1
Q
A patient presents with confusion, abdominal pain, peripheral neuropathy, constipation and blue lines on their gum. They drink 4 bottles of wine per week. What is the diagnosis?
A
Lead poisoning
2
Q
A patient’s bloods show microcytic anaemia, basophilic stippling and clover leaf red cells. What is the diagnosis?
A
Lead poisoning
3
Q
What is the management of lead poisoning?
A
DMSA - dimercaptosuccinic acid
D-penicillamine
EDTA
Dimercaprol
4
Q
Which things are raised in anorexia nervosa?
A
Growth hormone, glucose, salivary glands, cholesterol, carotinaemia, cortisol
5
Q
What does cyanide do?
A
Inhibits cytochrome c oxidase which causes cessation of mitochondrial electron transfer chain
6
Q
A patient presents with brick red skin and can smell bitter almonds. They are hypoxic, hypotensive and confused. What is the diagnosis?
A
Cyanide poisoning
7
Q
What is the management of cyanide poisoning?
A
1) 100% oxygen
2) Hydroxocobalamin
3) Amyl nitrite, sodium nitrite, sodium thiosulfate
8
Q
A 20 year-old female presents with a rash on the extensor aspect of her arms. It is intensely itchy. She gives a history of fatigue and diarrhoea for the last few months, but has been unable to book an appointment until now. Her past medical history includes recurrent chest, urine and ear infections throughout childhood requiring multiple courses of antibiotics. She still occasionally suffers with infections. On examination there is a blistering rash around both elbows. You suspect dermatitis herpetiformis and coeliac disease, and send off a coeliac disease blood test. She is started on a gluten free diet and improves. In the meantime her blood test comes back negative.
What is the reason for the negative coeliac test?
A
IgA deficiency
9
Q
How should you test for coeliac in IgA deficiency?
A
IgG-anti TTG antibodies
10
Q
How would you screen family members for haemachromatosis?
A
HFE gene analysis
11
Q
How would you test the general population for haemachromatosis?
A
Transferrin saturation
12
Q
What is the number needed to treat?
A
The number of people needed to treat to reduce the number of desired outcomes by 1
13
Q
How do you calculate NNT?
A
1/Absolute risk reduction
14
Q
How do you calculate absolute risk reduction?
A
Control Event Rate-Experiment Event Rate or vice versa
15
Q
What is control event rate?
A
Number of control with desired outcome/number of control
16
Q
What is experiment event rate?
A
Number of intervention with desired outcome/number of intervention
17
Q
Which collagen defect is seen in Goodpasture’s?
A
Type IV
18
Q
Which collagen defect is seen in Alport?
A
Type IV
19
Q
Which collagen defect is seen in osteogenesis imperfecta?
A
Type I
20
Q
Which collagen defect is seen in Ehlers-Danlos syndrome?
A
Type III and Type V (Type V more classical)
21
Q
Which phase of the cell cycle is influenced by p53 and determines cell cycle length?
A
G1
22
Q
What is Fanconi syndrome?
A
Global dysfunction of proximal renal tubules leading to impaired reabsorption of key substances
23
Q
What is lost in urine in Fanconi syndrome?
A
Glucose, bicarb, potassium, amino acids, uric acid, calcium, phosphate
24
Q
What are the features of Fanconi syndrome?
A
Polyuria and polydypsia
Growth failure in children
Muscle weakness
Bone pain/rickets/osteomalacia
Acidosis
25
What are the causes of Fanconi syndrome?
Cystinosis (children)
Sjogren's
Multiple myeloma
Nephrotic syndrome
Wilson's disease
26
What factor is protective for hepatotoxicity in paracetamol overdose?
Acute alcohol
27
What are the stages of sleep?
Non-REM 1
Non-REM 2
Non-REM 3
REM
28
What waves are seen in each stage of the sleep cycle?
N1 - theta
N2 - Sleep spindles
N3 - Delta
REM - Beta
29
What happens in N1 sleep stage?
Light sleep. Hypnic jerks
30
What happens in N2 sleep stage?
Deeper sleep. 50% of total sleep.W
31
What happens in N3 sleep stage?
Deep sleep. Night terrors, enuresis, sleepwalking
32
What happens in REM sleep?
Dreaming. Loss of muscle tone, erections
33
A patient has a provoked PE. How long should they be anticoagulated for?
3 months (3-6 if active cancer)
34
A patient has an unprovoked PE. How long should they be anticoagulated for?
6 months
35
What is expressivity in genetics?
The extent to which a genotype shows phenotypic expression in an individual
36
What is meant by genetic penetrance?
Genotype is present but there is variability in the observed phenotype e.g. 50 people have a genotype but only 45 of them show the phenotype of the condition
37
What are the autosomal dominant conditions?
