Clinical Sciences Flashcards
(349 cards)
1
Q
Bohr effect
A
increasing acidity or pCO2 means O2 binds less well to Hb
2
Q
Chloride shift
A
CO2 diffuses into RBCs, +H20 → (via carbonic anhydrase) HCO3- + H+. H+ combines with Hb, HCO3- leaves RBC, Cl- replaces it
3
Q
Haldane effect
A
increase pO2 means CO2 binds less well to Hb (opposite of Bohr effect)
4
Q
Lung compliance changes
A
increases with age, emphysema.
Reduces with pulm oedema, fibrosis, pneumonectomy, kyphosis
5
Q
What are involved in respiration control
A
central regulatory centres
Central and peripheral chemoreceptors
Pulmonary receptors
6
Q
Where are the central regulatory centres
A
medullary respiratory centre, apneustic centre (lower pons), pneumotaxic centre (upper pons)
7
Q
What are the central and peripheral chemoreceptors stimulated by
A
central (low pH in ECF stimulates respiration)
peripheral (carotid + aortic bodies, responding to pCO2, pH, lesser extent low pO2)
8
Q
What are the pulmoary receptors
A
stretch receptors (Hering-Bruer reflex - lung distension → lowered resp rate)
irritant receptor (leading to bronchoconstriction)
juxtacapillary receptors (stimulated by microvasculature stretching)
9
Q
What happens to pulmonary arteries with hypoxia
A
as paO2 reduces, pulmonary artery vasoconstriction occurs (diverts to better aerated areas to improve exchange)
10
Q
Pneumocyte types
A
Type 1 - thin squamous cells, cover 97% of alveolar surface.
Type 2 - cuboidal, secrete surfactants, develops from 24wks gestation, adequate surfactant from 35wks (prematures risk resp distress syndrome), can differentiate into Type 1 pneumocytes during lung damage.
Club cells: (clara cells) non-ciliated, dome-shaped cells in bronchioles. Protect against deleterious effects of inhaled toxins + secretes glycosaminoglycans, lysozymes
11
Q
Stages of cardiac action potential
A
Rapid depolarisation with rapid Na influx → Early repolarisation with K efflux → Plateau with slow Ca influx → Final repolarisation with K efflux → Restoration of ionic concentration with resting potential restored by Na/K ATPase
12
Q
Slowest to fastest cardiac conduction velocity
A
Atrial conduction 1m/s, AV node 0.05m/s, Purkinje fibres 2-4m/s (fastest)
13
Q
Where is renin from
A
renal juxtaglomerular cells
14
Q
What triggers renin
A
reduced renal perfusion, hypoNa, SNS stimulation.
15
Q
What does renin do
A
Angiotensinogen → angiotensin I
16
Q
Adrenal cortex zones and what they produce
A
GFR-ACD
17
Q
What happens to angiotensin I and where
A
Angiotensin I converted by ACE in lungs to angiotensin II
18
Q
What does angiotensin II do
A
vasoconstriction of vascular smooth muscle (raises bp) + efferent arteriole of glomerulus (increases filtration fraction, preserves GFR), stimulates thirst (via hypothalamus), stimulates aldosterone + ADH release, increases proximal tubule Na/H activity (increases Na reabsorption)
19
Q
What causes aldosterone secretion
A
angiotensin II
hyperK
ACTH.
20
Q
What does aldosterone do
A
Causes Na retention in exchange for K/H in DCT
21
Q
Stages of cell cycle
A
G0 - resting
G1 - increase in size, determines length of cell cycle, influence of p53, regulated by cyclin D/CDK4, CDK6, Cyclin E/CDK2 regulates transition from G1 to S
S - synthesis of DNA, RNA, histone, centrosome duplication, Cyclin A/CDK2 active
G2 - cells continue to increase in size, Cyclin B/CDK1 regulates transition from G2 to M
M - mitosis, shortest phase
22
Q
Mitosis phases
A
Prometaphase (nuclear membrane breaks down)
metaphase (chromosomes align at middle of cell)
anaphase (chromosomes separate and move to opposite ends)
telophase (chromosomes arrive at opposite ends)
cytokinesis (actin-myosin complex in centre of cell contracts → pinching into two daughter cells)
23
Q
Rough endoplasmic reticulum function
A
translation, folding of new proteins, manufacture of lysosomal enzymes, site of N-linked glycosylation. Extensive in pancreatic cells, goblet cells, plasma cells
24
Q
Smooth ER function
A
steroid, lipid synthesis. Extensive in adrenal cortex, hepatocytes, testes, ovaries
25
Golgi apparatus function
modifies, sorts, packages molecules destined for secretion
Addition of mannose-6-phosphate designates transport to lysosomes
26
Mitochondrion function
aerobic respiration, contains mitochondrial genome as circular DNA
27
Nucleus function
DNA maintenance, RNA transcription, RNA splicing (removes intervening, non-coding sequences of genes (introns) from pre-mRAN and joins the protein-coding sequences (exons))
28
Nucleolus function
ribosome production
29
Lysosome function
breaks down large molecules (proteins, polysaccharides)
30
Ribosome function
Translates RNA into proteins
31
Peroxisome function
catabolism of very long chain fatty acids, amino acids, forms hydrogen peroxide
32
Proteasome function
degrades protein molecules tagged with ubiquitin (Uniquitination is a post-translational process that tags proteins for degradation)
33
Muscle fibre types
Type 1 fibres: slow, red (myoglobin presence), used for sustained force, triglycerides, high mitochondrial density
Type 2 fibres: fast, white (absence of myoglobin), sudden movement, ATP, low mitochondrial density
34
Renal stone types
Ca oxalate 85%
Ca phosphate 10%
Uric acid 5-10%
struvite 2-20%
cystine 1%
35
RFs for ca oxalate stones
hypercalciuria, hyperoxaluria, hypocitraturia (citrate forms complexes with Ca, making it more soluble), hyperuricosuria.
