Health and Disease Week 27 Flashcards
1
Q
What do the primary endocrine organs do?
A
main function is to make and secrete hormones
2
Q
What do the secondary endocrine organs do?
A
they have a secondary function to secrete hormones, but it is not their main function
3
Q
What are the 4 main functions of the endocrine organs?
A
- reproduction
- growth and development
- maintenance of the internal environment
- regulation of energy
4
Q
What is the structure of the endocrine glands?
A
- ductless glands (secrete hormones directly into the blood)
5
Q
What are the 5 different types of mechanisms used for cells to signal to each other?
A
- intracrine
- autocrine
- paracrine
- endocrine
- neuroendocrine
6
Q
define intracrine
A
the cells release internal substances to signal to themselves
7
Q
define autocrine
A
the cells release substances onto themselves
8
Q
define paracrine
A
the cells release substances to adjacent cells
9
Q
define endocrine
A
the cells release substances into the circulation
10
Q
define neuroendocrine
A
modified neurones release hormones into circulation
11
Q
What are the 3 major chemical classes of hormones?
A
- amino acids/amines
- peptides and proteins
- steroids
12
Q
Which amino acid are amine hormones derived from?
A
tyrosine
13
Q
What are examples of hormones classes derived from tyrosine?
A
- catecholamines (noradrenaline)
- thyroid hormones (thyroxine)
14
Q
Which amino acid are indoleamines derived from?
A
tryptophan
15
Q
What is an example of an indoleamine?
A
melatonin
16
Q
What are the steps of adrenal catecholamine synthesis?
A
- tyrosine hydroxylase converts tyrosine to L-DOPA
- Dopa decarboxylase converts L-DOPA to dopamine
- dopamine-beta-hydroxylase converts dopamine to noradrenaline
- phenylethanoalmine transferase converts noradrenaline to adrenaline
17
Q
What are the steps of thyroid hormone synthesis?
A
- iodine is needed for thyroid hormone synthesis
- there are residues on tyrosine that can have iodine added to them
- if you add together two diiodotyrosines, this gives thyroxine also known as T4
- if you add a monoiodotyrosine and a diiodotyrosine, this gives triiodothyronine T3
18
Q
What is the main precursor for all steroid hormones?
A
cholesterol
19
Q
What is the basic structure of steroid hormones?
A
a tetra planar ring structure - 4 hydrocarbon rings with a hydroxyl group and hydrocarbon tail
20
Q
What are the steps of steroid hormone synthesis?
A
- lipid droplets of LDL transport cholesterol in the bloodstream into the cell
- cholesterol can be removed from LDL and transported into the mitochondria
- cholesterol is converted to pregnenolone by cytochrome P450 enzymes
- pregnenolone can be moved to the SER and depending on the cell type and enzymes present can be converted into steroid hormones
21
Q
What are the types of peptide hormone?
A
short amino acid chains, peptides, proteins
22
Q
What are examples of short amino acid chain hormones?
A
ADH (9AA)
vasopressin (9AA)
23
Q
What are examples of peptide hormones?
A
insulin (135AA)
prolactin (198AA)
24
Q
What are examples of protein hormones?
A
thyroid stimulating hormone, follicle stimulating hormone, growth hormone
25
What are the steps of peptide and protein hormone synthesis?
1. usually synthesised as a pre-prohormone and parts are cleaved off to produce the prohormone
2. the prohormone is packaged by the golgi apparatus and stored in vesicles
3. then secreted by fusion of vesicles with the cell membrane
4. may be modified by post-translational modification
26
What are the properties of amino acid and peptide hormones?
they are lipophobic and water soluble - EXCEPT thyroid hormones
27
What are the properties of steroid hormones?
they are lipophilic
28
What 2 types of hormone receptors exist?
1. cell surface receptors (water soluble hormones)
2. intracellular receptors (lipid soluble hormones)
29
How do cell surface receptors work?
- are G protein coupled receptors or kinase receptors
- G protein couples to a G-protein which regulates effector enzymes e.g. adenylyl cyclase
- tyrosine residues become phosphorylated when the hormone binds which activates enzymes
30
How do intracellular receptors work?
1. travel in the blood bound to carrier proteins and dissociate across the cell membrane
2. bind to nuclear receptors
3. the hormones regulate gene transcription
31
In which 2 ways in hormone release activated?
1. stimulus to endocrine cells that cause hormones to be released
2. neuroendocrine regulation
32
How is hormone release activated by neuroendocrine regulation?
