1
Q
what is hypertrophy
A
increase in size of tissue due to increase of its constituent parts where cells get bigger
2
Q
what is hyperplasia
A
increase in size of tissue due to increase in number of constituent cells in cells that can divide
3
Q
what is atrophy
A
decrease in number of cells or size of cells
4
Q
what is metaplasia
A
change in differentiation of cells
5
Q
what is dysplasia
A
morphological changes seen in cells in progression to becoming cancer
6
Q
what is the difference between resolution and repair
A
resolution - initiating factor removed tissue undamaged or regenerates
repair -initiating factor remains and tissue damaged
7
Q
describe repair in 2 steps
A
- replacement of damaged tissue by fibrous tissue
2. collagen produced by fibroblasts
8
Q
what is inflammation
A
reaction to injury or infection involving macrophage and neutrophil response
9
Q
what are the 4 types of inflammation
A
acute
chronic
autoimmune
overreaction
10
Q
3 reasons for inflammation
A
- fight off infection/injury
- increase heat to area kill bacteria
- make endothelial cells of vessels more permeable so macrophages/lymphocytes can escape to tissue
11
Q
what cells are present in acute imflammation
A
neutrophil polymorphs
12
Q
what cells are present in chronic inflammation
A
macrophages
lymphocytes - B for Ab, T for CTL
13
Q
what is a granuloma
A
collection of macrophages surrounded by lymphocytes
14
Q
what cell produces collagen
A
fibroblast
15
Q
which cells dont regenerate
A
myocardial cells
neurones in CNS
16
Q
5 stages in clotting cascade simplified (aka thrombus formation)
A
- endothelial injury = collagen exposed = turbulent flow
- collagen activates platelets to stick
- platelets release chemicals attract more platelets = aggregation with some RBC stuck inside
- clotting factors activated = fibrinogen activated into fibrin
- fibrin deposits on aggregation = thrombus
17
Q
virchows triad
A
- change in blood flow
- change in vessel wall
- change in blood constituents
18
Q
3 things to treat a thrombus
A
- aspirin inhibits platelet aggregation
- heparin = anticoagulant
- warfarin = anticoagulant
(compression socks)
19
Q
what is an embolus
A
mass of material in vascular system that becomes lodges within a vessel
20
Q
what is a thrombus
A
solid mass of constituents which are formed within the intact vascular system during life
21
Q
what is ischemia
A
reduction in blood flow to an area where no damage is done
22
Q
what is infarction
A
reduction in blood flow that results in cell death
23
Q
what is an atherosclerosis
A
fibrous tissue containing lipids, cholesterol, lymphocytes and SMC found within high pressure systems
24
Q
what is apoptosis
A
intracellular events leading to death of cell without release of harmful products
25
4 steps of apoptosis
1. nucleus condenses
2. cell shrinks
3. apoptotic bodies form
4. macrophages remove bodies
26
give an example of consequences of lack of apoptosis and too much apoptosis
lack = cancer
| too much = HIV
27
what is necrosis
traumatic cell death of big areas of cells
28
what is dermal elastosis
UBV light causes protein cross links = wrinkles because skin no longer elastic
29
what is carcinogenesis
transformation of normal cells to malignant neoplastic cells through permanent genetic alteration or mutation
30
what is oncogenesis
transformation of normal cells to neoplastic cells through permanent changes not necessarily malignant
31
what are carcinogens
cancer causing agents
32
what are oncogenes
tumour causing agents
33
what are mutagens
factors that alter DNA to cause mutations
34
5 classes of carcinogens
```
chemical
viral
radiation
biological factors
miscellaneous
```
35
what is a neoplasia
lesion resulting from autonomous or relatively autonomous abnormal growth of cells which persists after initiating stimulus has been removed
36
what is a tumour
abnormal swelling may be cause by neoplasm or due to inflammation, hypertrophy, hyperplasia
37
2 components of solid carcinoma
neoplastic cells
| stroma
38
features of benign neoplasm
localised
non-invasive
slow growth
resemblance to normal tissue
39
features of malignant neoplasm
invasive
can metastasise
rapid growth - many mitotic bodies (tho not necessarily faster than normal tissue)
variable resemblance to normal tissue
40
what is a papilloma
benign neoplasm of non-secretory non-glandular epithelium
41
what is an adenoma
benign neoplasm of secretory or glandular epithelium
42
what is a carcinoma
malignant neoplasm of epithelial cells
43
what is an adenomcarcinoma
malignant neoplasm of glandular secretory epithelium
44
if a cancer moves, what is it named in the new organ
same name as origin
45
what is a sarcoma
malignant neoplasm of connective tissue
46
what is the main effector cell in acute inflammation
neutrophil polymorph
