Clinical Sciences Flashcards
1
Q
What is the function of leptin?
A
Lowers appetite
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
3
Q
What does leptin stimulate?
A
The release of melanocyte stimulating hormone and corticotrophin releasing hormone
4
Q
Where is central control of respiration?
A
Medullary respiratory centre, apneustic centre in lower pons, and pneumotaxic centre in upper pons
5
Q
What do chemoreceptors respond to?
A
Raised CO2 and H+1
6
Q
Where are peripheral chemoreceptors located?
A
Carotid and aortic bodies
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.
8
Q
What is the change in lung volume per unit change in airway pressure?
A
Lung compliance
9
Q
What are the causes of increased and decreased lung compliance?
A
Increased - age, emphysema
Decreased - pulm oedema/fibrosis, kyphosis
10
Q
What is the main functioning component of pulmonary surfactant?
A
Dipalmitoyl phosphatidylcholine (DPPC)
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
12
Q
Name 4 physiological responses to hypoxia
A
Vasoconstriction of pulmonary arteries
Increased respiratory rate
Increased tidal volume
Tachycardia
13
Q
What test allows assessment of upper airway obstruction?
A
Flow volume loop
14
Q
What is transfer factor?
A
The rate at which a gas will diffuse from alveoli into blood
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
16
Q
Name 4 causes of raised TLCO
A
Asthma Pulm haemorrhage L-->R cardiac shunts Polycythaemia Exercise
17
Q
Name 4 causes of reduced TLCO
A
Pulm fibrosis/oedema
PE/pneumonia
Emphysema
Anaemia
18
Q
Name 3 conditions that increase KCO with a normal or reduced TLCO
A
Pneumonectomy
Scoliosis
Neuromuscular weakness
19
Q
What is tidal volume?
A
Volume inspired or expired with each breath at rest
20
Q
What is average vital capacity in males and females?
A
Males - 4.5L
Females - 3.5L
21
Q
What causes a left shift in oxygen dissociation curve?
A
Low H+
Low pCO2
Low 2,3-DPG
Low temp
22
Q
Macrophages produce which interleukins?
A
IL-1, IL-6, IL-8, TNF-alpha
23
Q
Which interleukin activates macrophages?
A
IFN-gamma
24
Q
Which interleukin causes neutrophil chemotaxis?
A
IL-8
25
What is the function of IL-5?
Stimulates production of eosinophils
26
What is the function of IL-2, IL-3, and IL-4?
IL-2: T cells
IL-3: myeloid progenitor cells
IL-4: B cells
27
Which cytokine is the anti-inflammatory cytokine, and what is it produced by?
IL-10
| Th2 cells
28
What is the function of IL-1?
Increased expression of adhesion molecules on endothelium
Stimulates release of PAF, NO, prostacyclin
Vasodilation
29
What is the function of Th1 cells?
Cell mediated response
Delayed type IV hypersensitivity
Secrete IFN-gamma, IL-2, IL-3
30
What is the function of Th2 cells?
Humoral immunity e.g. stimulate production of IgE in asthma
| Secrete IL4, IL-5, IL-6, IL-10, IL-13
31
What is the cause of macrophage activation syndrome?
IFN gamma activates macrophages
32
What is the diagnostic criteria of macrophage activation syndrome?
```
Ferritin >684 and 2 of:
-Plts<181
AST>48
Triglycerides>156
Fibrinogen<360
```
33
What is the least abundant antibody in the blood?
IgE
34
What is the most common antibody in the blood?
IgG
35
Which is the first antibody to be secreted in response to infection?
IgM
36
What is the function of complement?
Chemotaxis
Cell lysis
Opsonisation
37
What does deficiency of C1q, C1rs, C2, and C4 predispose to?
Immune complex disease
38
What does C3 deficiency predispose to?
Recurrent bacterial infection
39
What is Leiner disease?
C5 deficiency
| Diarrhoea, wasting, seborrheic dermatitis
40
What does C5 to C9 deficiency predispose to?
Neisseria meningitidis
41
What is the cause of hereditary angioedema?
C1 inhibitor deficiency leading to uncontrolled release of bradykinin
42
What is the function of the RER?