36
Ca oxalate stones - radio-opaque/lucent?
opaque
37
Ca phosphate stones RF:
RTA 1 and 3 → high urinary pH increases supersaturation of urine with Ca and phosphate
38
Ca phosphate stones radioopaque/lucent?
opaque
39
Uric acid stone risk factor
Purine metabolism, may precipitate when urinary pH low, may be caused by diseases with extensive tissue breakdown, more common in children with inborn errors of metabolism.
40
Uric acid stone radioopaque/lucent?
radiolucent
41
Struvite risk factor
urease-producing bacteria, proteus mirabilis
42
Struvite stone radio-opaque/lucent?
opaque
43
Cystine stone risk factor
inherited recessive disorder of transmembrane cystine transport, leading to reduced cystine absorption from intestine and renal tubule, multiple stones.
Cystinuria - Aut recessive, recurrent stones
44
Cystine stones - radioopaque/lucent?
radiodense (contains sulfur)
45
Causes of urinary red cell casts
Glomerulonephritis, Renal ischaemia, infarction
46
Causes of urinary white cell casts
pyelonephritis, interstitial nephritis
47
Muddy brown casts
ATN
48
Urinary Hyaline casts
non-specific, post-exercise/dehydration
49
Urinary Epithelial casts
ATN
50
Waxy urinary casts causes
Advanced CKD
51
Urinary fatty casts cause:
nephrotic syndrome
52
Ligand-gated ion channels
fast
anaesthetics (lidocaine), nACh, GABA-A,
53
G-protein coupled receptors (GPCRs): types
Gs: stimulates adenylate cyclase
Gi: inhibits adenylate cyclase
Gq: activates phospholipase C
54
G-s receptors mechanism
stimulates adenylate cyclase → cAMP increase → protein kinase A activation.
55
Gs receptors examples
Beta1, beta 2, H2, D1, V2, ACTH, LH, FSH, glucagon, PTH, calcitonin, prostaglandins
56
Gi receptor mechanisms
inhibits adenylate cyclase -> cAMP decrease → inhibits protein kinase A
57
Gi receptor examples
M2, Alpha 2, D2, GABA-B receptor
58
Gq receptor mechanism
Activates phospholipase C → splits PIP2 to IP3 +DAG → activates protein kinase C
59
Gq receptor examples
Alpha 1, H1, V1, M1, M3 receptors
60
Tyrosine kinase receptors example
insulin, IGF, EGF. Non-receptor tyrosine kinase: PIGG(L)ET Prolactin, Immunomodulators (IL2, IL6, IFN), GH, G-CSF, Erythropoietin, Thrombopoietin
61
Guanylate cyclase receptors mechanism
contain intrinsic enzyme activity.
62
Guanylate cyclase receptor examples
ANP, BNP
63
Nuclear receptor examples
lipid-soluble drugs, steroids, levothyroxine
64
CD1 function
MHC, presents lipids
65
CD2 on what
thymocytes, T cells, natural killer cells, acts as ligand for CD58, 59, signal transduction, cell adhesion
66
CD3 function
signalling component of TCR
67
CD4 function
on Th cells, MHC Class II co-receptor, Used by HIV to enter T cells
68
CD5 on what
mantle cell lymphomas
69
CD8 function
cytotoxic T cells, MHC Class I co-receptor, on subset of myeloid dendritic cells
70
CD14 function
macrophage cell surface marker
71
CD15 on what
Reed Sternberg cells along with CD30
72
CD16 function
Fc portion of IgG abs
73
CD21 on what
EBV receptor
74
CD28 function
interacts with B7 on APC as costimulation signal
75
CD45 function
protein tyrosine phosphatase, present on leucocytes
76
CD56 function
unique marker for natural killer cells
77
CD95 function
FAS receptor, involved in apoptosis
78
what's involved in the cAMP system
Primary effector: adenylyl cyclase. Secondary messenger: cAMP
79
examples of receptors using cAMP system
alpha 1, beta 1, 2 (epinephrine), M2 (acetylcholine), ACTH, ADH, calcitonin, FSH, glucagon, hC, LH, MSH, PTH, TSH, GHRH
80
What's involved in the phosphoinositol system
Primary effector: Phospholipase C. Secondary messenger: IP3, DAG
81
Examples of phosphoinositol system
alpha 1 (epinephrine), M1, M3 (acetylcholine), angiotensin II, GnRH, GHRH, Oxytocin, TRH.
