Cardiology Week 3-4 Flashcards
(412 cards)
1
Q
parts of mediastinum
A
superior
inferior - divided into anterior middle and inferior
2
Q
demarcation between superior and inferior mediastinum
A
manubriosternal junction - level of T4/5
3
Q
what vertebrae does heart sit in front of
A
T5,6,7,8
4
Q
layers in superior mediastinum from superficial to deep
A
thymus great veins aortic arch, vagus+phrenic nerves trachea oesophagus thoracic duct L recurrent laryngeal N
5
Q
names of great veins
A
internal jugular vein and subclavian on both sides meet to form brachiocephalic veins
6
Q
landmark for where IJV and subclavian meet
A
sternoclavicular joint
7
Q
differences between L and R brachiocephalic veins
A
R - short and vertical
L - longer and more horizontal
8
Q
where do brachiocephalic veins meet to form SVC
A
behind first costal cartilage
9
Q
what level does SVC enter right atrium
A
behind third costal cartilage
10
Q
why do you use R IJV as JVP not left
A
because on the right you have a vertical column
11
Q
where does azygous vein drain into SVC
A
level of 2nd costal cartilage, empties into back of SVC
12
Q
what part of mediastinum is arch of aorta
A
all in superior mediastinum
13
Q
where does arch of aorta become descending aorta
A
T4/5
14
Q
ligamentum arteriosum
A
remnant of ductus arteriosus from foetus between pulmonary trunk and aorta
15
Q
great arteries
A
R common carotid and subclavian come off brachiocephalic trunk
L common carotid and subclavian come off as separate branches
16
Q
where does brachiocephalic trunk divide
A
sternoclavicular joint T4/5
17
Q
retroesophageal right subclavian artery
A
from left to right coming off aortic arch:
R common carotid
L common carotid (on other side of trachea)
L subclavian
retroesophageal R suclavian artery - comes of the far left but goes behind oesophagus
causes swallowing difficulties
18
Q
course of Phrenic nerve on right
A
on scalenus anterior
b/w subclavian a and v
anterior to lung root
pierces diaphragm
19
Q
where does L and R phrenic nerve pierce the diaphragm
A
R - with SVC at T8
L - pierces on its own just near apex of heart
20
Q
What does the Phrenic nerve supply
A
motor to diaphragm from abdominal surface
sensory to mediastinal +diphragmatic pleura + pericardium (fibrous and parietal serous pericardium)
21
Q
course of R vagus nerve
A
descends in carotid sheath as part of neurovascular bundle of neck then alongside trachea behind lung root anterior to oesophagus
22
Q
course of L vagus nerve
A
lateral to aortic arch posterior to phrenic n crossed by superior IC vein gives off L recurrent laryngeal nerve behind lung root anterior to oesophagus
23
Q
where does recurrent laryngeal nerve travel back up
A
groove between trachea and oesophagus - trachoesophageal groove
24
Q
does oesophagus come away from vertebral column
A
yes - only distally when goes through diaphragm - goes forwards and to the left - swaps places with aorta
25
3 types of antimicrobial agents
antibiotics
chemotherapeutic agents- synthetic
semi-synthetic
26
why make semi-synthetic antibiotics?
alter pharmacological properties - change kinetics, reduce toxicity, modify antimicrobial spectrum
extend patent and make money
27
tetracyclin
naturally occurring but rapidly eliminated by body, modification is doxycyclin
28
threeclassifications of antimicrobial agents
source - natural or synthetic
broad mechanism of action - cidal or static
pharmacological class
29
bacteriostatic vs bactericidal
bacteriostatic - stops bacteria growing
| bactericidal - reduces viable count by 99.9% (kills)
30
they're both equally effective usually, why would you want to use bactericidal
if patient doesnt have functioning innate immune system
31
infected endocarditis
infection sits on heart valves, macrophages cant eat because valves moving
so need bactericidal antibiotics to kill
32
tetracyclines
phamacological type of antibiotic with 5 rings
33
beta-lactam antibiotics
all have square beta-lactam ring
| pretty much all of them
34
penicillin G
| administration and toxicity
injection
| least toxic - can have heaps and wont kill you
35
penicillin V - administration
acid stable so orally available, low toxicity
36
6-APA
precursor for all other penicillins (not G or V)
37
ampicillin
| how is it better than penicillin
broader spectrum - rods as well as cocci
| orally available, low toxicity
38
methicillin
effective against penicillin resistant staph
but toxic - to kidneys in particular
not orally available
39
carbenicillin
first one effective agaisnt pseudomonas aeruginosa - opportunistic pathogen - problem in hospitals
not orally available
40
clavulanic acid
for streptomyces bacteria
41
why do antibiotics work as effective treatments
because they have SELECTIVE TOXICITY = toxicity for microbe not us
42
rubidomycin
used to treat lymphomas (chemotherapy)
43
5 targets of antimicrobial agents
```
cell wall
cytoplasmic membrane
ribosomes
nucleic acid
folic acid
```
44
antibiotics against cell wall
beta lactams
| glycopeptides (vancomycin)
45
antibiotics against cytoplasmic membrane
why they're not good
polymyxins
polyenes
plasma membrane not good target because similar to ours - they're quite toxic
46
antibiotics against ribosomes
aminoglycosides
| chloramphenicol
47
antibiotics against nucleic acids and what they do
rifamycins - interfere with transcription
| quinolones - interfere with folding
48
antibiotics against folic acid
sulphonamides
| trimethoprim
49
why can folic acid be a target of antibiotics
because lots of bacteria HAVE to make folic acid for themselves (cant use ready formed)
(we have to get folic acid ready formed from diet)
50
structure of peptidoglycan
polysaccharide backbone of alternating N-acetyl glucosamine and N-acetyl muramic acid (one we dont have)
Off N-acetyl muramic acid have short 4 peptide chain of 4 different peptides (varies between bacteria)
then pentapeptide bridge from 3rd amino acid to 4th of next chain (made of glycine)
51
why do bacteria use D amino acids
they alternate D and L in peptidoglyan to make it rigid - cant fold
52
biosynthesis of peptidoglycan
- precursors synthesised from intermediates from cytoplasm
- becomes immobilised on inner aspect of plasma membrane
- synthesis of building block continues
- when complete, building block transported to exterior
- linked to growing peptidoglycan chain
53
structure of building block of peptidoglycan
has carrier pyrophosphate lipid
| precursor has an extra D-alanine
54
cross-linking of peptidoglycan
transpeptidases (penicillin binding proteins) catalyse removal of extra D-alanine, glycine attaches
forms link from 3rd (L-lys) to 4th (D-ala)
55
vancomycin action
binds to D-ala D-ala so can't cross link --> stops cell wall synthesis
causes signal to bacteria to say something wrong with cell wall
bacteria makes catalytic (autolytic) enzymes to remodel cell wall
kills itself
56
where does most binding of vancomycin occur
to terminal D-alanine
57
basis of vancomycin resistance in enterococci
enterococci replaces D-ala with D-lac
still allows peptidoglycan wall to form (because terminal aa doesnt end up in wall)
enterococci has new transpeptidases that can use D-ala D-lac precursor
58
why are people scared of vancomycin resistant enterococci
because enterococci likes to swap genes with other bacteria
vancomycin only antibiotic effective for treatment of golden staph - if enterococci gave genes for vancomycin resistance to golden staph we'd be fucked
59
vancomycin intermediate resistant SA (VISA)
| trouble with treatment?
