Week 4 Flashcards
(365 cards)
1
Q
What are some functions of the skeleton?
A
Support
Protection
Locomotion
Mineral reserve
Haematopoesis
2
Q
Which minerals are present in bone?
A
Calcium salts and phophate
3
Q
What is produced from bone marrow?
A
RBCs, WBCs and platelets
4
Q
Where is red bone marrow found in children?
A
All bones
5
Q
Where is red bone marrow found in adults? Yellow BM?
A
Red: skull, vertebral collumn, pelvis
Yellow: long bones
6
Q
What is yellow bone marrow composed of?
A
Adipose tissue
7
Q
What are osteons?
A
Layers of bone in circular layers
8
Q
What is the composition of bone?
A
30% organic type I collagen
70% inorganic calcium and phophate salts
9
Q
Function of calcium in bone?
A
Tensile strength
Allows bending
When ca is low in blood it can be taken from bone
10
Q
Function of minerals in bone?
A
Compressive sytrength: makes bones sturdy
11
Q
What is rickets?
A
Vitamin D deficiency - lack of sun exposure or calcium in diet
Vit D required for calcium absorption: lack of circulating calcium so cannot be taken up as calcium hydroxyaptite
Bones are overly flexible as they lack minerals
12
Q
What is osteogensis imperfecta?
A
Gentic disorder
Affects collagen production - mutations in type I collagen
Brittle bones which frature easily
Brittle bone disease
13
Q
Structure and Function of epiphyses in bone?
A
Articular surfaces of joints
Mostly spongy bone but compact on surface
14
Q
Structure of diaphyses?
A
Mostly compact bone, strong but a little flexible
15
Q
Function of epiphyseal growth plate?
A
Seperates epiphyses and diaphyses
Site of growth
16
Q
What happens in bones when growth is complete? What line is made?
A
Growth plate ossifies
Makes epiphyseal line
17
Q
What is the periosteum? What does it attach?
A
Covers outer surface of bone
Site of attachment for tendomns
18
Q
Endosteum function?
A
Lines intrnal surfaces of cavities in bones
19
Q
What does the medullary cavity contain?
A
Bone marrow
20
Q
Structure of skull bones?
A
Flat bones
No medullary cavity
2 sheets of compact bone with cancellous bone in the middle
Filled with red bone marrow
21
Q
What is spongy bone formed from and what is found in its spaces?
A
Trabeculae struts
Red bone marrow
22
Q
Examples of long bones?
A
Femur, humerus
23
Q
Examples of short bones?
A
Carpals, tarsals
24
Q
Examples of flat bones?
A
Skull, sternum, scapula, ribs
25
Examples of irregular bones?
Vertebrae, sacrum, facial bones
26
Functions of sesamoid bones in tendons?
Protect tendons and increase movement
27
Which bone is sesamoid?
Patella
28
How many bones in adult body?
206
29
How many bones in newborns?
270
30
3 types of joints? Examples?
Fibrous e.g. sutures
Cartilaginous e.g. IVDs
Synovial e.g. humerus
31
What makes up the axial skeleton?
Skull
Vertebral collumn
Ribs
Sternum
32
What makes up the appendicular skeleton?
Upper and lower limbs
33
What makes up the upper limb?
Pectoral girdle
Bones of arms/hands
34
What makes up the lower limb?
Pelvic girdle
Bones of hands/feet
35
How many skull bones are there?
22
36
How many bones are in the vertebral collumn?
33
37
How many pairs of ribs are there?
12
38
Function of skull?
Houses brain and special sense organs
39
What is the viscerocranium and how many bones does it contain?
Facial skeleton
14
40
What is the neurocranium and how many bones does it contain?
Surround brain
8
41
What are the 5 parts of the vertebral collumn and how many bones are in each?
Cervical 7
Thoracic 12
Lumbar 5
Sacrum 5 fused
Coccyx 4 fused
42
Structure of cervical bones?
Small and mobile
43
Which part of vertebral column is most susceptible to dislocation?
Cervical
44
What does the thoracic collumn articulate with and why does it have long processes?
Ribs
For mucle attachment
45
Which body of vertebral collumn is the largest and susceptible to herniated IVDs?
Lumbar as it bears weight
46
What does the sacrum articulate with?
Hip bones
47
What is the structure and function of the pectroal girdle?
Clavicle and scapula
Attaches UL to body
48
Which bone connnects UL to axial skeleton? Why?
Clavicle
Allows large range of movement
49
What makes up the UL?
Humerus
Radius and ulna
Carpals
Metacarpals
Phalanges
50
What makes up the lower limb?
Femur
Tibia and fibula
Tarsals
Metatarsals
Phalanges
51
How many carpals are there?
8
52
How many metacarapals are there?
5
53
How many phalanges are in the hands/feet?
14 each
54
How many tarsals are there?
