe the layer structure of the stomach?
Gastric mucosa: secretes acid, digestive enzymes and gastrin. Simple columnar epithelia for absorption. RUGAE: folds of the gastric mucosa forming longitudinal ridges in an empty stomach. Muscularis mucosae Sub mucosa Muscularis externa: oblique, circular and longitudinal layers of smooth muscle
91
Describe the layer structure of the jejunum
Pilicae circulares: circular folds of mucosa and submucosa that project into the gut lumen. Jejunal mucosa: epithelia (simple columnar), lamina propria, muscularis mucosae Submucosa Muscularis externa: circular and longitudinal smooth muscle
92
Describe the layer structure of the large intestine/colon
Epithelium: simple columnar for absorption Crypts of lieberkuhn producing lots of mucus and supplying cells to the surface. Absorbs water and electrolytes on the surface. Structure same as rest of GI tract: mucosa, submucosa, muscularis externae, serosa
93
What makes up the conducting portions and respiratory portions of the respiratory tract?
Conducting: nasal cavity to the bronchioles Respiratory: Bronchioles to the alveoli
94
What is the layer structure of the trachea?
Epithelium: pseudostratified ciliated Submucosa: connective tussue with sero mucous glands which decrease as they go closer to the bronchioles Fibroelastic membrane with trachealis muscle C shaped Hyaline cartilage: C shaped to prevent oesophageal collapse, also in bronchus but no further. Adventitia: loose connective tissue.
95
Describe the layer structure of the bronchus
Pseudostratified epithelium Smooth muscle Submucosa Crescent shaped cartilage
96
Describe the layer structure of a bronchiole
Simple columnar/cuboidal/ciliated. Samller bronchioles are not cilitaed. In terminal bronchioles small sacs extend, lined by ciliated cuboidal epithelium Smooth muscle Alveoli: no cartilages because surrounding alveoli keep the lumen open
97
What are the cell types of the alveoli? What are their functions?
One cell thick, purely epithelial Type 1 cells: squamous, cover 90% of surface area and permit gas exchange with capillaires Type 2 cells: cuboidal, cover 10% of the surface area. Produce surfactant. Numeroud macrophages line the alveolar surface, phagocytose particles Gas exchange across blood air barrier Alveoli are surrounded by a basketwork of capillaries and elastic fibres
98
Describe the layer structure of the ureter in the urinary tract
Transitional epithelium Lamina propria: fibroelastic Muscularis externa: circular
99
Describe the layer structure of the bladder wall
Transitional epithelium, impermeable to urine due to thick plasma membrane and intercellular tight junctions Smooth muscle in the lamina propria Muscularis externae, three interwoven layers
100
Describe the layer structure of the urethra How long is it in males and females?
Transitional epithelium. In penile urethra the epithelium is stratified columnar. Lamina propria Muscularis externae, circular and longitudinal Adventitia Stellate (star shaped) urethral lumen becomes ovoid as urine passes through
101
Describe the regenerative capabilites of various glands
Glandular cells of the mucous membranes of the digestive, respiratory and urinary tractscontinue to multiple throughout life, cells from the apical surface are continually replaced Liver, thyroid and pancreatic cells cease to multiply at puberty, but can regenerate in the case of tissue injury
102
What is neoplasia?
A malignant neoplasm derived from glandular epithelium is called an adenocarcinoma
103
# Define the term limit of resolution
The minimum distance at which two objects can be distinguished at
104
Why are electron microscopes capable of finer resolution than light microscopes? What is the theoretical limit of resolution of light and electron microscopes?
The limit of resolution is proportional to wavelength Electrons, much shorter wavelength than visible light Light: 0.2mm Electron: 0.002nm
105
What are the main differences between prokaryotic and eukaryotic cells?
Prokaryotic: no internal membranes, all processes in one compartment Eukaryotic: compartmentalised by internal membranes, ordely biochemical processes
106
Describe the properties and functions of membranes
Phospholipid (amphipathic molecules) bilayer Proteins are freely mobile, fluid mosaic Some proteins within the membrane are attached to the cytoskeleton Some proteins are glycosylated, pointing outwards, forms the glycocalyx FUNCTIONS: intercellualr adhesion, recognition, signal transduction, compartmentalisation, selective permeability, exocytosis and endocytosis
107
Describe the nucleus
Contains DNA, nucleoproteins and RNA Dense heterochromatin and lucent euchromatin Inactive: small and dense Active: large and sparse
108
Describe the nucleolus
Electron dense structure Site of ribosomal RNA synthesis for ribosome assembley, sub units exported Disappears in cell division
109
Describe the nuclear envelope
Double layer of membranes Nuclear pores Type of special ER, the perinuclear cisterna between inner and outer nuclear membranes, is continuous with the ER
110
Describe the rough ER
Ribosomes on surface Protein synthesis site Generates proteins for transport out of cell or to lysosomes Flattened cisternae Extensive Interconnecting membranes, vesicles Lysosomal enzymes made here, N linked glycosylation, intial
111
Describe the structure of cilia
Nine pairs of peripheral microtubules Two single central microtubules Plasmolemma covered extensions of cytoplasm Move material along the cell surface
112
Describe the smooth ER
No ribosomes Lipid and steroid synthesis: liver, mammary glands, testis, adrenals Not as flat as rough ER, less extensive Intracellular transport Continous with rough ER enclosing single lumen
113
Describe the golgi apparatus
Stacks of cisternae, cis and trans face Prioteins from the rough ER bud off and fuse with the convex cis face Proteins migrate to the concave trans face Sort, concentrate, package and modify proteins O linked glycosylation, add mannose 6 phosphate marker for lysosomal enzymes
114
Describe lysosomes
Generated by the Golgi apparatus Hydrolytic enzymes pH 5 Highly glycosylated membrane for protection Diverse in shape Primary and secondary - phagolysosome Many found in neutrophils and macrophages
115
Describe peroxisomes
Roughly spherical Granualr matricx bound by single membrane Self replicating, no genome in all cells, especially the liver and kidney Major sites of o2 utilisation and H2O2 production Detoxification Oxidises phenols, alcohols, fomic acid, formaldehyde
116
Describe mitochondria
Double membrane with inner membrane in ditinct folds, cristae Generation of ATP by oxidative phosphorylation Main substrates are glucose and fatty acids Matrix: enzymes and mitochondrial DNA, own genetic info, can divide. Female lineage Inner membrane is impermeable to small ions ATP synthase enzymes Endosymbiosis theory Many found in the liver and skeletal muscle
117
Describe the cytoskeleton
Maintains and changes cell shape Structural support for the plasma membrane and organelles Means of movement inside the cell Contractiblity in muscles Locomotor mechanisms for amoeboid movements like lymphocytes, and also for cilia and flagella
118
Describe microfilaments
Part of the cytoskeleton 5nm diameter Two strings of actin twisted together Associated with ATP - contractile Can assemble and dissociate, so is dynamic Core of actin filaments maintains microvilli
119
Describe intermediate filaments
Part of cytoskeleton Not dynamic, 10nm diameter Commonn in nerve and neuroglial cells Also common in epithelial cells that are made of cytokeratin. Tough supporting meshwork in cytoplasm and atr anchored to plasmamebrane at strong intracellular junctions - desmosomes Forming nuclear lamina
120
Describe microtubules
Part of cytoskeleton 13 alpha and beta subinits polymerise to form the wall of the hollow microtubules Originate from the centrosome Found at sites where structures in crlld are moved Long hollow cylinders of tubulin, 25nm diameter 9+2 arrangement in cilia and flagella Attachment proteins can attach to organelles and move them along microtubules
121
# Define the term connective tissue Explain some functions
A tissue of MESODERMAL origin With three basic components: cells, extracellular fibres and ground substance If forms a huge continnum throughout the body, linking together muscle, nerve and epithelial tissue, in a strcutural, metabolic and physical way Its functions include supporting organs, filling spaces between them and forming tendons and ligaments
122
What are the main functions of connective tissue?
Provide substance and form to body and organs Medium for nutrient and waste diffusion Attach muscle to bone, and bone to bone Cushion between tissues and organs Defend against infection Aid in injury repair
123
What are the main resident cell types in connective tissue?