produce extra peptidoglycan - acts to soak up vancomycin
| trouble - can't give more vancomycin because toxic
60
how does penicillin work
transpeptidases (penicillin binding proteins) which recognise D-ala D-ala also bind to site on Penicillin G which resembles this D-ala D-ala
enzyme now bound there and can't do anything
cell wall synthesis disrupted, tries to remodel, kills itself
=bacteriacidal
61
beta-lactamase
enzymes produced by bacteria
destroy beta lactam ring - very bond that recongised by penicillin binding proteins
provide bacteria with resistance to beta-lactam antibiotics
62
two types of resistance to beta-lactams
beta-lactamase
| altered penicillin-binding proteins
63
methicillin resistant staph aureus
resistant to all penicillins and probably all beta lactam antibiotics
due to low affinity penicillin binding proteins encoded by one gene taken up by the bacteria
--> instant resistance
64
pneumococcus
new gradually accumulated mutations leading to new penicillin binding proteins leading to resistance to beta-lactam antibiotics
65
why does antibacterial spectrum of beta-lactam antibiotics vary
bacteria have different PBPs
accessibility of antibiotic to PBPs varies - gram negative have plasma membrane in the way
susceptibility of antibiotic to beta-lactamase varies
66
vancomycin effective on gram negative bacteria??
NO - because highly charged, lipid insoluble, can't cross membrane to get to peptidoglycan wall
67
pseudomonas aeruginosa
intrinsically produces a beta-lactamase that destroys penicillin, ampicillin, amoxicillin but NOT carbenicillin
68
what kind of surface do you need for clotting, provided by what
phospholipid surface
| platelets
69
what does normal endothelium produce
thrombomodulin, protein C and protein S - to change thrombin from activator to inhibitor
70
what does fibrinolysis involve
release of tissue plasminogen activator (tPA)
| binds to fibrin and activates plasmin, plasmin breaks down fibrin
71
thrombus
clotted mass of blood within unruptured cardiovascular system, attached to vessel wall at point of origin, during life (not death)
72
components of thrombus
platelets, fibrin, red and white cells
73
lines of Zahn
red and white layers containing RBCs(red) and platelets and fibrin (white)
let you discriminate between clots formed in live person vs after death
74
2 types of thrombosis
arterial - higher proportion of platelets(and fibrin) - WHITE
- endothelial dysfunction/damage
venous - higher proportion of blood cells (and fibrin)
- RED
- blood stasis and hypercoagulability
75
drugs used for arterial vs venous thrombi
arterial - aspirin
venous - warfarin
76
why to thrombi form
imbalance between factors that promote thrombogenesis and those that promote thrombolysis
77
Virchow's triad
abnormal endothelium
abnormal blood flow
abnormal blood coagulability
78
2 causes of abnormal endothelium
1 - loss of endothelium exposing collagen
| 2 - endothelial activation or dysfunction (pro-coagulation)
79
types of abnormal blood flow and what happens
turbulence, stasis, loss of laminar flow
"activates" endothelium
brings platelets into contact with vessel wall
allows activated clotting factors to accumulate
80
Causes of abnormal blood coagulability
1 genetic ="primary" - factor V Leiden
2 - Not genetic ="secondary"
oestrogen, cancer, smoking, obesity, age, MI, atrial fibrillation
81
4 things that can happen to a thrombus
1 dissolution - fibrinolysis
2 organisation, sometimes recanalisation
3 propagation (grow bigger)
4 embolisation
82
embolus
intravascular mass carried in blood stream to some site remote from origin
solid, liquid or gas
blocks the vessel it lodges in
83
2 main types of embolism
1 pulmonary embolus - from DVT, can be asymptomatic, cause transient hypoxia or sudden death
2 arterial thromboembolism - from atheroma or heart, block artery downstream, cause ichaemia and infarction
84
venous thrombosis and embolism risk factors, where do thromboemboli usually arise
risk factors: stasis and hyperoagulability - family, surgery, pill
usually arise in deep veins of legs or pelvis
85
arterial thrombosis and embolism usually involve what
turbulence and/or platelets adhering to a dysfunctional blood vessel surface (e.g. atherosclerosis, MI, atrial fib)
86
what do emboli in heart usually affect
| do they go to coronary arteries?
can affect any downstream organ
uncommon for emboli from heart chamber to go into coronary arteries
87
ischaemia
not enough blood (causing shortage of O2)
88
infarction
tissue death due to inadequate blood supply
89
hypoxia
not enough oxygen
90
hypoxaemia
not enough oxygen in blood
91
3 causes of ischaemia
local vascular narrowing or occlusion
increased demand for O that isnt met
systemic reduction in tissue perfusion (systemic shock)
92
3 possible causes of chronic ischaemia
stable atherosclerotic disease causing atrophy of lower limbs
renal artery stenosis causing renal atrophy
hyaline arteriolosclerosis causing "benign nephrosclerosis"
93
angina caused by chronic or acute ischaemia
acute
94
7 P's of ischaemia
```
pale
pulseless
painful
purple (cyanotic)
paralysed
paraesthetic (tingling)
perishingly cold
```
95
pale infarction
where there is no haemorrhage
due to blocked 'end artery'
MOST organs
wedge shaped tissue death
96
red infarction
where there is a haemorrhage into infarcted tissue
due to: dual blood supply (lungs, liver), collateral blood supply (intestine), venous infarction, reperfusion after necrosis (brain)
97
coagulative necrosis
'ghost' outlines of dead cells
| takes at least 4h
98
digoxin
cardiac glycoside - inhibits Na/K ATPase, Ca build up in cell, increase Ca release with each AP
shortens ventricular AP so heart pump more efficiently, risk of dysrhythmias
99
```
glycosides
TI
tissues effects
toxicity changes
half life
Vd
```
low TI
affects all excitable tissues
increased toxicity with decreased K, high Ca, renal impairment
40h - long - if get dose wrong takes ages to go down
large Vd - binds to muscle with high affinity
100
Badrenoceptor agonist
NA, A
dobutamine - selective B1 agonist
only for short term support of HF
101
phosphodiesterase inhibitors
amrinone
only for short term support of acute HF
102
two ways of B1 adrenoceptors decreased sensitivity
problem?
