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MRCP > Clinical Sciences > Flashcards

Clinical Sciences Flashcards

1
Q

Name some blood film findings in hyposplenism

A 
Target cells
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
Acanthocytes
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2
Q

What is hereditary angioedema?

A

An autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein.

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3
Q

How do you diagnose HAE?

A

Low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool

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4
Q

Name the MOA of cyclophosphamide

A

Alkylating agent - causes cross-linking in DNA

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5
Q

Name some side effects of cyclophosphamide

A

Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma

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6
Q

Name some side effects of cisplatin

A

Ototoxicity, peripheral neuropathy, hypomagnesaemia

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7
Q

Which carcinogen increases the risk of HCC?

A

Aflatoxin (produced by Aspergillus)

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8
Q

Which carcinogen increases the risk of oesophageal and gastric cancer?

A

Nitrosamines

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9
Q

Name some causes of SVC obstruction

A

Common malignancies: small cell lung cancer, lymphoma
Other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
Aortic aneurysm
Mediastinal fibrosis
Goitre
SVC thrombosis

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10
Q

What percentage of those with coeliac disease have hyposplenism?

A

30%

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11
Q

Which drugs inhibit microtubule assembly?

A

Vincristine, vinblastine

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12
Q

Which drug prevents microtubule disassembly?

A

Docetaxel

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13
Q

Which conditions are thymomas associated with?

A

Myasthenia gravis (30-40% of patients with thymoma)
Red cell aplasia
Dermatomyositis
Also : SLE, SIADH

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14
Q

What are the signs and symptoms of AIP?

A

Abdominal: abdominal pain, vomiting
Neurological: motor neuropathy
Psychiatric: e.g. depression
Hypertension and tachycardia common

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15
Q

How do you diagnose AIP?

A

Classically urine turns deep red on standing
Raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
Assay of red cells for porphobilinogen deaminase
Raised serum levels of delta aminolaevulinic acid and porphobilinogen

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16
Q

What is the management for AIP?

A

Avoiding triggers
Acute attacks
IV haematin/haem arginate
IV glucose should be used if haematin/haem arginate is not immediately available

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17
Q

What is polycythaemia rubra vera?

A

A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.

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18
Q

What is Wiskott-Aldrich syndrome?

A

Wiskott-Aldrich syndrome causes primary immunodeficiency due to a combined B- and T-cell dysfunction. It is inherited in a X-linked recessive fashion and is thought to be caused by mutation in the WASP gene.

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19
Q

What is vitamin B6?

A

Pyridoxine - converted to pyridoxal phosphate - cofactor for many enzymes including transamination, deamination and decarboxylation

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20
Q

What are the clinical signs of B6 deficiency?

A

Peripheral neuropathy

Sideroblastic anemia

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21
Q

What is vitamin B3?

A

Niacin - a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.

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22
Q

What are the signs and symptoms of B3 deficiency?

A

Dermatitis, diarrhoea, dementia

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23
Q

Where is leptin produced?

A

Adipose tissue

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24
Q

Where is ghrelin produced?

A

It is produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas

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25
Q

What does leptin stimulate?

A

Leptin stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH). Low levels of leptin stimulates the release of neuropeptide Y (NPY)

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26
Q

What is HLA-DR4 associated with?

A

Type 1 diabetes mellitus*

Rheumatoid arthritis - in particular the DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)

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27
Q

What is HLA-B27 associated with?

A

Ankylosing spondylitis
Reactive arthritis
Acute anterior uveitis

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28
Q

What is HLA-DR2 associated with?

A

Goodpasture’s syndrome

Narcolepsy

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29
Q

Give some examples of type III hypersensitivity reactions

A

Serum sickness
Systemic lupus erythematosus
Post-streptococcal glomerulonephritis
Extrinsic allergic alveolitis (especially acute phase)

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30
Q

What is the function of the Golgi apparatus?

A

Modifies, sorts, and packages these molecules that are destined for cell secretion
The addition of mannose-6-phosphate to proteins designates transport to lysosome

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31
Q

What is the Mann-Whitney U test?

A

Compares ordinal, interval, or ratio scales of unpaired data

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32
Q

What is the Wilcoxon signed rank test?

A

Compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention

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33
Q

What are the ideal properties of a substance that measures GFR?

A
  1. Inert
  2. Free filtration from the plasma at the glomerulus (not protein bound)
  3. Not absorbed or secreted at the tubules
  4. Plasma concentration constant during urine collection
    examples: inulin, creatinine
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34
Q

Which part of the nephron is impermeable to water?

A

Thin ascending limb

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35
Q

What conditions are associated with HLA-DR3?