47
name an example of acute inflammation
appendicitis
48
granulomatous inflammation occurs in what disease
Crohns disease
49
what is the specific name of calcification in disease
dystrophic calcification
50
what cells produce antibodies
plasma cells
51
what disease is chronic inflammation from the start
infectious mononucleosis (mono)
52
how are cancerous neoplasms graded
better the tumour resembles the surrounding tissue the lower the grade
53
what is invasion
process of carcinoma cells breaking through basement membrane using enzymes and invading normal tissue structures
54
what is metastases
carcinoma that has spread from original site to form new carcinoma at a different site
55
what is the name of a carcinoma that has not invaded through the basement membrane
carcinoma in situ
56
3 step process of invasion
1. carcinoma in situ
2. carcinoma breaks throu bm using enzymes = micro-invasive carcinoma
3. eat through extracellular matrix = invasive carcinoma
57
how do carcinomas evade host defence in the blood 3 ways
1. aggregate with platelets to hide
2. shed surface antigens to confuse lymphocytes
3. adhere to other carcinoma cells
58
what types of carcinomas metastasis in the lungs
any that invades veins or lymph vessels
59
what types of carcinomas metastasise in the liver
carcinomas of the GI tract because blood drains to liver via portal system
60
cancers of which organs are most likely to metastasise in bone
```
BLT KP
breast
lungs
thyroid
kidneys
prostate
```
61
3 features of carcinoma
spread to lymph nodes
spread to blood to bone
micro-metastases can be present even if tumour is excised
62
main features of conventional therapy
non-selective for tumour cells
hits dividing cells causing bad side effects
good for fast growing tumours
63
which cancer never metastasises
basal cell carcinoma of the skin
64
what is a lipoma
benign neoplasm of adipocytes
65
what is a chondroma
benign neoplasm of cartilage
66
what is an osteoma
benign neoplasm of bone
67
what is an angioma
benign neoplasm of vascular tissues
68
what is a rhabdomyoma
benign neoplasm of striated muscle
69
what is a leiomyoma
benign neoplasm of smooth muscle
70
what is a neuroma
benign neoplasm of nerves
71
is radon gas a cause of lung cancer
yes
72
out of obesity smoking and drinking which is most likely to cause cancer
smoking
73
where does ovarian cancer commonly spread
peritoneum
74
5 ways to prevent pathogens harming the body
1. skin is physical barrier
2. pH
3. mucociliary escalator
4. phagocytic cells
5. lysozome in tears
75
what is innate immunity
defence system activated immediately after infection occurs
76
8 steps in response to trauma
1. coagulation
2. acute inflammation
3. kill pathogens and neutralise toxins
4. clear pathogens
5. proliferation of cells to repair damage
6. removal of blood clot
7. remodel extracellular matrix
8. reestablish normal tissue function
77
what cells detect microbes in the blood
monocytes
| neutrophils
78
what cells detect microbes in tissue
macrophages
| dendritic cells
79
what are PRR
pattern recognition receptors
80
how do cells sense pathogens
PRRs recognise PAMPs
81
what are PAMPs and what do they do
pathogen associated molecular patterns
| present on microbes and allow identification
82
what is DAMP
damage associated molecular pattern - damage is unique which allows identification
83
what is adaptive immunity
antigen specific immunity which is learned
84
what is cell mediated immunity
interplay between antigen presenting cells and T cells, requires cell to cell contact and MHC
85
what are T cell receptors TCR
similar structure to antibodies and act to recognise foreign antigens as long as antigen present on MHC
86
3 examples of antigen presenting cells
B cells
dendritic cells
macrophages
87
what is a MHC
major histocompatibility complex
| displays self and non-self-antigens
88
describe how the humoural and cell mediated immune response interact together 4 steps
1. T helper with complementary receptor to foreign antigen is selected
2. T helper interact with MHC2 on B cell with matching receptor
3. B cell undergoes clonal expansion to produce B memory and plasma cells (mitosis then differentiation)
4. T cell divide to form T memory cells
89
what is pattern recognition
recognition of microbes and viruses depending on ancient conserved features of them
90
name 3 different types of PRR and what do they detect
1. toll like receptors TLRs on cell surface membrane recognise range of patterns
2. nod like receptors NLR detect peptidoglycan and other bacterial cell wall components
3. rig like receptors RLRs recognise viral RNA/DNA
91
where does clonal expansion of B cells occur
lymph nodes
92
give 2 examples of a microbial peptide secreted in lining fluids and what do they do
defensin
