Phys/Pharm Flashcards
1
Q
Who were early discoveries of cell communication found by? (2)
A
John Newport Langley
Paul Ehrlich
2
Q
What does relative mass mean?
A
concentration
3
Q
What is the modern definition of affinity?
A
Tendency of a chemical/molecule to bind to a receptor
4
Q
What did Langley’s experiments with nicotine and curare on chicken legs show?
A
After muscle poisoned by curare COULD still Contract if directly stimulated by electrode
THEREFORE nicotine was acting VIA some accessory substance on Muscle to Produce contraction
5
Q
What do receptors do?
A
recognise and respond specifically to signal molecules
serve as recognition sites for neurotransmitters, hormones etc.
also refer to protein of cell that can bind a molecule/drug which modulate cell activity
6
Q
What are chemical mediators?
A
Extracellular Signal Molecules
e.g. hormones, neurotransmitters, inflammatory mediators etc., used in ‘chemical communication’
(detected by receptors)
7
Q
When does cell signalling occur?
A
when receptors detect extracellular signals and generate intracellular signals that alter cell behavior
8
Q
What is Signal Transduction?
A
The process of converting extracellular signal to an intracellular signal
9
Q
Can extracellular signal molecules act on more than one type of cell?
A
Yes
allows coordinated responses involving multiple organs
10
Q
What is Endocrine signalling?
A
Long distance: a cell signals to cells distributed widely in body.
Signaling molecules/mediators are secreted into bloodstream e.g. hormones
11
Q
What are 4 types of cell signalling? (4)
A
Endocrine
Paracrine
Neuronal
Contact-Dependant
12
Q
What is Paracrine signalling
A
Extracellular signal molecules/mediator act locally: cell signals to neighbouring cells
Mediator does not diffuse far
If cells respond to mediators they themselves produce then “autocrine”
13
Q
When are Is Paracrine Signalling often used?
A
inflammation, controlling cell proliferation and wound healing
14
Q
insert image slide 15 lecture 1
A
15
Q
What are neurones?
A
Neurons use specialized structures “Synapses” to restrict signaling to specific target cells
16
Q
What do drugs acting on neurotransmission do?
A
Influence neurotransmitter synthesis, storage (amphetamines), or release e.g. BoTox
Many drugs act on neurotransmitter receptors e.g. Nicotine, Curare
17
Q
What is Contact-dependant Signalling?
A
Cell-surface-bound signal molecule binds to a receptor protein on an adjacent cell
Many of the same types of signal molecules are used for endocrine, paracrine, and neuronal signaling
18
Q
Where is Contact-dependent signalling widely used?
A
In the immune system
19
Q
Insert image lecture 1 slide 19
A
20
Q
How is Contact-dependant Signalling used to kill cancer cells?
insert image lecture 1 slide 20
A
21
Q
Summarise the 4 types of cell to cell communication?
A
Endocrine Like advertising on a radio - reach large and diverse audience
Paracrine Local advertising with poster
Neuronal Phone call or TXT – Personal can be over short or long distances.
Contact dependent face to face
22
Q
What are Bioassays?
A
Experimental assay in which the concentration or potency of a substance is measured by the biological response it produces
23
Q
What are Bioassays used for? (3)
A
Measure the pharmacological activity of new or chemically undefined substances
Investigate the function of endogenous mediators
Measure drug toxicity and unwanted effects
24
Q
Who discovered chemical transmission? (2)
A
Henry Dale
Otto Loewi
25
What was the experiment do discover chemical transmission?
1) stimulate vagus
2) heart rate slows
3) remove fluid sample
4) add fluid to recipient heart
5) heart rate slows
26
Can the same neurotransmitter be used by multiple systems?
Yes, for example ACh used in:
somatic efferent
sympathetic
parasympathetic
27
What are the criteria for a mediator? (3)
1) released from cells in sufficient amounts to produce a biological action on target cells within an appropriate time frame
2) application of an authentic sample of the mediator reproduces the original biological effect
3) interference with the synthesis, release or action (e.g., Using receptor selective drugs, enzyme inhibitors, knock-down or knock-out techniques) remove or modulates the original biological response
28
What is the synthesis of small molecule mediators regulated by?
specific enzymes
29
What is peptide synthesised regulated by?
Transcription
30
What do which mediators a cell produces depend on?
which enzymes and genes are active
31
Can vesicles store more than one type of neurotransmitter?
Yes, for example ATP commonly found with peptides in sectory granules
32
Insert image lecture 2 slide 5
33
What are the two groups of chemical mediators? (2)
(1) Mediators which are Preformed are stored in vesicles from which they are released by exocytosis- allows for ‘rapid’ (msec) communication
(neurotransmitters, hormones, neuromodulators, cytokines, growth factors)
(2) Mediators produced on demand released by diffusion or constitutive secretion take longer (minutes-hours) to act
(nitrous oxide, lipid mediators like prostanoids)
34
insert image lecture 2 slide 6
The main mechanism of release of monoamine and peptide mediators is Ca2+-mediated exocytosis, but carrier-mediated release from the cytosol also occurs. T represents a typical amine transmitter, such as noradrenaline (norepinephrine) or 5-hydroxytryptamine. Nitric oxide (NO) and prostaglandins (PGs) are released by diffusion as soon as they are formed, from arginine (Arg) and arachidonic acid (AA), respectively, through the action of Ca2+-activated enzymes, nitric oxide synthase (NOS) and phospholipase A2 (PLA2
35
W hat does neurotransmission by chemical mediators and information coding by Action potential frequency require?
processes that will rapidly dispose of released neurotransmitter
36
How do Cholinergic synpases dispose if neurotransmitter?
