IMS Flashcards
(338 cards)
1
Q
Pataus
A
Trisomy 14 - affects midline structures, cleft lip, incomplete brain, congenital heart disease
2
Q
Klinefelters
A
47XXY
Infertility and poorly developed secondary characteristics as lacks testosterone
3
Q
Turners
A
45XO
99% Still born
Short in stature, primary amenorrhea, congenital heart disease, puffy feet, redundant skin at back of neck
4
Q
William Beurens
A
26 genes deleted from q arm of chromosome 7
Bright eyes, wide mouth, upturned nose, heart defect
5
Q
Digeorge/Velocardiofacial Syndrome
A
Section deleted from chromosome 22
Small mouth, prominent nose, heart defects
6
Q
Edward’s Syndrome
A
Trisomy 18 - clenched hands, overlapping fingers, multiple malformations
7
Q
Duchenne Muscular Dystrophy
A
X-linked recessive
Absence of dystrophin, invasion of fibrous tissue
Stands using Gavet’s manoeuvre
8
Q
Lever Hereditary Optic Neuropathy
A
Reduced vision and hyperarray of disc
9
Q
Genetic Imprinting
A
Marks on chromosomes show if maternal or paternal
Change in message doesn’t show the origin hence can cause problems
10
Q
Familial Hyperchilesterolaemia
A
Austomal Dominant
Can be caused by over 150 different mutations
If cholesterol is over 7.5mmol suspect the disease
Lipoprotein A may also be raised
Treat with lifestyle and statins
11
Q
Macrophages release…
A
TNF and IL-2
12
Q
MHC Class I are on…
A
All cells
13
Q
Th helper cell cytokines
A
Th1 - IL-2, IL-5
Th2 - IL-13, IL-16
14
Q
Myasthenia Gravis
A
May be due to thyroid tumour causing excess antibodies attacking receptors
Blurred vision, fatigue, decline in fitness
Relieved by edrophoneum, neostigme treats it
CMAP decreases each time due to muscle fatigue!
15
Q
What chiefly carries cholesterol in ester form
A
LDL
16
Q
Statins are…
A
HMG CoA Reductase Inhibitors
17
Q
Prenylation
A
Adds small lipid tail to small G proteins to anchor them to the membrane
18
Q
Rho
A
Prenylated by… regulates the cell cytoskeleton
19
Q
MRSA
A
Chlorineepexidene wash , isolate for 5 days
20
Q
Downs Syndrome
A
Trisomy 21 is the most common
Suspect Robertsonoan if high number of miscarriages in family history
21
Q
Differences between transcription in prokaryotes and eukaryotes
A
1) nucleus in eukaryotes
2) modification in eukaryotes
3) more than one RNA polymerase in eukaryotes
22
Q
Post transcriptional modifications
A
5’ end capped with 7 methyl guanine - looks like functional 3’ end
3’ end cleaved and polyA tail added
Splicing
23
Q
RNA transcription error rate
A
10^4
24
Q
Similarities/differences between DNA and RNA polymerase
A
Similarities: both form chain in 5’ to 3’, both form phosphidesater bonds, both use template strand
Differences: DNA polymerase needs a primer, need a free OH group for DNA, DNA adds deoxy nucleotides
25
DNA primate
makes RNA primers for DNA replication
26
Base/nucleotide excision
Repairs to 10^9!
27
Sickle Cell Anaemi
GAG->GAT 17th nucleotide Glutamic acid --> Hydrophobic valine
sickle cell crisis lasts 5 to 7 days
RBCS die after about 10/20 days
28
Creative
CKMM in muscle, CKMB in heart
CK peaks 12 hours after myocardial infarction
29
ADH and AldDh
Japanese people have efficient ADH, inefficient ALDH due to inactivity of mitochondrial and toxic enYmes of this
30
Ecstasy
Reverts the serotonin SERR transporter to work in the opposite directions!
Often hyponytraemia, hypokalkuraemia, low chloride due to over drinking
31
Hyponytraemia
Low blood sodium, can cause swelling due to uptake of water by tissues
32
Erections
NO stimulates guanyl Cyclase
cGMP, stimulates PKG, causes smooth muscles relaxation and dilation, causes erection
Viagra inhibits PDE5
Ginseng stimulates Nos to make NO
33
Therapeutic Index
Toxic drug dosage:Therapeutic dose
34
penicillin stable in acid
G unstable
| V stable
35
migraine
gastric stasis
36
Gentamicin
confined to body fluids whereas vancomycin treats c. diff as not absorbed by G proteins
37
Digoxin and erythromycin interact
gut bacteria usually inactivate digoxin, erythromycin kills this bacteria, less digoxin inactivated hence more drug absorbed
38
Ethinylesteadiol hepatic re circulation
Liver to vile to gut to liver, causes two 2 peaks so the antibiotics can prevent the ethinylestradiol from working
39
Cockcroft Gault equation
Estimates creative clearance = (140-age) x kg x constant all divided by serum creative
40
Enzyme inducing drug
phenytoin
41
enzyme inhibiting drug
erythromycin
42
H1 receptors
Mainly in mucous membranes
If you block causes drowsiness
Most H1 antagonists have anti cholinergic properties
43
H2 receptors
cause acid production
44
alpha adrenergic receptors
In blood vessels
45
Beta adrenergic receptors
beta 1 in heart
| beta 2 in bronchioles
46
Propanol ok
blocks beta 1 and 2 equally
47
Atenolol
Blocks beta 1 more than beta 2 but avoid in asthma
48
Insulin mechanism
binds to alpha subunit, enters cell insulin destroyed, beta subunit activates the tyrosine kinase
49
NSAIDS
Aspirin and ibuprofen are non specific
It is COX 2 that causes inflammation
50
Ramipril
ACE inhibitor
51
MAOIs
prevent breakdown of neurotransmitters in synaptic cleft hence treats depression
52
Local anaesthetics information
Charged hydrophilic amine group and lipid soluble hydrophilic aromatic group
Either Amide or Esther bond between them
Amide more common, stable, hypersensitive rare, more likely to be toxic, metabolised by lived, ionised at physiological ph
Ester rapidly hydrolysed by plasma esterases, produce PABA causing hypersensitivity!