reduced R expression
impaired coupling - cells make B-arrestin to bind to R
problem - ionotropic drugs become less effective as R population falls
103
ionotropic heart drugs
only short term use - increase work on heart, symptoms progress, cardiac remodeling - BAD
104
3 main causes of HF
loss of myocardial muscle - contractility
pressure overload - afterload
volume overload - preload
105
4 drugs to reduce preload
venodilators - nitrates
diuretics - furosemide/frusemide
aldosterone R antagonists
aquaretics - vasopressin R antagonists
106
spironolactone
aldosterone R antagonist
| K sparing diuretic
107
3 drugs to reduce afterload and preload
ACE inhibitors
AT1 antagonist
Badrenoceptor antagonist
108
first line therapy for heart failure
dose titration?
ACE inhibitors
improves symptoms, delay progression
must titrate dose due to side effects
109
why Badrenoceptor antagonists for HF
SV increases reduces tachycardia, cardiac work
inhibits renin release
protects against R downregulation
110
drugs for symptomatic relief vs reduce mortality for HF
symptomatic relief: ionotropes, diuretics, venodilators
reduced mortality: angiotensin inhibitors, Badrenoceptor antagonists, aldosterone antagonists
111
mechanism of vasoconstriction in damaged vessel
collagen exposed on damaged vessel
platelets stick and activate
ADP and 5-HT released
5-HT vasoconstrictor
112
mechanism of platelet activation and adhesion
ADP from activated platelets causes aggregation and changing shape
granule contents secreted (5-HT, ADP)
mediators synthesised (thromboxane)
platelets aggregate and adhere via fibrinogen bridging between GPIIb/IIIa Rs
113
some stimuli for platelet activation
collagen
thrombin
thromboxane
ADP
114
two pathways to activation of thrombin
1 - extrinsic - damaged tissues release thromboplastin (something outside blood causing cascade)
2 - intrinsic - exposed collagen or other material (intrinsic to blood itself)
115
which coagulation cascade pathway faster, extrinsic or intrinsic to
extrinsic - because not as many steps
116
2 ways of controlling blood coagulation
antithrombin III - enzyme inhibitor
fibrinolysis by plasmin
117
cascade leading to fibrinolysis
protein C inactivates inhibitor of tissue plasminogen
| plasminogen --> plasmin
118
3 ways coagulation drugs act
on coagulation (fibrin formation)
platelets
fibrinolysis
119
3 types of drugs affecting fibrin formation
procoagulant drugs - vit K
injectable anticoagulants - heparin
oral anticoagulants - warfarin
120
heparin
enhances activity of antithrombin III
(antithrombin III inactivates Xa adn thrombin)
ONLY short term use
121
low molecular weight heparin
still not orally available, longer elimination half life, patient administration at home
122
APTT
activated partial thromboplastin time
used to monitor anti-coagulant effect of heparin (measure of intrinsic pathway)
123
adverse effects of heparin
haemorrhage
thrombocytopaenia (platelet deficiency)
osteoporisis
124
vitamin K essential for what
formation of clotting factors 2 7 9 10
125
warfarin
coumarin derivative - oral anticoagulant - inhibit vit K reductase (stops K reduction so cant gamma carboxylate factors )
126
warfarin - reversible?
| adverse effect?
reversal with vit K
haemorrhage
127
problem with warfarin
levels and anticoagulant effects v labile - strongly bind to plasma proteins(small change in pp levels (hypermetabolic state, liver damage) will get big change in relative amount of active drug)
128
what things can lead to increased/decreased warfarin activity
increased: vit K deficiency, hepatic disease, hypermetabolic state, drug interactions, competition for cyt p450
decreased: drug interactions, pregnancy
129
PT
INR
prothrombin time
International normalised ratio - ration of patient PT (rate clot forms after addition of Ca and tissue factor) to that of normal
ratio needed varies between patients - e.g. if 3, blood will take 3 times longer to clot than normal
130
dabigatran
| advantage and problem
new anticoagulant drug
can be administered in fixed doses
problem - no antidote
131
3 types of drugs affecting platelet activation and adhesion
ADP R antagonists
aspirin
glycoprotein IIb/IIIa R antagonists
132
clopidogrel
ADP R antagonist -
133
streptokinase
| problem?
fibrinolytic drug - activates plasminogen to plasmin
| antigenic so single use
134
alteplase
| better than streptokinase?
fibrinolytic drug - human recombinant tissue plasminogen activators (hrtPA)
non antigenic
clot selective
135
abciximab
GpIIb/IIIa antagonist
136
as increase HR what happens to diastole
shortens
137
valve incompetence
=regurgitation = leaking
-> volume overload
138
what causes heart murmur
turbulence around stenosed or incompetent valves
139
are LV changes reversible or irreversible in regurgitation and stenosis when symptoms arise
irreversible LV changes occur at time of regurgitation symptoms
aortic stenosis symptoms indicate time to intervene - LV changes regres
140
echocardiography
used in assessment of valvular heart disease
| can show LV changes before they're irreversible
141
interventions for valvular heart disease
valve replacements - metal, plastic, bioprostheses
valve repair (mitral)
balloon valvotomy
stent valves
142
mechanical vs bioprosthetic valve
mechanical lasts forever, but thrombus develop so have to be on warfarin
bioprosthetic - no need for warfarin but degrades in 15 yrs
143
commonest valve lesion
```
aortic stenosis (fibrosis, calcification)
results in pressure gradient across valve
```
144
aortic stenosis LV response
pressure overload
| concentric hypertrophy
145
murmur from aortic stenosis
crescendo decrescendo
146
causes of aortic regurgitation
aortic leaflets damaged - endocarditis, rheumatic fever
aortic root dilated so leaflets dont close - marfans syndrome, aortic dissection, collagen vascular disorders, syphilis
147
physiological result of aortic regurgitation
increase SV, increase pulse pressure
148
what happens with prolonged aortic regurgitation
eventual decompensation:
| LVDV increases, LV function decreases, LVSV increases - at this point irreversible
149
causes of mitral regurgitation
```
myxomatous degeneration (mitral valve prolapse)
ruptured cordae tendinae (flail leaflet)
infective endocarditis
MI
Rheumatic fever
collagen vascular disease
cardiomyopathy
```
150
mitral valve regurgitation initial compensations and prolonged decompensations
initially: increase EDV, increased SV, normal ESV
if prolonged: increase LV diastolic volume, reduced SV, increased LV systolic volume --> irreversible changes
151
resulting problems of mitral regurgitation on atria and pulmonary circulation
increase LA pressure and volume
atrial fibrillation - thrombus - risk of embolus
increased pulmonary venous pressure - congestion, oedema, hypoxia
increased pulmonary artery pressure - pulmonary hypertension
152
mitral regurgitation murmer
pansystolic (constant)
153
mitral stenosis cause
rheumatic fever
154
resulting problems from mitral stenosis
increase LA pressure and volume, atrial fibrillation, thrombus in LA - embolism, increased pulmonary venous and artery pressure
155
hypertrophy
an increase in the size of cells resulting in increase in size of organ
156
```
hypertrophy:
no. of cells
production of intracellular structures
nucleus
type of cells
stimuli
```
```
same no.of cells
increased
increases in size, can change shape
permanent cells
mechanical stress, GFs, hormones
```
157
result of transcription in striated muscle in response to GFs
induction of embryonic/foetal genes - increase mechanical performance and decrease work load
increase synthesis of contractile proteins - increase mechanical performance
increase production of GFs
158
hyperplasia
increase in number of cells
159
```
hyperplasia:
stimuli
phys or path
type of cells
same time as hypertrophy?
