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Clinical Sciences Flashcards

1
Q

What is the function of leptin?

A

Lowers appetite

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2
Q

Which hormone stimulates hunger, and from where is it produced?

A

Ghrelin

P/D1 cells of fundus of stomach and epsilon cells of pancreas

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3
Q

What does leptin stimulate?

A

The release of melanocyte stimulating hormone and corticotrophin releasing hormone

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4
Q

Where is central control of respiration?

A

Medullary respiratory centre, apneustic centre in lower pons, and pneumotaxic centre in upper pons

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5
Q

What do chemoreceptors respond to?

A

Raised CO2 and H+1

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6
Q

Where are peripheral chemoreceptors located?

A

Carotid and aortic bodies

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7
Q

What is the function of the Hering Bruer-reflex?

A

Avoids lung over-distension through an inhibitory feedback loop; terminates inspiration and initiates expiration when stretch receptors are activated.

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8
Q

What is the change in lung volume per unit change in airway pressure?

A

Lung compliance

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9
Q

What are the causes of increased and decreased lung compliance?

A

Increased - age, emphysema

Decreased - pulm oedema/fibrosis, kyphosis

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10
Q

What is the main functioning component of pulmonary surfactant?

A

Dipalmitoyl phosphatidylcholine (DPPC)

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11
Q

What is the function of pulmonary surfactant?

A
  • Reduces alveolar surface tension, prevents alveoli from collapsing
  • Decreases work of breathing by reducing the muscular force needed to expand the lungs
  • Lowers elastic recoil at low lung volumes
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12
Q

Name 4 physiological responses to hypoxia

A

Vasoconstriction of pulmonary arteries
Increased respiratory rate
Increased tidal volume
Tachycardia

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13
Q

What test allows assessment of upper airway obstruction?

A

Flow volume loop

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14
Q

What is transfer factor?

A

The rate at which a gas will diffuse from alveoli into blood

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15
Q

What is the difference between TLCO and KCO?

A

TLCO - total gas transfer

KCO - gas transfer corrected for lung volume - transfer co-efficient

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16
Q

Name 4 causes of raised TLCO

A 
Asthma
Pulm haemorrhage
L-->R cardiac shunts
Polycythaemia
Exercise
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17
Q

Name 4 causes of reduced TLCO

A

Pulm fibrosis/oedema
PE/pneumonia
Emphysema
Anaemia

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18
Q

Name 3 conditions that increase KCO with a normal or reduced TLCO

A

Pneumonectomy
Scoliosis
Neuromuscular weakness

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19
Q

What is tidal volume?

A

Volume inspired or expired with each breath at rest

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20
Q

What is average vital capacity in males and females?

A

Males - 4.5L

Females - 3.5L

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21
Q

What causes a left shift in oxygen dissociation curve?

A

Low H+
Low pCO2
Low 2,3-DPG
Low temp

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22
Q

Macrophages produce which interleukins?

A

IL-1, IL-6, IL-8, TNF-alpha

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23
Q

Which interleukin activates macrophages?

A

IFN-gamma

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24
Q

Which interleukin causes neutrophil chemotaxis?

A

IL-8

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25
Q

What is the function of IL-5?

A

Stimulates production of eosinophils

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26
Q

What is the function of IL-2, IL-3, and IL-4?

A

IL-2: T cells
IL-3: myeloid progenitor cells
IL-4: B cells

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27
Q

Which cytokine is the anti-inflammatory cytokine, and what is it produced by?

A

IL-10

Th2 cells

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28
Q

What is the function of IL-1?

A

Increased expression of adhesion molecules on endothelium
Stimulates release of PAF, NO, prostacyclin
Vasodilation

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29
Q

What is the function of Th1 cells?

A

Cell mediated response
Delayed type IV hypersensitivity
Secrete IFN-gamma, IL-2, IL-3

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30
Q

What is the function of Th2 cells?