1. neurone in the hypothalamus sense a stimulus that leads to a regulatory hormone being released
2. this regulatory hormone stimulates the pituitary gland to release another hormone
3. the hormone acts on the endocrine glands to cause the final hormone to be released
33
How are hormones removed from the body?
1. can be excreted as urine or faeces (protein-bound hormones are protected from excretion and removal takes longer)
2. inactivated by metabolism (enzymes in the blood rapidly break down peptides and catecholeamines)
34
What is the short-loop feedback cycle of the endocrine system?
1. endocrine cells make a hormone that acts on target cell
2. target cell sends a signal that influences the endocrine cell
3. can have positive or negative feedback
35
What is the long-loop feedback cycle of the endocrine system?
the stimulus causes the hypothalamus, pituitary and endocrine cell to release hormones
36
What are the 4 main types of endocrine disorder?
1. hypo-secretion
2. hyper-secretion
3. hypo-responsive
4. hyper-responsive
37
define hypo-secretion and give example of a disorder
too little secretion of the hormone - insulin in type I diabetes
38
define hyper-secretion and give an example of a disorder
too much secretion of the hormone - pancreatic endocrine disorders
39
define hypo-responsive and give an example of a disorder
when effectors are not responsive enough to the hormone - insulin resistance type II diabetes
40
define hyper-responsive and give an example of a disorder
when effectors are too responsive to a hormone - for example, TSH receptor constitutive activation leading to hyperthyroidism
41
What happens to glucose after absorption?
1. oxidised to ATP for energy
2. stored as glycogen and triglycerides
3. used in the synthesis of many compounds
42
What happens to amino acids after absorption?
1. used in protein synthesis
2. oxidised for energy
3. synthesis of nitrogen-containing compounds
43
What happens to fats after absorption?
1. stored as triglycerides
2. oxidised for energy
3. synthesis of membrane lipids
44
What is the exocrine function of the pancreas?
it secretes digestive enzymes into the pancreatic duct to go to the duodenum
45
What is the endocrine function of the pancreas?
the alpha and beta cells of the Islets of Langerhans secrete insulin and glucagon
46
What types of cell signalling do cells in the Islets of Langerhans use?
paracrine and endocrine signalling
47
What is the overall effect of insulin?
decreases plasma glucose, amino acids and free fatty acids
48
What are the specific effects of insulin?
1. promotes the uptake of glucose via GLUT4 into muscle cells (transporter)
2. promotes the uptake of glucose into adipose tissue and the liver
3. promotes storage of glucose in the liver and muscle as glycogen
49
What are the specific effects of glucagon?
1. stimulates the breakdown of glycogen into glucose
2. stimulates fatty acid breakdown into the liver where ketones can be made and used as another substance for ATP production
50
What is the structure of insulin?
- polypeptide hormone
- 1 alpha chain and 1 beta chain
51
How is insulin synthesised?
1. it is made in the pancreatic beta cells as a preprohormone
2. the C-peptide is cleaved off
52
Which enzyme is insulin degraded by?
insulinase in the liver and kidney - has a short half-life
53
What are the steps of insulin release in response to a change in glucose/ATP?
1. glucose levels increase and it is taken up into beta cells
2. it is converted to glucose-6-phosphate which traps it inside cells
3. undergoes glycolysis to form ATP
4. the ratio of ATP to ADP in the cell increases
5. the beta cells have an ATP-sensitive potassium channel
6. the channels sense the rise of ATP, which closed the potassium channels
7. potassium levels build up
8. depolarisation causes VGCCs to open and calcium ions move into cell
9. causes vesicles of insulin to fuse and release insulin into blood
54
What are the main drug targets for type 2 diabetes medications?
the ATP-sensitive potassium channels - for example, sulfonylureas stimulate the pancreas to release more insulin to potentially improve sensitivity
55
What is the structure of the insulin receptor?
- 2 subunits of both alpha and beta
- joined by disulfide bridge
- when insulin binds to it, a dimer is formed
- it is a KINASE-LINKED receptor
56
What are the actions of insulin on carbohydrate metabolism?
1. insulin facilitates glucose entry into muscle and adipose cells
2. it stimulates the liver to store glucose and glycogen
57
What are the actions of insulin on lipid metabolism?
1. insulin promotes the synthesis of fatty acids the liver (when saturated with glycogen) - leads to an increase in lipoproteins in circulation to release fatty acids
2. inhibits breakdown of fat in adipose tissue
3. promotes glycerol synthesis from glucose and increases triglyceride synthesis
58
How is glucose uptake stimulated by insulin?