cathelicidin
lead to recruitment of immune cells
93
what are lectins and what is their role
carbohydrate containing proteins that bind carbs/lipids in microbe walls
= activate complement
= improve phagocytosis
94
what are cell-associated PRRs
present on cell membrane or in cytosol of cell and recognise range of molecular patterns
95
what does TLR4 detect
lipopolysaccharides of gram -ve bacteria (forms dimer)
96
what does TLR5 detect
flagella
97
what does TLR3 detect
virus double stranded RNA
98
what do TLR7 and 8 detect
single stranded virus RNA
99
what does NOD2 recognise and what is its action
recognises muramyl dipeptide MDP
| activates inflammatory signalling pathways
100
give a disease for the non-functioning of NOD2 and the hyperfunctioning of NOD2
```
non-functioning = Crohns disease
hyperfunctioning = Blau syndrome
```
101
what may TLR4 have a homeostasis effect on
blood neutrophil numbers
102
what are damage molecules and what do they indicate
molecules produced due to cellular damage and indicate presence of pathogen
103
how does damage recognition occur
appearance of host molecules in unfamiliar context = activate TLRs
TLR signalling for inflammation and tissue repair
(may also enhance local antimicrobial signalling)
104
give 3 examples of extracellular damage molecules
fibrinogen
hyaluronic acid
tenasin C
105
give 3 examples of intracellular damage molecules
mRNA
heat shock molecules
uric acid
106
how are PRRs present in adaptive immunity
TLR + other PRR activation = drive cytokine production through APC = increase likelihood of successful T cell activation
107
how can TLR therapy help in disease
can enhance or inhibit TLR signalling
108
what is the immunological theory
infection with an organism leads to generation of antibodies in serum = protection persists due to immunological memory = can be passed on in passive immunity
109
how does vaccination work in 5 steps
1. exposure to antigen
2. antigen presentation to T cells
3. IgM produced = causes establishment of highly specific IgG through clonal expansion of B cells
4. takes weeks to occur
5. IgGs produced = memory cells are formed
110
what is passive immunity
transfer of preformed antibodies to an individual but immunological memory is not activated so not long term
111
name the 2 types of passive immunity and give examples for each
1. natural = maternal antibodies across placenta
| 2. artificial = treatment with pooled human IgG or antitoxins
112
definition of inoculation
introduction of viable microorganism into a subject
113
definition of vaccination
generation of immunity through manipulation of the immune system
114
5 requirements of a good vaccine
1. safe
2. B and T cell response
3. induce suitable immune response
4. stable and easy to transport
5. not require boosters
115
what is an adjuvant in vaccination
any substance added to a vaccine to stimulate an increased immune response e.g. TLR agonist
116
what are capsular polysaccharides
cell surface polymers provide protective immunity to encapsulated bacteria by preventing opsonisation by antibodies and complement
117
pharmacodynamics definition
effect drug has on the body
118
pharmacokinetic definition
effect body has on drug
119
what is a summative effect of combined drug use
effect of 2 drugs is added together = greater effect equal to expected
120
what is a syngeristic effect of combined drug use
2 drugs added together = effect is greater than expected
121
what is an antagonistic effect of combined drug use
where 2 drugs work against eachother = no/less overall effect
122
what is a potentiation effect of combined drug use
2 drugs added together = one has greater effect on body than expected
123
what is bioavailability (F) and give the equation
fraction of administered drug that reaches systemic circulation unaltered
AUC oral/ AUC IV x 100
124
what is the effect of gut motility on the absorption of a drug
greater motility = faster absorption
sympathetic NS = slow down motility because fight or flight
parasympathetic NS = speed up motility as rest and digest
125
how does the acidity of a drug affect its absorption
unionised = can cross phospholipid bilayer
| changing acidity = changes portions of ionised and unionised
126
what is the significance of a high volume distribution of a drug
most of drug is found in tissue and not circulating in plasma
127
what is the significance of low volume distribution of a drug
drug found circulating in plasma
128
how does warfarin work
protein bound drug = inhibits vitamin K coagulation factors
129
why should we be careful with warfarin and other drugs
other protein binding drugs can inhibit or increase effect of warfarin
130
name 4 drug causes of AKI
NSAID usage
ACE inhibitors
furosemide
gentamicin
131
what is druggability