53
Local anaesthetics mode of action
1) diffuser through lipophilic nerve membrane unionised
2) low pH in cell ionises them, they then blocks Na channels and then impulses can't pass
Can also cause myocardial depression and vasodilation
Cocaine causes vasoconstriction
Adrenaline given to cause vasoconstriction to prolong effect as it lessens distribution but don't use in extremities
54
beta lactam antibiotics
inhibit cell wall synthesis, eg penicillin
55
macrolides
inhibit bacterial cell wall synthesis e.g. erythromycin
56
anti fungal a
Inhibited ergesterole in fungal cell membrane e.g. nyastin
57
Antihelminths
Ascarides treat worms by paralysing effect on the CNS
58
Nicotinic receptors
post synaptically at all autonomic ganglia and neuromuscular junctions
59
muscarinic
post synaptically at parasympathetic neuroeffector junction and at sympathetic sweat glands
5 Types
M1,3,5 activate phospholipase C
M2 in heart to reduce cAMP and reduce heart rate
M4 reduces cAMP this and M2 are negatively couples to adenyl Cyclase
60
Tyrosine forms
NA and ACh
61
Alpha adrenergic receptors
NA>Adrenaline>Isoprenaline
62
Beta adrenergic receptors
Isoprenaline>Adrenaline>Noradrenaline
63
Alpha 1 adrenergic receptor
vasoconstriction, activates phospholipase C
64
alpha 2 adrenergic receptor
inhibits adenylate Cyclase, inhibits neurotransmitter release
65
beta 1 adrenergic receptor
increases cardiac rate and force
66
beta 2 adrenergic receptor
bronchodilator and vasodilator
67
beta 3 adrenergic receptor
lipolysis
68
Alpha 1 antagonist
phenylenephrine
69
alpha 2 antagonist
clonindine
70
beta 1 agonist
dobutamine
71
beta 2 agonist
salbutamol
72
beta 1/2 antagonist
propnalol and atenolol (atenolol blocks 1 more than 2)
73
Beta blocker effects
cold extremities, bronchoconstriction, depression, bradychardia
74
A2B3 Platelet receptor
Aggregation
75
A2B1, GPV1
Adhesion --> binds collagen
76
CP1b/IX/V, PAR-1, TP, P2Y12
Activation --> binds thrombin
77
Thrombaxane in platelets
Used for auto activation, made by COX-1 and TX Synthase
78
Platelet alpha granules contain
fibrinogen, FV, vWF
79
Dense granules
Release ADP - an autocrine molecule, thromboxane is also an autocrine molecule
80
Sequence of blood clotting with platelets
Endothelial damage --> collagen exposed so binds to A2B1 and GPV1
Activated platelets release ADP and thromboxane, binds to P2Y12 and TP to activate others
A2B3 binds fibrinogen along with vWF holding the clot together
81
Clopidogrel, trigrelor, prasugel
ADP receptor inhibitors on platelets
82
Vitamin K Dependent clotting factors
II, VII, IX, X
83
Serine Proteases
VII, IX, X XI, thrombin
84
Extrinsic Pathway
Triggered by trauma, causes the initial coagulation
85
Intrinsic pathway
Consolidates thrombin generation, due to damaged surfaces
86
Platelet life span
5-9 days
87
Main trigger for coagulation
Tissue factor is the main trigger for coagulation, it is found on the surface of all perivascular cells and auto activates FVII when bound
88
Thrombin helps to activate which other factors
FXI, VIII, XIII (shows FXII has an almost irrelevant part in the clotting cascade as thrombin can activate FXI anyway)
89
T-lymphotrophic virus HTLV1 is associated with what disease
leukaemia
90
Leaukaemia
WBC's accumulate in blood causing bone marrow failure
Initially decreased RBC's and platelets but high WBCs, then WBC's also decrease
Hyper viscosity of blood due to high WBC count causes respiratory, neurological problems, tiredness, bleeding and bone pain.
91
Reed-Sternberg cells characterise what
Originate from B lymphocytes in Hodgkins lymphoma
92
Iron defeciency anaemia
Microcytic anaemia, reduced Hb production
93
Vit B12/folate defeciency
Macrocytic anaemia, macroavolocytes also form which causes hyperhsegmented neutrophils
It is also needed for DNA replication
94
Normocytic Anaemia
Caused due to blood loss
95
Kidney Failure Anaemia
Expo (erythropoeitin) is secreted by kidneys and needed for erythropoiesis, treat with rEPO
96
Haemolytic Anaemia
Reduces RBC lifespan from 120 days to just 20
97
Acquired Anaemias
Immune --> haemolytic disease of the newborn
| Non-immune --> snake bites, malaria, septicaemia, drugs, mechanical e.g. heart valves
98
Inherited Anaemias
Virtually all inherited anaemias are haemolytic
Spherocytosis --> mutation in alpha or beta spectrin in cell cytokskeleton
RBC enzyme defects --> e.g. glucose-6-dehydrogenase deficiency meaning the RBC lacks NADH
Haemoglobin defects
99
Sickle Cell Anaemia
Glutamic acid --> Hydrophobic Valine, causes sickling of RBC that can block microvasculature
100
Thalassaemias
Deletion of large sections of the alpha globin in haemoglobin
101
Beta thalassaemia
Point mutation in the beta globin gene, if both genes are affected then the patient has HbF and thalassaemia major
102
What is blood serum
Plasma without the clotting factors
103
Blood and plasma donors
O is the universal blood donor, AB is the universal plasma donor
104
Rhesus blood group
Based on a D antigen on transmembrane proteins in RBCs
Haemolytic disease of the newborn --> Rh- mother and Rh+ baby sensitisation occurs if previous pregnancy occurred
Treated with RhIgG at 28, 34 week and within 72 hours of delivery!