Fibroblasts: synthesise and maintain extracellular components. Synthesise collagen, elastin and reticular fibres and ground substance. Fibrocytes are mature and less active cells. Mesenchymal cells: undifferentiated cells, differentiate into other cells and maintain extracellular materials Macrophages: tissue histocytes derived from monocytes. Ingest foreign material such as bacteria, dead cells and cell debris. Specific names, in liver KUPFER cells, in CNS MICROGLIAL cells, in bone OSTEOCLASTS.
124
How do different connective tissue types vary in their composition?
Cell type Abundance and densitry of cells Constitution of extracellular matrix Ground substance composition Fibre type, abundance and arrangement
125
What are the main visitant cell types in connective tissue?
Mast cells: seen near blood vessels containing granules with histamine and heparin. They release phamacologically active molecules. Plasma cells: derived from lymphocytes. Fat cells - adipocytes: occur in small clusters or aggregates acting for storage. They store lipids and act as an insulator and shock absorber, cushioning organs and joints. Leukocytes (WBCs) - derived from blood vessels, responsible for the production of immunocompetent cells
126
What does the extracellular matrix of connective tissue define?
Whether the function is of primary mechanical importance or if it is loose packing material
127
What are the classes of connective tissue?
Embryonic: mesenchyme (gives rise to others) from mesoderm, mucous connective tissue Connective tissue proper: loose (areolar), dense (regular/irregular) Specialised: adipose, blood, cartilage, bone, lymphatic tissue, haeemopoietic tissue
128
What makes up ground substance in connective tissue?
Gel like matric which the fibres and cells are embedded in, and the ECF diffuses through it Core proteins with glycosaminoglycans attached (GAGs) , proteoglycans and glycoproteins Hyaluronic acid molecules with many proteoglycan molecules, incterweave with collagen fibrils Negative charges on GAGs attract water, forming a hydrated gel
129
What fibres are found in connective tissue, explain a bit about each
Collagen: occurs as bundles of non elastic fibres of varied thickness. Lots of different types but most commonly type 1, synthesis is on RER of cells. Reticular fibrils: type III collagen, thin branching fibres. Delicate network around smooth muscle cells, some epithelial cells, blood vessels, adipocytes and nerve fibres. Also makes the structural framework around organs such as the spleen, liver, bone marrow and lymphoid organs. Elastic: highly elastic, able to stretch 150% of resting length due to lysine content. Composed of amorphous protein, elastin and surrounded by fibrillin.
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Explain types of collagen and its distribution in the body
Type I: 90% of collagen, tendons, skin dermis, organ capsules, fribrils, fobres, fibre bundles Type II: no fibres, hyaline and elastic cartilage Type III: RETICULIN, fibres around muscle and nerve cells, within lympathic tissues and organs Type IV: basal lamina of the basement membrane Most common protein in the body Tunica adventitia 28 types
131
Describe the type I collagen fibril structure
Periodic banding every 68 nm Each fibril, staggered collagen molecules Each molecule is a triple helix of alpha chains, every third amino acid is glycine, 1.5nm wide Left handed helices into right handed super helix
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What do fibroblasts secrete?
PROCOLLAGEN Intamitely associated with collagen fibrils
133
Describe the properties and distribution of elastin
Occurs in most connective tissue to varying degrees Primary component of elastic fibres, surrounded by microfibrils called fibrillin Low electron density Found in the dermis of the skin, tunica media of the arteries, elastic cartilage in the epiglottis, ear pinna and eustachian tube
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What condition is caused by abnormal fibrillin? What are the symptoms of the condition?
Marfan's Tall, arachnodactyly, joint dislocation, aortic rupture
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What are the different types of loose connective tissue and where are they found?
Blood Mucous connective tiissue e.g. Wharton's jelly Areolar connective tissue, in skin, submucosa, below periteoneal mesothelium, adventitia of blood vessels, surrounding gland parenchyma Adipose Reticular tissue: framework of lymphoid tissues and the liver
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What are some examples of dense regular connective tissue?
Tendons Ligaments Aponeuroses
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What are some examples of dense irregular connective tissue?
Skin dermis, periosteum, perichondrium, dura mater, capsules, large septa and trabeculae of organs, deep fascia of muscles
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What does loose connective tissue do? What is it made up of? What happens to it in oedema?
Forms the septa and trabeculae that make up the framework inside organs and adipose tissue. Divides glands into lobules. Loosely packed fibres that are seperated by amorphous ground substance. Lots of hyaluronic acid, sparse collagen In oedema it becomes greatly distended with ECF
139
What is mucous connective tissue? Where is it found? What it is its composition?
Loose connective tissue: Such as Wharton's Jelly Only found in the umbilical cord and subdermal CTof the embryo Made up of large stellate fibroblasts, which fuse with similar adjacent cells. Some macrophages and lymphocytes are present. The ground substance is soft and jelly like with lots of hyaluronic acid. Delicate mesh of collagen fibres
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What is areolar connective tissue? Where is it found? What is its composition?
Loose connetive tissue Found deep under the skin, in the submucosa, below the mesothelium of the peritoneum, associated with adventitia of blood vessels, surrounds the parenchyma of glands Contains fibroblasts, macrophages and some mast cells Collagen fibres are the most abundant, but there are some elastic fibres present
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What is reticular connective tissue? What is it made up of? Where is it found?
Loose connective tissue Made up of type III collagen Forms the framework of lymphoid tissues and the liver
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What is adipose tissue? What are its properties?
Loose connective tissue Composed mostly of adipocytes, occuring singly or in groups Between collagen fibres Nuclei are often compressed against the cell membrane
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What is the constitution of dense connetive tissue? What are some properties?
Close packing of fibres Proportionally fewer cells Less ground substance Achieves mecahnical support and transmit forces (tendons)
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How are fibre bundles in dense regular connective tissue organised?
Fibres in parallel to provide maximum tensile strength
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What is the composition of ligaments? What do they do?
Collagen fibres interspersed with fibroblasts Less regularly arranged than tendons Elastic ligaments are mainly composed of elastin Connects bone to bone
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What does a tendon do? What is its composition?
Connects muscle to bone Collagen fibres interspersed withflattened fibroblasts, fascicles (bundles of collagen and fibroblasts), seperated by endotendium (loose CT) and held together by peritendium. A fibrous sheath surrounds the whole tendon
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What are aponeuroses?
Flattened tendons
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What is the make up of irregular dense connective tissue? What is its function?
Interwoven bundlesof colagen Small amount of reticular and elastic fibres Counteracts multidirectional forces to which the tissues are subjected
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Where is irregular dense connective tissue found?
Dermis of the skin, to withstand multidirectional forces and prevent tearing, elastic fibres allow a degree of stretch Capsules of some organs Large septa and trabeculae of many organs Deep fascia of muscles Periosteum Preichondrium Dura mater
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What is heparin?
An anticoagulant
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What i histamine and what does it do?s
Increases blood vessel wall permeability Substance attracting neutrophils and eosinophils Secretions for reactions
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What are the two types of adipose tissue? What are the functions of adipose?
White: single fat droplet in cells Brown: seperate droplets
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What are some disroders of connective tissue?
Systemic sclerosis: all organs have excessive accumulation of collage: fibrosis, hardening and functional impairment of skin, digestive tract, muscels, kidneys etc Keloid: forms scars on skindue to abnormal amounts of collagen Scurvy: vitamin D deficiencvcy, defective collagen synthesis as cofactor for prolyl hydroxylase. Degeneration of connective tissue, periodontal ligament affected, loosengng of teeth with loss, bleeding gums. Marfan's: defect in gene coding for fibrillin, which affects elastic fibres. Large elastic arteries like the aorta rupture due to bulging caused by a smaller lumen. Ehlers danlos: deficiency in reticular fibres (type III collagen) causing rupture in tissues with high reticulin
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What are types of variation in the macroscopic structure of human skin?
Colour: ehinicity, site (lips/areolae), UV exposure Hair: site (palms, soles, lips have none), sex (more body hair in men),, age (male baldness, greying), ethinicity (colour, character) Thickness Laxity: site, age, UV exposure (injury to dermal collagen/elastin) Oiliness: puberty, site
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How do some variation in the macroscopic structure of skin influence the susceptiibility/ manifestations of some skin diseases?