82
what's involved in the cGMP system
Primary effector: guanylate cyclase. Secondary messenger cGMP
83
examples of cGMP system
ANP, BNP, nitric oxide
84
Tyrosine kinase system - what's involved
Primary effector: receptor tyrosine kinase. Secondary messenger: protein phosphatase
85
Examples using tyrosine kinase system
insulin, GH, IGF, PDGF
86
Homocystinuria inheritence pattern
Autosomal recessive
87
Homocystinuria defect
cystathionine beta synthase def.
88
Homocystinuria features
Fine, fair hair, marfanoid, osteoporotic, kyphotic, LD, seizures, downwards (inferonasal) lens dislocation, severe myopia, arterial + venous thromboembolisms, malar flush, livedo reticularis.
89
Ix for homocystinuria
plasma and urine homocysteine concentrations high, cyanide-nitroprusside test +ve.
90
Rx for homocystinuria
Vitamin B6 (pyridoxine) supplements
91
Phenylketonuria genetics
Autosomal recessive
Chromosome 12
92
Phenylketonuria defect enzyme
phenylalanine hydroxylase
93
Features of phenylketonuria
fair hair, blue eyes, musky urine, LD, seizures, eczema,
94
Ix for phenylketonuria
Guthrie’s test, hyperphenylalaninaemia, urinary phenylpyruvic acid,
95
Alkaptonuria inheritance
Aut rec
96
Alkaptonuria enzyme def
HGD
97
Alkaptonuria features
(dark) urinary homogentisic acid (dark urine on standing)
renal stones, bones (intervertebral disc calcification), pigmented sclera, corneal deposits
98
Alkaptonuria Rx
vit C, restrict phenylalanine, tyrosine
99
Beckwith-Wiedemann syndrome features
Wilm’s, organomegaly, abdo wall defects, neonatal hypoglycaemia
100
Von Gierke's disease defect
(type I glycogen storage disesase):
Glucose-6-phosphatase def → hepatic glycogen accumulation.
101
Von Gierke's disease features
Hypoglycaemia
Lactic acidosis
Hepatomegaly
102
Pompe's disease enzyme def
Type 2 glycogen storage disease
Lysosomal alpha 1,4 glucosidase def → cardiac, hepatic, muscle glycogen accumulation
103
Pompe's disease salient feature
cardiac, hepatic, muscle glycogen accumulation
Cardiomegaly
104
Cori disease enzyme defect
Type 3 glycogen storage disease
alpha-1,6-glucosidase def
105
Cori disease features
hepatic, cardiac glycogen accumulation.
Muscle dystonia
106
McArdle's disease features
type 5 glycogen storage disease
The Ms: myophosphorylase (glycogen phosphorylase) def, Muscle glycogen accumulation → Myalgia and Myoglobinuria with exercise. Aut Recessive.
107
Gaucher's disease defect
beta glucocerebrosidase def.
108
Gaucher's disease features
Most common lysosomal storage disease
accumulation of glucocerebrosidase in brain, liver, spleen.
Hepatosplenomegaly
Aseptic necrosis of femur
109
Tay-Sachs disease features
Young presentation (by 6 months) with developmental delay, Spleen + liver normal sized, Cherry-red spots on macula, Hexosaminidase A def → GM2 ganglioside accumulation in lysosomes
110
Tay Sachs disease enzyme def
Hexosaminidase A def
111
Niemann-Pick disease enzyme def
sphingomyelinase
112
Niemann-Pick diseasse features
Hepatosplenomegaly + cherry red spots on macula
113
Fabry's disease inheritance
X recessive
114
Fabry's disease features
Fever, Angiokeratomas (bathing trunk distr), alpha galactosidase A def, Burning (peripheral neuropathy), Renal failure, Young, CVS disease/Corneal whorls keratopathy/lens opacification (cornea verticillata).
115
Fabry's enzyme defect
alpha galactosidase A def
116
Rx for fabry's disease
agalsidase alfa (enzyme replacement)
117
Krabbe's disease enzyme def
galactocerebrosidase
118
Krabbe's disease sx
Peripheral neuropathy, optic atrophy, globoid cells
119
Metachromatic leukodystrophy enzyme def
arylsulfatase A
120
Metachromatic leukodystrophy features
Demyelination of CNS, PNS
121
Hurler syndrome
Type 1 mucopolysaccharidosis
alpha-1-iduronidase def → glycosaminoglycan accumulation (heparan, dermatan sulfate). Gargoylism, hepatosplenomegaly, corneal clouding
Aut rec
122
Hunter syndrome
Type 2 mucopolysaccharidosis
iduronate sulfatase def → glycosaminoglycan accumulation. Coarse facial feature features, behavioural problems/LD, short stature, no corneal clouding
X recessive
123
Hurler syndrome inheritance pattern
Aut recessive
124
Hunter syndrome inheritance
X recessive
125
What do muscle biopsies show in mitochondrial disease?
red, ragged fibres
126
What feature do mitochondrial diseases show in relation to genotype:phenotype
Heteroplasmy
Poor genotype:phenotype correlation
127
MELAS in full
mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
128
Leber's optic atrophy features
aged>30yrs, central scotoma → colour vision loss → rapid, significant visual impairment
129
MERRF in full
myoclonus epilepsy with ragged-red fibres
130
Kearns-Sayre features
aged<20yrs, external ophthalmoplegia, retinitis pigmentosa, sometimes with ptosis, AV block, proximal myopathy
131
What do T helper 1 cells secrete
IFN gamma, IL2, IL3
132
What do T helper 1 cells mediate
cell-mediated response, T4 hypersensitivity.