Enzyme Acetylcholinesterase
37
How do other synapses remove neurotransmitters other than enzymic?
- Uptake back into supporting cells (e.g gilia)
| - Vesicle transporters
38
insert image lecture 2 slide 10
| The main processes involved in synthesis, storage and release of amine and amino acid transmitters
1, Uptake of precursors; 2, synthesis of transmitter; 3, uptake/transport of transmitter into vesicles; 4, degradation of surplus transmitter; 5, depolarisation by propagated action potential; 6, influx of Ca2+ in response to depolarisation; 7, release of transmitter by exocytosis; 8, diffusion to postsynaptic membrane; 9, interaction with postsynaptic receptors; 10, inactivation of transmitter; 11, reuptake of transmitter or degradation products by nerve terminals; 12, uptake and release of transmitter by non-neuronal cells; and 13, interaction with presynaptic receptors. The transporters (11 and 12) can release transmitter under certain conditions by working in reverse. These processes are well characterised for many transmitters (e.g., acetylcholine, monoamines, amino acids, ATP). Peptide mediators (see Ch. 18) differ in that they may be synthesised and packaged in the cell body rather than the terminals.
39
Mediator Release – Key Point Summary
- Most chemical mediators are packaged in storage vesicles. Fusion of vesicles allows the release of vesicle cargo. Most neurotransmitters, neuro-modulatory peptides, hormones and exocrine mediators are released through regulated exocytosis.
- Many secretory cells contain more than one type of vesicle, loaded with different mediators and secreted independently
- Intracellular rises in calcium in ‘secretory cells’ triggers the fusion of vesicles in regulated secretion
- Mediators that can ‘diffuse’ across membranes are not stored in vesicles but synthesized on demand.
- Stored mediators (e.g., Neurotransmitters) may be released directly from the cytosol independently of calcium and exocytosis by drugs that interact with membrane transport systems
- Intracellular rises in calcium may regulate the enzymes that control the production of diffusible mediators (e.g., NO, prostanoids, endocannabinoids)
- Calcium may also activate transcription factors, to induce the synthesis of some protein mediators (eg. Cytokines) which are then exocytosed by the constitutive pathway
40
What is a drug?
A chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect.
41
What are the 3 fundamental principle of pharmacology?
drug action must be explicable in terms of conventional chemical interactions between drugs and tissues
drug molecules must be ‘bound’ to particular constituents of cells and tissues in order to produce an effect
drug molecules must exert some chemical influence on one or more constituents of cells in order to produce a pharmacological response
42
insert image lecture 2 slide 14
Drugs can interfere with any aspect of Neurotransmission to alleviate the symptoms of neurological conditions
43
illegal drugs
| insert image lecture 2 slide 15
The mode of action of amphetamine, an indirectly acting sympathomimetic amine.
Amphetamine enters the nerve terminal via the noradrenaline transporter (NET) and enters synaptic vesicles via the vesicular monoamine transporter (VMAT), in exchange for noradrenaline (NA), which accumulates in the cytosol. Some of the NA is degraded by monoamine oxidase (MAO) within the nerve terminal and some escapes, in exchange for amphetamine via the noradrenaline transporter, to act on postsynaptic receptors. Amphetamine also reduces NA reuptake via the transporter, so enhancing the action of the released NA.
44
Can drugs target ion channels involved in regulating neurotransission
Yes, such as lignocaine (Na channel blockers)
45
What are the effects of drugs that target receptors involved in neurotransmission?
Opium from the poppy plant has powerful analgesic and euphoric effects – it also causes unwanted side effects constipation and respiratory depression
Activation of reward pathways leads to drug seeking behavior, gives rise to addiction
Long term/ frequent usage of opiates also leads to changes in receptor function – results in ‘tolerance’ – patients require increasing doses to achieve same effects
….addicts die of respiratory depression in overdose. Patients with chronic pain managed by opiates suffer from chronic constipation.
Understanding the molecular, cellular, physiological actions of opioids is leading to the development of novel drugs with reduced risks and problems.
46
What does activation of receptors by specific chemical mediators do? (3)
- regulate cellular processes
- enable communication between cells
- enables the coordination of tissue/organ/bodily responses
Drugs may regulate these processes through specific interactions with receptors
47
What are the 4 main classes of receptor targeted by therapeutic drugs? (4)
Ligand gated ion channels
G-protein coupled receptors
Kinase-linked receptors
Nuclear receptors
48
What is an Agonist?