105
Hormones causing vasoconstriction
Thromboxane (from activated platelets)
Serotonin (from activated platelets)
Angiotensin (from liver precursor)
Vasopressin/ADH (from pituitary gland)
106
Primary haemostasis
Platelet aggregation and activation
107
Secondary haemostasis
Clotting cascade producing the fibrin clot
108
Abdominal Aortic Aneurysm
Normal aorta is 2-3cm, anything over 5cm is inoperable
109
Disseminated Intravascular Conjugation
Infection which leads to Sepsis
TF is expressed by WBC's activating factor 7 leading to systemic coagulation causing clots
Clotting factors are all used up hence bleeding occurs
Clotting and bleeding occurring at the same time causing multiple organ failure
110
Vitamin K Dependent Factos
Factors 2, 7, 9, 10, proteins C & S
These undergo a post transcriptional modification of glutamic acid to gamma-carboxyglutamic acid - Gla then binds to -vely charged phospholipids provided by activated platelets via Ca2+
Vitamin K--> KH2-->Epoxide (KO) it is this last step which converts Glu to Gla
KO then converted back to vitamin K
111
VKOR Inhibitors
E.g. Warfarin, prevent the conversion of epoxide back to vitamin K hence prevents clotting as vitamin K dependent clotting factors aren't produced
112
Vitamin K Defeciency due to...
Malbsorption, liver disease, drugs, bleeding
113
Haemophilia A
Factor VIII defeciency
X-linked recessive
No consolidation of blood clot --> may need treatment with recombinant or plasma concentrates.
114
Haemophilia B
Factor IX Defeciency, Christmas Disease
For treatment of both haemophilias need recombinant or plasma concentrates of FVIII/FIX, but may develop immune resistance to them hence give immunosuppressants
115
Prothrombin Time
TF trigger, measure the extrinsic pathway! Prolonged clotting time in FVII defeciency
116
Activated Portal Thrombo-plastin (APPT)
Prolonged clotting time if deficiency in intrinsic pathway i.e. Factors XII, XI, IX, VII defeciency
117
PT Normal, Prolonged APTT
Haemophilia
118
vWF
vWF multiglomeric protein produced by Weibel Palade bodies in endothelial cells and alpha granules in platelets
Stabilises FVII and involved in platelet adhesion and aggregation
119
vWF Disease
Type 1 - heterozygous - autosomal dominant - mild
Type 2 - functionl - autosomal recessive - mild
Type 3 - complete deficiency - autsomal recessive - severe
Platelet Type - mutation in GPVI affects adhesion/aggregation
Symptoms: menorhaggia, nose bleeds, GI bleeds, petechia, joint or muscular pain
120
Thrombocytopaenia/thrombobasthenia
Acquired: Leukaemia, DIC, Immume thomobcytopenic Propura
Inherited: Congentital amegakaryotic thrombocytopoenia, Farconis Anaemia, Glanzmann (A2B3 mutation) or Bernard Souilleir (GPVI defeciecny)
Symptoms:Haemophilia symptoms but milder
Treatment: Underlying cause, steroids for ITP, platelet transfusion
121
Bernard Souillier
GPVI defeciency
122
Glanzmann
A2B3 mutation
123
DVT
Low blood flow and pressure, in valves of legs --> can cause PE
Thrombus is fibrin and erythrocyte rich!
Risk factors: immobilisation, genetics, pregnancy, cancer (cells express TF), surgery
Treatment: IV Unfractioned Heparin (helps antithrombin)
Slow onset: Warfarin and coumarins, direct thrombin inhibitors e.g. Dabigatran
124
Virchows Traingle
1) Change in endothelial state/injury
2) Hypercoagulative state
3) Circulatory status
125
Dabigatran
Direct thrombin inhibitor
| Oral tablet that doesnt need monitoring!
126
Antithrombin
Natural anti-coagulant
Inhibits FIX and X
Stimulated by Heparin
127
TF Pathway Inhibitor
Natural anti-coagulant
| Inhibits FXII/TF & X
128
Protein C
Natural anti-coagulant
| Proteolytically activates FVa and VIIIa
129
Protein S
Natural anti-coagulant
| Cofactor for protein C
130
Factor V Leiden
Arg-Glu mutation. activated Protein C usually cleaves FVa at 3 peptide bonds to inactivate
Mutation stops the cleavage, coagulation can still occur
131
Fibrolysis
Fibrin enhances plasminogen to be converted to plasmin. Plasmin degrades the fibrin clot
tPA and UPA activate plasminogen
PAI-I blocks the tPA and UPA active sites
TAF1 blocks enhancement
132
Atherosclerosis
Inflammation of vessel wall --> macrophages either the subintimal space and turned into foam cells, black rupture, collagen exposed binds A2B1 and GPV1, clotting occurs
133
Lysophosphatidic Acid (LPA)
Activates platelets via P2Y12
134
Arterial clotting
Thrombus is platelet rich
```
Treatment: Antiplatelets
Aspirin
Statins - lower cholesterol
Abciximab, tirofiban - anti A2B3
Clopidogrel - anti P2Y12
Fibrinolytic tPA and UPA
```
135
Aspirin
COX Inhibitor --> Stops inflammation but also stops production of thromboxane hence prevent platelet activation
136
Abciximab and tirofiban
Anti A2B3
137
Heparin
Inhibits Thrombin and FXa
Used in surgery and angioplasties
Heparin found in lungs or small intestine!