1) Achondroplasia
2) Acute intermittent porphyria
3) Adult polycystic disease
4) Antithrombin III deficiency
5) Ehlers-Danlos syndrome
6) Familial adenomatous polyposis (FAP)
7) Hereditary haemorrhagic telangiectasia
8) Hereditary spherocytosis
9) Hereditary non-polyposis colorectal carcinoma
10) Huntington's disease
11) Hyperlipidaemia type II
12) Hypokalaemic periodic paralysis
13) Malignant hyperthermia
14) Marfan's syndromes
15) Myotonic dystrophy
16) Neurofibromatosis
17) Noonan syndrome
18) Osteogenesis imperfecta
19) Peutz-Jeghers syndrome
20) Retinoblastoma
21) Romano-Ward syndrome
22) Tuberose sclerosis
23) Von Hippel-Lindau syndrome
24) Von Willebrand's disease.
38
Is there a carrier state in autosomal dominant conditions?
No
39
What percentage of children are autosomal dominant conditions passed down to?
50%
40
What is non-penentrance in inherited conditions?
Normal phenotype in someone with an affected gene.
41
Who is affected by autosomal recessive conditions?
Homozygotes
42
How many children will be affected by one homozygote parent and one unaffected parent with an autosomal recessive condition?
All children will be carriers
43
What are the inheritance patterns in heterozygote parents of autosomal recessive conditions?
25% chance of homozygote child
50% change of a heterozygote (carrier) child
25% chance of unaffected child
44
Which types of conditions are typically
a) autosomal dominant
b) autosomal recessive?
And what are the exceptions?
a) Structural
b) Metabolic
Autosomal dominant exceptions:
hyperlipidaemia type II, hypokalaemic periodic paralysis.
Autosomal recessive exceptions: inherited Friedreich's ataxias, ataxia telangiectasia.
45
What are the indications for plasma exchange?
GBS
Myaesthenia Gravis
Goodpasture’s syndrome
ANCA positive vasculitis
TTP/HUS
Cryoglobinaemia
Hyperviscosity syndrome
46
What are the complications of plasma exchange?
Hypocalcaemia
Metabolic alkalosis
Removal of systemic medications
Coagulation factor depletion
Immunoglobulin depletion
47
What is the job of T cells?
Helper - coordinate immune attack
Killer/cytotoxic - kill infected/cancer cells
48
What cell surface proteins are on T helper cells and what do they do?
CD3 - on all T cells - identifies them
CD4 - interacts with MHC II. Target for HIV cells
49
What cell surface proteins are on T killer cells and what do they do?
CD28 - get permission from helper cells to activate
CD8 - MHC I
50
What is the job of B cells?
Make antibodies
51
What cell surface proteins are on B cells and what do they do?
CD19 - on all B cells
CD20 - Mature B cells - present in mature B cell cancers, target for rituximab
CD21 - EBV
CD40 - works with CD40L on helper T cells to activate
52
What is the job of natural killer cells?
Kills cells without permission from T cells
53
What cell surface proteins are on NK cells and what do they do?
CD16 - helps recognise cells with antibodies
CD56 - Special ID badge
54
What is the job of macrophages and monocytes?
Gobble bacteria, dead cells and debris
Monocytes in the blood
Macrophages in the tissues
55
What cell surface proteins are on macrophages and monocytes and what do they do?
CD14 - recognise toxins and trigger sepsis pathway
CD68 - identity
56
What is the job of stem cells?
Turn into any cell type
57
What cell surface proteins are on stem cells and what do they do?
CD34 to identify them
58
What condition is related to CD15 and CD30?
Hodkin's lymphoms (Reed sternberg cell)
59
What condition is CD5 related to?
Mantle cell lymphoma
60
How is Noonan inherited?
Autosomal dominant
61
True or false: Noonan's is associated with a normal karyotype
True
62
Which cardiac defects are seen in Noonan?
Pulmonary stenosis
Hypertrophic cardiomyopathy
Atrial septal defect
Tetralogy of fallot
63
What are the 4 types of membrane receptors?
Ligand-gated ion channels
Tyrosine kinase receptors
Guanylate cyclase receptors
G protein-coupled receptors
64
What do tyrosine kinase receptors do?
Receptor: Insulin, Insulin-like growth factor, epidermal growth factor
Non-receptor: PIGG(l)ET
Prolactin
Immunomodulators (cytokines IL-2, IL-6, IFN)
GH
G-CSF
Erythropoietin
Thrombopoietin
65
What do ligand-gated ion channels do?
Mediate fast responses
e.g nicotinic acetylcholine, GABA-A + GABA-C, glutamate receptors
66
What do guanylate cyclase receptors do?