Translation and folding of new proteins
Manufacture of lysosomal enzymes
N-linked glycosylation
43
Where does steroid and lipid synthesis occur in the cell?
Smooth endoplasmic reticulum
44
Golgi adds mannose-6-phosphate to proteins for what reason?
Transport to lysosome
45
What is the function of the mitochrondria?
Aerobic respiration
Mitochondrial genome - circular DNA
Makes ATP
46
What is RNA splicing?
The process that removes introns (non coding gene sequences) from pre-mRNA and joins the exons
47
What occurs in the nucleolus?
Ribosome production
48
What is the function of the ribosome?
Translation of RNA into proteins
49
What is the function of the proteasome?
Degradation of protein molecules that have been tagged with ubiquitin
50
What is mean arterial pressure?
Average arterial pressure throughout cardiac cycle
| Diastolic blood pressure x 0.66 and systolic blood pressure x 0.33
51
What are the causes of increased pulse pressure?
Less compliant aorta, increased stroke volume
52
Define stroke volume
End diastolic LV volume - end systolic LV volume
53
Which part of the antibody binds with cell surface receptors?
Fc region
54
Why is thiamine important to the catabolism of sugars and amino acids?
One of its phosphate derivatives, thiamine pyrophosphate (TPPP) is a co-enzyme in reactions such as pyruvate dehydrogenase complex
55
Causes of thiamine deficiency?
Malnutrition
| Alcohol excess
56
What are the manifestations of thiamine deficiency?
Wernicke's encephalopathy: nystagmus, ophthalmoplegia, ataxia
Korsakoff's syndrome: amnesia, confabulation
Dry beriberi: peripheral neuropathy
Wet beriberi: dilated cardiomyopathy
57
Name 4 negative acute phase proteins
Albumin
Transferrin
Retinol binding protein
Cortisol binding protein
58
What causes depolarisation in the cardiac action potential?
Rapid sodium influx
59
What causes Phase 1 (early repolarisation) and Phase 3 (final repolarisation) in the cardiac action potential?
Efflux of potassium
60
What does slow influx of calcium do in the cardiac action potential?
Plateau (phase 2)
61
How is phase 4 of the cardiac action potential achieved?
Na/K/ATPase - slow entry of Na into the cell until the threshold potential is reached, triggering a new AP
62
What is the speed of atrial, AV nodal, and ventricular conduction?
Atrial - 1m/s
AV nodal: 0.05m/s
Ventricular: 2-4m/s
63
From where is ANP secreted from and why?
Right atrium and ventricle
| Response to increased blood volume
64
What is the function of ANP?
Promotes excretion of sodium, lowers BP, antagonises action of angiotensin II and aldosterone
65
What is the process of atherosclerosis?
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
What do the troponins bind to?
C: calcium ions
T: tropomyosin
I: actin, to hold the troponin-tropomyosin complex in place
67
Substances used to measure GFR have to be:
Inert
Free filtered (not protein bound)
Not absorbed or secreted at the tubules
Constant plasma concentration during urine collection
68
Which part of the Loop of Henle is impermeable to water?
Thin ascending limb
69
What is the typical GFR?
125mls/min
70
What is type 1 hypersensitivity?
Anaphylactic
| Antigen reacts with IgE bound to mast cells
71
Immune complex disease is an example of what type of hypersensitivity reaction?
Type 3
Free antigen and antibody combine
E.g. SLE, post strep GN, EAA
72
What is type 2 hypersensitivity?
Cell bound
| E.g. ITP, Goodpasture's, pernicious anaemia, rheumatic fever, pemphigus
73
What is type 4 hypersensitivity?
Delayed
T-cell mediated
E.g. TB, graft vs host, EAA, MS, GBS
74
Rheumatoid arthritis is associated with which HLA subtype?
DR4
75
On which chromosome are the HLA antigens encoded for?
6
76
What are the HLA associations for haemochromatosis, Behcet's disease, and coeliac disease?