A

Humoral immunity e.g. stimulate production of IgE in asthma

Secrete IL4, IL-5, IL-6, IL-10, IL-13

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31
Q

What is the cause of macrophage activation syndrome?

A

IFN gamma activates macrophages

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32
Q

What is the diagnostic criteria of macrophage activation syndrome?

A 
Ferritin >684 and 2 of:
-Plts<181
AST>48
Triglycerides>156
Fibrinogen<360
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33
Q

What is the least abundant antibody in the blood?

A

IgE

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34
Q

What is the most common antibody in the blood?

A

IgG

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35
Q

Which is the first antibody to be secreted in response to infection?

A

IgM

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36
Q

What is the function of complement?

A

Chemotaxis
Cell lysis
Opsonisation

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37
Q

What does deficiency of C1q, C1rs, C2, and C4 predispose to?

A

Immune complex disease

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38
Q

What does C3 deficiency predispose to?

A

Recurrent bacterial infection

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39
Q

What is Leiner disease?

A

C5 deficiency

Diarrhoea, wasting, seborrheic dermatitis

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40
Q

What does C5 to C9 deficiency predispose to?

A

Neisseria meningitidis

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41
Q

What is the cause of hereditary angioedema?

A

C1 inhibitor deficiency leading to uncontrolled release of bradykinin

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42
Q

What is the function of the RER?

A

Translation and folding of new proteins
Manufacture of lysosomal enzymes
N-linked glycosylation

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43
Q

Where does steroid and lipid synthesis occur in the cell?

A

Smooth endoplasmic reticulum

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44
Q

Golgi adds mannose-6-phosphate to proteins for what reason?

A

Transport to lysosome

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45
Q

What is the function of the mitochrondria?

A

Aerobic respiration
Mitochondrial genome - circular DNA
Makes ATP

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46
Q

What is RNA splicing?

A

The process that removes introns (non coding gene sequences) from pre-mRNA and joins the exons

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47
Q

What occurs in the nucleolus?

A

Ribosome production

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48
Q

What is the function of the ribosome?

A

Translation of RNA into proteins

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49
Q

What is the function of the proteasome?

A

Degradation of protein molecules that have been tagged with ubiquitin

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50
Q

What is mean arterial pressure?

A

Average arterial pressure throughout cardiac cycle

Diastolic blood pressure x 0.66 and systolic blood pressure x 0.33

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51
Q

What are the causes of increased pulse pressure?

A

Less compliant aorta, increased stroke volume

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52
Q

Define stroke volume

A

End diastolic LV volume - end systolic LV volume

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53
Q

Which part of the antibody binds with cell surface receptors?

A

Fc region

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54
Q

Why is thiamine important to the catabolism of sugars and amino acids?

A

One of its phosphate derivatives, thiamine pyrophosphate (TPPP) is a co-enzyme in reactions such as pyruvate dehydrogenase complex

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55
Q

Causes of thiamine deficiency?

A

Malnutrition

Alcohol excess

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56
Q

What are the manifestations of thiamine deficiency?

A

Wernicke’s encephalopathy: nystagmus, ophthalmoplegia, ataxia
Korsakoff’s syndrome: amnesia, confabulation
Dry beriberi: peripheral neuropathy
Wet beriberi: dilated cardiomyopathy

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57
Q

Name 4 negative acute phase proteins

A

Albumin
Transferrin
Retinol binding protein
Cortisol binding protein

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58
Q

What causes depolarisation in the cardiac action potential?

A

Rapid sodium influx

59
Q

What causes Phase 1 (early repolarisation) and Phase 3 (final repolarisation) in the cardiac action potential?

A

Efflux of potassium

60
Q

What does slow influx of calcium do in the cardiac action potential?

A

Plateau (phase 2)

61
Q

How is phase 4 of the cardiac action potential achieved?