138
Clopidogrel
Anti P2Y12
139
Formalin Fixer
Pros: Common, forms covalent bonds between proteins
Cons: Not good for cytoplasmic structure or nucleic acid
Irritant.toxic
140
Glutaraldehyde fixer
Pros: Good for sub microscopic structures & EM
Cons: Poor tissue penetration
141
Ethanol
Pros: Nucleic Acid
Cons: Poor Morphology
142
Freeze
Pros: Nucleic acid and protein
Cons: Poor morphology, uses up lots of space and energy!
143
Wax impregnation of samples
Wax is only soluble in benzene hydrocarbons, dehydrate the sample in alcohol, replace alcohol with xylene, samples then used for staining!
144
histological stains Haemoxylin & Eosin
H - basic and purple, stains acidic structures purple e.g. DNA
E - acidic and pink, stains basic structures pink e.g. protein
CONS: Fat not stained, can't tell the difference between collagen and elastin!
145
Massons Trichrome
Haemoxylin + Acid Fuschin + Methyl Blue
Collagen - Blue
Muscle, cytoplasm, RBC - red
Nuclei - Black
Good for collagen and connective tissue, shows liver fibrosis. Stains Mucis
146
Periodic Acid Schiffer Stain
Picks up mucin (but also glycogen hence use diastase enzyme to remove glycogen)
Can highlight tumours that produce mucin
147
Perls Prussian Blue
Detects iron, shows asbestos as iron binds to it
148
Ocein
Used in liver pathology, shows asbestos as iron binds to it and Hepatitis B stains copper proteins
149
Gram stain
Used for bacteria
150
Grocoh/PASD
Used for fungi
151
Ziehl Neelson
used for mycobacteria e.g. TB
152
Foci Formation
when cancer cells just begin to grow onto of each other
153
Hereditary cancer disease patterns seen in...
Li Fraumeni Syndrome and Eroderma Pigmentosam (mutation in DNA repair gene)
154
Hep B Causes
Liver cancer
155
H. Pylori
Causes stomach cancer
156
Heterocycln amines in cooked meats
Causes stomach cancer
157
UV and skin cancer
UV rays cause adjacent thymines to pair up forming covalent bonds and thymine dimers, problems for DNA replication hence cancer
158
Alfatoxin
Toxin produced by fungi, metabolised in liver to form a reactive intermediate and DNA adduct causing liver cancer.
Common in developing countries
159
DNA Adducts
make things more reactive
| e.g. benzopyrene binds to deoxyguanine
160
Tight Junctions
Occludin/Claudin seals at the apical of cell
161
Adherens Junctions
Transmembrane proteins connect across the cell cytoskeleton using actin filaments below the TJ's
162
Gap junctions
small ion channels allowing intracellular exchange
163
Desmosomes
TM proteins attach to other proteins on other cells
164
Hemi-desmosomes
attach to the underlying basement lamina
165
Exocrine/endocrine glands
Exocrine glands open onto surface of epithelial cells, can be simple glands with no ducts e.g. sweat
Endocrine glands are ductless glands that secrete directly into the circulation
Pancreas is both an exo and endoxrine gland!
166
Methods of Secretion
Merorcrine - mainly watery, secrete substances out of intact cells e.g. pancreas and sweat glands
Apocrine - portion of cell pinched off containing substances e.g. mammary glands used for proteins and fats
Halocrine - cell disintegrates releasing contents e.g. sebaceous glands most oily secretions
167
Epidermolysis Bullosa Simplex
Skin - congenital disease, affects keratin intermediate assembly causing bullae in areas of stress
168
Harlequin Ichthyosis
Skin - congenital hyperkeratinisation, fatal due to dehydration, thermoregulation and sepsis
169
Epithelilal Basement Dystrophy
In 2% of the population, causes corneal erosions, visual disturbances and material deposition
170
Autosomal Dominant PKD
Congenital, afects Ca2+ transport. Increased renal tube proliferation causing nephron cystic degradation, parenchymal compression and renal failure
171
Kartageners Syndrome
Congenital cilia dyskinesia with situs inversus. Causes chronic sinusitis, bronchiectasis and subfertilty!
172
Components of connective tissues
Extracellular matrix - a gel called ground substances containing proteins and elastic and collagen fibres
Cells - fibroblasts, adipocytes etc
173
Marfans Syndrome
Lack of fibrin causes joint laxity, cataracts, aortic dissection and valvular heart diseases
174
Neutrophils
Phagocytose bacteria, contain enzyme granules
175
Basophils
Rarely seen act like mast cells
176
Eosonopils
Bilobed uncles, tomato wearing sunglasses
177
Bone formation
Osteoblasts make osteoid in the extracellular matrix, mineralised with calcium to make bone, woven is immature bone which is then replaced by lamella
178
Cartilage formation
Chrondoplasts make ground substance and collagen fibres in the extracellular matrix and then become trapped as chondrocytes
Hyaline cartilage - nose, trachea, joints
Elastic - ears
Fibrocartilaed - pubic syphis and intervertebral discs!
179
C3a, C4a & C5a
Anaphylatoxins - trigger the degranulation of endothelial cells, mast cell and phagocytes
Cause smooth muscle contraction and enhance vascular permeability
C3a and C5a also attract other neutrophils!
180
MAC
C5b, C6,7,8,9 perforate the cell forming a pore in the membrane of the infected cell
181
C3b
For opsonisation, binds to the surface of bacteria and is cleaved to iC3b to bind macrophages causing phagocytosis!