```
stem cells stimulated by hormonal or GFs
phys and path!
labile cells (already with active stem cell population) or stable cells
often same time
160
metaplasia
reversible change in which one adult cell type is replaced by another adult cell type
161
metaplasia:
where occurs
stimuli
phys or path
frequently at junctions between different epithelial types
stimuli- altered environment
phys or path!
162
example of physiological metaplasia
onset of menarche - swelling of tissues exposes endocervical mucosa to acidic vaginal environment - simple columnar epithelium to stratified squamous epithelium
163
example of pathological metaplasia
Barrett oesophagus: gastro-oesophageal reflux disease - bile acids induce metaplasia of oesophageal stratified squamous epithelium to intestinal type with goblet cells
164
neoplasia
unregulated cell division that can now occur in absence of stimulus
due to genetic mutation
can be benign or malignant
165
"premalignant"
benign, but often can confer an increased risk for malignancy - the more replications you do the more likely you are to pick up a mutation
166
atrophy
a decrease in cell or organ size
167
atrophy
when does it occur (stimulus)
when is reversible
occurs when normal growth stimulus decreased or lost
| reversible if not accompanied by cell death and fibrosis
168
only cause of hypertrophy that can kill you
| how does it happen
myocardial hypertrophy
stretch on myocytes directly causes transcriptional changes
169
normal heart weight women and men
women
170
microscopic characteristics of myocardial hypertrophy
enlarged rectangular nuclei
bi-nucleated myocytes
increased connective tissue
171
nutmeg liver
result of left cardiac failure
| mixture of haemorrhage and necrosis
172
two causes or aortic valvular disease
congenitally bicuspid aortic valve
| dystrophic calcification
173
two causes of mitral valvular disease
myxomatous valve aka 'floppy' - causes prolapse, can cause mitral regurgitation - genetic or related to connective tissue disease
fibrosed mitral valve - from rheumatic valve disease
174
rheumatic fever
| rheumatic heart disease
streptococcus pyogenes
immune response to strep pyogenes - Ab that looks like something that wants to attack endocardium
can effect all valves - stenosis or regurgitation
most common cause of mitral stenosis
175
infective endocarditis
bacteria in blood - end up with collections of bacteria on valves themselves
176
equity vs equality
equity - ensuring everyone has equal outcome
equality - giving everyone the same thing
177
social determinants of health
```
social gradient
stress
early start
social exclusion
work
unemployment
social support
addiction
food
transport
```
178
roles of kidney
regulation of water and electrolyte balance
endocrine
excretion of endogenous waste
extretion of exogenous compounds
179
where does filtration, secretion and reabsorption occur along nephron
filtration - glomerulus
secretion - proximal tubule
reabsorption - proximal tubule, loop of henle, distal tubule, collecting duct
180
where is most of NaCl reabsorbed
proximal tubule
181
where is most of water reabsorbed
loop of henle
182
where is K+ reabsorbed and secreted
reabsorped - proximal tubule, distal tubule
| secreted - collecting duct
183
three types of drugs with therapeutic actions on kidney
diuretics
drugs that affect urine pH
drugs that alter secretion of organic molecuels
184
action of diuretics
decrease Na and Cl reabsorption = increase NaCl excretion = secondary water excretion
185
4 classes of diuretics
loop diuretics
thiazide
potassium-sparing
osmotic
186
loop diuretics mechanism of action
act on thick ascending loop of henle
| inhibit NA/K/2Cl carrier into cells
187
loop diuretics
absorption
plasma protein bound?
duration of action
well absorbed - onset
188
loop diuretics adverse effects
K+ loss from distal tubule - hypokalaemia
H+ excretion - metabolic alkalosis
reduce extracellular fluid volume (elderly) - hypovolaemia and hypotension
so normally given with K+ supplement
189
loop diuretics clinical uses
salt and water overload in acute pulmonary oedema, chronic HF, liver cirrhosis, renal failure
hypertension
190
thiazide diuretics
powerful?
two types
moderately powerful - less effect than loop diuretics
"true" thiazides and thiazide-like
191
thiazide diuretics mechanism of action
act on distal convoluted tubule
| inhibit Na/Cl cotransporter
192
thizide diuretics
oral availability
max effect
duration
orally active
max effect 4-6h (slower absorption and onset)
duration 8-12h (longer duration)
193
thizide diuretics adverse effects
K+ loss from collecting ducts (same as loop diuretics - K+ supplement)
increased plasma uric acid (inhibition of tubular secretion of uric acid)
indapamide - less effects
194
thiazide clinical uses
hypertension
| severe resistant oedema (in combo with loop diuretic)
195
potassium-sparing diuretics
why used
where do they act
used in combo with K+-loosing (loop and thiazide) diuretics to prevent K+ loss e.g. in patients with HF
act on collecting tubule and ducts
196
spironalactone
Potassium-sparing diuretic
aldosterone R antagonist - so get reduced activation of Na+ channel and reduced stimulation of Na+ pump transcription (actions of aldosterone)
197
spironolactone:
oral availability
onset
half life
```
orally active
slow onset (due to its action on transcriptional changes)
short half life (10mins) but metabolite long half life (16h) =long duration
```
198
spironolactone:
adverse effects
clinical use
hyperkalaemia
GIT upset
combo with loop or thiazide diuretics
HF
hyperaldosteronism
199
triamterene and amiloride
K+-sparing diuretic
block luminal sodium channels in collecting tubules and ducts
inhibit Na+ reabsorption, inhibit K+ secretion
200
triamterene and amiloride
absorption
onset
duration
triamterene - well absorbed, 2h onset, duration 12-16h
amiloride - poorly absorbed, slow onset, duration 24h
201
```
osmotic diuretics
pharmacological 'action'
reabsorbed?