7
55
How many metatarsals are there?
5
56
What is a condyle?
Rounded bone forming joint surfaces and muscle attachemnts
57
What are foramens?
Holes
58
What are fossas?
Dips in bones
59
What does the iliac crest help you locate? Significane?
Inigual ligamnt
Hernia locaion
60
Function of ribs?
Surrounds and protects thoracic organs
61
How are ribs made flexible?
Costal cartilages
62
Which level is the sternal angle?
T4/5
63
What does the sternal angle help locate? Why?
2nd ribs
Auscultation
Boundary of mediastinum: aorta/trachea splitting
Imaging
64
What are SIPCEPs?
Standard infection control precautions
Used by all staff at all times for all patients
65
Sources of potential infection?
Blood/body fluids
Secretions/excretions, not sweat
Non-intact skin
Mucus membranes
Any contaminated equipment
66
What are the standard precations?
Hand hygiene at 5 moments
Disposal of sharps
Use of PPE for potential infectious substances
Clean environemnt
Safe waste disposal
Safe used linen management
67
Why do we wash hands?
- healthcare environemnt is contaminated
- hands spread germs
- some patients are very vulnerable to infection and not washing hands could spread germs
68
What should you do before performing hand hygeiene?
- expose forearms
- remove all jewellery
- nails clean and short
- cover cuts with waterproof dressing
69
When should you perform hand hygeiene?
Before touching patient
Before aseptic procedure
After body fluid exposure
After touching patient
After touching patient surroundings
70
When should you wash hands with soap and water?
- hands are visibly soiled
- patient has suspected GI infection e.g. norovius/c. diff
71
When are hand wipes used?
When no running water is available
72
What is a healthcare associated infection?
Infection acquired as a result of healthcare related intervention or during healthcare that the patient would usully not catch
73
Most common healthcare associated infections?
GI infections
UTIs
Resp infections
Surgical site
74
Why is resp and cough hygeiene used?
To minimise risk of cross contamination of resp illness
75
How to do resp and cough hygeiene?
Cover mouth and nose with tissue when sneezing, coughing, wiping and blowing nose
Dispose of tissues into bin
Wash hands with liquid soap and water when coughing, sneesing, using tissues
Keep contaminated hands away from eyes, nose, mouth
76
Examples of PPE?
Gloves disposable/sterile
Aprons disposable/sterile
Eye protection
Masks/respirators
77
All PPE should...
- located close to point of use
- stored to prevent contamination in clean/dry area
- single use
- disposed of after use correctly
- reusable PPE should be decontaminated after usw
78
What are transmission based precautions?
Additional; infection control precautions taken with patients known or suspected to be infected with organisms posing a significant risk to other patients
79
4 types of transmission based precautions?
Contact
Enteric (intestines)
Droplet
Airborne
80
Examples of high risk fluids?
CSF
Pleural fluid
Semen
Synovial fluid
Vaginal secretion
Breast milk
(any body fluid containing visible blood)
81
Which body fluids are not high risk unless bloodstained?
Urine
Feces
Saliva
Sweat
Vomit
82
What is the most likely route of infection for healthcare workers?
Needlestick inury
Blood splashing onto broken skin
83
Examples of blood borne disease?
HIV, AIDS, Hep B, Hep C
84
Which receptor does COVID bind to?
ACE2
85
Symptoms of covid?
Cough, fever, shortness of breath, loss of senses
86
What is the R0?
The number of new cases oof infection arising from a single case
87
What R number is covid?
R3
88
What is covid spread by?
Droplets e.g. coughing sneezing
Surfaces
Aerosols
89
What PPE should you use when COVID is confirmed in a patient?
Eye protection
Fluid repellent face mask
Gloves
Apron
90
What is requird when aerosol generated infecton is present?
Filtering face piece
91
Order of putting on PPE?
Apron
Face mask
Eye protection
Gloves
92
What should you do before putting on PPE?
Hydrate
Tie hair back
Remove jewellery
Clean hands with gel rub
93
How is cortical bone arranged?
In osteons
94
Why do osteons have central canals?
For blood vessels
95
What are lamellae?
Circular layers of bone
96
Function of trabeculae?
Help to transfer weight through bone
Present in spongy bone
97
What are osteoprogenitor cells?
Stem cells differentiating into osteoblasts and osteocytes
98
Function of osteoblasts?
Lay down new bone
99
Function of osteocytes? Where are they found?
Mature osteoblasts trapped in bone matrix
In caves called lacunae
Respond to mechanical strain and send signals to intiate bone formation/resorption
100
Function of osteoclasts?
Break down bone
101
What is required for hardness and strength in bone?
Calcium hydroxapitate
102
What is decalcification?
Removing inorganic calcium salts from bone matrix
103
Why are bone shafts hollow?