182
3 Ways to activate the complement system (all involved C3 & C5)
1) Classical Way - C1 binds to an antigen/antibody complex --> cascade triggered however not usually the 1st way to trigger the cascade as takes time to produce antibodies
2) Lectin/mannose binding - mannose-binding lectin binds mannose then Masp1&2, complex then cleaves c2& 4
3) Alternative pathway - auto activation of C3 - occurs constantly at a low rate, but upon contact with bacteria C3b binds factor B & properdin, rapidly activates C3 and C5
183
Pathogens with Mannose Sugar
Yeasts - Candida Albicans
Viruses - HIV/Influenza
Bacteria - Salmonela & steptococci
Parasites - Leishmania
184
Macrophages - Residing In Tissues - Activation
Resting - collect debris, phagocytose and eliminate apoptic cells, express little MHC Class II
Primed (IFN from NK Cells and T helper cells)
Express more MHC II and take up larger objects by phagocytosis!
Hyperactive (IFN & LPS from gram -ve bacteria)
Macrophages stop proliferating, expand and increase rate of phagocytosis
Produce TNF & IL-1 when hyperactive!!
185
What cytokines do hyperactive macrophages produce
TNF & IL-1
186
Neutrophhils - reside in blood
Life span 5-9 days
1) Selectin/Ligand binding - SLIG always expressed on neutrophil
IL-1 & TNF from macrophages causes endothelium to express selectin
2) ICAM always on endothelium
LPS and C5a cause neutrophil to express integrin
These stop the neutrophil rolling!
187
What form of methionine do bacteria have?
bacteria have f-met, neutrophils track this f-met secreted by bacteria.
C5a and f-met allow the neutrophils to infiltrate the endothelium and surrounding vessels, they become extremely phagocytic
188
What cytokine do neutrophils produce?
TNF
189
What cytokines do natural killer cells produce?
IFN & IL-2
190
Natural killer cells
Produced in bone marrow, found in blood!
Fas ligand binds to Fas on infected cells, causes apoptosis
Perforin protein injects granzyme B, the suicide protein into the cell
191
Innate and viral infections
Opsonisation with C3b
MAC produced
TNF and IFN reduce viral production
NK cells cause apoptosis of infected cells
192
Which regions of gene segments change in antibodies?
V, D & J gene segments are mixed and matched
193
Which antibody is released first?
IgM - pentameric structure of the Fc region can bind up to 5 C1 complexes at a time hence activates lots of complement system! shows innate and adaptive immune repsonse working together!
194
Where does class switching occur
In the germinal centres of lymphoid tissues (germinal centres in secondary follicles of cortex of lymph nodes), t helper cells direct the type of antibody the B cells should produce!
195
Where are inactive B cells exposed to antigens?
in the lymph nodes - proliferating B cells causes swollen lymph nodes! B cells in both primary and secondary follicles of cortex!
196
Somatic hypermutation
High mutation rate in V, D & J segments upto 1 in 1000! Can increase/decrease affinity of antibody! Higher affinity, more likely to bind hence stimulated more so proliferates more
197
Through what processes do the Fc and Fab region of the antibodies change?
```
Fc - class switching
Fab - somatic hypermutation!
```
198
T cell tolerance
+ve selection - cells must recognise MHC molecules
-ve selection - cells stop expressing CD4 or CD8, if cells recognise self-antigens they are triggered to die!
but no all cells may encounter self antigen, but anergy still occurs if they meet self antigen later due to absence of second signal!
199
B Cell tolerance
Become tolerant in bone marrow
Clonal Deletion - if they recognise self antigens they die
Receptor tolerance - daily exposure to the same antigen creates a tolerance
Undergo anergy if they encounter an engine with no help from T cells!
200
Types of APC
1) Dendritic cells - in periheral tissues, travel to nearest lymph node to activate T cells
2) Macrophages - in tissues, stay in tissue to fight infection and continue to stimulate T cells when they reach the tissue!
3) B cells - only experienced B cells load antigens onto MHC class II cells, responsible for activating T cells when they encounter the antigen a second time!
201
B cell activation
Requires binding antigen
| Requires 2nd Signnal from T cells of non T-cells
202
How many antigen binding sites on the antibody?
2 antigen binding sites in the fab regions
203
IgM
initial response, in the blood stream, kills bacteria, activates complement system
204
IgG
Later response, blood ad interstial tissues, prepares the bacteria to be killed. For bacteria and viruses
205
IgE
Allergic reactions, parasites and causes most cells to release contents
206
IgA
Protects potential pathogen entry routes/ mucosal surfaces! Binds and removes viruses
207
IgD
in the B cell membrane to help divisoin
208
Hepatitis Antigens
HBsAg detected in the active disease
| HBcAb detected in current and previous infections! the vaccination uses only the surface antigen!
209
Graves disease
Autoimmune condition, produces antibodies mimicking TSH causing uncontrolled hyperthyroidism
210
T Helper cells have
CD4
211
T Cytotoxic cells have
CD8
212
T Cell Activation
```
Antigen presented with an MHC protein (class I or II)
Also second signal from CD28 on T cell interacting with CD80 on the APC
```
213
T Helper cells
release cytokines, chemoattraction, inflammation, stimulate antibody production and make phagocytes work better!
214
Cytotoxic cells
virus proteins loaded onto MHC class I molecules in ER and transported to the cell surface
215
Cytokines
Produced mainly by T helper cells
216
T helper 1 cells
Il-2, IL-5 activates cell mediated & cytotoxic T cells
217
T helper 2 cells
IL-4, IL-10, IL-13, act on B cells to control antibody production!
218
Th1 Disease
Tuberculoid Leprosry (cytotoxic)
219
Th2 Disease
Lepromatour leprosy (helper)
220
HIV
Has p120 surface antigen, binds CD4 on T helper cells causing cell death!