Drugs or chemical mediators that bind to a receptor producing a response are referred to as agonists
Eg. pilocarpine, nicotine, acetylcholine, morphine
49
What is an Antagonist?
Drugs that prevent or inhibit the response of an agonist. They may bind to the receptor but DO NOT elicit a response (Majority of clinically useful drugs)
E.g., atropine, curare, naloxone
50
What is a ligand?
Ligand refers to any molecule that binds to the receptor, it may be an agonist or an antagonist
51
What influences timing of a response?
```
Signal Transduction by Receptors Mechanism
(Different for each class of receptor)
```
52
What are receptors that are ion channels know as?
inotropic receptors
53
Describe ligand-gated ion channels (inotropic)?
Involved in fast synaptic transmission (milliseconds)
Endogenous agonists are fast/classical neurotransmitters stored in synaptic vesicles eg. Ach, Glutamate, GABA
Composed of 3-5 subunits ie. proteins
Each subunit has 2-4 Transmembrane spanning domains (TMs)
Complex arranged to form a central aqueous poreAgonist binding channel opening
54
What are endogenous agonists?
Endogenous agonists are fast/classical neurotransmitters stored in synaptic vesicles eg. Ach, Glutamate, GABA
55
What does Ions flowing through the open channels produce?
Changes in the ‘excitability’ / ‘potential’ of the cell
56
Describe activation of ionotropic receptors by excitatory neurotransmitters? (2)
- Membrane depolarisation
| - Action potential firing
57
Describe activation of ionotropic receptors by inhibitory neurotransmitters? (2)
- Inhibit membrane depolarisation
| - Reduce action potential firing
58
How can we identify protein subunit composition?
Use of agonists and antagonists
59
What does malfunction of ligand-gated receptors cause?
Autoimmune disseases
60
What are endogenous ligands? (2)
hormones (e.g., angiotensin), neuropeptides (e.g., opioids) and small molecule transmitters (e.g., Ach, noradrenalin, adrenaline, eicosanoids/prostanoids)
61
What are G protein coupled receptors formed from?
A single protein
62
What are G-portien coupled receptors important in?
Clinical drugs that interfere with cellular communication as it is mediated by GPCRs (roughly 30%)
63
What do G-protein coupled receptors do? (2)
may interfere with the synthesis or disposal of the endogenous mediator
OR they may be agonists that INDUCE signaling by the receptor OR antagonists that fit into the receptor, but do NOT induce signaling and thereby prevent the action of AGONISTS
64
How can activated G protein control the function of effectors?
Following AGONIST Binding to a GPCR, Signal Transduction occurs via activation of heterotrimeric G proteins
65
Describe the structure of G-protein-coupled-receptors? (2)
Single polypeptide containing seven membrane-spanning alpha helices
Two of the extracellular loops of the polypeptide form the transmitter binding sites
66
What determines which neurotransmitters, agonists, and antagonists bind to the receptor in GPCRs?
Structural variation in extracellular loops
67
What determines,ines which G-proteins and, consequently, which effector systems are activated in response to transmitter binding in GPCRs?
Structural variation in intracellular loops
68
Describe the structure of Heterotrimeric G proteins?
```
Composed of 3 subunits
a-alpha
b-beta
g-gamma
(Both a and bg subunit allow receptor to ‘talk’ to and regulate effectors)
```
69
Insert image lecture 4 slide 5 image 1
(A) In the unstimulated state, the receptor and the G protein are both inactive. Although they are shown here as separate entities in the plasma membrane, in some cases they are associated in a preformed complex. (B) Binding of an extracellular signal molecule to the receptor changes the conformation of the receptor, which in turn alters the conformation of the bound G protein. The alteration of the α subunit of the G protein allows it to exchange its GDP for GTP. This exchange triggers an additional conformational change that activates both the α subunit and a βγ complex, which dissociate to interact with their preferred target proteins in the plasma membrane (Movie 16.2). The receptor stays active as long as the external signal molecule is bound to it, and it can therefore activate many molecules of G protein. Note that both the α and γ subunits of the G protein have covalently attached lipid molecules (red ) that help anchor the subunits to the plasma membrane.
70
Insert image lecture 4 slide 5 image 2
When an activated α subunit interacts with its target protein, it activates that target protein for as long as the two remain in contact. (In some cases, the α subunit instead inactivates its target; not shown.) The α subunit then hydrolyzes its bound GTP to GDP—an event that takes place usually within seconds of G-protein activation. The hydrolysis of GTP inactivates the α subunit, which dissociates from its target protein and—if the α subunit had separated from the βγ complex (as shown)—reassociates with a βγ complex to re-form an inactive G protein. The G protein is now ready to couple to another activated receptor, as in Figure 16−15B. Both the activated α subunit and the activated βγ complex can interact with target proteins in the plasma membrane. See also Movie 16.2.
71
What are second messengers in GPCRs?
2nd messengers are small diffusible molecules, spread signal
72
Describe Signal Transduction by G proteins? (2)
- Enzymes which regulate levels of 2nd messengers
| - Ion channels
73
Insert image lecture 4 slide 7
The Second Messenger cAMP regulates the activity of other proteins involved in signal transduction including PKA, EPAC & CREB
74
```
What does
-ePAC
-PKA
-CREB
stand for?