To allow unrestricted movement of the thigh
Stronger than solid bar
Aids blood supply of bone
104
How are trabeculae arranged and why?
Lattice work
Even spread of weight
105
How does bone grown?
Appositional growth
Bone laid down on surface
Osteoblasts lay down osteoid (organic)
It is mineralisied (inorganic)
Osteoblasts trapped - become osteocytes
106
How can cartilage grow?
Appositional and interstitial growth
107
How does growth occur in epiphyseal plate?
Interstitial growth - cartilage expands and is replaced by bone
108
How does cartilae recieve nutrients?
Diffusion as its avascular
109
What are the 5 zones of the growth plate?
R - resting/reserve chondrocytes which replicate slowly
P - proliferation zone, cells divide rapidly
H - hypertrophy zone, chondrocytes mature and expand
C - calcification zone. cells become calcified and die via apoptosis, forms calcified matrix
O - blood vessels and bone cells invade calcified cartilage and replace it with bone
110
Which cartilage is growth plate formed from?
Hyaline
111
When willl bone stop growing in length?
When cartilage growth plate stops proliferating and is replaced entirely with bone
112
What is ossification?
The process by which bone is made
113
What is endochondral ossification?
Cartilage model made first and replaced e.g. long bones
114
What is intramembranous ossification?
Bone formed directly in mesenchyme e.g. skull bones
115
What is the primary ossification centre?
First part to form e.g. diaphyses in long bones
Allows flexibility
116
What is the secondary ossification centre?
Epiphyses
117
What are fontanelles? Function?
Soft spots between skull bones
Allow flexibility in birth
Allow rapid growth of brain in first 2 years of life
118
What can timing of bone fusion be affected by?
Males and females
Populaiton differences
Stress
Nutrition
Usually fuse in predictable pattern
119
Function of knowing ossification times?
Age fraud in sports
Age estimation in refugees
120
What are sutures? Which type of joints are these?
Joints between bones of the skull - fibrous joints, limited movement
121
What is osteoperosis?
Bone removed faster than laid down
Bone density reduced and more susceptible to fracture
122
When is OI common and why?
Post menopausal women
Oestrogen promotes osteoblast activity which reduces in menopause
123
What happens when you have osteoperosis in spine?
Trabeculae struts disappear
Kyphosis of thoracic spine - hunchback
Vertebral bodies collapse
124
What are enthesophytes?
Abnormal bony projections at attachment of tendon/ligament
125
What are osteophytes?
Abnormal bony projections in joint spaces
126
Symptoms of enthesophytes/osteophytes?
Pain/stiffness in back
Numbing/weakness in limbs
127
What is periostitis?
Inflammation of periosteum
128
Causes of periostisis?
Acute infection
Trauma/stress to bone (chronic)
129
Examples of perostitis causes?
Staph bacteria
Congenital syphilis
Leukaemia/cancer
Shin splints
Osgood-schlatter disease
130
What is the most common cancer in Scottish women?
Breast
131
What is the most common cancer in Scottish men?
Prostate
132
What is the most common cancer in Scotland overall?
Lung
133
What is a neoplasm?
- new growth
- abnormal
- uncontrolled cell division
- aka tumor
134
What does benign mean?
Grows slowly
Remains localised to site of origin
135
What does malignant mean?
Invades and spreads to different sites
Aka cancer
136
What is metastasis?
Tumor cells move from primary site to colonise secondary site
137
What are some characteristics of cancer cells?
Large variable shaped nuclei
Many dividing cells
Disorganised
Varied size and shape
Loss of normal features
138
What is anaplasia?
Loss of normal features in a cell
139
Why do cancer cells stain more basophilic aka blue than normal cells?
There is higher metabolic activity in the cell so more acidic molecules are present e.g. rRNA and mRNA
140
Describe the multistep development of cancer
Initiation: environmental carcinogens e.g. smoking
Mutation occurs
Oncogenes activated
Loss of tumor suppressors
Proliferation increases
Further mutations occur
One cell passes threshold of malignancy
141
Name molecules which are mutated in colon cancer
Beta catenin (e-cadherin)
K-ras pathway
p53
142
What are the six characteristics of cancer and molecules involved
Uncontrolled Proliferation: self sufficiency in growth factors due to oncogenes e.g. was, bcr-abl, HER-2
Increased growth capacity: tumor suppressor genes inactivated e.g. Rb
Evasion of apoptosis: increased BCL-2
Limitless replication potential: telomerase
Sustained angiogenesis:VEGF
Tissue invasion: cadherin, proteases
143
Function of platelet derived growth factor?
Matrix formation (inc fibroblasts)
Remodelling (produce proteases)
144
Function of vascular endothelial growth factor?
Angiogenesis - endothelial cell proliferation and migration
145
Function of colony stimulating factors?
Myeloid lineage in haematopoeisis
146
Function of erythropoeitin?