ability of a protein target to bind to small molecules with high affinity
132
what is a receptor
component of a cell that interacts with a specific ligand and acts to initiate a change in biochemical events leading to the ligands observed effect
133
name 3 things receptors communicate with
neurotransmitters
autacoids e.g. histamines
hormones
134
what are the 4 types of receptor
1. ligand-gated
2. G protein coupled
3. kinase-linked
4. nuclear receptors
135
give 2 diseases associated with imbalance of drug receptors
1. myasthenia gravis = loss of ACh receptor
| 2. mastocytosis = increased c-kit receptor
136
name the 4 types of receptor ligands
1. agonist
2. antagonist
3. partial antagonist
4. inverse antagonist
137
what is EC50
effective concentration needed to elicit a 50% response
138
what is efficacy
maximum response achievable from a dose of a drug = describes how well a ligand activates a receptor
139
what is affinity
how well ligand has capacity to bind to a receptor
140
what is intrinsic activity
ability of a drug receptor complex to produce a maximum functional response = level to which a receptor can cause a response
141
what is signal transduction
process that occurs between a ligand bonding to a receptor and a response occuring
142
what is signal amplification
process of a receptor increasing signal size
143
what is selective agonism
potency of a range of agonists
144
what factors govern drug action
1. receptors = affinity/efficacy
| 2. tissue related = no. of receptors, signal amplification
145
what is receptor reserve
condition in tissue where agonist need to activate only a small fraction of receptors to produce a maximal response
reserve can be large or small depending on tissue
146
what is tolerance
reduction in agonist effect over time
| down regulation of receptors with prolonged use which requires higher doses to be used for an effect
147
what is desensitisation
receptor decreases response to agonist at high concentration =
after prolonged agonist exposure receptor is uncoupled from signalling cascade
148
what are the 2 types of enzyme interaction
irreversible and reversible
149
give 2 examples of enzyme inhibiting drugs
1. statins
| 2. ACE inhibitors
150
what is a uniporter
uses ATP to pull molecules in
151
what is a symporter
use movement of 1 molecule to pull in another molecule against the concentration gradient
152
what is an antiporter
1 substance moves across a gradient using energy from another substance moving down a gradient
153
describe 3 ways drugs are used in parkinsons
1. target enzyme that breaks down dopamine
2. block conversion of dopamine to 3MT in the brain
3. central dopamine receptor agonists act on dopamine receptors = mimick dopamine
154
give examples of 3 drugs that work on voltage gated ion channels
1. amlodipine (Ca)
2. lidocaine (Na)
3. repaglinide (K)
155
what is dependency
individual has psychological need for drug and will suffer withdrawal without it
156
what is potency
whether drug is strong or weak = relates to how well drug binds to receptors based on receptor binding affinity
157
name 3 side effects of opioid addiction
1. respiratory depression
2. sedation
3. nausea and vomiting
158
what is the opioid antagonist
naloxone
159
what must you be aware of when admininstering naloxone
has short half life could wear off fast
160
definition of drug absorption
process of drug transfer from site of administration into general or systemic circulation
161
definition of drug distribution
process by which drug is transferred reversibly from general circulation to tissues as blood concentration increases then returns from tissues to blood when blood conc falls
162
what is the volume of distribution (Vd)
represents the degree to which a drug is distributed in body tissue rather than the plasma
higher Vd = indicates greater amount of tissue distribution
Vd = amount of drug in tissues/concentration of drug in plasma
163
drug metabolism definition
production of a new compound from a parent drug = ususally more hydrophilic so product can be removed in urine
164
what is first pass metabolism
drug metabolism occurs before target organ is reached, occurs in intestines liver and lungs
165
how to calculate total urine excretion
glomerular filtrate + tubular secretion - reabsorption
166
what is clearance CL
volume of blood or plasma cleared of drug per unit time
167
what is steady state (Css)
balance between drug input and drug elimination
168
what is a loading dose
if drug has long half life then will take long time to achieve steady state = high initial dose will shorten this time
e.g. giving IV bolus + IV infusion
169
what is the equation of loading dose
loading does = steady state x volume of distribution
170
what is the equation for steady state for iv doses (??)