```
ePAC - EXCHANGE PROTEIN (directly Activated by cAMP)
PKA - Protein kinase A
CREB - cAMP response element-binding protein (- is a cAMP regulated transcription factor – it travels into the nucleus to control gene expression)
75
What is a common downstream target regulated by cAMP?
PKA- Protein Kinase A
| Phosphorylation of downstream ‘effectors’ by PKA regulates their activity
76
What can amplification of signalling through GPCR be regulated by?
2nd messenger cascades
77
What is smooth muscle contraction is stimulated by?
receptors coupled to Gq & PLC signaling
78
What does the autonomic nervous system do?
autonomic nervous system ensures we survive despite a lack of conscious input
79
What are afferent neurones?
Neurones that receive information from our sensory organs (e.g. eye, skin) and transmit this input to the central nervous system
80
What are efferent neurones?
Neurons that send impulses from the central nervous system to your limbs and organs
81
What are the 2 major efferent pathways in the autonomic nervous system? (2)
Sympathetic and Parasympathetic
82
Fill in the table for sympathetic and parasympathetic nervous system?
sympathetic parasympathetic
generalised term
when is it activated ?
How is it activated?
sympathetic parasympathetic
generalised term fight or flight. rest and digest
when is it activated ? Exercise, excitement, Digestion, defecation,
emergency, embarrassment and diuresis
How is it activated? Co-ordinated, whole body response. Functions in a discrete,
or discrete and organs specific organ specific manner
83
What are examples of sympathetic stimulation? (6)
Fight or flight
Eye – (dilates pupils so you can see better what is around you)
Heart – (rate and contractility increases)
Blood vessels – (may want to increase dilation of blood towards muscles)
Lungs – (increase in expansion and breathing rate/smooth muscle in respiratory system dilates which widens airways to allow more o2 to get in)
Liver – (constriction of blood vessels to digestive system/ breaks down glucose)
Discrete functions
Reproductive systems – (involved in ejaculation)
84
What are examples of parasympathetic stimulation? (5)
Eyes – (contract pupils get smaller)
Heart – (slows down heart rate)
Gastrointestinal tract – (more blood flow, more enzymes and bile released so glands are stimulated, such as saliva from salivary glands)
Bladder – (wall of bladder contract and urinary sphincter relaxes to allow urination)
Reproductive organs – ( involved in arousal rather than ejaculation)
85
Describe the relationship between the sympathetic and parasympathetic pathway?
Balance between the two pathways
When one goes up other goes down
The two pathways systems generally innervate the same tissue but generally have opposing effects
Although the actions are antagonistic to one another they work synergistically
This allows for the rapid, precise control of tissue function
86
What are the exceptions to the rule: sympathetic innervation only?
Sweat glands, hair follicles, blood vessel smooth muscle and the adrenal medulla
87
Describe the general organisation of the autonomic nervous system(ANS)?
Insert image lecture 5 slide 14
Both sympathetic and parasympathetic pathways have this organisation
One exception within the sympathetic pathway – the adrenal medulla
88
Describe Preganglionic neurones? (3)
Always cholinergic fibres i.e. release ACh as their primary neurotransmitter
ACh activates nicotinic ACh receptors on the postsynaptic cell
Ligand gated ion channel acetyl choline is gated and lets ions in
89
Describe the sympathetic pathway?
- Short, cholinergic preganglionic neurones from thoracic and lumbar spinal cord
- Long, adrenergic postganglionic neurones
- Target tissue expresses α- and β- adrenergic receptors
(epinephrine = adrenaline)
90
What exception does adrenal medulla in CNS have?
Rather than exciting post ganglionic neuron causes cells in adrenal medulla to release adrenaline
Which moved out of adrenal medulla and into blood stream where it is carried all across body
One of the ways in which the sympathetic nervous system can affect the whole body due to hormonal response
91
Describe the parasympathetic system? (3)
Long, cholinergic preganglionic neurons from brainstem and sacral spinal cord
Short, cholinergic postganglionic neurons
Target tissue expresses muscarinic ACh receptors
Nicotinic receptors in pre (g-protein coupled receptors)
Muscarinic receptors in post (ligand gated ion channels)
92
Why is the vagus nerve important?
The Vagus nerve (cranial nerve X) carries ~80% of total parasympathetic outflow
93
What are the essential central components of the ANS? (2)
- Spinal chord
| - Brainstem nuclei
94
Why is spinal cord important in ANS? (2)
Mediates autonomic reflexes
| Receives sensory afferent and brainstem input
95
Why is the brainstem nuclei important in ANS?
Mediate autonomic reflexes
96
What does the hypothalamus do?