Produces red blood cells
147
Function of thrombopoietin?
Produces platelets
148
Which transduction pathway is present in keratinocyte proliferation?
Ras-map
149
How is a cell response signalled in a normal pathway?
Extracellular signal binds to receptor
This causes signal transduction
Nucleus eventually targeted and it is signalled to transcribe new molecules
150
What is an oncogene?
A gene who's product is involved In inducing cancer
151
How is an oncogene formed?
Mutated proto-oncogene
152
What is a proto-oncogene?
A normal gene involved in regulation of cell growth and proliferation, when mutated becomes oncogene
153
What is a tumor suppressor gene?
Inhibits cell proliferation and progression through cell cycle
154
What happens when TSGs lose their function?
They are oncogenic - cells can proliferate without checkpoints
155
How does uncontrolled cell proliferation occur in cancer?
Molecules that initiate/speed up proliferation are switched on
Molecules that slow/halt prolifeeration are turned off
156
What are some receptors that are protooncogenes?
EGFR
HER2 - amplified HER2
c-met
157
What are some cytoplasmic signalling molecules that are protooncogenic?
Ras, kI-RAS IN COLON CANCER
BRAF
Abl - bcr-abl in chronic myeloid leukaemia
158
Which nuclear molecules are protooncogenic?
Cyclin D - amplification
Myc - translocation
159
How does was become an oncogene? Usual role?
G protein transfusing signals from cell receptors
Point mutation
Ras signalling pathway switched on constantly so the cell will no longer need a growth factor
160
How does BRAF become an oncogene? Usual role?
Kinases transfusing signals from cell receptors
Point mutation
Switched on all the time so cell no longer needs growth factor
161
What is BRAF usually activated by?
Ras
162
How does EGFR become an oncogene? Usual role?
Cell surface receptor receiving extracellular signal
Point mutation deletes extracellular portion
Active in absence of EGF so constant cell proliferation
163
Which gene is amplified to induce cancer?
ERB B2
164
Which 2 genes undergo Philadelphia translocation (chromosome rearrangement) to form a gene present in chronic myeloid leukaemia?
BCR and ABL
forms bcr-abl
Persistently active kinase activity
165
Which cancers form when Rb is inactivated?
Bladder, breast, lung
166
Which cancers form when p53 is inactivated?
Brain, breast, colon, liver, lung, oesophageal
Most commonly mutated gene in cancer
167
Which cancers form when BRCA1 is inactivated?
Breast/ovarian
168
What is the two hit hypothesis of tumor formation?
Both copies of tumor suppressor gene must be mutated to induce cancer
169
What happens if there is no growth factor (Rb)?
Rb binds to E2F and the cell cycle is arrested
170
What happens if there is a growth factor (Rb)?
Rb is phosphorylated and the cell enters the cell cycle
171
What happens when Rb is lost?
There is unregulated entry into cell cycle as rb doesn't bind to e2f
172
What happens when Rb is mutated?
It can't bind to e2f and the cell cycle is unregulated
173
What is Li-farumeni syndrome caused by? What is it?
p53 mutation
increases risk of developing cancer
174
How do cancer cells avoid apoptosis?
Increased expression of BCL-2 which inhibits apoptosis
175
Function of telomeres?
Caps that protect ends of chromosomes
Prevent chromosomes fusing with other chromosomes
Ensure DNA is correctly copied
176
Why are telomeres unregulated in cancer?
They increase cell replication potential by protecting the chromosome
177
Why do cancer cells need their own blood supply?
They (tumors) initially get nutrients by diffusion but they become hypoxic (low oxygen) and can't proliferate without nutrients
178
How do tumor cells sustain angiogenesis?
Hypoxia stimulates them to produce VEGF so blood vessels are stimulated to grow near tumor
179
Which parts of adherens junctions become altered/defective in cancer?
Integrins
E-cadherin
Both form part of adheres junction
180
How do proteases aid in metastasis?
MMP-8 breaks down collagen in basement membrane
uPA activates plasmin which is a protease
181
What therapy is used in breast cancer?
Herceptin aka trastuzumab targets ERB B2
182
What therapy is used in colorectal cancer and non small cell lung cancer?
Bevacizumab targets VEGF
183
What therapy is used in chromic myeloid leukaemia?
Imatinib tagets ABL
184
What is targeted in melanoma?
BRAF
185
What is BRCA1 normally involved in?
DNA repair - tsg
186
What is embryology?
Study of development of embryo
From fertilisation to fetal stage
187
When is the preimplantation stage and what happens?
Week 1
First week after fertilisation
DFertilised embryo hasn't yet embedded into uterus
188
What happens in week 2-8 of pregnancy?
Embryonic stage aka organogenesis
Connection between embryo and uterus
All organ systems of body established
Placenta develops
189
What happens in week 9-38 of pregnancy?