main effect where
action
```
```
pharmacologically inert
filtered but NOT reabsorbed
main effect on water permeable parts of nephron - proximal tubule, descending limp of loop, collecting tubules
reduce passive water reabsorption
only small reduction in Na+ reabsorption
```
202
osmotic diuretics clinical uses
raised intracranial or intraocular pressure, prevention of acute renal failure
203
3 types of compounds with adverse effects on kidney
heavy metals
antibiotics
antineoplastic agents
204
why kidney susceptible to toxicity
receives 25% of blood supply
substances may be concentrated
kidney able to carry out metabolism - reactive species
205
mechanisms of direct toxicity or via metabolite
ROS - drug metabolism can lead to reactive O species - this may be why drug damaging, not actual drug
interfere with Ca metabolism
protein/enzyme building - inhibition of enzyme function, initiation of immune response (body thinks its foreign)
206
mercury
mechanism of toxicity
damage primarily where
direct toxicity and vasoconstriction
binds to thiol groups in proteins
damage primarily in proximal tubule
207
gentamicin
what used for
site of action
mechanism of action
Gram neg infections
site of action apical membrane of proximal tubule
binds phospholipids, changes Ca intracellular, impairs mitochondrial respiration, cell injury
208
gentamicin toxicity greater in patients with :
problem with elimination
existing renal disease, or taking other potentially nephrotoxic drugs
elimination is renal - nephrotoxicity can improve excretion - vicious cycle
209
antineoplastics - cisplatin :
what is it
causes what
cytotoxic anticancer agent - treatment of prostate tumours
| causes dose-limiting nephrotoxicity
210
cisplatin mechanism of nephrotoxicity
activated inside cells, forms reactive species, binds to neucleophilic cell components in distal tubule and collecting ducts
211
total cholesterol/HDL cholesterol ratio
increased ratio - increased heart disease risk
212
LDL vs HDL
LDL bad - increases risk of heart disease
HDL - good - decreases risk of heart disease
213
cholesterol hydrophobic or philic
NEITHER LOL
| amphipathic
214
4 fates of cholesterol made in liver
transport
bile acids
steroid hormones and vit D
membranes
215
cholesterol made in liver for transport
assembled into VLDL (very low density lipoprotein) for transport to tissues
216
role of cholesterol in membrane
optomise mammalian membrane fluidity - fits into kinks of unsaturated fatty acyl chains to make membrane less fluid
217
membrane rafts
higher levels of cholesterol, glycolipids and sphingolipids - little regions where membrane v rigid
218
cholesterol synthesis
```
acetyl-CoA generated in mitochondria
acetyl CoA converted to HMG CoA
HMG CoA converted to mevalonic acid
mevalonic acid converted to cholesterol
cholesterol feeds back to inhibit HMG CoA reductase (regulatable step)
```
219
HMG CoA reductase
converts HGM CoA into mevalonate
220
how is cholesterol carried around body
esterify cholesterol to make it more hydrophobic - incorporate into lipoproteins
221
chylomicrons
formed in intestinal mucosa
package triacylglycerol and cholesterol-ester from gut and take to tissue
remnants taken to liver
222
VLDL
takes TAG and cholesterol-ester stored/generated in liver to tissue
remnants taken to liver
223
LDL
some cholesterol-ester transferred from VLDL to LDL - LDL not taken up by liver as well so continues to circulate to supply cholesterol-ester to tissues
224
HDL
scavenger - takes cholesterol from membranes an cells to liver for bile salt formation
acts on macrophages to stop them becoming foam cells
225
apolipoprotein
protein part of lipoprotein
| involved in structure, uptake and activation of lipoprotein lipase
226
lipoprotein lipase
breaks down TAG in lipoproteins into free fatty acids
227
Apo-B100
apolipoprotein in LDL and VLDL - structure and uptake
228
Apo-CII
apolipoprotein in VLDL and chylomicrons - activates lipoprotein lipase
229
ApoA1
| where made
precursor of HDL
| made in liver and intestine
230
SR-B1 Receptor
scavenger receptor in liver - HDL binds to transfer cholesterol-ester
231
ACAT
in liver - helps VLDL form
232
LCAT
in plasma - helps HDL scavenge cholesterol from membranes
233
dyslipidaemia
disorders of LP metabolism
234
hypercholesterolaemia
increase total (free and esterified) cholesterol in blood - above 6.2mM
235
hypertriglyceridaemia
increase blood triglycerides
236
high circulating LDL =
higher risk of heart disease
237
process of LDL causing atherosclerosis
oxidised LDL accumulates in artery wall
endothelial cells react by displaying adhesion molecules
WBCs (monocytes and T cells) invade and secrete cytokines
macrophages appear - take up modified LDLs with scavenger receptors
macrophages engorged with cholesterol =foam cells
fibrous tissue develops to trap foam cells
foam cells produce tissue factor - can lead to blood clot on rupture of plaque
238
how reduce serum cholesterol levels
block HMG-CoA reductase (rate limiting enzyme in cholesterol synthesis)
239
statins
competitive inhibitors of HMG-CoA reductase
240
ischaemic heart disease definition
imbalance between myocardial O supply and demand
241
acute and chronic forms of ischaemic heart disease
acute - unstable angina, MI, sudden cardiac death
chronic - stable angina, chronic myocardial ischaemia
242
factors limiting coronary blood flow
perfusion pressure
coronary vascular resistance (coronary artery atherosclerosis)
external compression - vessels of subendocardium particularly get squeezed between muscles and pressure in ventricle
intrinsic regulation (endothelium and local metbolites)
243
non-transmural infarcts
just subendocardium
244
transmural infarct
subendocardium through whole wall
245
why is endocardium spared?