VITILIGO (autoimmune depigmentation): less of a problem in fair skin, hardly noticeable. Psychosocial effects in dark skinned as obvious. ALOPECIA AREATA/TOTALIS (autoimmune hair loss): More impact in women, psychosocial, especially if on scalp. ACNE: common in puberty UV INDUCED: more susceptible in fair skinned, to UV induced acute sunburn, freckling, ageing and skin cancer, especially if red hairded and blue eyed. No sunburn in blacks. Low basal cell carcinoma and malignant melanoma in blacks
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What is the epidermis made of? What are the different layers of the epidermis?
Stratified squamous keratinsied epithelium, made up mainly of keratinocytes and their products 4 layers Horny layer: stratum corneum Granular layer: stratum granulosum Prickle cell layer: stratum spinosum Basal layer: stratum basale
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What is the process of keratinocyte differentiation in each of the 4 layers of the epidermis?
Keratinocyte mitosis mainly in the basal layer, the daugther cells then move up to the prickle cell layer. In the prickle cell layer terminal differentiation begins and they lose the ability to divide. Keratinocytes synthesise keratins for strength. Joined by prickle like desmosomes. In the granular layer they lose their plasma membrane and begin to differentiate into corneocytes. This layer contrains keratohyalin granulesm, which are aggregations of keratins, other fibrous proteins (filaggrin and involucrin) and enzymes which degrade membranes. The horny layer is made up of layers of flattened corneocytes, highly keratinised squams, they have a major role in skin barrier function.
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What are keratins? What are they found in?
Heterodimeric fibrous proteins Epidermis Hair Nails
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What is the transit time of a keratinocyte from the basal layer to the horny layer?
30 to 40 days
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What other epidermal cells are there besides keratinocytes? What do they do and where are they found?
MELANOCYTES: dendritic cells of neural crest origin. Occur at invtervals along the basal layer. DIfficult to see without special stains. They produce melanin, the main skin pigment, more melanin is produced in dark skin. LANGERHANS CELLS: dendritic cells of bone marrow origin. Scatted throughout the prickle cell layer. Difficult to see without special stain. Specialised capacity to present antigens to T lymphocytes and mediate immune reactions - allergic contact dermatitis
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What are some disorders of the epidermis?
Psoriasis Akkergic contact dermatitis Malignant melanoma Vitiligo
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Describe psoriasis
A disorder of abnormal epidermal growth and differentiation Common: 1 in 50 people Cause is unknown, but runs in families Autoimmune and T cell mediated Extreme proliferation of epidermal basal layer, causing gross thickening of the prickle cell layer Production of excessive stratum corneum Clinically manifests as excessive scaling Treat with immunosuppresant Often causes psychosocial issues
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Describe allergic contact dermatitis
Mediated by Langerhans cells Present antigens to T lymphocytes Often in response to nickel
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Describe malignant melanoma
Aggressive neoplasm of melanocytes Retention above basement membrane of epidermis is associated with good prognosis More penetrating nodular melanomas have a poor prognosis Common moles are benign growths of melanocytes, sometimes hard to distinguish from melanomas clinically
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Describe vitiligo
Autoimmune attack of melanocytes Causes depigmentation Often symmetrical, may be due to neural control down to neural crest embryological origin of melanocytes Much more visible in dark skin, psychosocial issues
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What is alopecia areata?
Autoimmune attack of hair follicles
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Describe the dermo-epidermal junction
Basement membrane below the basal layer of the epidermis Best seen with a PAS stain: Period Acid Schiff InterdigitatingB asal cells connected by hemidesmosomes
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What is the structure of the dermis?
Dense irregular connective tissue: spiindle shaped fibroblasts. ECM main constituent with mainly type 1 collagens and elastins Blood vessels: small in the superficial dermis, large in deeper dermis. Lymph vessels Mast cells: arround blood vessels, histamine release in allergic reaction, leakage of plasma causing oedema. Nerves: cutaenous sensory nerves transmit sensation
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What is the main component of scar tissue?
Collagen
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What causes birthmarks and port wine stains?
Birthmarks: malformation of blood vessels Port wine stain: congenital malformation of blood vessels, always dilated
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What is the result of damage to collagen and elastin?
Solar elastosis Stretch marks: straie Scars: keloids
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What are examples of skin appendages?
Hair follicles and sebaceous glands: pilosebaceous unit Sweat glands: eccrine/apocrine Nails
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Describe a pilosebaceous unit
Sebaceous gland feeds into the hair follicle, side of hair shaft Sebaceous glands are a branched type of acinar gland Holocrine secretion of sebum, cell distintegration Arrector pili muscle for goosebumps Large on face, produce lots of sebum, obstructed in acne- infection
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Describe eccrine and apocrine sweat glands
ECCRINE: major sweat glands, found in skin and porduce clear odourless substance of water and NaCl which is reabsorbed in the duct. Active in thermoregulation, controlled by the hypothalamus. Composed of intraepidermal spiral duct, stright dermal portion and coiled acinar portion in the dermis APOCRINE: large sweat glands, most abundant in axillae (underarms), genital and submammary areas. No function of value, produce odourless protein rich apocrine secretion. Digestion by cutaneous microbes produces odour.
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What are the main functions of the skin?
Barrier function: stratum corneo prevents exogeneous absorption. Much studies as most be overcome by percutaneous absorption of drugs, can be disrupted in disorders like psoriasis (loss of fluid, protein, nutrients, heat. Excessive exogeneous absorption) Sensation: sensory nerves allow sense of touch, temperature, tissue damage. Disrupted in leprosy (peripheral nerves disorder) and diabetic sensory neuropathy Thermoregulation: vascular dilation leading to heat loss, contriction retains heat, gives pallor. Failure leads to serious consequences. Eccrine sweating, evaporation. Psychosexual communication: manipulated as a means of communication and expression, tattoos and piercings
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What are some properties and functions of cartilage?
Non-vascular, strong, pliable Semi solid, firm, tough jelly Support of organs, articulating surfaces of bones, greater part of the fetal skeleton
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Describe the composition of cartilage generally
Originates from mesenchyme which differentiates into chrondorblasts, which secrete the matrix The matrix surround and entraps these cells in lacunae, they are then referred to as chondrocytes Isogenous clusters of cells Ground substances made up of type I collagen, glycosaminoglycans, gproteoglycans Lots of hyaluronic acid for resistance to pressure No inorganic substances Mesenchymal cells
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What usually surrounds cartilage? What type of connective tissue is this? What are its layers?
Perichondrium Dense irregular connective tissue Couterfibrous layer, and inner cellular (CHONDROGENIC) layer with chondroblasts
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How does cartilage develop in the embryo?
Cartilage first appear in the 5th week of development Embryo skeleton composed of hyaline cartilage, until it is replaced by bone Hyaline cartilage remains in the epiphyseal growth plates and articular cartilage
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Describe where hyaline cartilage is found
Respiratory passages: C shaped cartilage Articulating surfaces of long bones Anterior ends of the ribs Fetal skeleon Nose Epiphyseal growth plates
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Describe the structure and function of hyaline cartilage
Matrix with proteoglycans, hyaluronic acid and type II collagen, bound to fine collagen matrix fibres Has perichondrium except on articular surfaces Avascular so must rely on diffusion for nutrient supply Offers firm and flexible support Only singular chondrocytes
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Describe where elastic cartilage is found
Ear (pinna) Eustachian tube Epiglottis
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Describe the structure and function of elastic cartilage
Matrix is like hyaline cartilage With collagen and many elastic fibres Has perichondrium and is avascular Provides support and maintains the shape of structures Gives extra flexibility, easier rebound
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Describe where fibrocartilage is found
Intervertebral discs Menisci of the knee Pubic symphysis Portions of the tendons Temporomandibular joint Sterno clavicular joint
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Describe the structure and function of fibrocartilage
Matrix like hyaline cartilage Abundant type I collagen in thick bundles Gives support and rigidity, strongest cartilage Very strong and resistant to stretching and compression, weight bearing Cells in rows in isogenous groups No perichondrium
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What is an articular surface?
Where bones and joints meet
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Describe how cartilage grows
Appositional growth inwards from the periphery, perichondrium Deeper in cartilage, interstitial growth from isogenous groups
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What clinical conditions can arise concerning hyaline cartilage?