Master regulator of autonomic functions
97
What does the hypothalamus integrate and co-ordinate? (6)
```
Feeding
Thermoregulation
Circadian Rhythms
Water Balance
Sexual drive
Reproduction
```
98
What regulates ANS output other than hypothalamus, spinal cord and brainstem nuclei? (2)
Forebrain
Minimal conscious cortical control BUT cortical processes do regulate autonomic output
For example:
anxiety and stress can lead to GI disturbance
fear initiates fight or flight response (limbic system)
Visceral Afferents
Sensory input from visceral afferent neurons takes priority over cortical functions i.e. nothing else seems to matter
For example, bladder distension.
99
What are the principle transmitters in the ANS? (2)
Acetylcholine and Noradrenaline
100
What blocks muscarinic effects?
Atropine
101
Large doses of acetylcholine with blocked muscarinic effects using atropine causes nicotine like effects which are?
Stimulation of ALL autonomic ganglia
Stimulation of Voluntary muscle
Secretion of ADRENALIN from adrenal medulla
102
How many muscarinic acetylcholine receptors (mAChR) are there?
5
103
mAChR subtypes, expression and function
| insert image lecture 6 slide 6
104
What channels do Muscarinic (M2) Receptor agonists activate?
GIRK Potassium Channels and inhibit L-type Calcium channels
105
Where are M2 receptors expressed?
In nodal tissue and atria
106
What does M2 receptor activation cause?
Cardiac slowing, decreased force of contraction (atria only) and inhibition of atrioventricular conduction
107
How does M2 receptor activation causes cardiac slowing, decreased force of contraction (atria only) and inhibition of atrioventricular conduction?
They do this by opening a potassium channel called GIRK which stands for Gprotein regulated inward rectifying potassium channel. In this case it is the beta-gamma subunit of the activated G protein which binds to the channel and causes is to open. Hyperpolarizing the pacemakers and slowing action potential firing. This is an example of an effector that is regulated by bg subunits rather than second messengers produced by the receptor.
108
What are M1 and M3 known as?
Gq coupled receptors
109
What do M1 and M3 do?
```
Stimulate contraction of smooth muscle
↑ bronchoconstriction
↑ gastrointestinal motility ⇢colicky pain
bladder
Stimulate secretion from exocrine glands
↑ mucus in the lungs
Stimulate lacrimal glands,
salivary glands, sweat glands
```
110
What affect does muscarine have on body?
Eating over 1 gram can cause nausea
Other effects, depend on dosage inc.
↓blood pressure (action on endothelial cells)
↑saliva, ↑ tearflow ↑ sweating
abdominal pain
Death from cardiac + respiratory failure
111
What is the Cholinergic agonist at mAChR?
Muscarine
112
Why does blood pressure decrease from muscarine?
Decrease in blood pressure comes from decrease in cardiac output (M2 receptors) and increased production of NO by endothelial cells (M3 receptors)
113
Why does saliva production increase from muscarine?
Increased saliva etc. due to activation of M3 receptors
114
What does pilocarpine do?
Reduces the pressure inside the eye by increasing the drainage of fluid from the eye into the blood stream, used to treat glaucoma
115
What are muscarinic antagonists?
Atropine
| non-selective
116
What are the effects of atropine?
```
Inhibition of secretion
salivary, lacrimal, bronchial, sweat
Smooth muscle relaxant
bronchial, biliary, urinary tract*
Pupillary dilation
(modest ↑ in HR)
↓ GI motility, acid secretion*
CNS - agitation and disorientation
↑ body temperature
```
117
How can drugs acting indirectly to enhance cholinergic transmission-cholinomimetic?
Inhibit Cholinesterase*
hydrolysis of ACh, by the enzyme acetylcholinesterase (AChE). CSF, synaptic cleft at cholinergic synapses & cholinergic nerve terminals
118
What are Anticholinesterase drugs?
Drugs that prevent breakdown of ACh
119
What are Anticholinesterase drugs used for?
- physostigmine used topically for glaucoma
| - Long acting (irreversible) anticholinesterases found in nerve gas (sarin), organophosphates, pesticides
120
What are receptors for Nordadrnaline?
GPCRs – Found on tissues responding to postganglionic sympathetic neurons
121
What are receptor subtypes characterised by?
Their signaling mechanism and pharmacology
122
What are clinical uses of adrenoceptor agonists? (2)
Adrenaline (non-selective)
Cardiovascular system
-Cardiac Arrest -Adrenaline
-Anaphylaxis -Adrenaline
B2 selective
Respiratory system
-Bronchodilator -Salbutamol (b2 selective)
-Nasal decongestant
-Ephedrine (indirectly acting sympathomimetic drug ie. causes NA release
123
Describe amphetamines?
- Indirectly acting Sympatomimetic drugs
- Structurally related to noradrenaline, don’t act directly on receptors but act indirectly by increasing release of endogenous noradranline
- Note exocytosis is NOT involved in the release process
- Also work in CNS, not just on Noradrenaline but also dopamine and 5HT
- Repeated use leads to tolerance probably as a result of depletion of neurotransmitter
124
What are Clinical Uses Adrenoceptor Antagonists? (3)
Hypertension prazosin (a1 selective)
Heart failure carvedilol (a & b)
Anxiety (somatic symptoms) propranolol (b1 & b2)
125
What are unwanted effects of Adrenoceptor Antagonists?