1. at normal glucose levels, some glucose is taken up into cells
2. cells have microsomes inside them
3. when insulin is released, it binds to receptors on muscle and liver cells
4. this causes some microsomes to release glucose transporters and increase their expression on the cell surface to take up more glucose
59
What are the steps of the effect of insulin on the muscles cells?
1. glucose inside cells is converted to glucose-6-phosphate and stored as glycogen
2. glucose-6-phosphate can also be metabolised to lactic acid which goes to the liver
3. amino acid uptake by muscle cells leads to protein synthesis inside the muscle
60
What are the steps of the effect of insulin on the liver cells?
1. glucose is converted to glucose-6-phosphate then glycogen in the liver cells
2. glucose can also be metabolised to pyruvate and fatty acids in the liver - these are packaged into lipoproteins and transported to the blood
3. the lipoproteins travel in the blood and arrive at the adipose tissue to be stored
4. insulin also promotes fatty acid and amino acid uptake into the liver
61
What are the steps of the effect of insulin on adipose tissue?
1. glucose is converted into glucose-6-phosphate then pyruvate, then acetyl CoA in the adipose cells to be used in fatty acid synthesis
2. the enzymes involved are stimulated by insulin
3. uptake of amino acids and lipoproteins from the liver are stimulated by insulin
62
What is the structure of glucagon?
- a peptide hormone
- single chain
63
What are the main effects of glucagon?
1. stimulates glycogenolysis
2. promotes gluconeogenesis
3. increases breakdown of fats
64
define counterregulatory hormones
two hormones that oppose each other
65
define hypoglycaemia
when blood glucose levels are constantly less than 3mM - the uptake of glucose by glucose-dependent tissues is not enough to maintain normal tissue function as not enough ATP
66
define hyperglycaemia
when blood glucose levels are constantly above 7mM
67
What are the 3 types of diabetes mellitus?
type I, type II, gestational diabetes
68
Which structures is the integumentary system made up of?
skin, hair, nails, glands, sensory receptors
69
define accessory structure
the additional structures making up the integumentary system including the hair, nails, glands and sensory receptors
70
What are the 3 main functions of the integumentary system?
1. protection
2. regulation
3. sensation
71
Which 4 main components is the integumentary system made up of?
1. skin
2. hair
3. nails
4. cutaneous glands
72
Which 2 types of glands are included in the cutaneous glands?
sebaceous (sebum) glands and the sweat glands
73
What are the 2 types of skin on the body?
1. hairy
2. glabrous (non-hairy)
74
Which type of skin covers 90% of the body?
hairy skin
75
What does the hair in the hairy skin contribute to?
tactile sensations, detecting foreign objects etc
76
What does the glabrous skin have to detect tactile details?
specialised sensory neurones
77
What are the 5 main functions of the skin?
1. protection
2. thermoregulation
3. humidity control (skin is a barrier to water loss)
4. produces vitamin D
5. skin microbiome protects from foreign microorganisms
78
What is the purpose of the skin microbiome?
protecting against pathogens
79
What factors influence a person's microbiome?
age, sex, environment, lifestyle etc
80
What are the 2 main layers of the skin?
1. epidermal layer
2. dermal layer
81
What are the features of the epidermal layer?
1. stratified epithelial cells
2. no blood vessel supply
3. made up of strata of keratinocytes
82
How does the epidermis receive blood?
by diffusion as there are no blood vessels flowing to it
83
What separates the epidermis and dermis?
the basement membrane
84
What are the 5 layers of the epidermis?
1. stratum corneum
2. stratum lucidum
3. stratum granulosum
4. stratum spinosum
5. stratum basale
85
What is the structure of the stratum corneum?
1. made of flat, dead keratinocytes and cross-linked fibres
2. has brick and mortar structure - lipids hold the corneocytes together
86
What is the difference between keratinocytes and corneocytes?
keratinocytes become corneocytes when they reach the stratum corneum and die
87
What is the structure of the stratum lucidum?
1. made up of rows of dead keratinocytes
2. only found in GLABROUS skin
3. the lipid-rich protein eleidin keeps out water
88
What is the structure of the stratum granulosum?
1. made up of mostly mature keratinocytes migrating from the spinosum
2. made up of keratohyalin granules and lamellar bodies to waterproof
3. keratinocytes are becoming flatter and more squamous here
89
What is the structure of the stratum spinosum?
1. made up of mature keratinocytes linked by desmosomes
2. the keratinocytes here produce keratin
3. also contains Langerhans cells that protect skin from microbes
90
What is the structure of the stratum basale?
1. new keratinocytes are made here
2. also contains melanocytes
3. the basal cells push older cells up
91
Which 2 parts is the dermis made up of?