Fetal stage
Fetus grows and organ systems differentiate and develop
190
How does fertilisation occurs?
Ovary release one oocyte every month
Oocyte leaves ovary, if in contact with sperm fertilisation occurs
191
What is a zygote?
Fertilised egg
192
By which day does the zygote reach the uterus?
Day 7
193
What is cleavage? Week 1
Mitotic divisions of fertilised oocyte
Overall size remains the same as each division creates smaller cells
194
How is cell division triggered in the zygote?
When the paternal and maternal genome fuse
195
What is the isthmus?
Narrowest part of uterine tube
196
Function and structure of zone pellucidA?
Touch glycoprotein coat preventing premature implantation and allows passage down isthmus
197
What is a morula? What is it held together by?
Cells maximising contact with each other
Forms cluster of cells
Held together by tight junctions
198
What are the first signs of cellular differentiation?
Inner cell mass and outer cell trophoblasts
199
What happens when the embryo enters the uterine cavity?
Fluid enters via the zona pellucid and into the spaces of inner cell mass
Fluid filled blastocyst forms
200
Wha does the inner cell mass go on to form?
Embryo and embryonic tissues
201
What do trophoblasts form?
Placental structures
202
Why does the blastocyst implant?
It begins to run out of nutrients
203
How is implantation facilitated?
ICM cells proloferate
Fluid builds up in cavity
Blastocyst hatches from zone pellucida
204
What is implantation an interaction between?
Embryo and endometrial layer of uterus
Connection becomes placenta
205
What is decidualisation and what does it trigger?
Changes in endometrium to prepare it for pregnancy - making cells bigger and longer
Triggers production of molecules to promote trophoblast cells to become invasive
206
What do trophoblast cells differentiate into in week 2?
cytotrophoblast - inner layer
synctiotrophoblast - outer invasive layer, establishes blood supply connection with placenta
207
What does the ICM differentiate into in week 2?
epiblast and hypoblast
bilaminar disc
208
Which molecule does synctiotrophoblasts produce?
HCG, early indicator of pregnancy
209
Summarise week 2 of pregnancy?
implantation occurs forming connection between embryo and maternal endometrium
icm forms 2 layers making bilaminar disc
trophoblast differentiates to form 2 placental layers
210
What is ectopic pregnancy?
Implantation occurs in abnormal sites
211
Why does ectopic pregnancy occur?
Slow transit in uterine tube
Premature hatching of blastocyst
212
When and where is ectopic pregnancy common?
ivf
- ovary surface
- uterine tube
- wall of go tract
213
What happens if ectopic pregnancy isn't treated with surgery/pill?
Trophoblast cells can cause life threatening haemorrhage
Uterine tube sometimes removes
214
What are the 4 extra embryonic membranes?
Amnion
Chrorion
yolk sac
allantois
215
Where is amnion found?
Function?
Life span?
Continous with epiblast of bilamiar disc
Lines amniotic cavity
Protects embryo
Up until birth
216
Structure and location of chorion?
Function?
Double layered membrane
Formed by trophoblast and extra embryonic membranes
Lines chorionic cavity in early pregnancy but disappears when amniotic cavity expands
217
Location of yolk sac?
Function?
Life span?
Continuus with hypoblast of bilaminar disc
Nutrient transfer in week 2-3
Disappears in week 20
Important in blood cell formation and gut formation
218
Structure and function of allantois?
Forms as outgrowth of yolk sac
Contributes to umbilical arteries and connects to fetal bladder
219
What is gastrulation?
Process of cell division resulting in 3 germ layers
220
What is the trilaminar embryo formed from?
bilaminar epiblast
221
What are the three germ layers?
ectoderm
mesoderm
endoderm
222
What are 3 important structures in trilmainar embryo?
primitive streak
notochord
neural tube
223
How are the three germ layers formed?
Epiblast cells proliferate - move towards primitive streak and push downwards to create new layers (invagination)
Epiblast forms ectoderm
Invaginating cells creates mesoderm
Epiblast cells push hypoblast to side to create ectoderm
224
Examples of ectoderm structures?
Outside things
Nervous system (nerve cells in skin)
Epidermis
Cornea
Tooth enamel
Adrenal medulla
225
Examples of mesoderm structures?
Notochord
Skeletal system
Muscular system
Excretory system
Circulatory/lympatic system
Dermis
Adrenal coortex
226
Examples of endoderm structures?
Epithelium of disgtive tract
Epithelium of resp system
Lining of urine system and reproductive system
Liver
Pancreas
Thymus
Thyroid glands
227
What is a teratoma?
Tumor with tissue/organ components resembling derivitaes of germ layers usually ectoderm
228
What are germ cell teratomas?
Develop from germ cells that have failed to differentiate from oocyte/sperm
Found in gonads - testes/ovary
229
What us cryptorchidism? Risks?