133
What do T helper cells express
CD4, recognises MHC class II antigens, also expresses CD3, TCR, CD28.
134
What do T helper 2 cells mediate
hummoral (antibody-led) immunity
135
What do Th2 cells secrete
Secrete IL4, 5, 6, 10, 13
136
What do cytotoxic t cells express
CD8, recognises MHC class I antigens, also expresses CD3, TCR,
137
What type of organ rejection do T cells mediate
acute, chronic rejection
138
What type of organ rejection do B cells mediate
hyperacute
139
What produces IL-1
macrophages
140
IL-1 function
Fever, inflammation
Costimulator of T, B cell proliferation.
Stimulates vasoactive factors (PAF, NO, prostacyclin) → vasodilation, increase vascular permeability → mediator of shock in sepsis.
141
IL-1 inhibitors and uses
anakinra for Rh Arth
Canakinumab for IL-1 beta for systemic juvenile idiopathic arthritis, adult-onset Still’s
142
what produces IL2
Th1 cells
143
IL2 function
T cell response growth and differentiation
144
What produces IL3
Activated T helper cells
145
IL3 function
Bone marrow stimulation
146
What produces IL4
Th2 cells
147
IL4 function
Stimulates B cells diff+prolif. IgE
148
what produces IL5
Th2 cells
149
IL5 function
Stimulates Eosinophil production. IgA.
150
what produces IL6
macrophages
Th2
151
IL6 function
Stimulates B cell diff, fever
152
What produces IL8
macrophages
153
IL8 function
neutrophil chemotaxis (IL8 brings a mate)
154
What produces IL10
Th2
155
IL10 function
Inhibits Th1 cytokine production. Anti-inflammatory. Known as human cytokine synthesis inhibitory factor
156
What produces IL12
dendritic cells, macrophages, B cells
157
Il12 function
Activates NK cells, stimulates naive T cell differentiation into Th1 cells
158
What produces TNF alpha
macrophages
159
TNF alpha function
fever
neutrophil chemotaxis
160
Interferon main uses
vs viruses, neoplasia
161
What produces interferon alpha
leucocytes
162
Interferon alpha function
Antiviral
HBV, HCV, Kaposi's
metastatic RCC
Hariy cell leukaemia
163
SE of IFN alpha
flu-like sx, depression
164
What produces IFN beta
Fibroblasts
165
IFN beta function
MS, antiviral
166
What produces IFN gamma
Th1 cells
natural killer cells
167
IFN gamma function
Activates macrophages. Key for granuloma formation. Used in TB, chronic granulomatous disease, osteopetrosis
168
What is macrophage activation syndrome associated with and how to diagnose it
Adult-onset Still’s, Juvenile Idiopathic Arthritis
Dx: fever + High ferritin>684 + one of pltlt<181, AST>49, triglycerides>156, fibrinogen <360. Hepatosplenomegaly common
169
How are leukotrienes produced
formed from arachidonic acid by action of lipoxygenase, secreted by leukocytes,
170
Leukotriene function and action
mediates inflammation, allergic reactions.
Causes bronchoconstriction, mucous production, increases vasc permeability, attracts leucocytes.
171
What is NSAID related bronchospasm in asthmatics due to
excess production of leukotrienes due to prostaglandin synthetase inhibition
172
Endothelin actions
long-acting, potent vaso + bronchoconstricton
G-protein linked phospholipase C activity → Ca release.
173
Endothelin activation
ecreted as prohormone by vascular endothelium, converted to ET-1 by endothelin converting enzyme.
174
What stimulates endothelin release
Angiotensin II, ADH, hypoxia, mechanical shearing forces.
175
What inhibits endothelin
nitric oxide, prostacyclin
176
What coditions is endothelin raised in?
PAH, MI, HF, AKI, asthma
177
Commonest to least commonest Ig
IgG (75%)
IgA (15%)
IgM (10%)
IgD (1%)
IgE (0.1%)
178
IgG features and actions
monomer, enhances phagocytosis, fixes complement, passes to foetal circulation
179
IgA features and actions
monomer/dimer, breast milk, secretions, transported via transcytosis
180
IgM features and actions
pentamer, primary responder to infection, fixes complement but does not pass to foetal circulation, Anti-A, B abs
181
IgD features and actions
monomer, activates B cells
182
IgE features and actions
monomer, T1 hypersensitivity, synthesised by plasma cells, binds to Fc receptors on mast cell/basophil surfaces, immunity vs parasites
183
How is nitric oxide made
Nitric oxide synthetase forms it from L-arginine and oxygen. Inducible form present in macrophages. Half-life seconds, before inactivation by oxygen free radicals.
184
nitric oxide actions
acts on guanylate cyclase, leading to raised intracellular cGMP, reduces Ca levels, vasodilation (venodilation), inhibits pltlt aggregation. Low/underproduction of NO → hypertrophic pyloric stenosis, atherosclerosis. High NO → sepsis.