Can calcify/ossify in old age and disease Susceptible to degenerative aging process, which is normal but accelerates in aging via the calcification of matrix due to increase in size and number of chondrocytes and cell death Joint pain can be the result of articular cartilage erosion at the ends of bones (osteoarthritis) Rheumatoid arthritis occurs when secondary destruction occurss by granulating synovial membrane tissue, autoimmune
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How does elastic cartilage differ from hyaline cartilage when an individual ages?
It does not calcify/ossify in old age
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What clinical conditions can arise concerning fibrocartilage?
Rupture of annulus fibrosus (intevertebral disc capsule) leads to a slipped disc Tearing of menisci
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What are the characteristics of bone?
Hardest tissue in the bone: can withstand compression, stress and deformation High vascular and well supplied with lymphatics and nerves (especially sensitive to pain in the periosteum) Contains cells, fibres and ground substance (calcified matrix)
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What are the main functions of bone?
Support Protection Mineral storage (calcium and phosphate) Haemopoiesis
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What are the two types of bone?
Spongey/cancellous/trabecular/medullar bone Compact/dense/cortical bone
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What is the structure of compact bone?
Hard, outer bone layer 80% of skeletal mass Covered and lined by connective tissue, PERIOSTEUM, tough, vascular fibrous layer Concentric lamellae with central neurovascular Haversian Canal, which communicate via Volkmann's canals Concentric circles are osteons
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What is the structure of spongey bone?
Deep, porous, highly vascular Meshwork of trabeculae filled with marrow, fine bony columns No haversian or volkmann's canals Irregular lamellae remodelled by osteoblasts and osteoclasts Osteocytes in lamellae
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What is marrow made up of?
Red marrow: RBC synthesis Yellow marrow: WBC synthesis Marrow cavity is lined with a thin cellular layer: ENDOSTEUM
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What is the difference in structure of immature and mature bone?
Immature bone: random arrangement of osteocytes - woven bone Mature bone: osteocytes arranged in concentric lamallae of osteon. Reabsorption cancals parallel with long axis
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What cells are found in bone? Describe each type
Osteogenitor - OSTEOBLASTS: synthesise the organic components of bone, making bone. They produce the osteoid matrix. OSTEOCYTES: found in lacunae cavities, maintaining bone. Trapped osteocytes. Slender cytoplasmic process, reach out to adjacent osteocytes via canaliculi. Nutrient transfer, also connect with central Haversian canal. OSTEOCLASTS: large multinucleated cells from monocytes, which digest bone. Release H+ ions, lysosomal enzymes.
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Describe the composition and properties of the bone matrix
65% inorganic, 35% organic Calcium hydroxyapatite crystals, calcium phosphate, calcium carbonat 23% Type 1 collagen, 10% water, 2% non collagen proteins Hardness and rigidity is due to interactions between calcium salts and collagen Flexibility is due to collagen
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What is the primary microstructure of bone - woven, immature bone
First bone to appear in development and repair, then replaced by mature bone Collagen fibrils arranged randomly in an interwoven fashion More cells and less minerals
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What is the secondary microstructure of bone - lamellar, mature bone
Compact dense bone: series of haversian canals, osteon, consisting of concentric lamellae of bone laid around a central canal containin blood vessels Spaces between Haversian systems are filled with bony lamellae (interstitial lamellae) Outer surface has extended lamellae (circumferential) Songey bone: meshwork of bone plates which are filled with marrow,. ALways surrounded by compact bone
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Briefly explain endochondral ossification
Cartilage to bone Cartilage is reabsorbeds and replaced with bone Begins at the primary centre in the diaphysis Later at each end at the seconday centre in the epiphyses Growth in length is at the epiphyseal growth plates
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Briefly explain how loose connective tissue or mesenchyme becomes bone
Intramembranous ossification Bone begins as highly vascularised loose connective tissue Mesenchymal cells differentiate to osteoblasts, surrounded by collagen fibres and ground substance Secrete uncalcified osteoid and then become osteocytes
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Briefly explain how bone is remodelled and repaired
ACtions of osteoblasts and osteoclasts Release and incorporation of calcium into and from the matrix
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what is a fracture?
Bleeding from multiple bleeding blood vesselsHa emotoma between broken bone ends
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Describe the cellular processes involved in bone repair following a fracture
Bone breaks, bone matrix is destroyed and bone cells adjoining the fracture will die . Blood vessels in periosteum and bone break. Haemtoma forms with fibrous tissue (PRE CALLUS or PRO CALLUS if periosteum is intact). Inflammatory cells invade to form this. New blood vessels into haemotoma, collagen spans break, hyaline cartilage forms. Osteoblsats start to reconstruct spngey bone, OSTEOCALLUS. Calcified to primary then secondary bone. New cancellous bone formed for about two months Bone remodelled via tendons, mechanical stress. Osteoclasts. Mature bone forms Bone heals without forming a scar
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Describe 5 steps in healing of a fracture
Break Haemotoma PRE/PRO CALLUS Cartilage callus Primary Bone Secondary Bone
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What are the three types of bone grafts used from bone banks?
AUTOGRAFT: donor is recipient, most successful HOMOGRAFT: donor is different human, may be rejected as foreign HETEROGRAFT: donor is of a different species, least successfulm although calf bone loses antigenicity with refridgeration
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What are the two types of ossification? Briefly explain the difference
Endochondral: from cartilage Intramembranous: from mesenchyme or loose connective tissue sheet
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Describe endochondral ossification
Bone formation in hyaline cartilage model, which is reabsorbed and replaced by bone = mineralised Most bones formed in this way, long bones such as femur and humerus STEPS: initial cartilage model, collar of periosteal bone in shaft Central cartilage in diaphyses calcifies, nuterient artery penetrates, osteogenic cells. Primary ossification centre medulla to cancellous bone. Secondary ossification centre at the epiphyses. Epiphyses ossify and growth plates move further apart, increased length Growth in diameter by depostion of bone at periphery of shaft, external modification by osteoblasts to create narrow diaphysis Epiphyseal growth plates replaced by bone when growth stops, hyaline cartilage at articular surface
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Where does intramembranous ossification occur?
Within condensations of mesenchyme Flat bones: skull (parietal, occipital, temporal, frontal), maxilla, mandible, pelvis, clavicle Also thickens long bone
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Describe the process of intramembranous ossification
Bone development starts in highly vascularised connective tissue e.g. flat skull bones Focus of activity is primary ossification centre Mesenchymal cells differentiate into osteoblasts, surrounded by collagen fibres and ground substance Osteoblasts secrete osteoid which later calcifieds Osteoblasts become osteocytes, embedded in osteoidMineral depostis in trabeculae radiate outwards from POC
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How is compact bone formed?
Initially spongey bone is formed Later transformed to compact Structure changes constantly by remoedelling
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Describe osteogenesis imperfecta (brittle bones)
Group of rare genetic disorders, affecting synthesis of type I collagen by osteoblasts and fibroblasts Weaknesses in structure which rely on collagen for strength: sclearae, skin, tendons, ears, skeleton, teeth, joints Various types: one of which is lethal before birth. Multiple fractures, bone deformities due to weak callus, bowing of bones, thin bones, some have blue sclearae Medicolegal importance as multiple fractures can be confused with deliberate injury = abuse
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Decribe osteoporosis
Loss of bone mass as age increases, reduced so there is a increased risk of fracture, as no longer provides adequate mechanical support Osteoclasts\> osteoblasts. Inadequate filling of osteoclasts resorption bays Risk areas: neck of femur, vertebral column, distal radius 2 types: Type 1 post menopausal due to loss of osteoclast inhibition by oestrogen. Type 2 senile, after age 70, lss of osteoblast function Risk factors: insufficient calcium intake, insufficient vitamin D, lack of physical activity, cigarette smoking, being female, genetic, blacks have high bone mass peak
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Describe the consequences of vitamin D and calcium deficiency on bone
Needed for normal ossification, promotes mineralisation of bone Rickets in children: bone matrix does not calcify normally, epiphyseal plate distorted by strains of body weight, bones grow slowly and become deformed. Pliable osteoid, bendy bones, fractures. Bowing of femur, enlarged chostochondral rib junctions, bossing of skull. Osteomalacia in adults: softening of bones. Deficient calcifcation of recently formed bone, partial decalcification of older matrix, causing fragility anf increased risk of fractures. Bone pain, back ache, muscle weakness
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Explain the importance of vitamin D in normal bone development
Both dietary and skin synthesised, essential for normal ossification As involved in calcium and phosphate absorption in small intestine In its absence, bone is poorly mineralised, a pliable matrix called osteoid (uncalcified, secreted by osteoblasts) Affected bones can't support weight and bend. Common cause of osteomalacia
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Hoow can osteomalacia be prevented?