Failure of testes to descend into scrotal sac
Risk to develop germ cell tumours
230
What are embryonal teratomas and where do they appear?
Congenital - baby born with it
Appear on midline of body
231
Example of cels that don't divide?S
Stratum granulosum cells, neutrophils, eythrocytes
232
Which cells only divide sometimes?
Lymphocytes
233
What is G0?
Phase when cells are not actively dividing
Not always permanent as cells can re enter cell cycle if their conditions are met
234
What is G0 a response to?
External signal
235
Examples of g0?
After antigen presentation, T lymphocyte undergoes clonal expansion and differentiation to memory and effector T cells
Erythrocytes permanently in G0
236
How long is G1, S, G2 and M phase?
11, 8, 4, 1 hours
237
What is interphase?
Growth and preparation for cell division
G1, S, G2
238
What happens in S phase?
dna synthesis
239
What happens in G1? What is it dependent on?
growth in size
rna and protein synthesis - prepare for s
needs growth factors
240
What happens in G2?
further growth
cell organelle replication
241
What happens in prophase?
chromatin condensation
nucleolus disappears
centrioles move to poles
242
What happens in pro metaphase?
nuclear membrane dissolves
chromosomes attach to microtubules
243
what happens in metaphase?
spindle fibres align the chromosomes along middle of cell nucleus aka metaphase plate
244
what happens in anaphase?
paired chromosomes separate and move to opposite ends of cell
245
what happens in telophase?
chromatids arrive at opposite ends of cell
new membrane form around daughter nuclei
chromosomes decondense
spindle fibres disperse
246
Function of CDKs?
regulate progression through cell cycle
247
what are CDKs regulated by?
cyclins
phosphorylation/dephosphprylation
CKIs
248
What are cyclins?
activator proteins up or down regulated depending on stage of cell cycle
unstable
249
What are CKIs?
Small proteins blocking cyclin/cdk activity
bind directly to cdk to form inactive complex or act as competitive ligand
250
3 families of CKIs?
p21 cip
p27 kip
p16 ink
251
What is progression to M phase dependent on?
cdk1/cyclin b
252
When do cyclin b levels rise?
in g2
253
What 3 things does MPF phosphorylate to induce mitosis?
- lamins to destroy nuclear envelope
- condensins/histones to condense chromeosomes
- microtubule associated proteins to form spindles
254
What do cell checkpoints monitor?
Precense of growth factors
sufficient growth
dna damage
replication errors
spindle attachment
chromosome integrity
255
3 cell cycle checkpoints?
restriction point (g1)
dna damage checkpoints (late g1 and g2)
metaphase/spindle checkpoint
256
What is progression of the cell cycle dependent on?
Growth factors
257
When does the cell commit to cell division?
restriction point in g1
258
What is progression to S phase dependent on?
accumulation of cyclin D
259
What is the gatekeeper of restriction point?
Rb
260
What happens when a growth factor is detected in restriction point?
Ras pathway produces cyclin D and activates cdk 4/6, kinases phosphorylate Rb and doesnt bind to E2F, so E2F can now transcribe genes for S phase
261
Function of Rb?
maintains integrity of genome
causes cell cycle arrest in abnormally dividing cells and repairs DNA damage
262
Function of p53?
Arrests cell cycle in DNA damage or apoptosis in irreparable damage
263
What are examples of dna damage?
chemical mutagens
radiation
replication errors
264
How does p53 arrest the cell cycle in response to DNA damage?
produces cdk inhibitor p21 which binds to sdks to inactivate them
265
What is the metaphase/spindle checkpoint?
delays anaphase
checks all chromosomes are attached to spindle fibres
anaphase promoting complex inhibited until all chromosomes are attached
266
What is pathology?
Using knowledge of cel biology to determine how illness arises
267
What is 'the patient journey'?
symtoms
investigations
diagnosis
management
268
What are some general common investigation?
bloods
imaging
cultures
269
What are some pathology specific investigations?
fluid sampling
tissue biopsy
genetic profiling
270
What is neoplasia?
Excessive irreversible uncontrolled growth which persists even after withdrawal of stimuli that caused it
271
What are 3 branches of neoplastic disease?
benign disease
dysplasia
malignancy
272
4 reactions to normal tissue undvrstress?
hyperplasia - cells increase in number
hypertrophy - cells enlarge
atrophy - cells get smaller
metaplasia - cells change from one type to another
all reverible
273
What are some irreversible cell changes to stress?
apoptosis - programmed cell death
necrosis - uncontrolled cell death
inflammation. reaction to cell death
neoplasia
274
Qualities of benign disease?
localised
well encapsulated
slow growing
resembles tissue of origin
regular nuclei
275
What is dysplasia?
anormal/atypical cells due to failure of differentiation
276
Three qualities of dysplasia?
disordered architecture of tissue - loss of normal structure
disordered cellular features: pleomorphic nuclei (larger and misshapen)
mitotic figures (nuclei in stages of mitosis)
277
Qualities of malignancy?