185
Type 1 hypersensitivity
Type 1: anaphylactic, Antigen vs IgE bound to mast cells, atopy
186
Type 2 hypersensitivity
cell bound, IgG/M vs antigen on cell surface. ITP, Autoimmune haemolytic anaemia, Goodpasture’s, pernicious anaemia, acute haemolytic transfusion reactions, rheumatic fever, pemphigus vulgaris/bullous pemphigoid
187
Type 3 hypersensitivity
IgG/A + antigen immune complex. Serum sickness, SLE, post-streptococcal glomerulonephritis, extrinsic allergic alveolitis (acute)
188
Type 4 hypersensitivity
delayed, T-cell mediated. TB, GvHD, contact dermatitis, scabies, extrinsic allergic alveolitis (chronic), MS, GBS
189
Hereditary angioedema
Aut dom. C1 inh deficiency (multifunctional serine protease inhibitor), uncontrolled release of bradykinin. C4 best screening tool, low C1 inh see in attacks. acute: V C1-inhibitor concentrate, FFP, prophylaxis: danazol (anabolic steroids)
190
C1q, 1rs, 2, 4 deficiency
(classical pathway, important for clearance of immune complexes): immune complex disease (eg SLE, HSP)
191
C3 deficiency
recurrent bacterial infections
192
C5 deficiency
Leiner disease - recurrent diarrhoea, wasting, seborrheic dermatitis, serious infantile erythroderma, recurrent local + systemic infections
193
C5-9 deficiency
(used for membrane attack complex), Neisseria meningitidis
194
Standard error calculation
measure of spread expected for the mean of the observations. SD/square root of n.
195
Standard deviation
square root of variance. 68.3% of values within 1 SD of mean, 95.4% within 2 SD, 99.7% within 3SD. 1.96 SD of mean encompasses 95% of distribution
196
Relative risk calculation
Experimental event rate/control event rate
197
Relative risk reduction/increase calculation
absolute risk change/control event rate
198
Odds ratio cacluation
divide odds in experimental group/odds in control
199
Hazard ratio calculation
similar to relative risk, but used typically for analysing survival over time
200
Sensitivity calc
TP/(TP+FN)
201
Specificity
TN/(TN+FP)
202
Likelihood ratio for positive test
sensitivity/(1-specificity). How much odds of disease increase when test is positive
203
Likelihood ratio for negative test:
(1-sensitivity)/specificity. How much odds of disease decrease when test is negative
204
Numbers needed to treat:
1/absolute risk reduction
205
point vs period prevalence
point prevalence - cases/number of people at a time. Period prevalence - cases identified in a time/number of people in population.
Prevalence = incidence x duration of condition
206
T1 error
null hypothesis rejected when it is true
207
T2 error
null hypothesis accepted when it is false
208
Power
1 - probability of type 2 error
209
Parametric tests
Student’s t-test (paired - single group/unpaired - different groups), Pearson’s for correlation
210
Non-parametric tests
Mann-Whitney U test: for ordinal, interval, or ratio scales of unpaired data
Wilcoxon signed-rank: before vs after in same population
Chi-squared: compare proportions or percentages
Spearman, Kendall rank: correlation
211
Negatively skewed distribution
mean
212
+vely skewed distribution
mean>median>mode (peak skewed to left) (postive going forward ->)
213
What are RCTs limited by
practical/ethical issues
214
Cohort studies
relative risk as outcome, prospective.
215
Case-control studies
odds ratio as outcome, retrospective.
216
cross-sectional survey
provide weak evidence of cause and effect
217
What are new drugs tested for (3 types)
New drugs tested to either show superiority (large sample size required), equivalence (shown by use of equivalence margin and overlapping of CIs), non-inferiority (only lower CI needs to lie within equivalence margin)
218
Funnel plots
to assess publication bias. Treatment effects on horizontal axis, study size on vertical axis
219
Selection bias
sampling bias (unrepresentative of population), volunteer bias, non-responder bias, loss to follow up bias, prevalence/incidence bias, admission bias (hospital settings), healthy worker effect
220
Recall bias
problem in case-control studies
221
Publication bias
negative/uninteresting result studies excluded
222
Work-up bias
studies comparing new diagnostic tests vs gold standard tests (often gold standard tests invasive so reluctant to order these tests)
223
Expectation bias
in non-blinded trials
224
Hawthorne effect
group changing behaviour as they know they’re being studied
225
Late-look bias
gathering information at inappropriate time
226
Procedure bias
subjects in different groups receive different treatment
227
Lead-time bias
when two tests compared with new test diagnosing disease earlier, making survival times look more promising for new test
228
Clinical trial phases
Phase 0: exploratory, assess drug behaviour in human body, assesses pharmacokinetics, pharmacodynamics
Phase I: side-effects, healthy volunteers