O from ventricle lumen diffuses
246
vascular supply of heart:
- anterior wall and 2/3 septum
- lateral wall
- posterior wall
LAD
LCX
PD
247
MI caused by
acute plaque event - plaque forming an occlusive thrombus
248
angina/reversible injury
no macroscopic or microscopic changes
intracellular changes
rapid loss of contractility
249
minutes -hours of MI
irreversible injury - disruption of cell membrane (sarcolemma)
250
what does disruption of sarcolemma cause
leaking of cardiac proteins (troponin, CK)
leaking of current - STEMI, NSTEMI, myocardial irritability (more likely to spark arrhythmia)
251
STEMI
ST elevation MI - severe ECG change - due to transmural infarct
252
NSTEMI
non-ST elevation MI - due to non-transmural infarct - less severe ECG changes
253
hours of MI
irreversible injury
cell death
haemorrhage
oedema
254
12-24h post MI
contraction band necrosis, neutrophil invasion (acute inflammation)
255
1-3 days post MI
acute inflammation - heavy neutrophil infiltration, necrosis
256
peak of destruction of heart muscle in MI
troponin peak - 3 days
257
3-7 days post MI
end of acute inflammation, start of early granulation - macrophages ingest dead monocytes, fibroblasts and vessels appear, collagen at 5-6 days
258
3 ways to rupture wall
1 - rupture of free ventricular wall - blood into pericardium "haemopericardium", compresses heart until stops "cadiac tamponade"
2 - rupture of papillary muscle
3 - rupture of IV septum
2 and 3 --> cadiogenic shock = acute severe cardiac failure
259
1-8 weeks post MI
vascular granulation tissue becomes fibrous granulation tissue
collagen - flexible and may stretch (aneurysm = infarct expansion) causing thinning of wall
260
8 weeks post MI
fibrosis/scar - fixed
261
stable angina vs unstable angina presentation
stable - chest pain on exertion, goes away with rest
unstable - chest pain, may occur at rest
262
stable angina due to
atherosclerotic narrowing of vessel, endothelial dysfunction, symptoms at 70% stenosis
263
unstable angina due to :
| resolves?
acute plaque event, coronary artery thrombosis
RESOLVES - no irreversible damage
264
chronic myocardial ischaemia
small areas of subendothelial ischaemia, patchy myocyte necrosis and replacement by fibrosis
265
sudden cardiac death
unexpected death in short time period (
266
cardiac arrest
sudden cessation of cardiac output and effective circulation
usually precipitated by ventricular fibrillation and or ventricular asystole
267
3 examples of aminoglycosides
gentamicin, tobramycin, amikacin
268
mechanism of aminoglycosides action
two stag system: at low concentrations: binds to particular site on ribosome, causes abnormal reading of genetic code,incorrect proteins made,
cell wall weakene
higher concentrations get in - then get total ribosomal blockade
269
way bacteria get around aminoglycosides
1. enzymatic covalent modification - add extra charge groups
2. ribosomal mutation (aminoglycoside cant bind)
3. active eflux
4. modified outer membrane - reduced entry
270
4 mechanisms of resistance to antimicrobial agents
1. drug inactivation
2. altering the target of drug action
3. reduce access of drug to target
4. failure to activate inactive precursor of drug
271
metronidazole - action
strictly on anaerobes
nitroreductase converts to active form
272
3 things apart from infection antibiotics important for
surgical procedures
malignancies (protect them when immune system down)
immunodeficiencies, cystic fibrosis
273
where does antibiotic resistance originate
1. innate resistance - (gram neg for vancomycin, enterococci for sulfonamides (no folic acid synthesis))
acquired - change in bacterial phenotype reflecting altered genotype due to:
mutation
acquisition of new genes via horizontal transfer
274
transfer of genes between bacteria occurs by:
transformation
phage-mediated transduction
plasmid-mediated conjugation
275
process of transformation
- lysis of cell or DNA release
- uptake into competent cell (must be closely related)
- homologous recombination
276
what is necessary for transformation to occur
- DNA has to be methylated in a particular way so its not restricted
- homologous recombination
so can only occur between closely related bacteria
277
lysogenic and lytic cycle of bacteriophages
lysogenic - temperate phage - replicates harmlessly with bacteria
lytic - virus replicates in bacteria, makes lots of copies, kills bacteria
278
largest cause of antibiotic resistance
harmless comensals - every time we take an antibiotic they want to be resistant to not get removed
mutations make harmless bacteria pathogenic
279
transduction
rarely an abnormal phage produced: phage that has taken up bacterial DNA
Then goes and transfers this DNA to another bacteria by infecting it
280
plasmid mediated conjugation
plasmid from one bacteria to another
plasmid encodes cytoplasmic bridge - allows transfer of DNA
can occur between entirely unrelated bacteria
281
3 factors that favour the development of resistance
evolutionary advantage:
vast numbers
rapid growth
promiscuity
282
3 factors that favour emergence /persistence of AMR
way antimicrobials act - selective pressure to become resitant
power of natural selection
283
muli-resistance plasmid
BAD because with one genetic step - organisms go from being susceptible to all to being resistant to like 12 antibiotics
284
why is resistance increasing
using antimicrobials promotes resistance
285
time for bacteria to develop resistance
getting shorter! bacteria getting better at getting resistant
286
MIC
measure of susceptibility - test of bacteriostatic
287
MBC
minimum bactericidal concentrations
288
E-test strip
MIC by diffusion - where the oval stops is MIC
289
considerations regarding choice of antibiotic
```
antimicrobial spectrum
efficacy
route of administration
route of excretion
pharmacokinetics/dynamics
availability
cost
```
290
common prescribing errors
1. prescribing an antimicrobial when not needed
2. prescribing wrong antimicrobial
3. using correct one inappropriately - wrong dose, course, route, patient
291
rationale for antibiotic combinations
```
temporary measure when unknown cause
delay emergence of resistance
mixed infections
reduce toxicity
synergistic effect
```
292
antagonism in antibiotic combinations - e.g.
bactericidal with static
293
mechanisms of synergy
1. block sequential steps of metabolic pathway
2. inhibit enzymatic degradation
3. enhance antimicrobial uptake by bacterial cell
294
synergy example - blocking steps of metabolic pathway
sulphonamides with trimethoprim in folic acid synthesis
| =co-trimoxazole
295
synergy example - inhibit enzymatic degredation
beta-lactam + beta-lactamase inhibitor
| amoxycillin + clavulanate
296
synergy example - enhance antimicrobial uptake
beta-lactam + aminoglycoside
297
4 mechanisms of antagonism
- inhibition of bactericidal activity by bacteriostatic
- induction of enzymatic degradation
-competition for binding to same target
inhibition of target
298
Jawetz's laws
bacteriostatic + bacteriostatic = additive or indifferent
bacteriostatic + bactericidal = antagonistic
bactericidal + bactericidal = synergistic
299
dyslipidaemia
abnormal lipid profile
300
are "normal " total cholesterol levels necessarily healthy?