Invasive
Can metastasise
Grows fast
Dysplasia features
May not resemble tissue of origin
278
How is colon tissue arranged?
In crypts
279
3 ways metastasis can spread?
through lymphatics
through blood
transcoelomic - spreading across body cavity e.g. pleural/pericardial cavity
280
What is cancer of unknown primary?
Metastasis that you cannot easily identify the site of origin
281
Which pathway does HER2 work via?
Receptor tyrosine kinase
282
What does an over expression of HER2 in breast cancer suggest?
A more aggressive cancer
283
How are breast cancers tested for HER2?
immunohistochemistry
284
What is immunohistochemistry?
shows where certain proteins are expressed and in what quantities
285
What is microsatellite instability and when does it occur?
Higher chanvce of mutation and therefore cancer caused by failure of mismatch repair system
When theres a failure of the mechanism to repair damaged DNA in the cell cycle
286
What is microsatellite instability in colon cancer associated with?
lynch syndrome
287
What is neoplasm grading?
How closely the neoplasm corresponds with normal cells for that tissue
Higher dysplasia = higher grade
288
What is neoplasm staging?
How far the neoplasm has spread through the body
289
How is neoplasm staging measured?
Tumour - measures local invasion
Node - measures spread to lymph nodes
Metastasis - measures spread to distant tissues
290
Local effects of neoplasm
symptoms e.g. pain, lump, mass
ulceration
bleeding/anaemia
compression of surrounding structures
291
Metastatic effects of neoplasm?
depends on site
brain - swelling, raised pressure, stroke, seizure
292
Systemic effects of neoplasm?
weight loss
appetite loss
fever
infection
293
What cyclin and cdk is associated with G1?
cyclin d
cdk 4/6
294
What cyclin/cdk is associated with g1/s?
cyclin e
cdk2
295
What cyclin/cdk is associated with s phase?
cyclin a
cdk 2/1
296
What cyclin/cdk is associated with m phase?
cyclin b
cdk1
297
Examples of signals?
nutritional status e.g. glucose level
oxygen supply
temperature
pathogens
hormones
growth factors
298
Examples of responses to signals?
die
grow
divide
differentiate
migrate
change shape
produce protein
release hormones
299
Example of a morphogen?
Sonic hedgehog - substance secrete from cell to surroundings, cell closer to signal will recieve more of signal than those far away
300
What is cyclopean?
failure of SHH signalling in development
only have one eye
301
Why do we need signals?
coordinating development
maintaining normal physiological function
to avoid disease
302
What happens when there is high blood sugar?
insulin released
glucose taken into cells and used/stored as glycogen
303
What happpens when there is low blood sugar ?
Glucagon released
glycogen turned back into glucose in the liver and released into the blood stream
304
What is the cause of type I and type II diabetes?
Type I - lack of sufficient insulin production
Type II - reduced responsiveness to insulin in target cells
305
Which signals mutation causes pancreatic cancer?
k-ras is too active and causes cells to grow/divide/survive in absence of growth signals
306
Which drug and target is involved in asthma relief?
salbutamol
beta 2 receptor
307
Which drug and target is involved in chronic myeloid leukaemia?
Gleevec
bcr-abl
308
What does Avastin target in cancer?
VEGF
309
3 examples of signal types and examples of these?
physical - temp and pressure
electrical - nerve cells
biochemical - hormones, growth factors, neurotranmitters
310
2 ways to classify biochemical signals?
chemical structure
range of action
311
3 ways to classify hormones and examples?
amino acid derivatives
steroid hormones
eicosanoids
312
Examples of amino acid derived hormones
adrenaline - modified AA
oxytocin - peptide hormone
insulin - protein hormone
313
Examples of steroid hormones?
testosterone, cortisol
314
Examples of eicosanoid, where are they derived from?
prostaglandin
lipids
315
4 ranges of action in biochemical signals?
long distance, endocrine: via blood
nearby cells, paracrine: via diffusion
neighbouring cell, juxtacrine: cell to cell contact
same cell, autocrine
316
example of juxtacrine?
apc mediated T cell activation
317
example of autocrine?
activated T cell sending information to effector t cells
318
What are 3 stages of signal transduction?
detecting signal via receptor
transfusing signal from site of detection to part of cell that will respond
responding - activation of cellular response
319
How do intracellular receptors get activated? Examples?
Hydrophobic signalling molecules diffuse through plasma membrane
steroid hormones, nitric oxde
320
Explain how steroid hormones alter gene expression?
- bind directly to intracellular receptor proteins
- hormone receptor complex acts as transcription factor
- complex binds to DNA and alters gene expression
321
How do cell surface receptors cause a cellular response? Examples?