Phase IIa: optimal dosing. IIb: efficacy
Phase III: effectiveness, 100-1000s of people, RCTs
Phase IV: postmarketing surveillance, long-term SE, effectiveness
229
X-recessive conditions
Androgen Insensitivity syndrome, Becker/Duchenne, Colour blindness, Diabetes insipidus (nephrogenic), Eyes (retinitis pigmentosa, most inherited eye diseases: retinitis pigmentosa, ocular albinism, colour blindness), Fabry’s, G6PD def, Haemophilia A/B, Hunter’s, Lesch-Nyhan, Wiskott-Aldrich
230
X dominant conditons
FAIR COX Fragile X, Alport’s, Incontinentia Pigmenti, Charcot Marie Tooth type X, Orofaciodigital syndrome, X-linked hypophosphataemic rickets (Vit D resistant rickets)
231
Autosomal recessive conditions
metabolic, except inherited ataxias Albinism, Ataxic telangiectasia, Congenital adrenal hyperplasia, CF, Cystinuria, Familial mediterranean fever, Fanconi’s anaemia, Fiedreich’s ataxia, Gilbert’s, Glycogen storage disease, Haemochromatosis, Homocystinuria, Lipid storage disease, mucopolysaccharidoses (Hurler’s), PKU, Sickle cell, Thalassaemia, Wilson’s
232
Autosomal dominant conditions
structural, except Gilbert’s, Hyperlipidaemia Type II. Very Powerful DOMINANT H6umans: Von Willibrand’s/Von Hippel Lindau, Pseudohypoparathyroidism, Dystrophia myotonica, Osteogenesis imperfecta/Osler-Weber-Rendau, Marfan’s, Intermittent porphyria, Neurofibromatosis, Achondroplasia, APCKD, Noonan’s, Tuberous Sclerosis, Hypercholesterolaemia, Huntington’s, HOCM, Hereditary spherocytosis, HNPCC, Hereditary haemorrhagic telangiectasia, Hypokalaemic periodic paralysis
233
HLA A3 association
Haemochromatosis
234
Which Chromosome is HLA on
Chr 6
235
HLA B51
Behcet's
236
HLA B27
Ank spond
reactive arthritis
acute anterior uveitis
psoriatic arthrits
237
HLA DQ2/8
coeliac
238
HLA DR1
Bronchiectasis
239
HLA DR2
narcolepsy
Goodpasture's
Also SLE
240
HLA DR3
Dermatitis herpetiformis, Sjogren’s, PBC
(Also autoimmune hepatitis, T1DM, SLE)
241
HLA DR4
T1DM, Rh arth (DRB1*04:01, 04:04)
242
Down's features
Shortened neck, protruding tongue, Brushfield’s spots (white spots in iris), ALL, hypothyroid, cardiac compl, subfertility, LD, repeated resp infections, Alzheimer’s, atlantoaxial instability
243
Risk of child getting Down's based on age
risk at 30 1/800, 35 1/270, 40 1/100, 45 1/50.
244
Down's cause
Maternal nondisjunction 94%, Robertsonian translocation 5%, mosaicism 1%
245
Turner's features
bicuspid aortic valve 15%, coarctation 5-10%, dissection, cystic hygroma, high-arched palate, short 4th MC, multiple pigmented naevi, neonatal lymphoedema, hypoT4, horseshoe kidney, autoimmune, Crohn’s. High gonadotrophin.
246
Noonan's features
Aut dom, Chr12 (noon’s at 12pm), ‘male Turner’s’ short stature, dysmorphic features, congenital cardiac disease (pulmonary stenosis), normal fertility in women, cryptorchidism in men, triangular face, Factor 11 def
247
William's features
Microdeletion in Chr 7. Friendly, social, LD, short, supravalvular AS, transient neonatal hyperCa. Dx: FISH studies
248
Achondroplasia features
Aut dom, FGFR-3 mutation, shortened limbs/fingers, large head, midface hypoplasia, trident hands, lumbar lordoses
249
What feature is common in trinucleotide repeat disorders
anticipation common (earlier age onset with successive generations)
250
Fragile X genetics and features
X-linked CGG. Facial feature, Reduced tone, Autism, Giant scrotum, Inability to learn, Loose mitral valve (prolapse), Escaped by female (normal to mild). Dx: Southern blot, CGG repeats detected using restriction endonuclease digestion.
251
Huntington's genetics and features
CAG. Aut dom. Chr 4 huntingtin gene. Cholinergic, GABAergic neuronal degeneration in basal ganglia striatum. Chorea, personality changes, intellectual impairment, dystonia, saccadic eye movements (age>35)
252
Myotonic dystrophy genetics and features
Aut dom. Delayed skeletal (myotonia, weakness), cardiac (Heart block, CDM), smooth muscle relaxation, cataracts, diabetes, dysarthria. Other features: b/l ptosis, frontal balding, myotonic facies (long, ‘haggard’ appearance)
Type 1: Distal. CTG repeat at end of DMPK gene on Chr 19
Type 2: Proximal. ZNF9 gene repeat expansion on Chr 3
253
Friedrich's ataxia genetics and features
GAA rpt on X25 gene on Chr 9 (frataxin), no anticipation. Aut Rec. 10-15yrs onset. Gait ataxia, kyphoscoliosis. Absent ankle jerks/extensor plantars (mixed UMN/LMN), optic atrophy (pale discs), spinocerebellar degeneration, HOCM (90%), DM, high-arched palate
254
Prader-Willi genetics and feature
paternal 15q11-13 microdeletion (70%), maternal uniparental disomy Chr 15. (Angelman’s if paternal). Hypotonia, dysmorphia, short, hypogonadism, infertility, LD, obesity, behavioural issues
255
Factors increasing ADH
extracellular fluid osmolality increase, volume decrease, pressure decrease, angiotensin II.