A

Dermatitis herpetiformis
Sjogren’s syndrome
Primary biliary cirrhosis

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36
Q

What is the triad of Wernicke’s encephalopathy?

A

Confusion, ophthalmoplegia, ataxia

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37
Q

Name the types of correlation tests

A

Spearman, Kendall rank - correlation - non parametric

Pearson’s - parametric

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38
Q

Give some examples of ligand gates ion channel receptors

A

generally mediate fast responses
e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate receptors

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39
Q

Give some examples of tyrosine kinase receptors

A

receptor tyrosine kinase: insulin, insulin-like growth factor (IGF), epidermal growth factor (EGF)
non-receptor tyrosine kinase: PIGG(L)ET: Prolactin, Immunomodulators (cytokines IL-2, Il-6, IFN), GH, G-CSF, Erythropoietin and Thromobopoietin

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40
Q

Give some examples of guanylate cyclase receptors

A

contain intrinsic enzyme activity
e.g. atrial natriuretic factor, brain natriuretic peptide

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41
Q

Name some G protein coupled receptors

A

generally mediate slow transmission and affect metabolic processes
activated by a wide variety of extracellular signals e.g. Peptide hormones, biogenic amines (e.g. adrenaline), lipophilic hormones, light
7-helix membrane-spanning domains
consist of 3 main subunits: alpha, beta and gamma
the alpha subunit is linked to GDP.Ligand binding causes conformational changes to receptor, GDP is phosphorylated to GTP,and the alpha subunit is activated
G proteins are named according to the alpha subunit (Gs, Gi, Gq)

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42
Q

What is the main source of IFN-gamma and what does it activate

A

Source: Th1
Activates: macrophages

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43
Q

Name some characteristics of IgM

A
  • First immunoglobulins to be secreted in response to an infection
  • Fixes complement but does not pass to the fetal circulation
  • Anti-A, B blood antibodies (note how they cannot pass to the fetal circulation, which could of course result in haemolysis)
    Pentamer when secreted
44
Q

What is the MoA of GH?

A

Mechanism of action
acts on a transmembrane receptor for growth factor
binding of GH to the receptor leads to receptor dimerization
acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver

45
Q

What happens in prophase?

A

Chromatin in the nucleus condenses

46
Q

What happens in prometaphase?

A

Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes

47
Q

What happens in metaphase?

A

Chromosomes aligned at middle of cell

48
Q

What happens in anaphase?

A

The paired chromosomes separate at the kinetochores and move to opposite sides of the cell

49
Q

What happens in telophase?

A

Chromatids arrive at opposite poles of cell

50
Q

What happens during cytokinesis?

A

Actin-myosin complex in the centre of the cell contacts resulting in it being ‘pinched’ into two daughter cells

51
Q

What is the risk of Down’s with increasing maternal age?

A

One way of remembering this is by starting at 1/1,000 at 30 years and then dividing the denominator by 3 (i.e. 3 times more common) for every extra 5 years of age

52
Q

Name some autosomal recessive conditions

A

Albinism
Ataxic telangiectasia
Congenital adrenal hyperplasia
Cystic fibrosis
Cystinuria
Familial Mediterranean Fever
Fanconi anaemia
Friedreich’s ataxia
Gilbert’s syndrome*
Glycogen storage disease
Haemochromatosis
Homocystinuria
Lipid storage disease: Tay-Sach’s, Gaucher, Niemann-Pick
Mucopolysaccharidoses: Hurler’s
PKU
Sickle cell anaemia
Thalassaemias
Wilson’s disease

53
Q

Which surface markers are expressed on Reed-Sternberg cells?

A

CD15 and CD30

54
Q

What are the nerve roots of the axillary nerve?

A

C5, C6

55
Q

Describe iron metabolism

A

Absorption
upper small intestine especially the duodenum
about 10% of dietary iron absorbed
Fe2+ (ferrous iron) much better absorbed than Fe3+ (ferric iron)
absorption is regulated according to body’s need
increased by vitamin C, gastric acid
decreased by proton pump inhibitors, tetracycline, gastric achlorhydria, tannin (found in tea)

Distribution in body
total body iron = 4g
haemoglobin = 70%
ferritin and haemosiderin = 25%
myoglobin = 4%
plasma iron = 0.1%

Transport
carried in plasma as Fe3+ bound to transferrin

Storage
stored as ferritin in tissues

Excretion
lost via intestinal tract following desquamation

56
Q

Name some properties of the normal distribution

A

The normal distribution is also known as the Gaussian distribution or ‘bell-shaped’ distribution. It describes the spread of many biological and clinical measurements

