Clinical sciences

Question 1

Antiphospholipid antibody syndrome

Answer 1

Antiphospholipid antibody syndrome can be diagnosed if the patient has anticardiolipin antibodies, or lupus anticoagulant on two occasions, over a period of 12 weeks, and has had either a thrombus, or a history of recurrent <10 week pregnancy loss, or one pregnancy loss >10 weeks in gestation when other causes of pregnancy loss have been excluded.

Question 2

Hypomagnesemia

Answer 2

Diuretic therapy is a common cause of hypomagnesaemia

Question 3

The effects of neurotransmitter release are principally terminated by neuronal uptake.

Answer 3

The action of noradrenaline released at sympathetic nerve endings is terminated by the reuptake of noradrenaline (NA) by the axonal terminals.

Question 4

Immune system

Answer 4

Proteins are displayed on the cell surface by MHC I human leukocyte antigen (HLA) antigens.

If the MHC I is presenting material recognised as foreign, then it is detected and destroyed by CD 8 plus T cells.

CD10 is a marker of B cells that have passed through the germinal centre of the lymph node.

CD5 is a T cell marker often present in B cells in CLL.

Question 5

Th1 and Th2 cells

Answer 5

> > > Th2 CD4 positive lymphocytes are involved in the pathogenesis of anaphylaxis, via the production of IL-4/IL-13 that act on B cells to increase IgE production and precipitate the development of acute hypersensitivity.

IL-4 also exacerbates anaphylaxis by acting synergistically with other vasoactive mediators to increase vascular permeability.

> > > Th1 cells lead to increased production of:

Interferon gamma
IL-2, and
Tumour necrosis factor.

Question 6

Antidiuretic hormone

Answer 6

• Synthesized in the supraoptic nuclei of the hypothalamus, released by the posterior pituitary.
  -Promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels

Question 7

Atrial Natriuretic peptide

Answer 7

• Secreted by both the right and left atria (right&raquo_space; left)
• 28 amino acid peptide hormone, which acts via cGMP.
• natriuretic, i.e. promotes excretion of sodium
• Lowers BP
• antagonises actions of angiotensin II, aldosterone

Question 8

Breastfeeding Contraindications

Answer 8

-Antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides
-Psychiatric drugs: lithium, benzodiazepines
-Aspirin
-Carbimazole
-Methotrexate
-Sulfonylureas
-Cytotoxic drugs
-Amiodarone

Question 9

Cell Cycle

Answer 9

The cell cycle is regulated by proteins called cyclins, which in turn control cyclin-dependent kinase (CDK) enzymes.
5 phases. G0,G1,S,G2,M
G0 is the resting phase.
G1 phase determines length of cell cycle.
M phase is the shortest phase of the cell cycle.

Question 10

Cell division

Answer 10

MITOSIS
-Occurs in somatic cells
-Results in 2 diploid daughter cells
-Daughter cells are genetically identical to parent cell

MEIOSIS
-Occurs in gametes
-Results in 4 haploid daughter cells
-Daughter cells contain one homologue of each chromosome pair and are therefore genetically different.

Question 11

Phases of Mitosis

Answer 11

-Prophase Chromatin in the nucleus condenses

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

-Metaphase Chromosomes aligned at middle of cell

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

-Telophase Chromatids arrive at opposite poles of cell

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

Question 12

CD4

Answer 12

CD4 Found on helper T cells.
Co-receptor for MHC class II
Used by HIV to enter T cells

Question 13

CD8

Answer 13

CD8 Found on cytotoxic T cells.
Co-receptor for MHC class I
Found on a subset of myeloid dendritic cells

Question 14

CD14

Answer 14

CD14 Cell surface marker for macrophages

Question 15

Clinical Trial phases

Answer 15

1- Exploratory studies
2- Safety assessment
3- Assess Efficacy
4- Assess Effectiveness
5- Post Marketing surveillance

Question 16

Hereditary Angioedema

Answer 16

• C1-INH Deficiency
• Multifunctional serine protease inhibitor
  -Uncontrolled release of bradykinin

Question 17

Rubella

Answer 17

Sensorineural deafness
Congenital cataracts
Congenital heart disease (e.g. patent ductus arteriosus)
Glaucoma

Question 18

Toxoplasmosis

Answer 18

Cerebral calcification
Chorioretinitis
Hydrocephalus

Question 19

Cytomegalovirus

Answer 19

Low birth weight
Purpuric skin lesions
Sensorineural deafness
Microcephaly

Question 20

Cytokines

Answer 20

IL-1, IL-6,IL-8,IL-12, TNF alpha&raquo_space;macrophages.
IL-2,IL-3,Interferron gamma» Th1 cells
IL-4,IL-5,IL-6, IL-10,IL-13»>Th2 cells

Question 21

Leukotrienes

Answer 21

Leukotrienes actually cause bronchoconstriction, which is a key feature of their role in asthma.
-Leukotrienes secreted by leukocytes.
- Leulotrienes formed from arachidonic acid by action of lipoxygenase.