Contain intrinsic enzyme activity
e.g atrial natriuretic factor, brain natriuretic peptide
67
What do g protein coupled-receptors do?
Generally mediate slow transmission and affect metabolic processes
68
How are G protein-coupled receptors activated?
A variety of extracellular signals e.g. peptide hormones, biogenic amines e.g. adrenaline, lipophilic hormones (e.g cortisol and thyroid hormones), light
69
Describe the process of activation of GPCR?
1) GPCR senses substrate e.g adrenaline
2) Sends signal to paired g protein (either gs, gi or gq)
3) GDP -> GTP on alpha subunit activates it
4) Effect exerted depending on which g protein
70
What are the 3 g protein subunits?
Alpha
Beta
Gamma
71
How do Gs proteins work?
Stimulates acetylate cyclase which increases cAMP and activates protein kinase A
72
How do Gi proteins work?
Inhibit acetylate cyclase which reduces cAMP and inhibits protein kinase A
73
How do Gq proteins work?
Activates phospholipase C which splits PIP2 to IP3 and DAG which activates protein kinase C
74
Give examples of GPCRs that pair with Gs proteins?
Beta 1 (adrenaline)
Beta 2 (adrenaline)
D1 (dopamine)
H2 (histamine)
V2 (vasopressin)
ACTH, LH, FSH, glucagon, PTH, calcitonin, prostaglandins
75
Give examples of GPCRs that pair with Gi proteins?
M2 (acetylcholine)
Alpha 2 (adrenaline)
D2 (dopamine)
GABA B
76
Give examples of GPCRs that pair with Gq proteins?
Alpha 1 (adrenaline)
H1 (histamine)
V1 (vasopressin)
M1, M3 (acetylcholine)
77
What method would you use to measure survival over time?
Hazard ratio
78
A 1 year old presents with developmental regression, coarse facial features, hepatosplenomegaly, corneal clouding and skeletal abnormalities. What is the likely cause?
Lysosomal storage disorder - mucopolysaccharidosis (MPS)
79
Why do lysosomal storage disorders occur?
Deficiency of specific lysosomal enzymes needed to break down substrates leading to accumulation in tissues
80
How does the golgi apparatus affect lysosomal storage?
Tags lysosomal enzymes with M6P (mannose-6-phosphate) which then facilitates transport to the lysosomes
81
When is a funnel plot used?
To demonstrate the existance of publication bias in meta-anylses
82
What is responsible for virutally all adrenaline secretion?
Adrenal medulla
83
In normal distribution, what percentage of values lie within 1 SD?
68.3%
84
In normal distribution, what percentage of values lie within 2 SD?
95.4%
85
In normal distribution, what percentage of values lie within 2 SD?
99.7%
86
What is anakinra and how does it act?
IL-1 receptor antagonist
Reduces inflammation as IL-1 is respondible for fever and inflammation
Secreted by macrophages
87
Which statistical test should you use in paired data which is not normally distributed? E.g comparing BP pre and post treatment
Wilcoxon signed-rank test
88
Which statistical test would you use in paired data if it was normally distibuted?
Student's paired t test
89
What statistical test would you use in unpaired data that is not normally distributed?
Mann-Whitney U test
90
What statistical test would you use to compare proportions or frequencies between groups?
Chi-squared e.g compares percentage of patients who improved following two different interventions
91
What statistical test would you use to assess the strength and direction of association between two ranked variables?
Spearman's rank correlation
92
Which type of renal stones are patients with recurrent proteus (urease positive) infections predisposed to?
Struvite (ammonium magnesium phosphate)
93
What is the function of rough endoplasmic reticulum?
Translation and folding of new proteins
Manufacture of lysosomal enzymes
Site of N-linked glycosylation
94
What is the function of smooth endoplasmic reticulum?
Steroid and lipid synthesis
95
What is the function of golgi apparatus?
Modifies, sorts and packages proteins
Mannose-6-phosphate designates transport to lysosome
96
What is the function of mitochondria?
Aerobic respiration
ATP synthesis and apoptosis trigger
Contains mitochondrial genome as circular DNA
97
What is the function of nucleus?
DNA maintenance
RNA transcription
RNA splicing
98
What is the function of lysosome?
Breakdown large molecules
99
What is the function of nucleolus?
Ribosome production
100
What is the function of ribosome?
Translates RNA to proteins
101
What is the function of peroxisome?
Catabolism of very long chain fatty acids and amino acids
Formation of hydrogen peroxide
102
What does C1 inhibitor protein deficiency cause?
Hereditary angioedema
103
What does C1q, C1rs, C2, C4 deficiency cause?
Predispose to immune complex disease e.g. SLE, HSP
104
What does C3 deficiency cause?