1. papillary dermis
2. reticular dermis
92
What is the structure of the papillary dermis?
- mostly loose connective tissue and some elastic fibres, capillary loops and nerves
93
What is the structure of the reticular dermis?
- dense irregular connective tissue
- contains collagen fibres, elastin, proteoglycans and glycosaminoglycans
94
What is the function of collagen in the reticular dermis?
it retains the sponginess of the skin
95
Why is the reticular dermis important?
it is a nutrient-rich environment so provides nutrients and allows cells to grow before being pushed up to the stratum corneum
96
What is the function of the basement membrane?
1. separates the epidermis and dermis
2. forms a connective point allowing nutrients and cells to move between the layers
97
What are the 6 types of cells making up the dermis?
1. fibroblasts and keratinocytes
2. macrophages
3. adipocytes
4. mast cells
5. myofibroblasts
6. myoeipthelial cells
98
What are fibroblasts?
a type of cell that contributes to the formation of connective tissue
99
What do fibroblasts do?
produce collagen, elastic and reticular fibres and extracellular matrix
100
What is the function of macrophages in the dermis?
attack and remove foreign objects
101
What are adipocytes?
fat cells in the dermis
102
What is the function of adipocytes?
insulation, energy storage and wound healing
103
What is the function of mast cells in the dermis?
they are inflammatory cells that help with collagen remodelling and wound healing
104
What are myofibroblasts?
cells rich in actin and myosin and are essentially a hybrid of smooth muscle cells and fibroblasts
105
What are myoepithelial cells?
cells with contractile properties in sweat glands
106
What are keratinocytes essential for?
stratification and forming the protective skin barrier layer
107
What does the 'brick and mortar' model describe?
bricks (keratinocytes) surrounded by lipids (mortar)
108
Which 3 main components make up keratinocytes?
1. keratins
2. desmosomes and hemidesmosomes
3. lamellar granules
109
What is the function of desmosomes and hemi-desmosomes?
they anchor keratinocytes to each other and the basement membrane
110
What is the function of the lamellar granules?
they help to form the lipid protective barrier (mortar)
111
What is the structure of desmosomes and hemi-desmosomes?
1. found inside the keratinocytes
2. they are proteins with finger-like projections - one end stays in that cell, the other end reaches onto another desmosome on another cell
112
Which type of protein are desmosomes mainly made of?
cadherins proteins
113
What do desmosomes do?
connect keratinocytes to each other
114
What do hemi-desmosomes do?
connect keratinocytes to the basement membrane via integrin receptors
115
What do keratin bundles do in keratinocytes?
they form a network of fibre bundles extending from the cell membrane to the nucleus - they are the main components of the cytoskeleton
116
Why is drug administration through the skin so difficult?
few drugs can disrupt the keratin intermediate filaments
117
What are lamellar granules?
secretory organelles that contain glucosylceramides, lipids, enzymes and other proteins - these are all needed for desquamation (skin shedding)
they help form the impermeable lipid-containing barrier
118
What do lamellar granules do?
carry substances and excrete them into the extracellular matrix
119
Which 4 types of cells make up the epidermis?
1. keratinocytes
2. melanocytes
3. Langerhans cells
4. Merkel cells
120
What do melanocytes do?
produce melanin which creates skin colour and protect against UV radiation
121
What are Langerhans cells also known as?
dendritic cells
122
What is the structure of Langerhans cells?
they have dendrites that extend through the intracellular tight junctions towards the stratum corneum
123
What is the function of Merkel cells?
tactile sensations by their connection to neurones
124
What contains the melanin inside melanocytes?
melanosomes
125
How do the melanocytes transfer melanosomes to keratinocytes?
melanocyte dendrites squeeze into gaps between keratinocytes through the epidermal layer and release melanin caps which spread into keratinocytes
126
define epidermal melanin unit
the anatomical relationship between melanocytes and keratinocytes (how many keratinocytes each melanocyte is in contact with)
127
define hyperpigmentation
discoloured or darkened skin
128
What is the major issue with hyperpigmentation?
the lighter skin is more prone to sunburn and skin cancer due to less natural protection
129
What are the 2 main causes of hyperpigmentation?