Adequate intake of calcium, vitamin D and phosphate Adequate sun exposure (especially in dark skinned individuals)
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Outline the cause and features of achondroplasia
Congential and often hereditary skeletal disorder, caused by failure of proliferation and column formation of epiphyseal cartilage cells Defect in endochondral bone formation impirs longitudinal growth of the tubular bones, short limbs Skull unaffected as formed by intramembranous ossification Autosomal dominant, gain of function in fibroblast growth factor, increased proliferation of chondrocytes in growth plates, less matrix Epiphyseal growth plates are thin, few cells in the proliferating zone, hypertrophic cartilge cells form irregular columsn, zone of provisional calcified cartilage is smalll and does not provide adequate scaffolding for bone matrix depostion by metaphyseal osteoblasts
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What is the effect of growth hormone on bone?? Lack and excess
Lack of GH affects epiphyseal cartilage causing pituitary dwarfism if before puberty. After, no effect, no growth plates in epiphyses Excess before pubery, excess long bone growth, gigantism. In an adult, periosteal growth, acromegaly. Usu ally due to benign anterior pituitary tumour
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What is the effect of sex hormones on bone?
Influence time and appearance of ossification centres Precocious sexual maturity close epiphyseal growth plates prematurely retarding bone growth Sex hormone deficiencies delay plate closure causing tall statuere, later puberty. Androgens and oestrogens influence pubertal growth spurt.
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What is the effect of thyroid hormone deficiency on bone?
In newborn hypothyroidism causes cretinism Stunted physical and mental development Short stature
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What are the three types of muscle?
Striated: cardiac and skeletal Non striated: smooth
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What is the banding structure of muscle?
MHAZI M line is in the H band, which is in the A band Z line is in the I band
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Describe actin and myosin simply, and where they are
Thin filament is ACTIN, mainly in I band Thick filament is MYOSIN, mainly in A band so H and M too
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What is a sarcomere?
Z line to Z line distance
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What forms the thin filaments in skeletal and cardiac muscle?
Actin and tropomyosin molecules wrap around each other Troponin complex attached to each tropomyosin molecule, covering the binding sites for the myosin filament TnI binds to Actin TnC binds to clcium TnT binds to tropomyosin
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What makes up the thick filament?
Many myosin molecules Heads protrude at opposite endsCent Centre of sarcomere is devoid of heads
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Describe the sliding filament theory of muscle contraction
A band length is constand Length of the H and I bands decrease Actin filaments move in to overlap with myosin
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Describe the sarcotubular system of skeletal muscle
AI junction, one transverse (T) tubule T tubule extends from sarcolemma 2 terminal cisternae per tubule, TRIAD
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Explain the mechanism of the sliding filament model of muscle contraction
Troposmyosin blocks actin binding site for myosin. Calcium ions bind to TnC, moving tropomyosin away, allowing myosin heads to bind actin and begin contraction. 1. Myosin head is tightly bound to actin in rigor conformation. Lack of ATP. 2. ATP binds to the myosin head causing it to uncouple from actin. 3. Hydrolysis of ATP causes uncoupled myosin head to bend and advance 5nm 4. Myosin head binds weakly to actin releasing Pi, causing power stroke. in which myosin head returns to former position. Actin moves to M line, binds to myosin head tightly again. Myosin heads attach at different times causing movement
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Describe the mechanism of muscle innervatio and excitation contraction coupling
ACtion potential at presynaptic neron terminal, calcium infklux from ECF to ICF Influx causes presynaptic vesicles to release ACh in synaptic cleft ACh binds to nicotinic acetyl choline receptors bound to motor end plate, ligand gated ion channels open allowing sodium ions to diffuse in, depolarising the sarcolemma, spreading to the T tubules Voltage senor proteins of T tubule membrane change their conformation. Gated calcium ion release channels in adjacent terminal cisternae of SR are activated by this Rapid release of calcium into sarcoplasm Calcium binds to TnC, initiating the contraction cycle Calcium ions return to the terminal cisternae of the SR
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Describe the structure of skeletal mucl from the epimysium to the muscle fibres
Epimysium: thick connective tisssue around muscle, sheath Perimysium: around fascicles, a group of fibres, carries nerves and blood vessels Endomysium: surrounds individual muscle fibresIn Interdigitation of muscle fibres with surrounding connective tissue such as tendon at myotendonous junction - sarcolemma always between collagen bundles and muscle fibres microfilaments
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What connective tissue is associated with skeletal muscle?
Tendons connect muscle to bone Aponeuroses: muscle to bone or adjoining structures, flat and broad Layers of dense connective tissue bind muscles into functional groups, DEEP FASCIA. Contain large blood vessels, nerves, and some fat.
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What are muscle fibres (cells) composed of?
Myofibrils, which are composed of myofilaments, actin and myosin Sarcolemma Mitochondria Nucleus
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How do the A band and I band of skeletal muscle appear under a microscope?
A is dark I is light
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How are skeletal muscle cells formed?
Derived from the mesoderm, from multipotent myogenic stem cells Give rise to myoblasts, which fuse to form a primary myotube, a chain of multiple central nuclei The nuclei are displaced to the cell periphery by myosin and actin filaments
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Describe the features of red muscle
Would fnid lots in a marathon runner Smaller Rich vascularisation Rich myoglobin Numerous mitochondria Slow, weak contraction SLow fatigue Rich in oxidative enzymes, poor in ATP ase Few neuromuscular junctions
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Describe the features of white muscle
Wider Poor vascularisation Little myoglobin Few mitochondria Fast, strong contraction Rapid fatigue Poor in oxidative enzymes, rich in ATPase More NM junctions
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Describe the main features of skeletal muscle?
Long fibres, cylindrical Many peripheral nuclei Fascicle bundles, tendon connect to bone Somatic neuronal voluntary control Rapid forceful contraction Striated
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Describe the main features of cardiac muscle
Short branched cylindrical fibres Single central nucleus, 1 or 2 Striated Adherens type junctions join cells end to end, anchor cells and provide achorage for actin Gap junctions for electrical coupling with adjacent cells, intercalated discs, Z bands Intrinsic rhythm, involuntary, autonomic Life long variable rhythm T tubules on Z disc SR less developed, diad not triad
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Descibr the main features of smooth muscle cells
Spindle shaped with tapering ends Central single nucleus Gap and desmosome type junctions Not striated, no sarcomeres or T tubules Contraction still actin myosin based Slower more sustained contraction, longer Involuntary, autonomic, local stimuli Form sheets, bundles or layers Thick and thin filmaents are arranged diagonally, spiralling down the long axis for a twisting contraction
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What is the term to describe the spontaneous and rhythmic contractile capabilites of the heart? What sort of cells transmit action potentials from the atrioventricular node to the ventrical walls?
Myogenic Purkinje fibres
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Describe the microscopic structure of a cardiac muscle cell
T tubules on Z disc Sarcoplasmic reticulum less developed Diad not triad
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Describe the conduction of the action potential in cariac muscle Describe how purkinje fibres are involved
Action potential in sino atrial node To atrioventricular node Carried to ventricles by purkinje fibres by rapid conduction, enabling the ventricles to contract in a synchronous manner
246
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Describe the structure of purkinje fibres
Large cells, modified monocytes ABundant glycogen Sparse myofilaments Extensive gap junction sites
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Compare the regenerative capabilities of the three muscle types
SKELETAL: cells can not divide by tissue can regenetate by mitotic activity of satellite cells, so that hyperplasia follow muscle injury. Satellite cells fused with existing muscle cells to increase mass, hypertrophy. Gross damage repaired by connective tissue leaving a scar. If nerve or blood supply is interrupted, muscle fibres degenerate and are replaced by fibrous tissues CARDIAC: incapable of regeneration, following damage, fibroblasts invade and divide, laying down scar tissue SMOOTH MUSCLE: reatin mitotic capabilities, can form new smooth muscle cells. Evident in pregnant uterus, muscle wall becomes thicker with hypertrophy and hyperplasia of individual cells
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Where is smooth muscle found? How is it innervated?