221
T & B Cell interaction
B cells are APC with MHC Class II and bind with CD4 receptor on T helper cells
Also CD28 and CD80 interaction
T helper cells they produce cytokines to stimulate antibody production
222
Pernicious anaemia
autoimmune disease attacking cells in the stomach needed for B12 absorption
223
Non organ specific autoimmune disease
Can attack any part of the body e.g. systemic lupus erythematous!
224
Cytoplasm
Cytosol + organelles
225
Microtubules
2 globular alpha and beta proteins polymerised into proto filaments
13 protofilaments form a tube, can then be doubled or tripled
Provides tracks for organelles to move on and axonal transport occurs
Anterograde transport - transport can occur in both directions on the same microtubule
226
Microtubule assosciated proteins
These proteins cross-link the microtubules, one of these proteins in tau which accumulates in alzheimers disease
227
Cilia and flagella are composed of what?
Microtubules
228
Nucleus double membrane
Inner membrane is smooth, the outer membrane is continuous with the ER
229
Golgi apparatus
Flattened containers in the cytosol, proteins are transferred here from the ER in vesicles.
Modifies proteins and lipids by adding carbs, etc. and distributing them and packaging them.
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Proteosomes
Specialised structures to degrade cytosolic proteins.
Enzyme has four rings around a central core
Proteins to be degraded are marked with ubiquitin, this directs them to the core of the proteasome where they are degraded!
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Gram Staining Bacteria
Gram +ve bacteria have a second outer membrane of peptidoglycan hence retain the crystal vile stain and are purple
Grab -ve bacteria take up the counter stain as only have one membrane of peptidoglycan hence giving them a pink colour
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Nucleoli
An assembly of ribosomes, stains darkly, contains RNA and proteins
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Grifftiths DNA
Heat killed virulent and non-virulent. When heat killed virulent mixed with non-virulent - kills mice, shows protein or DNA responsible
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Avery
Only DNA changes non-virulent to virulent
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Hershey & Chase
Grew phages with radioactive P & S, only P found in infected bacteria hence DNA carrier or genetic material
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Watson & Crick
Double helix structure, sugar/phosphate backbone, A+T = 2 bonds
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Semi-conservative replication
Shown by meselsohn & Stahl
DNA replicates at replication fork (where DNA is unwound by DNA Helicase
Single stranded binding proteins bind to stabilise the strand and prevent them recombining
Terminator polymerase sequence produces unstable RNA sequence causing the polymerase to release the RNA
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What polymerase is used for DNA replication
DNA Polymerase III
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DNA Replication the lagging strand -
DNA can only replicate in 5' to 3' direction. On the lagging strand DNA is laid down is Okazaki segments, DNA primes lays down regular primers, DNA polymerase I removes primers and DNA ligase seals the gaps
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What provides the energy to form new phosphodiester bonds?
The hydrolysis of dNTPS as new nucleotides are added
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Uracil-n-glycosylase
used to repair DNA, cutes out uracil and DNA polymerase repairs damage
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Which strand of DNA is copied in transcription?
The antisense strand - this means mRNA is that same as the sense strand but with thiamine instead of uracil.
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What direction does RNA polymerase II move in>
3' to 5', mRNA is sythesised in a 5' to 3'
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What promoter regions in genes are there?
TATA box - 25bp away from transcription site
CAAAT box
CpG islands
Allows the binding of transcriptional factors and RNA polymerase to bind and position correctly
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Types of RNA Polymerase
1 type in bacteria
3 Types in eukaryotes
RNA Polymerase I & III = tRNA and rRNA
RNA Polymerase II = mRNA
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Modification of RNA
Splicing - splice some (collection of small RNA and protein) removes introns from pre-mRNA
7-methyl-guanine to 5' end of mRNA - occurs by 3 enzymes, makes the 5' end look like the functional 3' end to avoid degradation
Poly-A Tail added - 200 adenine nucleotides added to the 3' end, helps transport mRNA out of the nucleus and direct protein synthesis
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tRNA
80 nucleotides, amino acid on the 3' end, anticodon complimentary to mRNA codon
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What added amino acids to tRNA
tRNA synthetases
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What are the 3 sites on tRNA
A - arrival
P - tRNA already in place
E - tRNA binding
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What forms the peptide bonds between amino acids
RIbosomes
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Terminator mRNA sequences
UAA, UAG, UGA produce release factors
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Wobble-base pairing
Where as long as the first 2 bases on the tRNA anticodon are correct the 3rd base can bind to several bases!
Allows folding a tertiary structure to form
Limits numbers of tRNA required!
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Purine-->Pyrimidine change
Transversion
Transition if same type of base is kept
2
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2 Pathways of protein assemble
1) 20 hydrophobic amino acids added, then incorporated into the lipid bilayer and the rest is synthesised in the cytosol
2) Protein entirely synthesised in cytosol, carboxyl terminal cleaved, fatty acid chain linked to Cys and anchored to the membrane via a G protein (Ras/Rho)
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BRCA1 Gene
Increases the chance of breastcancer
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Polymorphism
A mutation in at least 1% of the population
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Epigenetics
The control of gene expression or cell phenotype by means other than genetic variation! (basically the same DNA but expresssed differently)
e.g. cytosine methylated at CpG sites affects gene expression
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Menstrual Age
Day of last period, starts at day 0, 3 equal trimesters
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Fertilisation Age
Starts at point of fertilisation, 3 unequal periods
1) 0-2 weeks - Early development
2) 3-8 weeks - Embryonic - organogenesis
3) 8 weeks+ - growth and maturation of organs
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Teratogens
Environmental causes of birth defects, body most susceptible in weeks 3-8, week 5 the highest as this is when organogenesis is occurring. CNS and heart have longest critical time in organogenesis hence increased risk of defects
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Toxiplasmosis
1/3 of the population have it, only infectious if caught weeks 3-8 in cat faeces/undercooked meet
Microcephaly, hydrocephaly, microopthalmia
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Rubella
Virus, only harmful if caught weeks 3 to 8
| Microcephaly, cataracts, deafness, heart defects
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Cytomegalovirus
Bodily fluids, asymptomatic only causes problems if caught weeks 3 to 8
Causes cereberal calcifcation, intrauterine growth retardation (small at birth), microcephaly, microopthalmia
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HSV (Type 1 - cold sore, type 2 - gential herpes)
Rarely transmitted in utero, usually at delivery
| Causes skin lesions, scars, microcephaly, seizures, vision problems!