A

Na/K/ATPase - slow entry of Na into the cell until the threshold potential is reached, triggering a new AP

62
Q

What is the speed of atrial, AV nodal, and ventricular conduction?

A

Atrial - 1m/s
AV nodal: 0.05m/s
Ventricular: 2-4m/s

63
Q

From where is ANP secreted from and why?

A

Right atrium and ventricle

Response to increased blood volume

64
Q

What is the function of ANP?

A

Promotes excretion of sodium, lowers BP, antagonises action of angiotensin II and aldosterone

65
Q

What is the process of atherosclerosis?

A
  1. Endothelial dysfunction
  2. Pro-inflammatory, reduced NO, pro-oxidant changes to endothelium
  3. Fatty infiltration of subendothelial space by LDL particles
  4. Monocytes –> macrophages
  5. Macrophages phagocytose oxidised LDL and turn into foam cells
  6. Macrophages die
  7. Smooth muscle proliferation and migration from tunica media –> fibrous capsule covering the fatty plaque
66
Q

What do the troponins bind to?

A

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

67
Q

Substances used to measure GFR have to be:

A

Inert
Free filtered (not protein bound)
Not absorbed or secreted at the tubules
Constant plasma concentration during urine collection

68
Q

Which part of the Loop of Henle is impermeable to water?

A

Thin ascending limb

69
Q

What is the typical GFR?

A

125mls/min

70
Q

What is type 1 hypersensitivity?

A

Anaphylactic

Antigen reacts with IgE bound to mast cells

71
Q

Immune complex disease is an example of what type of hypersensitivity reaction?

A

Type 3
Free antigen and antibody combine
E.g. SLE, post strep GN, EAA

72
Q

What is type 2 hypersensitivity?

A

Cell bound

E.g. ITP, Goodpasture’s, pernicious anaemia, rheumatic fever, pemphigus

73
Q

What is type 4 hypersensitivity?

A

Delayed
T-cell mediated
E.g. TB, graft vs host, EAA, MS, GBS

74
Q

Rheumatoid arthritis is associated with which HLA subtype?

75
Q

On which chromosome are the HLA antigens encoded for?

76
Q

What are the HLA associations for haemochromatosis, Behcet’s disease, and coeliac disease?

A

Haemochromatosis: A3
Behcet’s: B51
Coeliac: DQ2/DQ8

77
Q

What are the HLA associations for ankylosing spondylitis, narcolepsy/Goodpasture’s, dermatitis herpetiformis, and Sjogren’s syndrome

A

AS: B27
Narcolepsy/Goodpasture’s: DR2
DH/Sjogren’s: DR3

78
Q

Give 3 examples of ligand-gated ion channels.

A

Nicotinic acetylcholine, GABA-A/C, glutamate

79
Q

Insulin and IGF-1 act on what type of membrane receptors?

A

Tyrosine kinase

80
Q

Which type of membrane receptors transmit messages slowly?

A

G-protein coupled

81
Q

What do the following tumour suppressor genes correspond to?

  1. p53 (controls apoptosis)
  2. APC
  3. BRCA1 or 2 (controls DNA repair)
  4. NF-1
  5. Rb (freezes the cell cycle)
  6. WT1
  7. MTS-1 and p16
A
  1. Li-Fraumeni syndrome
  2. Colorectal Ca
  3. Breast/ovarian Ca
  4. Neurofibromatosis 1
  5. Retinoblastoma
  6. Wilm’s tumour
  7. Melanoma
82
Q

Where is iron absorbed?

A

Upper small intestine especially the duodenum

83
Q

What inhibits and increases iron absorption?

A

Inhibits: PPI, tetracycline, tannin
Increases: vitamin C, gastric acid

84
Q

Where is the majority of iron stored?

A

Haemoglobin

85
Q

How is iron transported?

A

Carried in plasma as Fe3+ bound to transferrin

86
Q

Name 4 causes of increased iron levels without iron overload

A

Inflammation
Alcohol XS
Liver disease
CKD

87
Q

In what condition are Mallory bodies seen?