Haemochromatosis: A3
Behcet's: B51
Coeliac: DQ2/DQ8
77
What are the HLA associations for ankylosing spondylitis, narcolepsy/Goodpasture's, dermatitis herpetiformis, and Sjogren's syndrome
AS: B27
Narcolepsy/Goodpasture's: DR2
DH/Sjogren's: DR3
78
Give 3 examples of ligand-gated ion channels.
Nicotinic acetylcholine, GABA-A/C, glutamate
79
Insulin and IGF-1 act on what type of membrane receptors?
Tyrosine kinase
80
Which type of membrane receptors transmit messages slowly?
G-protein coupled
81
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
1. Li-Fraumeni syndrome
2. Colorectal Ca
3. Breast/ovarian Ca
4. Neurofibromatosis 1
5. Retinoblastoma
6. Wilm's tumour
7. Melanoma
82
Where is iron absorbed?
Upper small intestine especially the duodenum
83
What inhibits and increases iron absorption?
Inhibits: PPI, tetracycline, tannin
Increases: vitamin C, gastric acid
84
Where is the majority of iron stored?
Haemoglobin
85
How is iron transported?
Carried in plasma as Fe3+ bound to transferrin
86
Name 4 causes of increased iron levels without iron overload
Inflammation
Alcohol XS
Liver disease
CKD
87
In what condition are Mallory bodies seen?
Alcoholism
88
What are the histological features of granulosa cell tumours and yolk sac tumours?
Granulosa: Call-Exner bodies
| Yolk sac: Schiller-Duval
89
In what condition are Aschoff bodies seen?
Rheumatic heart disease
90
Which cell surface protein is found on mantle cell lymphomas?
CD5
91
CD4 is found on T helper cells and used by which virus to enter T cells?
HIV
92
What is the cell surface marker for macrophages?
CD14
93
Which cell surfaces marker are expressed on Reed-Sternberg cells?
CD15 and CD30
94
CD21 is the cell surface receptor for which virus?
EBV
95
Which cell surface markers are unique markers for natural killer cells, and cytotoxic T cells?
NK: CD56
Cytotoxic: CD8
96
Which cells are involved in hyperacute, acute, and chronic organ rejectin?
Hyperacute: B cells
| Acute and chronic: helper T cells
97
What is nitric oxide formed from?
L-arginine and oxygen
| By nitric oxide synthetase
98
Why does nitric oxide have a very short half life?
It is in activated by oxygen free radicals
99
What are the effects of nitric oxide?
Vaso, mainly venodilation
Inhibits platelet aggregation
Acts on guanylate cyclase leading to raised intracellular cGMP, therefore decreasing Ca2+
100
What receptors do interferon alpha, beta, and gamma bind to?
Alpha and beta - type 1
| Gamma - type 2
101
What is IFN-a used in the treatment of?
Hepatitis B and C
Kaposi's sarcoma
Metastatic renal cell carcinoma
Hairy cell leukaemia
102
What are the side effects of IFN-a
Flu like symptoms, depression
103
Which interferon is used in reducing the frequency of exacerbations in relapsing-remitting MS?
IFN-b
104
Which cells produce interferons?
Leucocytes - IFN-a
Fibroblasts - IFN-b
NK and T helper - IFN-g
105
What is the role of IFN-g?
Weaker antiviral action compared to IFN-b and IFN-a
Immunomodulation --> macrophage activation
Useful in osteopetrosis and chronic granulomatous disease
106
Where is endothelin secreted and how is it activated?
Secreted by vascular endothelium
| Converted to ET-1 by endothelin converting enzyme
107
What is the mechanism of action of endothelin?
Interacts with a G protein linked to phospholipase C
| Leads to calcium release
108
What inhibits and promotes endothelin release?
Inhibits: NO, prostacyclin
Promotes: Angiotensin II, ADH, hypoxia, mechanical shearing forces
109
In what conditions is raised endothelin seen?
PAH
MI, CCF
AKI
Asthma
110
Where is renin secreted?
Juxtaglomerular cells
111
What is the function of renin?
Hydrolyses angiotensinogen to produce angiotensin I
112
What causes renin secretion?
Hypotension --> reduced renal perfusion
Hyponatraemia
Sympathetic nerve stimulation
Catecholamines
113
What reduces renin secretion?