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Thalidomide
Shortened limbs etc
| Treats leprosy.
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Where does fertilisation occur?
At the ampulla
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Day 4 embryology
Morula which is 16-32 cells, differentiates into inner embryo blast cells and outer trophoblast cells
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Day 5 embryology
Blastocyst hatching into uterus, leaves zone pellucida and implants, usually on the posterior endometrial wall
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Day 7 embryology
further differentiation: Trophoblast into the cytotrophoblast and syncytiotrophoblasts
Embryo blast into hypoblast (ventral) and epiblast (dorsal)
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Day 8 embryology
The amniotic cavity develops in the epiblast! syncytiotrophoblasts secreting enzymes to prevent immune response, only nutrients from diffusion via the uterine gland
271
Day 9 embryology
Full implantation, yolk sac and trophoblastic lacuna from
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Day 10/11 embryology
Trophoblastic lacune and extramebryonic mesoderm form
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Day 12/13 embryology
chorionic cavity forms in the extra embryonic mesoderm!
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Day 14
Secondary yolk sac forms. A secondary wave of hypoblast cells migrate to form the secondary yolk sac!
Embryo and amniotic cavity are suspended in the chorionic cavity by the connecting stalk!
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Pregnancy Tests
Test for Human Chorionic Gonadotrophin hormone ( HcG_
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Placenta pruvia
Implantation occurs near the cervix, baby can damage placenta during delivery causing haemorrhage. Spot on ultrasounds and consider caesarean
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Tubal (ectopic)
80% of ectopic pregancy, uterine tubes can rupture, extreme pain often mistaken for appendicitis
278
Abdominal
Occurs in the rectouterine pouch, if placenta attaches to other organs it can sometimes suvive e.g. the liver
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Lithapaedion
Abdominal implantation of the egg, becomes calcified as too large to be reabsorbed by then boy and the mother needs to be protected from nephrotic tissues
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Hydatidiform Mole
When an empty egg is fertilised, trophoblasts still form showing paternal genes favour this
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Day 15 embryology
Primitive steak forms on dorsal surface establishing the body axis
Definitive endoderm also forms
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Day 16 embryology
Formation of the mesoderm and ectoderm
Ectoderm - Skin, NS
Mesoderm - bones, muscle ,cartilage, kidneys, reproductive system
Endoderm - lungs, glands or liver and pancreas, GI tract lining
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Day 17 embryology
Mesoderm becomes highly organised! divides into:
Paraxial - Skeleton, skeletal muscle, skin
Intermediate - Reproductive system and kidneys
Lateral Plate -linings of the body cavities
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Day 20 embryology
Paraxial mesoderm becomes highly organised, splits into 3/4 somites a day, can estimate the age of an embryo from this, goes cranial to caudal
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Ectoderm
Forms skin and nervous system
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Mesoderm
Forms muscle, bone, cardio, kidneys and reproductive system
287
Endoderm
Forms lungs, GI linings, glands of liver and pancrease
288
Paraxial mesoderm
Forms skeleton, skeletal muscle, skin
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Intermediate mesoderm
Reproductive trace and kidneys
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Lateral plate mesoderm
Forms the lining of the body cavities.
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Sirenomella
Abnormal gastrulation, as the primitive streak regresses it disappears to early. Insufficient mesoderm in the caudal region hence limbs fuse and abnormalities of the urogenital system
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Sarcococcygeal Teratoma
Primitive streak persists - tumours form as too much mesoderm but good prognosis. 80% females!
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Day 19
Notochord initiates neuralation. Notochord causes the overlying ectoderm to thicken in induction forming the normal plate
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Notochord organises the Paraxial mesoderm further
Sclerotome - forms bone and cartilage
Myotome - Forms skeletal muscle
Dermatome - Form dermis
This means the notochord organises vertebrae formation from somites!
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Vertebrae formation
Organised by the notochord! Sclerotome cells surround the notochord forming the vertebral body and surround the neural tube forming the vertebral arch
Majority of notochord degenerates, remounts as nucleus pulposus in the intervertebral discs!
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Spina Bifida Occulta
Vertebral arch doesn't form properly, only skin and fat protect the spinal cord, marked by dimpling of skin and tuft of hair
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Meningocele
Meninges sac containing only CSF protrudes through vertebral defect covered by skin
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Myelomeningocele
Meninges sac and spinal cord protrude through defect, not covered by skin. Usually occurs in lower back, easy to damage in birth causing lower limb, continence and reproductive problems.
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Day 22
Fusion of neural folds in the midline - cranially and cardially, as neural folds fuse they detach from the ectoderm and can then be covered by skin
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Day 25
Anterior Neuropore fuses
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Day 28
Posterior Neuroporse fuses
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Anencephaly
Failure of anterior neuropore to fuse - forebrain doesn't form, only have brainstem, cause premature birth
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Rachischisis
Failure of posterior neuropore to fuse, neural tissue remains fused to the ectoderm, spinal cord doesn't form properly causing paralysis. Open neural tube prevent vertebrae formation ( a from of spin bifida) and flap plate neural tube exposed at birth!