nope - its ratio of LDL to HDL
as ratio increases, risk of adverse events increases
301
treatment for dyslipidaemia
1. establish fasting plasma lipid profile for diagnosis
2. consider cardiovascular status and risk factors
3. treat secondary causes (obesity, diabetes)
4. manage modifiable risk factors
302
which fats contribute mostly to cholesterol
saturated and trans
303
rate limiting step in cholesterol synthesis
HMG-CoA reductase
| cholesterol has negative feedback on it
304
4 fates of cholesterol
1. stored in liver for export in VLDL
2. bile acids
3. steroid hormones and vit D synthesis
4. membrane synthesis adn maintenance
305
chylomicrons
transport dietary triglycerides and cholesterol
306
cholesterol transport and metabolism
- dietary chol into chylomicrons, from liver in VLDL
- circulates to tissues - broken down by lipoprotein lipase in capillaries and tissues - hydrolysis of triglycerides, release of FFAs - energy for tissues
- chylo and VLDL remnants taken up by liver or converted to LDL
307
HDL
reverse cholesterol transport: when liver needs cholesterol for bile acids, increase HDL removes cholesterol from tissues and takes back to liver
308
LDL
bad - contains apolipoprotein B-100 - can transport lipids into artery walls
309
statins
HMG-CoA reductase reversible competitive inhibitors
| - primary treatment for hypercholesterolaemia
310
action of statins
- decrease synthesis of mevalonic acid, so reduces cholesterol synthesis in liver
- so compensatory upregulation of LDL Rs - so increase LDL clearance
- increase levels of HDL
- decrease TG
311
statin ceiling effect
increasing dose has little effect
312
problem with statin compliance
perceived lack of efficacy
313
precautions with statins
- common cytP450 - drugs and grapefruit juice
- statin levels increased by some drugs and decreased by others
- elevation of aminotransferase (liver damage)
- increase creatine kinase (muscle pain)
314
statins in pregnancy?
no - impaired fetal myelination
315
bile acid sequestrants/resins
bind bile acid, preventing gut absorption - increase bile excretion
- increase demand for bile acid synthesis - upreg of hepatic LDL Rs, removal of LDL from plasma,
316
ezetimibe
```
specifically inhibits cholesterol absorption in intestine - binds sterol transporter
lowers LDL
(but dietary chol doesnt contribute much to circulating chol)
```
317
when ezetimibe used
used as adjunct to statin, or in statin-intolerant patients
318
nicotinic acid/niacin
mechanism unclear:
- decrease VLDL secretion from liver
- reduce plasma LDL and triglyc
- increase LDL R
- increase HDL
- lowers potentially atherogenic lipoprotein (a)
319
lipoprotein (a)
formed from LDL, found in plaques, inhibits thrombolysis
320
nicotinic acid/niacin widely used?
not really - bad side effects (reduced with lengthy use, but lack of patient compliance)
321
fibrates
treat hypertriglyceridaemia
- agonist at PPA nuclear R - increases synthesis of lipoprotein lipase (LPL)
- increase lipolysis of lipoprotein triglyceride
- reduction in plasma triglyc
(variable effects on LDL)
- increase HDL
322
fish oils
treatment of hypertriglyceridaemia:
- omega 3 fatty acids
- reduce triglyc and VLDL
- increase HDL
323
stable angina
chest pain wiht exertion, stress
| arteries/arterioles already dilated, stiff walls - can't dilate to meet oxygen demand
324
ways to increase O2 supply
- dilate coronary arteries
| - reduce HR - heart longer in diastole, coronary arteries longer to fill
325
ways to decrease O2 demand
- decrease CO
- reduce preload (dilate veins, reduce venous return)
- reduce afterload (dialate arterioles, decrease resistance)
326
4 drugs to treat stable angina
1. nitrates - preload
2. Ca channel blockers - afterload, myocardium
3. B-adrenoceptor antagonists - HR/SV
4. ivabradine - HR
327
nitrates mechanism of action
- drug undergoes biotransformation (prodrug)
- release NO
- stimulats guanyate cyclase in vascular smooth muscle
- GTP to cGMP
- dephosphorylates myosin light chain
- relaxation
328
short and long acting nitrates
short - glyceryl trinitrate (GTN)
| long - isosorbide dinitrate (prodrug to isosorbie-5-mononitrate)
329
GTN - 1st pass metabolism, route of administration (3 types)
1st pass metabolism - inactive metabolite so not oral
- sublingual for acute attack
- transdermal for prophylaxis
- IV for emergency
330
isosorbide dinitrate
| 1st pass metabolism, rout of administration
prodrug!
| oral for anticipation of effort or prophylaxis
331
GTN and viagra
GTN - increases cGMP
viagra - phosphodiesterase inhibitor (phosphodiesterase breaks down cGMP) - would get massive increase in cGMP - fatal BP drop
332
GTN and tolerance
has tolerance! - drug free period required
- depletion of tissue thiols required or NO production from GTN
- increase sensitivity to vasoconstrictors
333
verapamil and nifedipine
L-type calcium channel blockers for heart disease
334
verapamil ad nifedipine vascular or cardiac selective
verapamil - non-selective
| nifedipine - vascular selective
335
adverse effects of verapamil
never taken with
(ca channel blocker)
flushing, headache, oedema, bradycardia, AV block
never taken with beta blocker
336
adverse effects nifedipine
vascular selective ca channel blocker
| flushing, headache, oedema, hypotension, reflex tachycardia
337
selective B1 antagonist
atenolol
338
ivabradine
"pure" HR reduction:
| - "specific" selective inhibition of inward Na-K If(ifunny) current in SA node
339
when ivabradine used in patients
patients with IHD, LV dysfunction, HR>70bpm
340
variant angina
coronary vasospasm at rest
341
treatment for variant angina
relieve coronary vasospasm with short acting nitrate
| prophylaxis with dihydropyridine ca channel blocker
342
give beta blockers to variant angina patient??
NO- alpha-adrenoceptor mediated vasospasm may be worse if B2 coronary dilation blocked
343
treatment for unstable angina
as for stable, add aspirin
344
naming of parietal pleura
cervical
mediastinal
costal
diphragmatic
345
costodiaphragmatic recess
where parietal pleura touches parietal pleura
346
does pleural cavity peak out of thoracic cage anywhere?
yes - either side of vertebral column where T12 attaches
347
why do we have a pulmonary ligamnet
so pulmonary veins can expand in times of hypercapacitance
348
pyothorax
puss in the pleural cavity
349
pain from visceral vs parietal pleura
visceral pleura - dull ache b/c only visceral nerve supply
| parietal - V PAIN - somatic nerve supply
350
where does trachea begin
neck at C6
351
RMB different to LMB?