A

Alcoholism

88
Q

What are the histological features of granulosa cell tumours and yolk sac tumours?

A

Granulosa: Call-Exner bodies

Yolk sac: Schiller-Duval

89
Q

In what condition are Aschoff bodies seen?

A

Rheumatic heart disease

90
Q

Which cell surface protein is found on mantle cell lymphomas?

91
Q

CD4 is found on T helper cells and used by which virus to enter T cells?

92
Q

What is the cell surface marker for macrophages?

93
Q

Which cell surfaces marker are expressed on Reed-Sternberg cells?

A

CD15 and CD30

94
Q

CD21 is the cell surface receptor for which virus?

95
Q

Which cell surface markers are unique markers for natural killer cells, and cytotoxic T cells?

A

NK: CD56
Cytotoxic: CD8

96
Q

Which cells are involved in hyperacute, acute, and chronic organ rejectin?

A

Hyperacute: B cells

Acute and chronic: helper T cells

97
Q

What is nitric oxide formed from?

A

L-arginine and oxygen

By nitric oxide synthetase

98
Q

Why does nitric oxide have a very short half life?

A

It is in activated by oxygen free radicals

99
Q

What are the effects of nitric oxide?

A

Vaso, mainly venodilation
Inhibits platelet aggregation
Acts on guanylate cyclase leading to raised intracellular cGMP, therefore decreasing Ca2+

100
Q

What receptors do interferon alpha, beta, and gamma bind to?

A

Alpha and beta - type 1

Gamma - type 2

101
Q

What is IFN-a used in the treatment of?

A

Hepatitis B and C
Kaposi’s sarcoma
Metastatic renal cell carcinoma
Hairy cell leukaemia

102
Q

What are the side effects of IFN-a

A

Flu like symptoms, depression

103
Q

Which interferon is used in reducing the frequency of exacerbations in relapsing-remitting MS?

104
Q

Which cells produce interferons?

A

Leucocytes - IFN-a
Fibroblasts - IFN-b
NK and T helper - IFN-g

105
Q

What is the role of IFN-g?

A

Weaker antiviral action compared to IFN-b and IFN-a
Immunomodulation –> macrophage activation
Useful in osteopetrosis and chronic granulomatous disease

106
Q

Where is endothelin secreted and how is it activated?

A

Secreted by vascular endothelium

Converted to ET-1 by endothelin converting enzyme

107
Q

What is the mechanism of action of endothelin?

A

Interacts with a G protein linked to phospholipase C

Leads to calcium release

108
Q

What inhibits and promotes endothelin release?

A

Inhibits: NO, prostacyclin
Promotes: Angiotensin II, ADH, hypoxia, mechanical shearing forces

109
Q

In what conditions is raised endothelin seen?

A

PAH
MI, CCF
AKI
Asthma

110
Q

Where is renin secreted?

A

Juxtaglomerular cells

111
Q

What is the function of renin?

A

Hydrolyses angiotensinogen to produce angiotensin I

112
Q

What causes renin secretion?

A

Hypotension –> reduced renal perfusion
Hyponatraemia
Sympathetic nerve stimulation
Catecholamines

113
Q

What reduces renin secretion?

A

BB have direct effect on adrenoreceptors in JGA

NSAIDs

114
Q

What are the symptoms of congenital toxoplasmosis?

A

Cerebral calcification

Chorioretinitis

115
Q

What are the symptoms of congenital rubella?

A

Sensorineural deafness

Congenital cataracts

116
Q

How does N-acetylcysteine work in paracetamol overdoses?

A

NAC is a precursor of glutathione, which conjugates the toxic metabolite of paracetamol (N-acetyl B benzoquinone imine) to mercapturic acid

117
Q

How does the toxic metabolite of paracetamol cause liver or kidney failure?