Css = rate of infusion / CL
171
what is the equation for steady state for oral doses (??)
Css = Dosing rate/CL = dose (D) x bioavailability (F) / CL x dosage interval
172
what is a stereoisomer
molecule that has same structural formula and sequence of bonded atoms but differ in 3 dimensional orientations of their atoms in space
173
what is immunotherapy
passive transfer of antibodies, they must be species specific
174
what is a sulphonamide nucleus
an unreactive and rigid group often found on drugs
175
what is an adverse drug reaction
unwanted or harmful reaction following administration of a drug/combination of drugs under normal conditions of use and suspected to be related to drug - has to be unintended and noxious
176
how do side effects differ from ADRs
unintended effect of drug but related to pharmacological properties and can include benefits
177
what is a toxic effect
effect caused by level of drug beyond therapeutic range
178
what is a hypersensitivity effect
effect caused by level of drug far below therapeutic range
179
what is a type A ADR
```
= augmented
predictable
dose dependent
common
e.g. morphine and constipation
```
180
what is a type B ADR
```
= bizarre/idiosyncratic
unpredictable
not dose dependent
inherited response = enzyme deficiency
abnormal receptor activity = e.g. calcium rise = increase muscle contraction
e.g. penicilin and anaphylaxis
```
181
what is a type C ADR
= chronic
chronic use of a drug causes adverse effects
e.g. steroids and osteoporosis
182
what is a type D ADR
= delayed
delayed effect occurs due to drug
e.g. malignancies after immune suppression
183
what is a type E ADR
= end of treatment
abruptly stopping drugs can cause bad reaction
e.g. when ending antiseizure medication
184
what is a type F ADR
= failure of therapy
| drug not working due to other drugs
185
what is DoTS
dose relatedness
timing
patient susceptibility
186
when should you suspect an ADR
1. start after new drug started
2. occur after dosage increase
3. disappear when drug stopped
4. reappear when drug restarted
187
name 6 most common ADRs
```
confusion
nausea
balance problems
diarrhoea
constipation
hypotension
```
188
what is an allergy
abnormal response to harmless foreign material
189
what is atopy
tendency to develop allergies
190
what is non immune anaphylaxis
reaction identical to allergic anaphylaxis but directly caused by direct mast cell degranulation - some drugs can cause, no previous exposures required
191
how do allergies occur - 2 steps
1. interaction of drug/metabolite with individual = cause antibody formation/immunity
2. subsequent re-exposure to drug/metabolite = causes a reaction
192
describe a type 1 allergic reaction
e.g. anaphylaxis
IgE Ab form after initial exposure
IgE attach to mast cells
re-exposure = mast cell degranulation = histamine release
193
describe a type 2 allergic reaction
e.g. autoimmune haemolytic anaemia
allergen combines with protein = body treats as foreign and forms IgG+IgM Ab
Ab-Ag = complement activation
damages cells
194
describe a type 3 allergic reaction
e.g. rheumatoid arthritis
Ag-Ab form large immune complex's
activates complement
cause small vessel damage = leucocytes attracted to site = inflammation
195
describe a type 4 allergic reaction
e.g. coeliac disease
delayed hypersensitivity
Ab specific receptors form on T cells at first exposure
2nd exposure = local reaction occur
196
what is zero order kinetics
decline of concentration of drug within blood over time decreases at a constant rate often due to enzymes becoming saturated
197
what is second order kinetics
decline of conc of drug in blood decreases exponentially as drug is distributed to the tissues
198
what is half life (T1/2)
time taken for concentration of drug within blood to half (elimination rate from plasma)
199
what is the equation for half life
t1/2 = 0.693 / k (rate constant of elimination)
200
how do you work out clearance CL
```
CL = dose of drug (IV) / area under blood conc/time curve
CL = dose of drug (oral) x F bioavailability / area under curve
```
201
what is the rate constant of elimination
k = CL/Vd
202
why is Vd important/what does it determine
total amount of drug that has to be administered to produce a particular plasma concentration