Properties of the Normal distribution
symmetrical i.e. Mean = mode = median
68.3% of values lie within 1 SD of the mean
95.4% of values lie within 2 SD of the mean
99.7% of values lie within 3 SD of the mean
this is often reversed, so that within 1.96 SD of the mean lie 95% of the sample values
the range of the mean - (1.96 *SD) to the mean + (1.96 * SD) is called the 95% confidence interval, i.e. If a repeat sample of 100 observations are taken from the same group 95 of them would be expected to lie in that range

Standard deviation
the standard deviation is a measure of how much dispersion exists from the mean
standard deviation = square root (variance)

57
Q

What is a Mann-Whitney U test used for?

A

Compares ordinal, interval, or ratio scales of unpaired data

58
Q

What is the function of the Golgi apparatus?

A

Modifies, sorts, and packages these molecules that are destined for cell secretion
The addition of mannose-6-phosphate to proteins designates transport to lysosome

59
Q

Name some examples of type II hypersensitivity reactions

A
  • Autoimmune haemolytic anaemia
  • ITP
  • Goodpasture’s syndrome
  • Pernicious anaemia
  • Acute haemolytic transfusion reactions
  • Rheumatic fever
  • Pemphigus vulgaris / bullous pemphigoid
60
Q

Which cancers can EBV cause?

A

Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma

61
Q

Which cancers can HPV 16/18 cause?

A

Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer

62
Q

What is the Hering-Breuer reflex?

A

The Hering-Breuer reflex is a physiological mechanism that prevents over-inflation of the lungs. It involves stretch receptors in the lung parenchyma, which send inhibitory signals to the medullary respiratory centres via the vagus nerve when the lungs become overly distended during inspiration. This ultimately results in a decrease in the respiratory rate and volume, protecting against potential lung damage from over-inflation.

63
Q

What is the function of the lysosome?

A

Breakdown of large molecules such as proteins and polysaccharides

64
Q

Where are the trunks of the brachial plexus located?

A

Located posterior to middle third of clavicle
Upper and middle trunks related superiorly to the subclavian artery
Lower trunk passes over 1st rib posterior to the subclavian artery

65
Q

Where are the cords of the brachial plexus located?

A

Related to axillary artery

66
Q

What is lead time bias?

A

Occurs when two tests for a disease are compared, the new test diagnoses the disease earlier, but there is no effect on the outcome of the disease

67
Q

What is the function of the ribosome?

A

Translation of RNA into proteins

68
Q

What are interferons?

A

Interferons (IFN) are cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.

69
Q

Name some properties of interferon alpha

A

produced by leucocytes
antiviral action
useful in hepatitis B & C, Kaposi’s sarcoma, metastatic renal cell cancer, hairy cell leukaemia
adverse effects include flu-like symptoms and depression

70
Q

Explain the mechanism of Gs receptors

A

Stimulates adenylate cyclase → increases cAMP → activates protein kinase A

71
Q

Explain the mechanism of Gi receptors

A

Inhibits adenylate cyclase → decreases cAMP → inhibits protein kinase A

72
Q

Explain the mechanism of Gq receptors

A

Activates phospholipase C → splits PIP2 to IP3 & DAG → activates protein kinase C

73
Q

Name some features of Fabry disease

A

Overview
X-linked recessive
deficiency of alpha-galactosidase A

Features
burning pain/paraesthesia in childhood
angiokeratomas
lens opacities
proteinuria
early cardiovascular disease

74
Q

Name some functions of vitamin D

A

increases plasma calcium and plasma phosphate
increases renal tubular reabsorption and gut absorption of calcium
increases osteoclastic activity
increases renal phosphate reabsorption

75
Q

What complement deficiencies can result in SLE?

A

C1q, C1rs, C2 and C4

76
Q

Name some characteristics of mitochondrial inheritance

A

inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
none of the children of an affected male will inherit the disease
all of the children of an affected female will inherit the disease
generally, encode rare neurological diseases
poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy

77
Q

How do you calculate the likelihood ratio for a positive result?

A

sensitivity / (1 - specificity)

78
Q

How do you calculate the likelihood ratio for a negative result?

A

(1 - sensitivity) / specificity

79
Q

Name some features of PKU

A

usually presents by 6 months e.g. with developmental delay
child classically has fair hair and blue eyes
learning difficulties
seizures, typically infantile spasms
eczema
‘musty’ odour to urine and sweat*

80
Q

Which CD is associated with EBV?

A

CD21

81
Q

Which CD is associated with HL?

A

CD15 and CD30

82
Q

What is the inheritance pattern of albinism?