256
Factors reducing ADH
extracellular fluid osmol decrease, volume increase, temperature decrease
257
What passes through the optic canal
ophthalmic artery, CNII
258
What passes through the superior orbital fissure
superior + inferior ophthalmic vein, CN III, IV, lacrimal, frontal and nasociliary branches of ophthalmic nerve (V1), VI
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What passes through the inferior orbital fissure
inferior ophthalmic veins, infraorbital artery + vein. Zygomatic nerve, infraorbital nerve of maxillary nerve (V2), orbital branches of pterygopalatine ganglion
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What passes through the foramen rotundum
Maxillary nerve (V2)
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What passes through the foramen ovale
Accessory meningeal artery. Mandibular nerve (V3)
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What passes through the jugular foramen
Posterior meningeal artery, ascending pharyngeal artery, inferior petrosal sinus, sigmoid sinus, internal jugular vein. CNs IX, X, XI.
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Corneal reflex
V1/7
264
Jaw jerk reflex
V3/V3
265
Gag reflex
9, 10
266
Carotid sinus reflex
9, 10
267
Pupillary light reflex
2/3
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Lacrimation reflex
V1/7
269
Musculocutaneous nerve roots
c5-7
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Musculocutaneous nerve motor
elbow flexion + supination.
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Musculocutaneous nerve sensory
lateral forearm
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Axillary nerve roots
C5-6
273
Axillary nerve motor
shoulder abduction (deltoid
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Axillary nerve sensory
inferior deltoid muscle region.
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Injury mechanism for axillary nerve and feature
humeral neck #, flattened deltoid
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Radial nerve roots
C5-8
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Radial nerve motor
extension (forearm, writs, fingers, thumb).
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Radial nerve sensory
small area between dorsal aspects of 1st and 2nd metacarpals.
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Injury of radial nerve
humeral midshaft # → wrist drop
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Median nerve root
C6,8, T1
281
Median nerve motor
LOAF (lateral 2 lumbricals, opponens pollicis, abductor pollicis brevis, flexor pollicis brevis) muscles.
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Median nerve sensory
palmar aspect of lateral 3.5 fingers
283
Median nerve injury
wrist lesion → carpal tunnel syndrome, paralysis of thenar muscles, opponens pollicis. Elbow lesion → loss of pronation of forearm and weak wrist flexion
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Ulnar nerve roots
C8, T1
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Ulnar nerve motor
medial two lumbricals, adductor pollicis, interossei, hypothenar muscles (abductor + flexor digiti minimi), flexor carpi ulnaris.
286
Ulnar nerve sensory
medial 1.5 fingers (palmar + dorsal).
287
Ulnar nerve injury
medial epicondyle #
Damage at wrist: ‘claw hand’ hyperextension at MCP joints, flexion at 4th, 5th DIP+PIP joints, wasting + paralysis of intrinsic hand muscles (except lateral 2 lumbricals), hypothenar muscles, sensory loss to medial 1.5 fingers
Damage at elbow: + radial deviation of wrist
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Long thoracic nerve root
C5-7
289
Long thoracic nerve motor
serratus anterior
290
long thoracic nerve injury
sports/mastectomy → winged scapula
291
Erb-Duchenne palsy
waiter’s tip, upper brachial plexus, 2 to shoulder dystochia, arm hangs by side, internally rotated, elbow extended
292
Klumpke's palsy
lower brachial plexus, 2 to shoulder dystochia or sudden upward jerk of hand. Assx: horner’s
293
Dermatomes
C2: posterior half of skull (cap)
C3: high turtleneck shirt
C4: low-collar shirt
C5: Ventral axial line of upper limb
C6: thumb + index finger (Make a 6 with left hand with thumb + index finger together)
C7: middle finger + palm of hand
C8: ring + little finger
T4: Nipples (T4 at the Teat Pore)
T5: inframammary fold
T6: xiphoid process
T10: umbilicus
L1: inguinal ligament
L4: knee caps
L5: big toe, dorsum of foot (except lateral aspect)
S1: lateral foot, small toe
S2,3 genitalia
294
Which is the only cervical nerve root that comes out below vertebra
c8
295
What is in direct contact with the right kidney
right suprarenal gland, duodenum, colon.
296
What is in direct contact with the left kidney
left suprarenal gland, pancreas, colon
297
What is associated with vitamin B1 deficiency
ETOH excess, malnutrition
298
Consequences of vitamin B1 defiency
Wernicke’s: nystagmus, ophtalmoplegia, ataxia. → Korsakoff’s: amnesia, confabulation
Dry beriberi: rapidly progressive poly + peripheral neuropathy
Wet beriberi: dilated CDM
299
Vitamin B1 name
thiamine
300
Vit B2 name
riboflavin
301
Vit B1 function
catabolism of sugars, aminoacids.
302
vit B2 function
cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN).
303
Vit B2 deficiency
angular cheilitis
304
Vit B3 name
niacin
305
vit B3 function
precursor to NAD+ and NADP+.