A

The toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death

118
Q

Why is there a lower threshold for treating patients for paracetamol overdose with NAC, if they take P450 inducers such as phenytoin or rifampicin?

A

During an overdose, the conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases

119
Q

What is cryoglobulinaemia?

A

Immunoglobulins which undergo reversible precipitation at 4 degrees, and dissolve when warmed to 37 degrees

120
Q

What is type 1 cryoglobulinaemia?

A

Monoclonal (IgM/IgG)

Associated with multiple myeloma and waldenstrom’s macroglobulinaemia

121
Q

What is the difference between type 2 and type 3 cryoglobulinaemia?

A

T2 mixed monoclonal and polyclonal, T3 polyclonal.

Both associated with RA and Sjogren’s but only T2 associated with hepatitis C

122
Q

What are the features of cryoglobulinaemia?

A 
Raynaud's in type 1
Vascular purpura and ulcers
Arthralgia
Diffuse glomerulonephritis
Low complement, esp C4
123
Q

What is the treatment of cryoglobulinaemia?

A

Immunosuppression

Plasmaphresis

124
Q

What is the function of Vitamin A in the body?

A

Required by the retina to produce rhodopsin

125
Q

What is the cause of Vitamin B3/niacin deficiency and how does it manifest?

A

Isoniazid (inhibits the conversion of tryptophan to niacin)
Malnutrition

Pellagra: dermatitis, diarrhoea, dementia

126
Q

Which vitamin is required as a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)?

A

Vitamin B2 (ribaflavin)

127
Q

What are the symptoms of Vitamin B2 deficiency?

A

Angular cheilitis

128
Q

What are the features of transfusion-associated graft versus host disease?

A

Occurs 2-6 weeks after transmission

Diarrhoea, liver damage, rash

129
Q

What are the phase I and II stages of drug metabolism?

A

Phase 1: oxidation, reduction, hydrolysis

Phase 2: conjugation

130
Q

What is first pass metabolism?

A

Where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism

131
Q

Which drugs are affected by first pass metabolism?

A

PHIL V GAIT

Propanolol
Hydrocortisone
Isoprenaline
Lidocaine

Verapamil

GTN
Aspirin
Isosorbide mononitrate
Testosterone

132
Q

What is zero order kinetics?

A

Metabolism of a drug is independent of the concentration

Due to metabolic pathways becoming saturated

133
Q

Which drugs exhibit zero order kinetics?

A

PSHE:

Phenytoin
Salicylates
Heparin
Ethanol

134
Q

What is acetylator status?

A

50% of the UK population are deficient in hepatic N-acetyltransferase

135
Q

What drugs are affected by acetylator status?

A

D-SHIP

Dapsone
-
Sulfalsalazine
Hydralazine
Isoniazid
Procainamide
136
Q

If a drug binds to nuclear receptors, what must it be?

A

Lipid soluble

137
Q

Name 2 examples of drugs that act on nuclear receptors.

A

Levothyroxine

Prednisolone

138
Q

Give an example of a G-protein coupled receptors

A

Adrenoreceptors

139
Q

Name 5 immunological changes in HIV.

A 
Reduced CD4
Increased B2 microglobulin
Decreased IL-2
Polyclonal B cell activation
Decreased NK cell function
 Reduced T4 hypersensitivity response
140
Q

What are 5 types of mutations?

A 
Frame-shift
Mis-sense
Nonsense
Insertion
Point
141
Q

What is a frame shift mutation?

A

Insertion of nucleotides not in a group of 3, therefore changes the frame in which translation occurs

142
Q

What is a mis-sense mutation?

A

Codon codes for a different amino acid

143
Q

What is a nonsense mutation?

A

A triplet coding for an amino acid now codes for a termination codon

144
Q

What is a read through mutation?

A

Termination codon changes to a codon that codes for an amino acid

MRCP (17 decks)

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