- Bronchoconstriction*“beta blockers” avoided in Asthma Patients
- Cardiac depression (elderly)
- Bradycardia
- Fatigue
- Cold extremities
126
What is epithelia?
one of the four basic tissue types
127
What are the 4 basic tissue types? (4)
Muscular
Nervous
Connected
Epithelial
128
Describe epithelia?
Separate controlled internal environment from uncontrolled external environment
Develop from all germ layers:
Endoderm – e.g. GI lining
Mesoderm – e.g. lining of CV system
Ectoderm – e.g. epidermis
All organs contain epithelia in some form
129
What are the fictions of epithelia? (4)
Protection - skin
Diffusion - lung
Absorption - small intestine
Secretion - gland
130
What is a common property of epithelial cells?
Polarity
| Polarity critical to function – determines specialisations
131
Describe epithelial structure?
Internal and external epithelial tissue present
All epithelial tissue composed entirely of cells, things need to pass by living sentinel to get though to body
has polarity, may have microvilli, cilia and transport proteins
132
Describe the basement membrane?
Vital component of all epithelia separative from underlying connective tissue (collagen IV)
```
Basal lamina (BL)
Reticular lamina - reticular fibres anchoring BL to underlying connective tissue (collagen/elastin)
```
Basal lamina comes from epithelial cells, can be split into lamina looseder and lamina denser
Reticular lamina is secreted by fibroblasts
Acts as filter
133
How is cell adhesion and communication achieved?
- Lateral communication through gap junctions of water, ions and small molecules
- Cell-matrix attachments bond epithelial tissue to connective tissue beneath
- Strong adhesion between cells
- Stress-bearing cytoskeletons linked from cell to cell by adhesive junctions
- Adhering junctions form belt around the cell linked to bundles of actin filaments
- Myosin filaments can pull on the actin to contract the cell (NB development)
134
insert image
epithelium structure
lecture 7 slide 5
135
Insert image lecture 7 slide 8
| cell junction recap
136
Describe the process of cell death?
Cells die often so need to replace themselves
More hostile environment = more replacement of cells by the stem cells
Variation between tissue types
137
Describe how Epithelial-Mesenchymal Interactions Regulate Epithelial Fate?
- Epithelial cells can disassemble and migrate away
- Switched expression of adhesion molecules (cadherins), induces mesenchymal cells (e.g. fibroblasts) to form an epithelium
- Epithelium in close contact with the underlying mesenchyme.
- Mesenchymal tissues control epithelial cell-fate
- Assembly of cells into an epithelium a reversible process:
- These epithelial-mesenchymal transitions important in embryonic development as well as pathology – e.g. cancer (~85% of cancers derived from epithelia)
138
What are the epithelia classifications? (4)
Two main types:
- Simple – single layer of cell (lung)
- Stratified – many layers of cells (skin)
Some do not fit into either category:
- Pseudo-stratified (upper respiratory tract)
- Transitional (urothelium) - found in bladder allowed to shape
139
What are the basic types of epithelia? (8)
- Simple squamous
- Simple cuboidal epithelia
- Simple columnar epithelia
- Pseudo-stratified columnar epithelia
- Stratified squamous epithelia
- Stratified cuboidal epithelia
- Stratified columnar epithelia
- Transitional epithelia
140
Describe simple squamous epithelia?
- Nucleus on squamous epithelia are flat like their nucleus
- Always present when rapid passage of cells require, capillaries and lining of lungs (facilitate rapid passage of molecules)
- Also found in other areas, as they are thin
141
Describe Simple cuboidal epithelia?
- Single layer of cells
- Nucleus in centre of box like presentation
- Doesn’t move right in the middle
- Involved in secretion and movement of ions with active transports
- Lots of support structures
142
Describe Simple columnar epithelia?
- Tall cuboidal presentation
- Nucleus still as the basal end of the cells (bottom)
- Involved in active transport during abortion and secretion
- Ciliated surfaces line fallopian tubes to move egg, and parts of respiratory system to remove particulate matter
143
Describe Pseudo-stratified columnar epithelia?
- Single layer of cells with appearance of multiple layers as nuclei at different levels.
- All in touch with basement membrane
- Some do not reach the apical surface
- Ciliated or uncilliated
- Described as heterogenous, usually have extra cell types in epithelia, such as goblet cells
144
Describe Stratified squamous epithelia?
- Most common type of stratified epithelium in the human body
- Areas of high abrasion
- Appear thin and flattened like squamous epithelia, basal cells appear more cuboidal
- Upper layers are often dead cells with a high degree of keratin
145
Describe Stratified cuboidal epithelia?
Stratified cuboidal less common, found in glands
| Protects ducts and tubes of glands, multi-layered but there is led of them
146
Describe Stratified columnar epithelia?
- Rare, found in conjunctiva, pharynx, anus, male urethra and embryo
- Epithelia is stratified, contains goblet cells to secrete musin, allows eyes to open and close easily, and allows tissue to stretch and contracts
147
Describe Transitional epithelia?