Recurrent bacterial infections
105
What does C5 deficiency cause?
Predispose to Leiner disease. Recurrent diarrhoea, wasting and seborrhoeic dermatitis
106
What does C5-9 deficiency cause?
Membrane attack complex
Prone to Neisseria meningitidis infection
107
A 28-year-old man presents with recurrent burning pain in his hands and feet, worse in hot weather. He also complains of reduced sweating and has noticed clusters of small, dark red spots over his lower trunk and groin. His father died of renal failure at age 45.
On examination, he has angiokeratomas over the buttocks and hips. Blood pressure is 148/92 mmHg. Urinalysis shows proteinuria.
What is the most likely diagnosis?
Fabry disease
108
How is Fabry disease inherited?
X linked recessive
109
How is Fabry disease treated?
Enzyme replacement
110
What causes Fabry disease?
Alpha Galactosidase A deficiency
111
What activates immature t cells?
IL1 and IL12
112
What do T Helper 1 cells produce?
IL-2, IL-3, IFN gamma
113
What do T Helper 2 cells produce?
IL-4
IL-5
IL-6
114
What does IL 10 do?
Negative feedback, inhibits macrophages
115
What does IL 1 do?
Cause fever
116
What does IL 2 do?
T cell stimulator
117
What does IL 3 do?
Bone marrow stimulator
118
What does IL 4 do?
IgE, B cell growth/differentiation
119
What does IL 5 do?
IgA, eosinophils
120
What does IL 6 do?
Differentiation of B cells
121
What does IL 8 do?
Neutrophil chemotaxis
122
What does IL 12 do?
Activate NK cells and turns t cell to TH1
123
What does IFN gamma do?
Activate macrophages
124
What does IgG do?
Crosses placenta. Chronic infection. Complement memory. Most abundant.
125
What does IgA do?
Secretions. Mucosal defence. Breast milk.
126
What would IgA deficiency cause?
Anti-IgA antibodies -> anaphylaxis to blood transfusion
127
What does IgM do?
First secreted in acute infection. Anti A,B blood antibodies. High in Waldenstrom's Macroglobulinaemia
128
What does IgE do?
Attached to mast cells and basophils. Type 1 hypersensitivity reactions. Least abundant.
129
A 34-year-old man is referred to ophthalmology following a deterioration in his vision. He is noted to be tall with thin, long fingers and a degree of learning disabilities. Following review he is suspected as having a displacement of his lens on the right side. What is the most likely underlying diagnosis?
Homocystinuria
130
How is homocystinuria inherited?
Autosomal recessive
131
How is homocystinuria treated?
Vitamin B6 (pyridoxine)
131
What is homocystinuria?
Cystathionine beta synthase deficiency causing severe increase in plasma and urine homocysteine concentration
132
Which DNA mutation does not change the amino acid but causes base change in the 3rd position of codon?
Silent
133
Which DNA mutation results in a stop codon?
Nonsense
134
Which DNA mutation causes point mutation that changes the amino acid sequence which may make the protein non-functional?
Missense
135
Which DNA mutation causes insertion/deletion of a number of nucleotides leading to reading of DNA downstream being completely young?
Frameshift
136
What is Li-Fraumeni syndrome?
Autosomal dominant condition causing p53 mutation leading to early onset sarcoma, breast ca and leukaemia
137
What does p53 do?
Prevents entry into S phase until DNA has been checked and repaired
138
How do you calculate LV ejection fraction?
Stroke Volume / End diastolic LV volume
139
How do you calculate stroke volume?
End diastolic LV volume - End systolic LV volume
140
How do you calculate cardiac output?
Stroke Volume x Heart Rate
141
How do you calculate pulse pressure?
Systolic pressure - diastolic pressure
142
How do you calculate systemic vascular resistance?
Mean arterial pressure / Cardiac output
143
How is pseudoxanthoma elasticum inherited?
Autosomal recessive
144
What are the features of pseudoxanthoma elasticum?
Plucked chicken skin
Retinal angioid streaks
MV prolapse
Inc. risk of IHD
GI haemorrhage
145
What is the management of HAPE (High Altitude Pulmonary Oedema)?
Descent +
Nifedipine, acetazolamide, dexamethasone, phosphodiesterase V inhibitors
146
What does vitamin A deficiency cause?
Visual deterioration and night blindness
147
What does vitamin B2 deficiency cause?
Angular cheilitis
148
What does vitamin B3 deficiency cause?
Pellagra: dermatitis, diarrhoea and dementia
149
What does vitamin B6 deficiency cause?
Peripheral neuropathy
150
What does vitamin D deficiency cause?
Osteomalacia
151
What does vitamin K deficiency cause?
Bruising and bleeding
MRCP Part 1
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