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Neurofibromatosis
genetic mutation in the NF1 gene (a tumour suppressor gene), gene switched causing benign tumours of nervous system, skin and cranial bones. It is an abnormality in neural crest cell development
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Week 4 embryology
Folding of the embryo! Lateral plate mesoderm splits into parietal (with ectoderm) and visceral (with endoderm and organs)
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Ectopia Cordis
Lateral folds fail to fuse in the thoracic region leaving the heart outside the body
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Gastroschisis
Lateral folds fail to fuse in the abdominal region, investing left outside the body
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Anterior pituitary
Produces hormones
309
Posterior pituitary
Stores hormones from the hypothalamus
310
Prolactin secretion
Under inhibitory effects from the hypothalamus
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Glands not controlled by the pituitary gland
Parathyroid glands
Adrenal medulla (produces adrenalin)
Pancreas
Gut Hormones
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How many lobes of the thyroid gland
2 lobes
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What does the parathyroid gland control?
Controls calcium levels, secretes PTH to increase absorption of calcium from kidneys and gut and release calcium from bones
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What do the adrenal glands produce?
Cortex 10% of gland - corticosteroids, androgens and mineral corticoid (aldosterone but this isn't controlled by the pituitary)
Medulla 10% of gland - Catecholamines (adrenaline etc.) - not controlled by the pituitary
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Testes cells
Intersitial/leydig cells - produce testosterone
Seminiferous tubules - contain germ cells to produce sperm
Sertoli cells - produce inhibit
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Classification of gland abnormalities
Primary - affects gland itself
Secondary - affects pituitary
Tertiary - affects hypothalamus
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Static tests used for
Thyroid and Sex hormones
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Synacthen Test
Used for adrenal failure, give ACTH expect to see cortisol rise, if not then fails!
319
Insulin Stress Test
Give insulin to reduce BGL, causes stress, body should produce cortisol and cause glucose to be released. If not shows pituitary problem! (glucagon stimulation test is an alternative)
320
Steroid suppression test
Give steroids, measure endogenous production should decrease in normal
321
GH Test
Give glucose, should switch off growth horome
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Prolactin oversecretion Causes
Prolactinoma - a prolactin secreting pituitary tumour. Micro tumours are less than 1cm in diameter
Non-functioning pituitary tumour - compressing the hypothalamus and stops the inhibiting effect
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Prolactin oversecretion symptoms
Galactorrhea, amenorrhea, sexual dysfunction in men (as it lowers testosterone), headaches and visual problems (tumours can compress the optic chasm)
Diagnose with spot test, MRI of pituitary
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Prolactin oversecretion Treatment
Generally a higher prolactin means a prolactinoma. Prolactinomas are the only tumour that can be traced medically - rarely require surgical intervention
325
Growth Hormone Oversecretion Causes & Symptoms
Causes: Tumour
Symptoms: In children - excessive growth, large hands and feet, gigantism
In adults - acrogmegalic face, large hands/feet, sweating
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Growth Hormone Oversecretion Diagnosis & Treatment
Diagnosis: Glucose suppression test, imaging to see if tumour
Treatment: Surgery to remove the tumour, radiotherapy/medical therapy
327
Steroid Under Secretion Causes & Symptoms
Causes: Adrenal and pituitary failure
Symptoms: Growth arrest in children, tiredness, dizzy due to low blood pressure, abdominal pain, low aldosterone
328
Steroid Undersecretion Diagnosis and Treatment
Diagnosis: Synacthen test - give ACTH expect steroids to rise, detects primary adrenal failure!
IF HYPOTENSION THEN INJECT STEROID STRAIGHTAWAY AS STEROID DEFECIENCY CAN BE FATAL
Treatment: Tablets to replace hormone
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Hypothyroidism Causes and Symtpoms
Causes: Primary - thyroid failure, usually autoimmune
Secondary - pituitary failure, usually complete
Symptoms: Often older women, weak, dry skin, cold, decreased sweating, impaired memory, constipation, weight gain, hair loss
330
Hypothyroidism Diagnosis and Treatment
Diagnosis: Static Test, high TSH in primary failure, low TSH in secondary
Treatment: Thyroid replacement tablets ( contain the inactive T4)
331
Sex hormone defeciency causes and symptoms
Causes: Primary and secondary gland failure
Symptoms: ED, reduced libido, menstrual problems
332
Sex hormone deficiency tests and treatment
Tests: Static test
Treatment: Hormone replacement, generally replace the sex hormones and pituitary hormones are difficult to replace
333
Causes of Amenorrhea
Uterine problems
Ovarian problems (hypogonadism, polycystic disease, ovarian failure)
Pituitary or hypothalamus problems (common in athletes)
Prolactinomas
334
Pituitary failure
Causes: Large tumours, often high growth hormone levels
Diagnosis: Usually involve multiple hormones
335
Increased parathyroidism
Causes: Cancers produce a similar thing to PTH, Drugs
Tests: High calcium and high PTH = primary failure
High calcium and lowP PTH = not parathyroid problem, potentially cancer
336
Cushing Syndrome (High Cortisol) Causes and Symptoms
Causes: Pituitary tumour secreting ACTH
Adrenal tumour secreting cortisol
Cancers producing cortisol
Symptoms: Growth arrest in children, round face, truncal obesity, acne, thin extremities, think skin, easy brushing, hypertension, diabetes, higher risk of infection
337
Cushings syndrome diagnosis and treatment
Dexamethasone suppression test - should reduce cortisol
High ACTH is secondary cushings, low is
Treatment: Surgery to remove tumours and radiotherapy etc.
338
Hyperthroyidism causes (primary is common, secondary rare)
Graves Disease - autoimmune disease attacks thyroid, causes enlarged smooth thyroid (80%) of cases
Toxic nodules - multinodular thryoid
Thyroiditis - inflammation of thyroid, causes initial release of hormones then cells die and it decreases. Tender enlarged thyroid
Drug induced e.g. amiodarone, TSH secreting tumours or iatrogenic