- Cells have round shape when relaxed
- Allows change in shape in distension without damaging the epithelial lining
- Circular cells, appear more squamous when contracted
- From empty bladder relaxed, full when distended
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What do glands mostly consist of?
epithelial cells
149
What are the two different types of glands?
Exocrine - open to extrarenal environments
Endocrine – ductless, secrete straight to internal environment like blood stream
150
What is the function of glands?
Major communication system in the body
| Single cell types such as goblet cells, embedded in other tissues,
151
What does the endocrine system regulate?
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Growth
Development
Reproduction
Blood pressure
Concentrations of ions in the blood
Behaviour
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152
What are the basic principle of the endocrine system?
- Chemicals known as hormones are secreted from endocrine tissues or ‘glands’ into extracellular fluid
- Transported by the blood to distant target tissues
-Receptors can be found:
On the cell surface
In the cytosol
In the nucleus
-Exerts action via signal transduction:
Within seconds e.g. HR increase evoked by adrenaline
Over hours or even days e.g. protein synthesis increases evoked by growth hormone
153
What are the classic 7 endocrine glands? (7)
- Pituitary - anterior and posterior
- Thyroid
- Parathyroids
- Adrenals (cortex and medulla)
- Ovaries
- Testes
- Endocrine pancreas
154
What are endocrine tissues that aren't glands?
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Hypothalamus
Kidneys
GI tract
Heart
Liver
Adipose tissue
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155
Describe the thyroid gland?
-Requires an essential trace element - Iodine
-Hormones T3 and T4 are:
Produced by follicular cells
Stored extracellularly as a prohormone in colloid
-Hormonal actions:
Via nuclear receptors
Regulate transcription of proteins
Essential for development, growth, metabolism
156
Describe the Parathyroid Gland
Synthesises and secretes the peptide hormone, parathyroid hormone
Hormonal actions:
- On bone, GI system and kidneys
- Regulate plasma levels of calcium and phosphate
157
Describe the Adrenal Gland?
Adrenal cortex
- Releases steroid hormones
- Glucocorticoid e.g. cortisol
- Mineralocorticoid e.g aldosterone
Adrenal medulla
- Chromaffin cells release adrenaline
- Releases catecholamines - adrenaline, noradrenaline
158
Describe the ovary glands (Gonads)?
- Cells within the developing follicles of the ovary produce Oestrogen and Progesterone
- Oestrogen stimulates cellular proliferation of endometrium
- Progesterone stimulates secretions and maturation of tissues
159
Describe the glands in the testes (Gonads)?
- Leydig cells in the testes produce testosterone
- Stimulates protein synthesis
- Can lead to development and growth
160
Describe the Endocrine Pancreas glands?
Not the Exocrine (digestive enzymes)
Islets of Langerhans
- B cells - release Insulin
- α cells - produce glucagon
- Both released into portal blood to influence the liver
161
describe the hypothalamus and pituitary glands?
Adenohypothesis
- Anterior lobe of pituitary
- Develops from an upward projection of the pharynx
Neurohypothesis
- Posterior lobe of pituitary
- Develops from a downward projection of the brain
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Describec Adenohypophysis?
Troph cells stimulated by releasing hormones from small diameter neurons of the hypothalamus
163
Describe Neuorohypophysis?
Releases hormones from the large diameter neurons directly into systemic circulation
164
How is hormone secretion regulated?
Regulation of hormone secretion
Neural mechanisms:
e.g. indirect feedback via physiological responses
Cortical control - limbic system/stress
Direct actions of hormones
Negative or positive
164
How is hormone secretion regulated?
Regulation of hormone secretion
Neural mechanisms:
e.g. indirect feedback via physiological responses
Cortical control - limbic system/stress
Direct actions of hormones
Negative or positive
165
Why is the hypothalamus important?
- The hypothalamus links neural activity to whole body function
- Regulation can occur via feedback loops
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| lecture 8 slide 19
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insert image
| lecture 8 slide 19
167
What are the layers of the skin? (3)
Epidermis (uppermost)
Dermis
(Hypodermis – areolar or adipose tissue between skin and muscle)
168
Describe the dermis?
- Connective tissue layer beneath epidermis
- Thicker than epidermis
- Mainly collagen with elastic and reticular fibres, 2 zones (unclear boundary):
Papillary layer – thin region of loose connective tissue (areolar) allowing mobility of leukocytes, mast and macrophage cells
Reticular layer – thick layer of dense irregular connective tissue, less cells, but often with adipocyte clusters (stretch the skin in weight gain – striae)
169
What is found in the dermis?
- Fibroblast – produce proteins laminin and fibronectin of the ECM
- Accessory organs (hair, nails, oil and sweat glands)
- Rich layer of blood and lymphatic vessels
- Includes arteriovenous anastomoses – NB thermoregulation
- Numerous nerve endings
170
What is the Dermal-epidermal boundary?
-Finger like projection, which interlock, encourages a strong boundary between the two. Having a very strong barrier reduces the risk of shearing.
- Dermal papillae- going up, helps nerves to reach right to the surface
- Epidermal ridges- going down.