203
what is the equation for Vd
Vd = total amount of drug in body (dose) / plasma concentration
204
acute inflammation defintion
initial and usually transient series of tissue reactions to injury
205
name 5 causes of inflammation
1. microbial infection
2. hypersensitivity
3. physical agents
4. chemicals
5. tissue necrosis
206
describe the physiological process of inflammation
1. vasodilation = brings neutrophil polymorphs to damaged area
2. increase vascular permeability = fluid leak into extracellular space = oedema
3. cellular exudate formation = neutrophils through endothelial cells to extracellular space
207
describe the functions of histamine
vasodilation
emigration of neutrophils (chemotaxis)
increased vascular permeability
pain and itching
208
microscopic appearance of chronic inflammation
fibrosis
chronic ulcer
abscess cavity
granulatomous inflammation
209
what is a histiocytic giant cell
indigestible foreign material cause macrophages to fuse together = become multinuclear giant cells and collect to form granulomas
210
describe the healing process from abrasion
1. epidermis scraped off = scab forms
| 2. new epidermis grows under scab = normal regeneration
211
describe 1st intention healing (positive)
1. thin incision = fibrinogen exudation
2. fibrin stitches 2 sides together
3. collagen production and epidermis regrowth = small scar
212
describe 2nd intention healing (negative)
1. large loss of tissue=granulation tissue formation
2. wound heals from bottom up = organisation and capillary formation
3. fibrous tissue formation = large scar
213
what is the consequence of a venous system embolism
goes to right side of heart = to pulmonary system = pulmonary embolism
214
what is the consequence of an arterial system embolism
goes to left side of heart = into systemic circulation = embolism anywhere
215
describe reperfusion injury
1. reactive hyperaemia = cells overwhelmed with oxygen
| 2. reactive oxygen species formation = tissue damage and inflammatory response
216
what are watershed areas
parts of brain have dual blood supply but ischaemia can occur with low BP
217
what is a transmural MI
ischemia in the subendocardium spreads to the epicardium and involves full thickness of the myocardium
218
what is a subendocardial MI
also called NSTEMI
| involves ischaemia and necrosis of the innermost part of myocardium
219
what is cleft palate
cells fail to migrate and join fulcrum of mouth
220
what are some effects of downs syndrome
increased beta amyloid production
cause earlier dementia
increased cataracts risk
221
describe 4 features of age related cell damage
1. cross linking of DNA/proteins
2. loss of Ca influx control = mitochondrial damage
3. free radical generation and peroxidation of cell membrane
4. accumulation of toxic byproducts
222
describe the effects of adrenaline following anaphylaxis (4)
1. vasoconstriction = raise BP
2. stimulate beta 1 adrenergic receptors = postiive ionotropic and chronotropic effects = increase SV and HR
3. stimulate beta 2 adrenergic receptors = bronchodilation and less oedema
4. increase intracellular cAMP = reduce inflammatory mediators + prevent histamine release from mast cells/basophils
223
describe the emergency treatment for anaphylaxis
ABCDE (disability and exposure)
1. adrenaline 500 micrograms IM
2. establish airway and give O2
3. fluids 500-1000ml bolus
4. steroids = hydrocortisone 200mg IM/slow IV
antihistamines = chlorphenamine 10mg IM/slow IV
224
why might a 2nd dose of adrenaline be required for anaphylaxis
adrenaline = 2-3 min half life
| may need more to continue effects
225
what blood test is needed to confirm anaphylaxis and when does it need to be taken
mast cell tryptase
high tryptase = anaphylaxis or an allergy
negative tryptase = its NOT anaphylaxis
1. asap after Tx
2. 1-2 hrs but no later than 4hrs after symptom onset
3. 24hrs/at follow up
226
describe why a lower does of morphine is given in renal failure
morphine -> morphine-6-glucuronide = very potent
M6G excreted very quickly by kindeys
if kidney are not healthy/in failure = M6G build up in kidneys = nephrotoxicity and respiratory depression
= lower dose
= longer dose intervals