BB have direct effect on adrenoreceptors in JGA
| NSAIDs
114
What are the symptoms of congenital toxoplasmosis?
Cerebral calcification
| Chorioretinitis
115
What are the symptoms of congenital rubella?
Sensorineural deafness
| Congenital cataracts
116
How does N-acetylcysteine work in paracetamol overdoses?
NAC is a precursor of glutathione, which conjugates the toxic metabolite of paracetamol (N-acetyl B benzoquinone imine) to mercapturic acid
117
How does the toxic metabolite of paracetamol cause liver or kidney failure?
The toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death
118
Why is there a lower threshold for treating patients for paracetamol overdose with NAC, if they take P450 inducers such as phenytoin or rifampicin?
During an overdose, the conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases
119
What is cryoglobulinaemia?
Immunoglobulins which undergo reversible precipitation at 4 degrees, and dissolve when warmed to 37 degrees
120
What is type 1 cryoglobulinaemia?
Monoclonal (IgM/IgG)
| Associated with multiple myeloma and waldenstrom's macroglobulinaemia
121
What is the difference between type 2 and type 3 cryoglobulinaemia?
T2 mixed monoclonal and polyclonal, T3 polyclonal.
| Both associated with RA and Sjogren's but only T2 associated with hepatitis C
122
What are the features of cryoglobulinaemia?
```
Raynaud's in type 1
Vascular purpura and ulcers
Arthralgia
Diffuse glomerulonephritis
Low complement, esp C4
```
123
What is the treatment of cryoglobulinaemia?
Immunosuppression
| Plasmaphresis
124
What is the function of Vitamin A in the body?
Required by the retina to produce rhodopsin
125
What is the cause of Vitamin B3/niacin deficiency and how does it manifest?
Isoniazid (inhibits the conversion of tryptophan to niacin)
Malnutrition
Pellagra: dermatitis, diarrhoea, dementia
126
Which vitamin is required as a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)?
Vitamin B2 (ribaflavin)
127
What are the symptoms of Vitamin B2 deficiency?
Angular cheilitis
128
What are the features of transfusion-associated graft versus host disease?
Occurs 2-6 weeks after transmission
| Diarrhoea, liver damage, rash
129
What are the phase I and II stages of drug metabolism?
Phase 1: oxidation, reduction, hydrolysis
| Phase 2: conjugation
130
What is first pass metabolism?
Where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism
131
Which drugs are affected by first pass metabolism?
PHIL V GAIT
Propanolol
Hydrocortisone
Isoprenaline
Lidocaine
Verapamil
GTN
Aspirin
Isosorbide mononitrate
Testosterone
132
What is zero order kinetics?
Metabolism of a drug is independent of the concentration
Due to metabolic pathways becoming saturated
133
Which drugs exhibit zero order kinetics?
PSHE:
Phenytoin
Salicylates
Heparin
Ethanol
134
What is acetylator status?
50% of the UK population are deficient in hepatic N-acetyltransferase
135
What drugs are affected by acetylator status?
D-SHIP
```
Dapsone
-
Sulfalsalazine
Hydralazine
Isoniazid
Procainamide
```
136
If a drug binds to nuclear receptors, what must it be?
Lipid soluble
137
Name 2 examples of drugs that act on nuclear receptors.
Levothyroxine
| Prednisolone
138
Give an example of a G-protein coupled receptors
Adrenoreceptors
139
Name 5 immunological changes in HIV.
```
Reduced CD4
Increased B2 microglobulin
Decreased IL-2
Polyclonal B cell activation
Decreased NK cell function
Reduced T4 hypersensitivity response
```
140
What are 5 types of mutations?
```
Frame-shift
Mis-sense
Nonsense
Insertion
Point
```
141
What is a frame shift mutation?
Insertion of nucleotides not in a group of 3, therefore changes the frame in which translation occurs
142
What is a mis-sense mutation?
Codon codes for a different amino acid
143
What is a nonsense mutation?
A triplet coding for an amino acid now codes for a termination codon
144
What is a read through mutation?
Termination codon changes to a codon that codes for an amino acid