Found in contractile walls of cavities, passageways, vasculature, gut, airways, genitourinary, uterus, ducts, glands, iris Innervated by autonomic, unmyelinated nerves
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What is the clinical significance of smooth muscle? How can smooth muscle be modified for different functions?
Hypertension, dysmenorrhoea, asthma, atherosclerosis Modified in myoepithelial cells in acini of gland, myofibroblasts producing collagen and contract
251
Explain the use of troponin assays
TnI and TnT are useful markers Cardiac ischaemi Release in one hour Must measure within 20 hours Smallest change in troponin is MI
252
How often are contractile proteins replaced in skeletal muscle?
Every 2 weeks
253
What is atrophy? What problems can it cause and how does it arise?
Wasting of muscle due to lack of use, in the aged, loss of nerve supply following injury. Muscle cell shrinks in size. Disuse atrophy: maintenance requires frequent movement against resistance or fibres shrink and weaken Loss of protein so reduced fibre diameter, loss of power More atrophy with age Destruction is greater than replacement of myofibrils Can also be caused by denervation
254
Describe how atrophy occurs with age
Above the age of 30, muscle mass decreases 50% loss of muscle by age 80 Important in temperature regulation, so loss of non shivering thermogenesis
255
What are the general functions of skeletal muscle?
Movement Posture Stability of joints Heat generation
256
How does muscle atrophy occur due to denervation?
Muscle no longer receives contractile signals which are required to maintain normal size Indications of lower motorneurone lesions include: weakness, flaccidity, muscle atrophy with fasciculatations (spontaenous twitiching of small groups of muscle fibres), and degeneration of muscle fibres 10 to 14 days after injury. Reinnervation within 3 months for good recovery, completely lost after 2 years Muscle fibres are replaced with fibrous and fatty tissue which requires daily stretching as it causes shortening
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What occurs in hypertrophy of skeletal muscle?
Replacement of fibrils is greater than destruction Increase in muscle mass from work performed against load leads to More contractile proteins, increase in fibre diameter Metabolic changes: enzyme activity for glycolysis, mitochondria, stored glycogen, blood flow Increased muscle length, addition of sarcomeres
258
Outline the physiology of the neuromuscular junction
Motor neurone synaptic knob releases acetyle choline into synapse as a result of calcium influx ACh binds to nicotinic receptor on folded end plate region Sodium ion channel opens, action potential down T tubules Causes calcium ion release from SR, muscle contraction Only 25% of ACh receptors need filling for a contraction
259
What is ACh terminated by? At high motor neurone firing rates, what happens?
ACh is terminated by acetylcholinesterase ACh release decreases at high neurone firing rates
260
Describe the pathophysiology of myasthenia gravis
Automimmune destruction of the end plate ACh receptors and loss of end plate junctional folds Widening of the synaptic cleft
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Describe the symptoms of myasthenia gravis and when the crisis point occurs
Fatigability and sudden falling due to reduced ACh release, muscle relaxes Drooping eyelids Double vision Affected by general state of health and emotion Test: hold out arm when sat down, see if it collapses quickly Crisis when it affects respiratory muscles
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How is myasthenia gravis treated?
Acetylcholinesterase inhibitors Stops it beraking down ACh Neostigmine, physostigmine Also can place eyes on the eyelids to decrease acetylcholinesterase activity
263
How is neuromuscular transmission affected in botulism?
Toxins block ACh release Clostridium botulinium bacteria in soill Can not breath properly Used in botox
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How is neuromuscular transmission affected in organophosphate poisoning?
Inhibits acetylcholinesterase irreversibly ACh remains in the receptors Muscle stays contracted
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What are muscular dystrophies?
Genetic disorders group Progressive muscle wasting and weakness Failure of body to produce proteins, or not enough, in the muscle cell membrane
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What is dystrophin?
Long rod shaped protein Anchors sarcolemma to actin and myosin fibrils
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Describe the pathophysiology of duchenne muscular dystrophy
Complete absence of dystrophin Actin not anchored to sarcolemma, so fibres tear themselves apart on contraction Creatine kinase liberated into serum Calcium enters cell causing necrosis Pseudohypertrophy (swelling), before fat and connective tissue replace muscle fibres
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Describe the symptoms of duchenne muscular dystrophy Describe some possible treatments
Early onset, Gower's sign, push hands on knees to push strength up Slow, late walking, falls Contractures: stiff joints. Imbalance between agonist and antagonist muscles Steroids: prednisolone, helps to build up muscle fibres Genetic reseatch, to make dystrophin with stem cells, gene therapy. Ataluren drug trials, ribosomal interaction to make dystrophin
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Give examples of myopathies
Inflammatory: poliomyostitis (chronic inflammation, viral/autoimmune), myalgia (muscle pain) and influenza Electrolyte imbalances: cramps, diuretic therapy (hypokalaemia) Thyrotoxicosis: increased BMR and protein catabolism Hypoparathyroidism: hypocalcaemia causing tetany Channelopathies: malignant hyperthermia
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Describe the pathophysiology of malignant hyperthermia
Rare, autosomal dominant condition, life threatening reaction to some general anaesthetics Volatile anaesthetic agens and NM blocking agent succinylcholine, which is a non competitive inhibitor of ACh on muscle nicotinic receptors. It is degraded by butyrlcholinesterase much more slowly than ACh by acetylcholinersterase Uncontrolled increase in calcium release in the muscle, and uncontrolled increase in oxidative metabolism, overwhelming body's capactiy to supply o", remove co2 and regulate body metabolism. Heat production, circulatory collapse and death. Can be treated with dantrolene a muscle relaxant
271
How are nerve fibres structured outside the CNS?
Bound together by connective tissue To form the peripheral nerves
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What are fibres that carry impulses towards the CNS called?
Afferent or sensory fibres
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What are fibres that carry impulses away from the CNS called?
Motor or efferent fibres
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What is an entire nerve sheathed by?
Epineurium
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What is a nerve fascicle ensheathed by? And what travels in this? What is the clinical relevance?
Perineurium Point where blood vessels travel within the nerve Potential malignancy transport
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What is a single nerve axon ensheathed by?
Endoneurium
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Describe the structure of a neuron
All neurones have one axon Cell body with or without dendrites Myelinated or unmyelinated Axonal terminal
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Describe the basic neuron types
Multi polar: multiple dendrites, one axon, motoneuron Bipolar: one dendrite and one axon, interneuron, rare, in retina of eye Unipolar/ pseudounipolar: no dendrites, one axon, sensory neuron
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Describe how peripheral nerves are myelinated
Sleeve of Schwanna cells, the neurolemma Wound in several concentric layers Discntionous, with gaps called nodes of ranvier To increase the speed of conduction, correlates to level of axonal myelination
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How are myelin sheaths histologically processed?
Myelin is mainly lipid, so poorly preserved in routin processing techniques Special fixatives and stains Osmium tetroxide
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How are axons myelinated in the CNS?
Glial cells called oligodendrocytes Produce and maintain the myelin coating Covering up to 250 axons
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Describe the myelination in the autonomic and somatic nervous systems
Autonomic (involuntary): myelinated (CNS) and unmyelinated (PNS) neurones Somatic (voluntary): all myelinated neurones for faster action potentials
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What neurotransmitters do excitatory neurones use? What to they do to the next neuron?
Glutatmate/aspartate Depolarise next neuron
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What neurotransmitters to inhibitroy neurones use? What do they do to the following neuron?
Glycine or GABA (g amino butyric acid) hyperpolarises the next neuron
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What causes neurotranmitters to be released?
Depo[Add](../new)larisation of the axon terminal Influx of calcium ions Presynaptic vesicles release contents
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What is the neuron proximal to the synapse called? What is the neuron distal to the synapse called?
Pre synaptic is proximal Post synaptic is distal
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How does demyelination cause a slowing of conduction veloctiry within a nerve?