1. increased melanin production by melanocytes
2. increased number of melanocytes
130
How is epidermal hyperpigmentation dealt with?
usually easily corrected by ointments or creams to give extra UV protection and prevent further darkening
131
Why is dermal hyperpigmentation harder to treat?
it is more difficult to get into the lower layers and the melanin crosses the damaged basement membrane so is deeper
132
What are examples of treatments for hyperpigmentation?
treatment is varied:
- photoprotection to prevent new spots and darkening
- could use inhibitors of melanin production
133
What is an example of a disease involving the Merkel cells?
allodynia
134
What causes allodynia?
when someone has too many Merkel cells leading to hypersensitivity of the skin - normal movements can be painful
135
What do Langerhans cells do?
1. extend their dendrites through the intracellular tight junctions and can detect stimuli from the external environment
2. they tell the immune system to fire an immune response if needed
136
What is the issue with having too many dendrites or Langerhans cells?
1. the immune response is heightened and overactive
2. the Langerhans cells work with keratinocytes to get T lymphocytes to cause a response and the body depletes immune resources - this can cause ORGAN DAMAGE
3. when a real infection occurs, the body is not as sensitive
137
What is Langerhans cell histiocytosis?
the build up of excess immature Langerhans cells forming granulomas (tumours) in the skin and other organs
138
Why is Langerhans cell histiocytosis so dangerous?
the immune system is constantly on alert which can cause organ failure and severely affect the immune system - not the same as too many Langerhans cells
139
How is Langerhans cell histiocytosis treated?
depends on severity: from topical therapy to chemotherapy and surgery
140
Where does hair grow from?
the dermis from a hair follicle
141
How does hair growth occur?
keratinocytes get pushed up, become flattened keratinised cells - like the skin
142
What are the 3 main parts of the hair?
1. shaft
2. hair root
3. hair bulb
143
What is the hair shaft?
the hair that is exposed on the skin surface
144
What is the hair root?
the part of the hair within the follicle
145
What is the hair bulb?
the region of the follicle that actively produces the hair
146
Which 4 main phases does hair growth include?
1. anagen phase
2. catagen phase
3. telegen phase
4. exogen phase
147
What is the anagen phase?
the growing phase
148
What is the catagen phase?
the transition phase
149
What is the telegen phase?
the resting phase
150
What is the exogen phase?
when the hair shaft is above the skin and already dead - shedding phase
151
What is the main function of the hair?
to protect from sun, prevent heat loss, trap particulates, prevent sweat running into the eyes
152
Why is the hair much more sensitive to environment changes than the skin?
it contains arrector pili muscles
153
What is alopecia?
baldness in places where there is usually hair
154
What is alopecia caused by?
genetic sensitivty to the adrogen hormone dihydrotestosterone (DHT) meaning there is less blood flow at the hair follicle, preventing growth
155
What causes male pattern baldness?
a mutation on the X chromosome
156
What is the function of the nails?
to prevent the fingers from constantly being bruised
157
What are the nails made of?
packed dead keratinocytes
158
What type of gland are the glands in the integumentary system?
exocrine - they secrete substances into a duct
159
What are 4 examples of glands in the integumentary system?
1. sudoriferous glands
2. sebaceous glands
3. ceruminous glands
4. mammary glands
160
What are the 2 subcategories of the glands in the integumentary system?
1. simple - a single duct
2. compound - multiple, branched ducts
161
What are the secretion methods of the glands in the integumentary system?
1. merocrine
2. apocrine
3. holocrine
162
define merocrine
excretion via exocytosis
163
define apocrine
when parts of the cell membrane pinches off into the duct and carries the substance
164
define holocrine
the substance is pinched off inside an entire cell
165
What are the sudoriferous glands?
the sweat glands
166
What are the 2 types of sudoriferous glands?
1. eccrine glands
2. apocrine glands
167
What do eccrine sudoriferous glands do?
open directly onto the surface of the skin
168
What do apocrine sudoriferous glands do?
open into hair follicles
169
What types of secretion do eccrine glands use?
merocrine secretion
170
What are the functions of eccrine glands?
thermoregulation and ion excretion
171
When do the apocrine glands become active?
from puberty
172
What are the sebaceous glands?
oil-producing glands that release sebum into the follicular duct
173
What is the function of sebum?
it coats, moisturises and protects the skin
174
What type of gland are the sebaceous glands?
holocrine - so entire cells are pinched off
175
When are the sebaceous glands highly active?
at puberty - this causes acne
176
What are the ceruminous glands?
modified apocrine sweat glands that produce cerumen (ear wax) along with sebaceous glands
177
What are the mammary glands?
a type of apocrine gland allowing production of milk after birth
178
What are the 3 main types of sensory receptors in the SKIN?
1. mechanoreceptors
2. thermoreceptors
3. nociceptors
179
What do mechanoreceptors detect?
physical change
180
What do thermoreceptors detect?
temperature change
181
What do nociceptors detect?
pain due to large physical or mechanical pain
182
What are examples of specific mechanoreceptors?