Signal binds to receptor, it is activated, alters shape/activity which causes a cellular response
Insulin/adrenaline
322
3 types of cell surface receptors?
ion-channel linked
gpcr linked
enzyme linked
323
how do ion channel linked receptors cause a response in the cell?
when signal binds, the channel pens and ions move along concentration gradient in or out of the cell
this changes electrical properties of the cell
324
example of ion channel linked cells?
glutamate neurotransmitter
325
How do G protein linked receptors cause a response in the cell?
when signal binds it activates a g protein which activates an enzyme and passes a signal onto the cell
326
Examples of GPCR molecules?
adrenaline
serotonin
glucagon
327
How do enzyme linked receptors cause a response in a cell?
When a signal binds to an inactive receptor it brings the two parts of the receptor together and causes activation of an enzyme inside the cell
328
Which type of molecule is usually present in enzyme linked receptors?
Dimers
329
Give an example of an enzyme linked binding signal?
insulin, growth factors
330
Which type of receptor are rtfs usually?
enzyme linked
331
What type of protein dephosphorylates?
Protein phosphatases
332
What is the reason for kinase to phosphorylate a protein? What is required?
alters protein function
atp
333
What type of receptor does EGF use?
rtks
334
Which molecules are produced when signals are transduced?
Relay molecules
335
What are two main methods of signal amplification?
Enzyme cascades
Second messengers
336
Example of an enzyme cascade?
MAPK cascade
337
When are MAPK cascades activated?
In response to growth factor RTK activation e.g. EGF
338
Explain how a EGF MAPK kinase cascade would be activated
EGF binds to RTK receptor
Relay proteins activate ras
Ras activates MAP KINASE cascade
Enzyme cascade amplifies signal and transcription factors are phosphorylated
339
What is a second messenger?
Small molecule produced in large amounts inside cell after receptor activation
340
Example of second messenger?
cAMP
341
Example of adrenaline second messenger process?
Binds to GPCR
GPCR activates cAMP
cAMP activates PKA
PKA activates effector proteins by phosphprylation
342
Examples of responses to signal transduction?
gene expression
protein ectivity e.g. phosphorylation
protein binding e.g. to DNA or activor/inhibitor proteins
protein localisation e.g. transcription factor activated by moving from cytosol to nucleus
343
Which pathways are often overactive in cancer?
RTK pathways
344
What drug type is Herceptin?
antibody
345
What drug targets VEGF in colorectal cancer?
Drug type?
Avastin
Antibody
346
What drug targets EGFR in lung cancer? Drug type?
Odessa
inhibitor
347
How to treat overactive RTK pathways?
inactivating antibodies, small molecule kinase inhibitors
348
How does adrenaline cause fight or flight reaction?
Sympathetic nervous system is active when seeing a threat
This activates arenal cortex to produce adrenaline
349
What is adrenaline?
Hormone produced in acute stress response
350
3 outcomes of adrenaline?
inc heart rate
inc respiration
inc blood glucose
351
Examples of GPCRS?
Adrenaline
Rhodopsin
Glutamate
352
How are GPCRS activated?
Ligand binds to receptor
Conformational change in cytoplasmic domain
Conformational change allows g protein to bind or be activated by receptor
Activated g proteins actuvate intracellular enzyes
353
What happens when gdp vs gtp is bound in GPCR?
GDP - inactive
GTP - active
354
What exactly does activated G protein produce?
downstream effector proteins
355
What is the off switch for GPCRs?
gap/rgs
356
Effect of GPCR activation?
secondary messenger molecules are produced
lots of targets activated
357
How are G proteins turned off?
RGS hydrolyses GTP to turn it to inactive GDP
358
How does adrenaline converted glucose store to glucose?
Adrenaline binds to GPCR
Alpha unit is activated and activates adenylyl cyclase molcule
this activates camp then pka
PKA phosphorylates phosphorylase kinase which activates phosphorylase and converts glycogen store to glucose
359
How does adrenaline stop convert glucose to glycogen store?
Adrenaline binds to gpcr
Alpha unit is activated and activates adenylyl cyclase molecule
This activates camp then pka
pka phosphorylates glycogen synthase which stops glucose being turned to glycogen
360
What happens when adrenaline isnt bound to gpcr?
gtp hydrolysed to gdp
adenylyl cyclase not made any more
phosphodiesterases break down camp
glucose stored as glycogen
361
Which 3 responses can EGF cause?
survival - inhibits apoptosis
proliferation
invasion
362
Which molecule activates p53 in low cell damage?
ser15
363
Which molecule activates p53 in high cell damage?
ser15 and ser46
364
Which responses can adrenaline cause?
glucose release from sekeltal muscle, liver
inc heart rate
vasodilation/constriction
bronchodilation
365
Which cells do adrenaline bind?
muscle/liver