RMB shorter, wider and more vertical
352
muscle making up posterior aspect of trachea
trachealis muscle
353
each segmental bronchus supplies a
bronchopulmonary segment
354
right apical segment lower lobe (bronchopulmonary segment)
bronchopulmonary segment something aspirated when patient on back will likely go (first segmental bronchus that comes off directly posteriorly)
355
right lung fissures and lobes
3 lobes and 2 fissures
356
left lung fissures an lobes
oblique fissure, 2 lobes
357
lingular
on left lung - functions as middle lobe (same no. of bronchopulmonary segments)
358
position of veins and bronchi at hilum
veins - anterior and inferior
| bronchi posterior
359
two branches of Right main pulmonary artery
pulmonary artery
| right uper love branch of pulmonary artery
360
two branches of RMB
```
bronchus intermedius (continuation of RMB)
right upper lobe bronchus
```
361
lymphatics in lung
superficial (just beneath visceral pleura) and deep (within tissue of lung)
362
first port of call for superficial and deep lymphatics of lung
hilar lymph nodes
363
series of lymph nodes from lung
hilar
bronchopulmonary
tracheobronchial
bronchomediastinal
364
more xrays vs fewer xrays, e-density, black or white
more xrays get through, high e-density - white
| less x rays through, low e-density - black
365
when can interface in x ray be seen
if tissues of different e-densities next to each other
366
requirements for erect PA (posterior to anterior) CXR
- full inspiration
- PA
- scapulae moved away from chest wall
- erect
- straight
367
how do you make sure someone is straight on CXR
sternal notch line up with spinous processes
368
how do you know if full inspiration on CXR
must see 7 anterior ribs in mid clavicular line
369
how do you know if heart enlarged on CXR
heart diameter 50% or less of inside diameter of rib cage
370
CXR divided into what zones
upper middle lower
lower 1/2 or lower zone is base
upper 1/2 of upper zone is apex
371
air or fluid in pleural spaces goes where
fluid - sinks to bases
| air - rises to apices
372
hydrothorax
fluid accumulation in pleural cavity
373
hydropneumothorax
air and fluid in pleural cavity
374
meniscus in CXR
fluid in pleural cavity
375
what happens when xrays hit film (what chemically are they doing)
convert silver-halide crystals to silver
376
does CT use film?
| how take CT
NO - radiation detector
| spiral scan
377
hounsfeild units
absolute measure of xray attenuation
| digital "grey scale" rather than film density
378
CT spatial and contrast resolution compared with X-radiography
poorer spatial and better contrast than X-ray
379
what is the orientation of a CT slice
from feet up, toes up
380
reconstruction orientation : axial coronal and sagittal
axial - from feet up
coronal - from front
sagittal - from left
381
post processing
after data acquired and patient gone home - make things better looking and easier to understand
382
cons of CT
```
ionising radiation (dramatic icnreased exposure)
expensive
```
383
disorders of haemoglobin type of genetic inheritace
autosomal recessive
384
alpha-like globin genes:
- where located
- what are they
- chromosome 16
| - alpha 1 and 2, pseudo zeta and alpha (not expressed), zeta
385
beta-like globin genes
- where located
- what are they
- chromosome 11
| - beta, deta, pseudo beta, G gamma and A gamma(two versions, only differ by one base), epsilon
386
LCR
locus control region - essential for regulation fo B-like globin genes
387
embryonic Hbs
zeta2epsilon2
zeta2gamma2
alpha2epsilon2
388
fetal Hb
alpha2gamma2
389
HbA
alpha2beta2
390
HbA2
alpha2delta2
391
time course of Hbs in life
- first 3 months - embryonic and foetal
- 2nd trimester - fetal, some HbA
- last trimester to birth - cross over of fetal and HbA
392
alhpa and beta thalassaemias
decreased synthesis of one or more globin chains
393
structural variants haemoglobinopathies
altered globin polypeptide without altering rate of synthesis (e.g. sickel cell)
394
types of haemoglobinopathies
- alpha and beta thalassaemias
- structural variants
- hereditary persistence of fetal haemoglobin
395
what results from thalassaemias
imbalance in relative amounts of alpha and beta chains - get homotetramers instead of heterotetramers
396
alpha thalassaemias mostly caused by what mutation
large deletions
397
beta thalassaemias mostly caused by what mutation
point mutations
398
B+ and B0
```
B+ = reduced B
B0 = no B
```
399
two issues in thalassaemia
homotrimers form aggregates, accumulate and precipitate in RBCs causing damage, RBCs destroyed prematurely
ineffective erythropoiesis/ dyserythropoiesis leads to breakdown of erythroid precursors in bone marrow
both lead to haemolytic anaemia
400
pathophysiology of untreated beta thalassaemia
liver enlargement - goes back to making RBCs
- bone marrow expands - trying to make more RBCs
- splenomegaly - abnormal RBC breakdown
401
microscopic features of RBCs in B-thalassaemia
microcytic, hypochromic
| tear drop shaped (due to aggregates of alpha)
402
usually more or less HbA in B-thalassaemia
more - compensatory mechanism
403
treatment of B-thalassaemia
- transfusions
- splenectomy - prefer to remove before it ruptures
- chelation therapy - remove iron
404
alpha-thalassaemias
- which Hbs it effects
- what homotetramers produced
- effects fetal and adult Hbs
| - homotetramers that are less soluble
405
why is carrier genotype important
south east asian - 1/4 chance of hydrops fetalis (4 alpha genes absent)
whereas mediterranean mutation - produce all alpha-/alpha-
406
what kind of mutation causes sickle cell disease, what happens
point mutation
--> polar residue to hydrophobic one, forms aggregates - forms sickle cell shape
blocks capillaries
407
treatment of sickle cell
hydroxyurea
408
can you detect sickle cell with MVC/MCH
no - may be normal or reduced, need to look for abnormal cells
409
compound heterozygotes
individuals with two different mutations (e.g. B-globin and sickle cell , or two different B-globin mutations
410
double heterozygote
B-globin and alpha-globin mutation
411
gene therapies for thalassaemia
- alter imbalance of chains (e.g. knock down alpha chains in beta-thalassaemia
- epigenetic modificcations to induce HbF
412
why is there a high rate of alleles for haemoglobinopathies in some parts of the world
carriers have some resistance to malaria