Meissner's corpuscle, Pacinian corpuscle, hair etc
183
What are the 2 types of thermoreceptors in the body?
1. cold receptors
2. warm receptors
184
How do thermoreceptors in the skin work?
1. when changes in temperature occur, the opposite receptor stops discharging
2. the exchange of ions across protein channels helps you determine if hot or cold
185
How do the protein channels in thermoreceptors work?
1. the thermoreceptor reacting to capsaicin (in chillies) and other heat-producing chemicals is TRPV1
2. in response to heat, the TRPV1 receptor opens allowing ions to pass through
3. causes a burning sensation
186
What is the trigger for nociceptors?
when tissue damage occurs and inflammatory markers bind to the nociceptors
187
In which 5 ways is the skin a barrier?
1. microbial barrier
2. physical barrier
3. chemical barrier
4. immunological barrier
5. neurosensory barrier
188
What is atopic dermatitis?
a chronic, recurrent and inflammatory disease of the skin
189
What is the structure of a healthy stratum corneum?
- corneocytes are held together by desmosomes and the space in between is filled a lipid-rich matrix
- the lipid matrix prevents transepidermal water loss
190
What happens to the skin in atopic dermatitis?
disruption to the skin occurs and there is an increased loss of water and allergen penetration
191
What causes atopic dermatitis?
1. genetic predisposition - mutation in filaggrin protein which forms a protective layer around corneocytes
2. environmental factors - increase expression of some proteins such as serine proteases with decrease corneocytes adhesion
192
What are the 4 stages of wound repair in the skin?
1. haemostasis
2. inflammation
3. proliferation
4. maturation
193
What happens in haemostasis?
vasoconstriction of the blood vessels and platelet aggregation to prevent bleeding
194
What happens during inflammation?
the body send neutrophils and macrophages to the site and they undergo differentiation
195
What happens during proliferation?
the formation of granulation tissue (new connective tissue)
196
What happens during maturation?
any clots that were formed are digested by enzymes and broken down and the new matrix begins to mature
197
define transdermal drug delivery
the non-invasive delivery of drugs via absorption over the skin
198
What are the advantages of transdermal drug delivery?
1. no drug loss due to hepatic first pass
2. no pH, enzyme, gut microbiome interference
3. minimal burden on patient
4. used for all ages
199
What is the challenge with transdermal drug delivery?
the skin is an effective and protective barrier
200
What are the 3 main routes for transdermal drug delivery?
1. intercellular
2. intracellular
3. follicular
201
How does intercellular transdermal drug delivery occur?
the drug travel in between corneocytes - more likely for lipophilic drugs as they go around lipid-rich membrane
202
How does intracellular transdermal drug delivery occur?
the drug goes all the way through the cells - more likely for hydrophilic drugs as cells contain lots of water
203
How does follicular transdermal drug delivery occur?
the drug passes through hair follicles
204
What are the 2 main ways for transdermal drug delivery?
1. active
2. passive
205
define active transdermal drug delivery
the drug need encouragement to be absorbed - normally disruptive methods
206
define passive transdermal drug delivery
the drug will diffuse without you having to do anything to it - doesn't disrupt the stratum corneum
207
What are 6 examples of active delivery methods?
1. iontophoresis
2. sonophoresis
3. electroporation
4. photomechanical waves
5. microneedling
6. thermal ablation
208
define iontophoresis
using a power source to get ionically charged drugs across the skin barrier
209
define sonophoresis
using ultrasound to push the drug through the skin
210
define electroporation
electrical impulses start to create pores within the corneocytes of the stratum corneum
211
define photomechanical wave transdermal delivery
using photodynamic waves and needles to pierce the outer layer of the skin
212
define microneedling
using needles to piece the stratum corneum
213
define thermal ablation
using localised heat to create microchannels in the skin
214
Which of these methods are invasive?
electroporation and microneedling
215
What does ITS stand for?
ionotophoretic trandermal system
216
What is the fentanyl ITS used for?
managing post-operative pain
217
How does fentanyl ITS work?
it is a pre-programmed device used to deliver fentanyl using an electrical current and it transports ionised drug molecules actively through the skin into the circulation
218
What is botulinum toxin type A used to treat?
hyperhidrosis (sweaty palms)
219
How is botulinum toxin delivered for sweaty palms?
solid microneedling
220
What are 3 examples of passive delivery methods?