Question 22

HPV 16/18

Answer 22

Cervical cancer
Anal cancer
Penile cancer
Vulval cancer
Oropharyngeal cancer

Question 23

HHV-8

Answer 23

Kaposi’s sarcoma.

Question 24

Epstein bar virus

Answer 24

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

Question 25

T-Helper Cells

Answer 25

There are two major subsets of T-Helper cells: Th1 involved in the cell-mediated response and delayed (type IV) hypersensitivity secrete IFN-gamma, IL-2, IL-3 Th2 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

Question 26

DiGeorge syndrome

Answer 26

- T cell disorder CATCH22: C - Cardiac abnormalities A - Abnormal facies T - Thymic aplasia C - Cleft palate H - Hypocalcaemia/ hypoparathyroidism 22 - Caused by chromosome 22 deletion

Question 27

mRNA

Answer 27

mRNA is produced in the nucleus, matures in the cytoplasm, binds to the ribosome, and initiates protein synthesis.

Question 28

ALP in pregnancy

Answer 28

In pregnant women ALP levels are usually two to three times higher than non-pregnant values as ALP is produced by the placenta.

Question 29

Bilirubin conjugation

Answer 29

Bilirubin conjugation is catalysed by glucuronyl transferase

Question 30

Ethanol poisoning

Answer 30

Very high osmolality with normal anion gap and acid-base balance reflects the presence of ethanol.

Question 31

Tumour lysis syndrome

Answer 31

Tumour lysis syndrome is recognised after the onset of chemotherapy in patients with acute leukaemia. Whilst ensuring adequate hydration and alkalinisation of urine is of value, rasburicase, (recombinant urate oxidase) is effective when used both pre and post the onset of chemotherapy in reducing urate accumulation. Other options for the management of tumour lysis syndrome include - Prophylactic allopurinol - Acetazolamide to drive urine alkalinisation. - Intravenous fluid

Question 32

Remnant Hyperlipidaemia

Answer 32

Palmar crease xanthoma are associated with remnant hyperlipidaemia (type III hyperlipidaemia)

Question 33

Hypercalcemia

Answer 33

1- Primary hyperparathyroidism - overproduction of parathyroid hormone (PTH) due to hyperplasia or an adenoma of the PTH glands. 2- Tertiary hyperparathyroidism - in a patient with chronic renal failure with prolonged hypocalcaemia the parathyroids become autonomous, even if renal function is improved with transplantation. This can lead to hypercalcaemia. 3- Malignancy - commonly myeloma, prostate, breast, lung, thyroid, and kidney cancers. 4- Drugs: lithium, vitamin D overdose, vitamin A toxicity, thiazides. 5- Thyrotoxicosis - most patients with thyrotoxicosis have minor alterations in serum calcium, but a minority have significant symptomatic hypercalcaemia, probably due to increased bone turnover. Treating the thyroid disease causes resolution of the hypercalcaemia. 6- Addison's disease - although it would be uncommon to have significant hypercalcaemia. 7- Granulomatous disease - sarcoidosis, leprosy, TB. 8- Infections - HIV, histoplasmosis. 9- Williams' syndrome - a rare genetic disease affecting chromosome 7 and characterised by hypercalcaemia in infancy, anxiety and learning disability. 10- Milk-alkali syndrome - the triad of hypercalcaemia, metabolic alkalosis and renal impairment secondary to the ingestion of large amounts of calcium and absorbable alkali (such as sodium bicarbonate for the treatment of peptic ulcer disease). 11- Familial hypercalcaemic hypocalciuria - autosomal dominant mutations in the calcium sensing receptor gene, leading to calcium hyposensitivity, compensatory hypercalcaemia and hypocalciuria.