306
vit B3 def causes
Hartnup’s disease (hereditary, reduces tryptophan absorption)
carcinoid syndrome (increased tryptophan metabolism to serotonin).
307
Vit B3 deficiency
pellagra (dermatitis, diarrhoea, dementia)
308
Vit B6 name
pyridoxine
309
vit B6 function
converted to pyridoxal phosphate (involved in transamination, deamination, decarboxylation).
310
vit B6 deficiency risk factor
isoniazid
311
vit B6 deficiency consequences
peripheral neuropathy
sideroblastic anaemia
312
vit B12 deficiency causes
pernicious anaemia, post gastrectomy, terminal ileum disorders eg Crohn’s (absorbed in terminal ileum), vegan diet, metformin (rare)
313
How to treat vit b12 def
IM hydroxycobalamin 1mg 3 times/wk for 2 wks then once every 3 months if no neuro
314
vit C deficiency features
impaired collagen synthesis. Bleeding gums/gingivitis, follicular hyperkeratosis, perifollicular haemorrhage, ecchymosis, easy bruising, poor wound healing, sjogren’s, arthralgia, oedema, impaired wound healing, weakness, malaise, anorexia, depression
315
Vit C in iron absorption
Vit C can improve iron absorption (Fe3+ to Fe2+ conversion)
316
vit D - water or fat soluble
fat soluble
317
vit D forms in plants and skin
D2 ergocalciferol (plants), D3 cholecalciferol (dairy, sunlight).
318
vit D actions
increasing renal Ca + PO4 reabsorption, increases osteoclastic activity, increases gut Ca absorption.
319
vitamin K water or fat soluble?
fat soluble
320
vit K function
cofactor for Factors 2,7,9,10.
321
When vit K is given how long does it take to reverse warfarin
4 hrs for INR change
322
Vit K deficiency causes
after prolonged abx, conditions affecting fat absorption
323
Where is iron absorbed
upper small intestine, esp duodenum
324
What ion of iron is better absorbed?
Fe2+ better than Fe 3+
325
Factors improving iron absorption
vit C
gastric acid
326
Factors reducing iron absorption
PPIs
Doxy
Gastric achlorhydria
Tannin
327
Sleep stages and waves
The Sleep Doctor’s Brain
N1: Theta waves, light sleep, hypnic jerks
N2: Sleep spindles + K complexes, Deeper sleep, 50% of total sleep
N3: Delta waves, deep sleep, parasomnias (night terrors, nocturnal enuresis, sleepwalking)
REM: Beta waves, dreaming, atonia, erections
328
What happens in REM parasomnia
incomplete/absent atonia → sleepwalking, acts out dreams
329
What produces collagen?
fibroblasts
330
What vitamin is important for collagen?
vitamin c
331
Collagen structure
3 polypeptide strands
helical
332
Where do you find type 1 colalgen
bone, skin, tendon
333
Osteogenesis imperfecta
Type 1 collagen defect
Aut Dom
8 subtypes, low pro-alpha 1 or pro-alpha 2 collagen polypeptides
blue sclera, otosclerosis, normal biochem.
Type 1: poor quantity. Type II: poor quantity + quality. Type III, IV: poor quality
334
Where do you find type 2 collagen?
hyaline cartilage
vitreous humour
335
Where do you find type 3 collagen?
reticular fibre
Granulation tissue
336
Ehlers-Danlos syndrome
Vascular variant:
collagen type 3 defect
COL3A1 gene mutations, Aut dom, AR, MVR, A diss, SAH, angioid streaks
Classical variant:
Collagen type 5 defect
COL5A1, COL5A2 gene mutations
337
Where is Type 4 collagen found?
basal lamina
lens
basement membrane
338
Defects in type 4 collagen
Alport's
Goodpasture's
339
Where is type 5 collagen found?
most interstitial tissue
placental tissue
340
What do different molecular biology techniques test for
SNOW DROP
Southern blotting DNA
Northern blotting RNA
Western blotting Proteins
PCR used for prenatal dx, detecting mutated oncogens, infections, forensics
341
Flight rules: no flights for which conditions?
Unstable angina
Uncontrolled HTN
Uncontrolled arrhythmia
Decompensated HF
Severe Valvular diease
342
Rules for flights for MI
no flights for 7-10 days for uncomplicated
4-6 wks for complicated
10 days for CABG
3 days after PCI
343
Rules for flights with strokes
10 days post event
3 days if stable
344
Rules for flights with pneumonia?
Only if clinically improved with no residual infection
345
rules for flights with pneumothorax?
2 wks post successful, complete drainage
346
Rules for flights with pregnancy
not after 36wks or 32wks for multiple pregnancy.
347
Rules for flights after surgery
avoid for 10 days following abdominal surgery, after 24hrs post lap, 24hrs post colonoscopy, 24 hrs for plaster cast (if <2hrs), (48 hrs for longer flights)
348
Rules for flights with low Hb
Hb<8 - restrictions
349
Layers of epidermis
Come Let’s Get Sun Burnt
Stratum Corneum (dead cells with keratin, sheds)
Lucidum (clear, in thick skin)
Granulosum (forms links with neighbours)
Spinosum (squamous cells begin keratin synthesis, thickest layer)
Basale/germinativum (basement membrane, gives rise to keratinocytes, contains melanocyte)
