Internal Med CBD Study (PE Case)

Question 1

How does malignancy increase the risk of PE?

Answer 1

Acquired hypercoagulable state

• Tumours may release prothrombotic molecules
• Tumours may produce proteases that activate factor X
• Tumours may produce cytokines, TNF etc which act on endothelial cells to stimulate prothrombotic molecules

Question 2

What are the two pathophysiological pathways involved in colorectal cancer and what do they produce?

Answer 2

1. Adenoma-Carcinoma Sequence/ Chromosomal Instability sequence
   - somatic copy number mutations
   - 5q21 –> KRAS + TP53 –> carcinoma
2. Sessile Serrated Pathway/Microsatellite instability pathway
   - mutations in DNA mismatch repair –> high mutation rate
   - MSH2 and MLH1 –> BRAF –> carcinoma

Question 3

What does Lynch syndrome and FAP predispose you to?

Answer 3

FAP: 100% chance of colorectal cancer by 40, Adenoma-carcinoma pathway, prophylactic colectomy by 25

Lynch: colonoscopy every year, Microsatellite pathway

Question 4

What are the symptoms of parkinsons?

Answer 4

TRAP:
Tremor
Rigidity: cogwheel rigidity
Akinesa/bradykinesia
Postural instability

SMART:
Shuffling gait
Mask-like facies
Akinesia/bradykinesia
Rigidity
Tremor

Question 5

What is Parkinson’s?

Answer 5

Neurodegenerative disorder

Loss of dopaminergic output from the basal ganglia due to the loss of dopaminergic neurons in the substantia nigra
Might be due to mis-folding on alpha synuclein –> protein aggregation

Question 6

How do you diagnose Parkinson’s?

Answer 6

Clinically with a dopaminergic agent trial

Levodopa, MAO-B inhibitors, amantadine

Question 7

What is the aetiology of aortic stenosis?

Answer 7

• Mostly from fibrosis and calcification of the valve
• Congenitally bicuspid
• Rheumatoid heart disease

Question 8

How does aortic stenosis present?

Answer 8

TRIAD

Exertional angina
Dyspnoea
Syncope

Question 9

What does an aortic stenosis murmur sound like?

Answer 9

ESM over the aortic auscultation area, loudest mid-systole
Radiates to the carotids
Loudest over the right sternal border
Sometimes there will be a soft P2

Question 10

How do you manage aortic stenosis?

Answer 10

Valve replacement
Warfarin
Statins and anti-hypertensives
Antibiotic prophylaxis when needed

Question 11

What are the complications of aortic stenosis?

Answer 11

Acute HF
ACS
Thrombosis

Question 12

What is rivaroxaban?

Answer 12

NOAC/DOAC

Selective Xa inhibitor. Inhibits free and bound Xa

Question 13

What is levodopa?

Answer 13

Precursor to dopamine, can cross the BBB whereas dopamine cant.

Bradykinesia and rigidity are the most responsive symptoms.

SEs:
- Hair loss
- Narcolepsy
- Nausea
- Arrhythmias
- HTN
- GIT bleeding
- End of dose deterioration
- Drug resistance in parkinsons

Question 14

What is denosumab?

Answer 14

RANK-L inhibitor (pre-osteoclasts have a RANK-L receptor) –> prevents the development of pre-osteoclasts into osteoclasts

SEs:
- Joint and muscle pain
- Osteonecrosis of the jaw
- Hypocalcaemia
- HYpersensitivity reactions
- Greater risk of infections

Contraindicated: hypocalcaemia, check Vit D and Ca before commencing

Question 15

What is frusemide?

Answer 15

Loop diuretic.

Inhibits the NaKCl channel in the thick ascending LOH. Sodium, chloride and potassium stay in the urine so water is drawn in at the DCT. Potassium wasting diuretic

SEs:
- Hypokalaemia
- Hyponatremia
- Hypochloremia
- Ototoxic
- Can increase free thyroid hormone

Question 16

What is venlafaxine?

Answer 16

SNRI: blocks serotonin and noradrenal reuptake. Also increases prefrontal DA

SEs:
- GI
- Sexual dysfunction
- Headache

Question 17

What are the tumour markers for colorectal cancer?

Answer 17

CEA and CA19-9

Question 18

CTPA vs V/Q Scan

Answer 18

CTPA is more sensitive and specific BUT can’t do in renal disease because of contrast nephropathy or young people because of radiation dose

Consensus:
CXR is clear but you’re still concerned for PE, you can do a V/Q scan
CXR has signs of pneumonia, pleural effusion etc, do a CTPA. More sensitive and specific so better when considering PE mimics

Question 19

What are NOACS?

Answer 19

Non-vitamin K oral anti-coagulants

• Don’t need regular monitory
• Apixaban, rivaroxaban, edoxaban, dabigatran

Question 20

What is dabigatran?

Answer 20

Selective thrombin antagonist

Question 21

What are Xa Inhibitors?

Answer 21

Rivaroxaban, apixaban, edoxaban are all direct and selective Xa inhibitors
- Less conversation of prothrombin to thrombin
- Easily manageable, don’t need regular monitory
- Prolong PT and PTT

Question 22

What is UFH?

Answer 22

MOA: increases the activity of anti-thrombin
- Indirectly inhibits Xa and thrombin
- Short half life, need to monitor the aPTT
- Cleared hepatically

Question 23

What is LMWH?

Answer 23

MOA: binds anti-thrombin III –> indirectly inhibits Xa
- Renally cleared

Question 24

What is the prothrombin G20210A mutation?

Answer 24

Increased prothrombin/factor II so you clot more

Question 25

What is the factor V leiden mutation?

Answer 25

Mutated factor V is resistant to protein C so it is harder to inactivate

Question 26

Protein C and protein S deficiency:

Answer 26

Protein C can’t inactivate factor V and VIII. Protein S is the vitamin-k dependent co-factor of protein C

Question 27

What is the antithrombin III deficiency?

Answer 27

Can’t inhibit the proteases: II, IX, X and XI

Question 28

What are antiphospholipid antibodies?

Answer 28

Associated with autoimmune diseases and increase clotting (e.g. SLE)