Impulse has further to travel as saltatory propagation is inhibitied, slower response EG Multiple Sclerosis
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Describe multiple sclerosis
The myelin sheath is destructively removed from the axon and replaced by scar tissueOligodendrocytes and axons can also be damaged Condction velocity and saltatory propagation is impaired Scar tissue does not permit conduiction therefore the axon is useless
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Describe the structure of a nerve cell body (perikaryon)
Engine of neurone, 4 to 120 micrometres in diameter Varies in shape, may have dendrites, axonal hillock last site of summation Nissl substane, aggregration of RER for protein synthesis Golgi packages neurotransmitters into vesicle
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Describe dendrites
Specialisations to increase cell body surface area From cell body, proximal, further away, distal Dendritic tree Dendritic spines for learning experiences, Down's can't express Does not matter where the signal is received, it is maintained
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Describe the variety of connections between neurones
Lightly (one cell to one cell) to heavily (one nerve cell to thousands)
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How many pairs of spinal/segmental nerves are there?
31
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What s the nervous system made up of? What are nerves from the brain called?
Brain, spinal cord and nerves Cranial nerves
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How is the central nervous system encased?
3 layers of connective tissue Meninges
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What are the 3 meninges, from outside to inside?
Dura Mater Arachnoid Mater Pia Mater
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What is CSF?
Cerebrospinal fluid Equivalent to arterial and venous fluid of the CNS Formed by choroid plexus of arteries Butrition and oxygenation of CNS neurones, carries away metabolites
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What are the clinical implications of too much CSF?
Brain death High hydrostatic pressure
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What are the leptomeninges?
Arachnoid mater and pia mater
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What is the sub arachnoid space?
The space between the pia mater and arachnoid mater
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What is within the subarachnoid space? How does it arise?
Cerebral spial fluid flows here, and blood vessels Dilations occur floowing failures of arachnoid mater to follow brain furrows, and adher to pia mater Dilations are CSF cisterns Important clinically to confine brain bleeds
301
What are the two major cell types in the CNS?
Neurons, functional 10% Glial cells, make sure neurones thrive, 90%
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What is the function of glial cells generally?
Support neurones, help maintain homeostasis, form myelin, insulate neurones, destroy pathogens
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What are various glial cell types? What are their functions? Where are they found?
Astrocytes: blood brain barrier, assist in transfer of nutrients and waste, in the CNS Oligodendrocytes: myeliantion, up to 250 axons per cell, in CNS Microglia: immune and inflammatory reactions, macrophages, in CNS and PNS Schwann cell: myelination, many cells per axon, in PNS Satellite cells: physical support of peripheral neurones (afferent and efferent), PNS
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What are the types of input summation?
+ excitatory - inhibitory SPATIAL: summated with respect to spatial location on cell Temporal: summated with respect to time of arrival on cell body
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What are the functions of an axon?
Summates all inputs to the neuron Initiates action potentials Conducts action potentialsm away from the cell body to the terminals Depolarisation of terminals leads to release of neurotransmitters Communicates with follower cell
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What are the functional classes of neurone? Explain each
Sensory, pseudounipolar: receptros that transduce to electrical impulses . Conduct to cell body, then spinal cord/brain , some are fastest conducting neurones in body, AFFERENTS Motor, multipolar: carry out brain instructions to move muscles, conduct from brain to muscle, largest neurones, integrate large array of inputs to one output, clinically very important. EFFERENTS Inter, multipolar: 95% of nervous system, smallest, wholly in CNS, info relays between sensory and motor neurones, probably most complex neurones in the body. RELAYS
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Describe the cell membranes of neurones
Bilipid, selectively permeable to certain ionic species. Development of ionic concentration gradients between inside and outside of cells. ELECTROCHEMICAL GRADIENT Makes the neurone electrically charged
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How are ion channels gates on neurones?
Voltage gates: opened or closed by voltage changes Others opened by nurotransmitters: ligand gated
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What value is the neuron hyperpolarised at? resting potential
-70mV
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Describe the charges of the neuron at rest
Net negartive inside, net negative outside Active transport of Na+/K+ pumps More sodium out, potassium in 3:2, potassium can get back out, sodium can't get back in
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Describe how an action potential is generated?
Stimulus above threshold -55mV, causes Na+ channels to open, Na+ flows back in, membrane is depolarised, local area positive Depolarisation moves along membrane After actional potential, K+ channels open, flow out and restore the resting potential Goes too far: refractory period
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What is a ganglion?
Accumulation of nerve cell bodies outside the CNS Afferent cell bodies are in the spinal or cerebral ganglia in the dorsal root of spinal nerves
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What is the autonomic nervous system?
The involuntary nervous system
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What are the two main divisions of the autonomic nervous system?
Sympathetic Parasympathetic
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TheANS is comprised of a series of how many neurones? Describe
Series of 2 neurone, pre-ganglionic and post-ganglionic 1 cell has a cell body in the CNS, the other cell has a cell body in the PNS
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What to ANS neurones exert actions on?
Viscera Smooth muscle Secretory glands
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What is grey matter? What is white matter? What is in the central canal? What is used to stain a TS spinal cord?
Grey matter: neuronal cell bodies White matter: neuronal axons CSF in the central canal Cresyl violet stain
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In the CNS, what is the name for collections of: Neuronal cell bodies? Neuronal axons?
Nuclei Fibre tracts
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In the PNS, what is the name for collections of: Neuronal cell bodies? Neuronal axons?
Ganglia Nerves
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How is the nervous system divided into different levels and areas?
CNS and PNS to Afferent and Efferent Efferent to Somatic and Autonomic Autonomic to Sympathetic, Parasympathetic and Enteric
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Describe somatic efferents
Voluntary Simplest possible layout 1 neurone carries output, terminates directly on effector organs Activate when needed, otherwise inactive Efferents undeveloped at birth, fully developed at puberty
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What are the functions of the autonomic nervous system?
Fundamental life functions, non stop Balance of opposing systems, sympathetic and parasympathetic Maintains constant homeostasis Promotes excretory mechanisms intermittently
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Describe autonomic innervation
Most innervated by ANS dually, PNS and SNS Dominance of each depends Exception: sweat = SNS only
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What happens when the sympathetic or parasympathetic nervous systems are overactive?
SNS overactive: constriction of blood vessels (oreserve heat) , shortage of substrate to body tissues PNS overactive: dilated blood vessels, shortage of substrate to brain
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Describe CNS and PNS neurones in the autonomic nervouse system
CNS: pre-ganglionic, myelinated, white rami communicantes PNS: post-ganglionic, not myelinated, Grey rami communicantes
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What is the main function of the sympathetic nervous system?
Involved in the fight/flight/fright response Expressed mainly in stress situations Diversion of blood to muscles and heart, increase in heart rate, increase in blood pressure, reduced blood floow to GIT and skin, pale, hyperventilation.
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Describe the outflow of the sympathetic nervous system
Thoraco-Lumbar Nerve fibres have cell bodies in all 12 thoracic sections, and first 2 lumbar sections Dorsal, LATERAL and ventral horns in TS spinal cord
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Describe the two nerve fibres of the sympathic nervous system and their synapsing
Short pre ganglionic, long post ganglionic Paravertabral chain of ganglia along sympathetic trunk, parallel to vertebrae, skull to sacrum May synapse at same levels as origin (paravertebral origin) May synapse a different level to origin May not synapse in the paravertebral chain (splanchnic nerves)
329
Describe the neurotransmitters and receptors in the sympathetic nervous system
Preganglionic neurones are CHOLINERGENIC (Acetylcholine) So post ganglionic receptors are NICOTINIC Post ganglionic receptors are NORADRENERGENIC (noradrenaline) Two classes of adrenoreceptors: alpha 1 and 2, and b 1 and 2 Exceptions: some synapses are cholinergenic, perspiration and ejaculation pathways
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In the ejaculation pathway, which division of the ANS is responsible for erection? ejaculation?
Erection: Parasympathetic POINT Ejaculation: Sympathetic SHOOT
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What are the main functions of the parasympathetic nervous system?
BASAL, relaxation, calm Reduced heart rate and force of contraction Promotes digetion Promotes bodily functions such as bladder emptying Promotes sleep
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Describe the outflow of the parasympathetic nervous system
Cranio sacral outflow
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Describe the two nerve fibres of the parasympathetic nervous system
Long pre ganglionic Short post ganglionic Post ganglionic neurones in walls of effector organs
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Describe the neurotransmitters and receptors in the parasympathetic nervous system
Pre ganglionic neurones are CHOLINERGENIC (acetyl choline) Post ganglionic receptors are NICOTINIC Post ganglionic neurones are CHOLINERGENIC Effector organs are MUSCARINIC
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How can neurotransmitters be exploited in the therapeutic domain?