1. vesicles
2. polymer nanoparticles
3. nanoemulsion
221
How does passive drug delivery by vesicles work?
water-filled particles with a bilayer carry drugs into the skin
222
How does passive drug delivery using polymer nanoparticles work?
nanoparticles are used to carry drugs to the correct area
223
How does passive delivery using nanoemulsions work?
a mixture of oil and water is used to carry the drug - the ratio of oil to water determines whether it is an intracellular or intercellular mechanism
224
What are 2 examples of drugs that use passive delivery?
butrans skin patches and lipid nanoparticles
225
What is the active ingredient in butrans skin patches and what does it treat?
buprenorphine which is used to treat opioid use disorders and is a strong painkiller
226
How do butrans skin patches work?
the patch is used to mix the API into a polymer formula which is put onto the skin to be released
227
How are lipid nanoparticles being used for drug delivery?
they are lipophilic so can easily pass through the mortar between cells - now being used for targeted therapies, such as gene therapy
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What is the name for drug delivery via the hair?
transappendageal/transfollicular
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How are nanoparticles being used in drug delivery via the hair?
1. as the hair strand moves, it creates a space that nanoparticles with drugs can pass through
2. the hair moves back again and the channel closed
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What is drug delivery via the nails called?
transungual drug delivery
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What is the main disease trated by transungual drug delivery?
fungal nail infections
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How can we delivery drugs via the nails?
- use iontophoresis after scratching the nail
- using lacquers (a nail varnish with antimycotic agents) to increase residence time
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What are the steps of regenerative medicine?
1. take biopsy from patient
2. isolate and expand cells
3. use a biocompatible material to 'seed' the cells on
4. the cell and scaffold material are stimulated until it mimics the tissue
5. structure is reintroduced to the patient
6. it should be accepted as it is the patient's own cells
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What is the potential for regenerative medicine in the future?
wounds of patients may be scanned and a machine 3D prints directly into the patient's wound, saving their life
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define bioprinting
combining material and cells in a 'printable ink'
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What is an example of a personalised biomedical device?
1. a soft implantable drug delivery device to treat epilepticus
2. the wireless monitoring system triggers subcutaneous release of drug when it senses and epileptic episode coming on
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Where is calcium present in the body?
99% in the skeleton and 1% in the blood and other tissues
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Which 3 ways is calcium distributed in the blood?
1. protein-bound calcium
2. complexed calcium (calcium complexed to anions)
3. free ionised calcium
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Which type of calcium in the blood IS physiologically active?
ONLY the free ionised calcium
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What are the 6 main functions of calcium?
1. nerve function (release of neurotransmitters)
2. muscle contraction
3. blood clotting (clotting factor activation)
4. skeletal mineralisation
5. cellular metabolism
6. cell signalling
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Which 3 main organs is the amount of calcium in the body controlled by?
intestines, kidneys, bones
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What do low calcium levels in the body cause?
leads to increased excitability of neuronal and muscular plasma membranes
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What do high calcium levels in the body cause?
cardiac arrythmia
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What are the 3 main hormones involved in calcium homeostasis?
1. parathyroid hormone
2. calcitriol
3. calcitonin
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Where is parathyroid hormone produced?
by the chief cells in the parathyroid gland
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What is parathyroid hormone derived from?
the precursor peptides pre-proPTH and proPTH which are cleaved to form the active PTH hormone
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What are the steps of PTH secretion?
1. cells in the parathyroid glands have calcium sensing receptors at the top of them
2. calcium from the blood binds to these receptors
3. if there is no calcium binding or decreased ionised plasma calcium, the receptors send a signal through a G-protein coupled receptors
4. causes secretion of parathyroid hormone
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What happens if there is a long-term decrease in calcium levels?
calcitriol can influence the formation of the pre-proPTH and acts as a transcription factor to control its formation
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What are the steps of how calcitriol prevents pre-proPTH release?
1. calcitriol binds to receptors in the parathyroid gland and acts on preproPTH mRNA to lower the levels of it
2. calcitriol will also increase calcium absorption in the gut, correcting low calcium levels
3. so, if calcitriol is already present in high amounts, the body will assume calcium homeostasis is being handled and suppresses further pTH production to prevent overshoot
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What are the effects of PTH on the bones (indirect)?
causes release of calcium stored in bones- it does this by acting on the osteoclasts
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What are the effects of PTH on the kidneys (direct)?
PTH causes the kidneys to reabsorb more calcium so less is lost from the blood by excretion
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What are the effects of PTH on the intestines (indirect)?