A

Autosomal recessive

83
Q

What is vitamin B2?

A

Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism.

84
Q

Name some features of congenital toxoplasmosis

A

Cerebral calcification
Chorioretinitis
Hydrocephalus

85
Q

Describe the layers of the epidermis

A

Stratum corneum Flat, dead, scale-like cells filled with keratin
Continually shed
Stratum lucidum Clear layer - present in thick skin only
Stratum granulosum Cells form links with neighbours
Stratum spinosum Squamous cells begin keratin synthesis
Thickest layer of epidermis
Stratum germinativum The basement membrane - single layer of columnar epithelial cells
Gives rise to keratinocytes
Contains melanocytes

86
Q

Name some features of DiGeorge syndrome

A

C - Cardiac abnormalities
A - Abnormal facies
T - Thymic aplasia
C - Cleft palate
H - Hypocalcaemia/ hypoparathyroidism
22 - Caused by chromosome 22 deletion

87
Q

Name some non parametric tests

A

Mann-Whitney U test
compares ordinal, interval, or ratio scales of unpaired data
Wilcoxon signed-rank test
compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention
chi-squared test
used to compare proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
Spearman, Kendall rank - correlation

88
Q

Describe the subunits of troponin

A

troponin C: binds to calcium ions
troponin T: binds to tropomyosin, forming a troponin-tropomyosin complex
troponin I: binds to actin to hold the troponin-tropomyosin complex in place

89
Q

Explain the pathophysiology of Lesch-Nyhan syndrome

A

It is a genetic condition with an X-linked pattern of inheritance. It is caused by a defect in the purine salvage pathway due to the absence of the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme which catalyzes the conversion of hypoxanthine to inosine monophosphate (IMP) and guanine to guanosine monophosphate (GMP).

90
Q

What is the function of Th1 cells?

A

involved in the cell-mediated response and delayed (type IV) hypersensitivity
secrete IFN-gamma, IL-2, IL-3

91
Q

What is the function of Th2 cells?

A

involved in mediating humoral (antibody) immunity
e.g. stimulating production of IgE in asthma
secrete IL-4, IL-5, IL-6, IL-10, IL-13

92
Q

Explain the goal of phase II trials

A

Involves small number of patients affected by particular disease

May be subdivided into
IIa - assesses optimal dosing
IIb - assesses efficacy

93
Q

What is lung compliance?

A

Lung compliance is defined as change in lung volume per unit change in airway pressure

94
Q

Name some causes of decreased compliance

A

pulmonary oedema
pulmonary fibrosis
pneumonectomy
kyphosis

95
Q

What conditions are associated with HLA-DR4?

A

type 1 diabetes mellitus*
rheumatoid arthritis - in particular the DRB1 gene (DRB104:01 and DRB104:04 hence the association with DR4)

96
Q

What conditions are associated with HLA-DR3?

A

dermatitis herpetiformis
Sjogren’s syndrome
primary biliary cirrhosis

97
Q

What does leptin stimulate?

A

Leptin stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH). Low levels of leptin stimulates the release of neuropeptide Y (NPY)

98
Q

What is leptin secreted by?

A

Adipose tissue

99
Q

Name some features of Fabry disease

A

burning pain/paraesthesia in childhood
angiokeratomas
lens opacities
proteinuria
early cardiovascular disease

100
Q

What is the defect in Gaucher’s disease?

A

Beta-glucocerebrosidase

101
Q

Name some features of Tay-Sachs disease

A

Accumulation of GM2 ganglioside within lysosomes. Key features include developmental delay, cherry red spot on the macula, liver and spleen normal size (cf. Niemann-Pick)

102
Q

Describe the anatomy of the renal hilum

A

The renal vein lies most anteriorly, then renal artery (it is an end artery) and the ureter lies most posterior.

103
Q

Where is IL-1 normally produced?

A

By macrophages and monocytes

104
Q

Give some examples of IL-1 inhibitors

A

anakinra
IL-1 receptor antagonist
used in the management of rheumatoid arthritis
canakinumab
monoclonal antibody targeted at IL-1 beta
used systemic juvenile idiopathic arthritis and adult-onset Still’s disease

105
Q

Name some features of Fragile X syndrome

A

learning difficulties
large low set ears, long thin face, high arched palate
macroorchidism
hypotonia
autism is more common
mitral valve prolapse

106
Q

Name some features of Noonan syndrome

A

cardiac: pulmonary valve stenosis
ptosis
triangular-shaped face
low-set ears
coagulation problems: factor XI deficiency

107
Q

What is penetrance?

A

Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype.

MRCP (13 decks)

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