Agonist (triggers response) and antagonists (block agonists) Beta blockers in heart stop sympathetic stimulation
336
What are blood cells initially produced by in the foetus?
Mesoderm of the yolk sac Liver Spleen Bone marrow
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What is haemopoeisis?
The production of red and white blood cells, and platelets
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Describe the process of haemopoeisis
PROLIFERATION:stem cell divides into 2, one replaces the original step cell (self renewal) and the other cell differentiates DIFFERENTIATION: Haemopoetic progenitor will first differentiate to form either a myeloid blast (RBC, WBC, platelets) or a lymphoid blast (immunoresponse cells) The progenitor will differentiate into a certain cell type under the influence of a particular cytokine
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What is a cytokine? Give some examples
A hormone, signalling molecule Some types cause differentiation of blood cells Erythropoietin: RBCs when pO2 is low Thrombopoeitin: platelets G-CSF, GMCSF, IL-6: colony stimulating factors
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How many types of white blood cell are there? Where do they circulate?
5 types Blood and lymphatic systems
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Where do T cells mature?
Thymus
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Describe Neutrophils
Multilobed nucleus, small granules in cytoplasm (polymorphonuclear granulocyte) Most common circulating WBCs, inactive in circulation, 10 hour lifespan Migrate out to site of infection CHEMOTAXIS PHAGOCYTOSIS G-CSF (granulocyte CSF) increases production
343
Describe eosinophils
Bi lobed nucleus, large granules (polymorphonuclear granulocytes) PHAGOCYTOSIS, of antigen antibody complexes, releases cytotoxic particles Hypersensitivity reactions Lifespan 8 to 12 days Migration to serosa
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Describe basophils
Quite rare, bi or tri lobed nucleus, dense granules, polymorphonuclear granulocytes Mediate acute inflammatory reactions with histamin and heparin: oedema Also hyaluronic acid and seratonin Half life 2.5 days
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Describe monocytes
Large kidney shaped single nucleus, mononuclear cells, no granules Migrate to tissues to become macrophages PHAGOCYTOSIS, interact with T cells, CHEMOTAXIS DIAPEDESIS: intact through capillaries Response to inflammatio and antigenic stimuli
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Describe lymphocytes
Large deep staining nucleus, mononuclear cells B: humoral immunity, stimulated by antigens, transform to plasma cells, secrete immunoglobulins, antibody forming T: express CD4 on surface (helper), can be killer cells, permit transformation of B cells into plasma cells, CD8+ suppressor cells. Mature in thymus Natural killer cells too
347
Describe the structure of erythrocytes
8 micrometre diameter , biconcave disc Carries haemoglobin, 4 globin chains, 2 alpha, 2 beta, each with a haem group Spectrin and actin affect shape Membrane with glycoproteins and antigens If changes in shape, congenital or acquired, removed by spleen
348
What is the lifespan of a red blood cell?
120 days
349
What is the function of an erythrocyte?
Carrie oxygen to the tissues from the lungs, and carbon dioxide to the lungs Maintains osmotic eqbrm of the circulation Generates ATP from glucose making lactate Flexible to pass through narrow capillaries Provides oxygen when low, increase RBC production in response to hypoxia
350
What are the two main metabolic pathways in RBCs?
Glucose to lactate and ATP, glycolysis and lactate dehydrogenase Hexosemonophophate - G6P to ribose sugars by glucose 6 phosphate dehydrogenase to generate NADPH
351
Describe haem catabolism
RBCs broken down in spleen, Hb to Haem The iron is conserved Unconjugated bilirubin yellow Bilirubin conjugated in the liver, more watersoluble with glucaronic acid, less toxic Liver to kidney, urobilinogen, yellow Liver, gall bladder, in bile through bile duct, into intestines stercobilin, brown, egested
352
What does bilirubin in the blood cause?
Yellow colour, in the skin and sclearae Bilirubin produced when prophyrin opens up Toxic Attaches to albumin as not very water soluble
353
Describe the structure and fucntion of reticular cells
Synthesise reticular fibres and surround them with cytoplasm Type of fibroblast, type III collagen Direct T and B lymphocytes to specific regions with the lymphatic tissues
354
What is the structure of platelets? How are they formed?
Small round blue particles Cell fragments, stored in the spleen Produced from megakaryocytes in the bone marrow Complex surface membrane Alpha granules with fibrinogen and von Willebrand's factor Dense granules with ADP and calcium ions
355
What is a reticulocyte?
An immature RBC
356
What is the function of platelets?
Adhesion to damaged cell walls and aggregate together Provides phospholipid surface as a binding site for clotting factors in the cascade Aggregation: release of ADP from granules, glycoprotein receptors exposed Interacts with factors VII, IX and X Fibrin mesh traps platelets and RBCs
357
What does the bone marrow do? Where is it found?
Produces RBCs, platelets and WBCs Extensive bone marrow in infant More limited in adult, mainly pelvis, sternum, skull, ribs and vertebrae Blood cells released into sinusoids then the blood stream
358
What is the reticuloendothelial system?
Part of the immune system, containing phagocytic cells: Monocytes, kupffer cells, macrophages, tissue histiocytes, microglial cells Cells of RES identify and mount an appropriate immune resposne to antigens Main organs: spleen, liver and LN
359
What are the types of T cells?
CD4 helper cells CD8 suppressor cells
360
Describe the components of the innate humoral immune system
Transferrin and lactoferrin, deprive microorganisms of iron Interferons, inhibit viral replication Lysozyme, breaks down petptidoglycan in cell walls of bacteria Antimicrobial peptides Fibronectin: opposes bacteria and promotes their phagocytosis Complemet: causes microbe destruction directly with or without phagocytic help TNF a: suppresses viral replication and activates phagocytes
361
Describe the cellular components of the innate immune system
Macrophages/monocytes: phagocytosis and antigen presentation to lymphocytes Neytrophils: phagocytic and antibacterial Eosinophils: anti parasite and allergic respoinse Basophils and mast cells, allergic response Natural killer cells, recognise and kill abnormal cells such as tumours
362
Describe the humoural components of the adaptive immune system
Cytokines: promote differentation and proliferation of lymphocytes Perforin: released by T killer cells to destroy cell walls Antibodies: protect host by neutralisation, prevents binding to epithelia, opsonisation and complement activation
363
Describe the cellular components of the adaptive immune system
T cells: T helpers which become activated when CD4 binds to a specific antigen on MHC/antigen complex of an antigen presenting cell. Once activated, it clones itself to form active T helper cells and T memory cells T killer, releases perforin when cell is already infected B cells: divide to form plasma cells and memory cells when activated by a T helper, and release cytokines. Plasma cells produce specific immunoglobulins for a non self antigen
364
What are the roles of proteins in pathogens?
Nutrient acquisition Reproduction Respiration Locomotion
365
How is the immune system alerted to damage?
By causing damage, breaking barriers to prosperous regions Detect differences in proteins, different amino acid sequences
366
What does epithelial tissue do as the first barrier to pathogens?
Innate immune system Adaptations to clear pathogens from the surface, cilia, regeration, tears, nasal hairs, coughin, enzymes etc Natural antibiotics Cytokines Chemokines (attracts other cells) When pathogens break through, endothelium is leaky to let cells out, phagocytosis, opsonisation
367
What is opsonisation?
Pathogen marked for ingestion and destruction by phagocyte
368
Describe the features of the innate immune system
Present from birth Non specific Not enhanced by second exposure No memory Poorly effective without adaptive response Cellular and humoral Triggers and amplifies adaptive response Importance shown by rarity of innate inherited disorders
369
Describe features of the adaptive immune system
Arises from exposure to microorganisms Specific pathogen immunity Enhanced by second exposure Acquires memory (memory cells) Poorly effective without innate immunity Cellular and humoral Antibodies reflect infections to which they have been exposed, diagnostic tool
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When do the innate and adaptive immune systems start to work?
Innate: immediate, quicker to respond Adaptive: slower to respond, multiplication of cells, but lasts much longer after infection
371
What happens if innate or adaptive immune systems are lacking?
Innate lacking: does not respond well at all, microbes quickly multiply Adaptive lacking: innate initially responds, then microbes proliferate