Question 34

Hypercalcemia

Answer 34

- 'bones, stones, groans and psychic moans' - corneal calcification - shortened QT interval on ECG - hypertension

Question 35

Hyponatremia

Answer 35

Hypertonic saline (typically 3% NaCl) is usually indicated in patients with acute, severe, symptomatic hyponatraemia (< 120 mmol/L)

Question 36

PCOS

Answer 36

Infertility in PCOS - clomifene is typically used first-line

Question 37

Oral allergy syndrome

Answer 37

Itching and tingling of the lips, tongue, and mouth are the most common symptoms of oral allergy syndrome.

Question 38

Paget disease

Answer 38

Paget's disease - increased serum and urine levels of hydroxyproline

Question 39

Vitamin C

Answer 39

Vitamin C deficiency (scurvy) leads to defective synthesis of collagen resulting in capillary fragility (bleeding tendency) and poor wound healing Features vitamin C deficiency gingivitis, loose teeth poor wound healing bleeding from gums, haematuria, epistaxis general malaise

Question 40

Essential Tremors

Answer 40

Essential tremor (previously called benign essential tremor) is an autosomal dominant condition which usually affects both upper limbs Features postural tremor: worse if arms outstretched improved by alcohol and rest most common cause of titubation (head tremor) Management - propranolol is first-line - primidone is sometimes used

Question 41

Menstrual cycle

Answer 41

> Menstruation 1-4 > Follicular phase (proliferative phase) 5-13 > Ovulation 14 > Luteal phase (secretory phase) 15-28

Question 42

PET

Answer 42

Positron Emission Tomography (PET) is a form of nuclear imaging which uses fluorodeoxyglucose (FDG) as the radiotracer. This allows a 3D image of metabolic activity to be generated using glucose uptake as a proxy marker. The images obtained are then combined with a conventional imaging technique such as CT to decide whether lesions are metabolically active.

Question 43

Serum Tryptase

Answer 43

Anaphylaxis - serum tryptase levels rise following an acute episode

Question 44

Facial Hirsutism

Answer 44

Topical eflornithine is the treatment of choice for facial hirsutism

Question 45

Animal bite

Answer 45

The most common isolated organism is Pasteurella multocida. - The current BNF recommendation is co-amoxiclav if penicillin-allergic then doxycycline + metronidazole is recommended

Question 46

Human Bite

Answer 46

Common organisms include: Streptococci spp. Staphylococcus aureus Eikenella Fusobacterium Prevotella Co-amoxiclav is recommended,

Question 47

High anion gap metabolic acidosis

Answer 47

The normal anion gap ranges between 8-14 mmol/L and values above this level show raise suspicion of: Methanol Uraemia (renal failure) Diabetic ketoacidosis Paracetamol use (chronic) Iron, isoniazid Lactic acidosis Ethylene glycol Salicylate overdose

Question 49

Respiratory Alkalosis

Answer 49

Common causes - Anxiety leading to hyperventilation - Pulmonary embolism - salicylate poisoning* - CNS disorders: stroke, subarachnoid haemorrhage, encephalitis - Altitude - Pregnancy

Question 50

Rhabdomyolysis

Answer 50

Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged epileptic seizure and is found to have an acute kidney injury on admission. Causes - seizure - collapse/coma (e.g. elderly patient collapses at home, found 8 hours later) - ecstasy - crush injury - McArdle's syndrome - drugs: statins (especially if co-prescribed with clarithromycin) Features - Acute kidney injury with disproportionately raised creatinine elevated creatine kinase (CK) - The CK is significantly elevated, at least 5 times the upper limit of normal - elevations of CK that are 'only' 2-4 times that of normal are not supportive of a diagnosis and suggest another underlying pathophysiology - Myoglobinuria: dark or reddish-brown colour - hypocalcaemia (myoglobin binds calcium) - elevated phosphate (released from myocytes) - hyperkalaemia (may develop before renal failure) - metabolic acidosis Management - IV fluids to maintain good urine output - Urinary alkalinization is sometimes used

Question 51

DKA

Answer 51

The diagnostic criteria of diabetic ketoacidosis are glucose > 11mmol/L (or known diabetes), pH < 7.3, bicarbonate < 15mmol/L and ketones > 3mmol/L

Question 52

Lactic Acidosis

Answer 52

lactate levels > 5mmol/L.

Question 53

Alcoholic Ketoacidosis

Answer 53

Metabolic acidosis Elevated anion gap Elevated serum ketone levels Normal or low glucose concentration - The most appropriate treatment is an infusion of saline & thiamine. Thiamine is required to avoid Wernicke encephalopathy or Korsakoff psychosis