1. PTH causes an increase in uptake of calcium in small intestine
2. causes increase in the activity of 1 alpha-hydroxylase and a decrease in activity of 24-hydroxylase causing an increase in calcitriol (it does this by activating vitamin D3 or calcitriol)
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What is the overall effect of PTH on calcium levels?
INCREASE the plasma levels of calcium, so calcium can now bind to parathyroid hormone receptors and prevent further PTH secretion
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Which 2 forms does vitamin D exist in?
Vitamin D2 and D3
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Where is vitamin D2 derived from?
the diet
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Where is vitamin D3 derived from?
it is synthesised in the body by the action of UV radiation on a cholesterol derivative in the skin
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What is active vitamin D called?
calcitriol
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What are the steps of the synthesis of calcitriol?
1. cholecalciferol is obtained from both the sunlight and diet
2. cholecalciferol is converted to calcidiol in the liver by the enzyme vitamin D 25-hydroxylase
3. calcidiol is converted to calcitriol in the kidney by the enzyme vitamin D 1 alpha-hydroxylase
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How does PTH have a role in the synthesis of calcitriol?
PTH regulates the activity of the vitamin D 1-alpha hydroxylase in the kidney, so it can help generate more calcitriol to increase absorption of calcium in the intestines
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What type of hormone is calcitriol?
a secosteroid (it has an open B ring) - it interacts with a nuclear receptor
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Which enzyme regulates the breakdown of calcitriol?
24 hydroxylase
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What is the rate of conversion of calcidiol to calcitriol known as?
the activation step
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What are the plasma levels of calcitriol determined by?
1. the activation step (the conversion of calcidiol to calcitriol)
2. the inactivation step (the conversion of calctriol to calcitrioic ACID)
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What is the overall effect of calcitriol in the body?
calcitriol increases plasma calcium
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How does calcitriol affect the intestines?
1. it binds to hormone receptors and influence the translation of proteins in the intestinal tract
2. these proteins are thought to cause calcium to be absorbed
3. it also stimulates the absorption of phosphate in the jejunum and ileum
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How does calcitriol affect the bones?
1. it increase the number and activity of osteoclasts - INDIRECT - increase bone resorption
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How does calcitriol affect the kidneys?
calcitriol increases calcium reabsorption in the kidneys
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Where is calcitonin secreted from?
the parafollicular 'C' cells in the thyroid gland
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What stimulates calcitonin release?
an INCREASE in plasma calcium levels
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What is the overall effect of calcitonin?
a decrease in plasma calcium levels
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What are the effects of calcitonin on the bones?
calcitonin inhibits bone resorption by acting on osteoclasts - DIRECT
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What are the effects of calcitonin on the kidneys?
decreases the reabsorption of calcium and more is excreted in the urine
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What are the effects of calcitonin on the intestines?
no significant effect of calcium absorption in the small intestine
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What are the assumed reasons why we need calcitonin if calcium levels are too high?
1. protect against sudden increase in calcium after a meal
2. protects female skeleton during pregnancy and lactation
3. may be released in medical conditions to prevent bone destruction
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Which hormones has DIRECT influence on osteoclasts?
ONLY calcitonin
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How do PTH and calctriol have indirect influences on osteoclasts?
the act on the osteoblasts, which are invovled in the differentation of osteoclast precursor cells into active osteoclasts
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How does PTH indirectly affect osteoclasts?
1. RANK ligand (RANKL) is produced by osteoblasts and their precursor cells as a cell surface protein
2. PTH binds to osteoblasts and increases the expression of RANKL
3. there is more RANKL for the osteoclasts precursor cells to bind to so more osteoclast precursor cells mature into osteoclasts
4. bone resorption leading to calcium release
5. the interaction between RANKL and its receptor RANK triggers activation of pathways involved in osteoclast differentiation
6. it is assumed calcitriol has similar effects
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How does PTH interact with osteoprotegerin?
1. osteoprotegerin is another surface protein on osteoblasts
2. it has inhibitory effects, so stops osteoclasts from differentiating
3. PTH also inhibits the action of osteoprotegerin to help with osteoclast differentiation
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What is hypercalcaemia thought to be often caused by?
tumours in the parathyroid gland, so there is excess release of PTH, increasing calcium plasma levels
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What is hypocalcaemia usually caused by?
PTH resistance - or lack of vitamin D due to lack of intake, drug interactions etc
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What are symptoms of hypocalcaemia like?
lots of neuromuscular excitability - so the patient may experience convulsions, arrythmias, tetanus or spasms (CATS)
282
What is the adult version of rickets?
osteomalacia
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How is hypocalcaemia treated?
taking vitamin D supplements or give calcitriol as a drug
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