171
Describe the epidermis?
Skin types:
Thick skin – palms of hands (fingertips) and feet, no hair, 5 layers (stratum)
Thin skin – rest of body, 4 layers
Stratified
Stratum basale
Stratum spinosum
Stratum granulosum
Stratum corneum
Lacks blood vessels – NB diffusion from underlying connective tissue
Self-regeneration throughout life cycle 2 – 4 weeks
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What cells are contained in the epidermis?
- Stem cells right at the bottom, in contact with the basement membrane.
- Keratinocytes make up to 80-90% of the membrane
- Melanocytes- synthesis the pigment of melanin
- Langerhans cells- dendritic cells of the skin, macrophages that originate in the bone marrow but migrate to the epidermis, density of 800 per square millimetre, stand guard against toxins, microbes and other -pathogens.
- Merkel cells- tactile cells in relatively low numbers, touch receptors associated with the underlying dermal nerve fibres.
173
Describe the stratum basale?
| Insert image lecture 9 slide 10
-Keratinocytes (most prevalent), mitotically active on basement membrane
Melanocytes give skin colour:
- Pheomelanin – red soluble pigment
- Eumelanin – brown insoluble pigment
Tactile/Merkel cells – connected to sensory nerves (sense of touch)
174
Describe melanocytes?
| Insert image lecture 9 slide 11
- Have branching processes. Release melanin, has antioxidant and radical scavenging which protect the skin from UV.
- Carotene pigments- obvious on the feet
- The higher the oxygen content the redder the haemoglobin will be
- Melanocytes spread amongst the keratinocytes, continually shed small fragments that contain melanin.
- Keratinocyte's phagocytes the fragments, internalise them, helps the keratinocytes accumulate melanin around their nucleus and will orientate the melanin to the sunny side.
175
Describe the stratum spinosum?
| Insert image lecture 9 slide 12
- Several layers of keratinocytes
- Usually thickest layer (except in thick skin – stratum corneum)
- Deepest cells mitotic, pushed upwards and cease to divide
- Produce keratin filaments causing cells to flatten (more in upper layers)
- Keratinocytes strongly linked by desmosomes
- Tight junctions ensure water retention of skin
- Dendritic cells present
176
Describe the stratum granulosum?
| Insert image lecture 9 slide 13
- 3-5 layers of flat keratinocytes (thick > thin)
- Post-mitotis
- Contain dark-staining keratohyalin granules – bind to cytoskeleton and converted to keratin
- Cells undergo apoptosis
- Produce glycolipid-filled vesicles – which spreads over cell surface forming waterproof barrier between Stratum spinosum
177
Describe the Stratum Lucidum?
| insert image lecture 9 slide 14
- Thin translucent zone
- Only exist in thick skin
- Keratinocytes densely packed, no nuclei or organelles
- Indistinct cell boundaries
- Granules of Eleidin within proteoplasm - a product of keratohyalin
178
Describe the stratum corneum?
| Insert image lecture 9 slide 15
-Most superficial - 15-30 layers
-Upper terminally differentiate dead keratinocytes (squames-desquamation)- Stratum disjunctum beneath apical acid mantle and lipid barrier
-Stratum compactum - cohesive
-‘Cornified envelope’ :
Keratins
Enclosed within insoluble amalgam of proteins
Cross-linked by transglutaminases
Surrounded by lipid envelope
-Especially resistant to abrasion, penetration and water loss
179
What are nails made up of?
- Stratum corneum
| - Dead scaly cells packed with keratin fibres
180
What is hair made up of?
- Filament of keratin, keratinised dead cells.
- Hair changes through life time
- In infants hair is very fine, downy hair.
- Will become vellus, similarly fine and unpigmented
- Terminal hair is longer and coarser, highly pigmented.
181
Describe the barrier function of the skin?
-Physical barrier – cross-linked keratin layer upon a scaffold of keratinocytes (except cuts, burns, vectors)
-Biochemical barrier
Slight acidity (pH 4-6)
Bacteriocidal agents: saturated and unsaturated fatty acids inhibit growth of bacteria and lysozyme cleaves cross linkages in bacterial cell walls
cis-6-hexadecanoic acid (C6H) can inhibit induction of antibiotic resistance
-Immunological barrier
Microbiota and microflora, have essential roles in protecting our body, protect us against pathogens and educate our immune system and break down some natural products.
182
How is temperature regulated in the skin?
-Skin - major role temp regulation, thermoreceptors in epidermis
-Countercurrent heat exchange between arterial and venous blood flow in extremities (dermis)
-Over-perfused for nutritional requirements:
True capillaries provide nutrition
Arteriovenous anastomoses assists in thermoregulation
-Hypothalamus regulates (ANS)
-Postganglionic sympathetic fibres release norepinephrine, causing vasoconstriction.
-Preganglionic sympathetic fibres release Ach and cause vasodilation (perhaps mediated by formation of bradykinin)
183
Describe thermoregulation methods?
Piloerection- hairs pull straight and form an insulating layer
Can sweat- cools body by evaporation
Vasodilation/vasoconstriction by these anastomosis
