Pastest 2 Flashcards
What are exons?
Coding sequences of DNA which code for peptides produced from mRNA
What is the function of introns?
Code for switches that control gene expression in splicing
From where does hyaline cartilage receive its nutrients?
Diffuses from synovial fluid - it is avascular
What type of collagen does hyaline cartilage contain?
Type 2
What do chondrocytes secrete?
Proteoglycans and collagen
What is the cause of familial hypercholesterolaemia?
LDL receptor dysfunction
Familial apolipoprotein B-100 or PCSK-9 mutation
In which patients should you suspect familial hypercholesterolaemia?
Serum cholesterol >7.5mmol
Family/personal history of CHD before 60 years
Tendon xanthomas
Pyruvate kinase is the rate limiting enzyme in which processes?
Glycolysis
Gluconeogenesis
How do thiazides cause hypokalaemia?
Increase delivery of sodium to the DCT where sodium is reabsorbed and potassium excreted
How does aciclovir work?
Converted into tri-phosphate form by host cell kinases
This allows it to incorporate into viral DNA resulting in chain termination
Viral DNA polymerase is then unable to function
What is the treatment of an acute attack of acute intermittent porphyria?
IV haemin/300g dextrose IV
What is the prophylaxis for acute intermittent porphyria attacks?
IV haem arginate once or twice weekly
- risk of iron overload
GnRH analogue
Liver transplant
What is the equivalent prednisolone dose to match with glucocorticoid production in humans?
0.1mg per kg bodyweight
E.g 60kg –> 6mg
What enzyme is high in the serum in Gaucher’s disease?
Acid phosphatase
Which cytokines stimulate the HPA axis by inducing secretion of CRH from the hypothalamus?
And what is the function of this?
TNF-alpha
IL-1
Cortisol released which reduces the stress response and prevents a lethal over-activation of the immune response
How do you reverse alteplase?
FFP and tranexamic acid
What is the mechanism of action of alteplase?
Converts plasminogen to plasmin, which degrades fibrin
What type of b-adrenoreceptors line the airways?
B2
How do beta-2 agonists influence bronchodilation?
Relaxation of bronchial smooth muscle by affecting b-2 receptors
Inhibition of mast cell mediator release
Enhanced mucociliary clearance
Why does tachycardia and increased cardiac output occur with b-2 agonists?
Stimulation of cardiac b-adrenoreceptors
Reflex response to peripheral vasodilation
What is the most common mutation causing hereditary spherocytosis?
Spectrin and ankyrin
What is the criteria for liver transplant following paracetamol toxicity?
pH <7.3
OR
INR>6.5 AND Creatinine>300 AND grade 3/4 encephalopathy
What are 6 causes of large kidneys?
Amyloidosis PKD Stage 1 diabetic nephropathy Hydronephrosis Acromegaly Renal vein thrombosis
What is the treatment of radiation pneumonitis?
Prednisolone >60mg/day
What is the cause of carpal tunnel syndrome in patients undergoing long term haemodialysis?
B2 microglobulin deposition
What is the diastolic plop of left atrial myxomas?
The tumour is attached to the wall in a way so that it is mobile
It plops in and out of the mitral orifice, leading to a murmur that changes with position
What is posterior column syndrome?
Tabes dorsalis - neurosyphilis
Loss of function of dorsal columns
What metabolic abnormality is seen in aspirin overdose?
Initially respiratory alkalosis –> stimulates central respiratory centres causing rapid deep breathing
Then toxicity –> metabolic acidosis
What type of bone is affected by osteoporosis and why?
Trabecular
Trabecular = outer surface and middle of bones.
Osteoclasts and osteoblasts inhabit surface of bones therefore trabecular bone is more subject to cell turnover
How is giardiasis diagnosed?
Stool antigen test
How do you prevent transfusion-related graft vs host disease in at risk patients such as Hodgkin’s lymphoma?
Irradiated blood products
What is the cause of diarrhoea with metformin?
Bile acid malabsorption
Which type of leukaemia is associated with DIC?
APML
Where is the azygos lobe seen on CXRs?
Right upper zone behind medial end of clavicle
Reverse comma sign
0.5% CXRs
Name 5 muscarinic effects
Miosis Hypersalivation Sweating Diarrhoea Bradycardia Excessive bronchial secretions
How do nerve agents and organophosphate poisoning work?
Inhibit AChE so ACh accumulates at nicotinic and muscarinic receptors
Name 2 nicotinic effects
Muscle fasciculation
Tremor
Which tumours secrete ACTH and what are the features?
Small cell lung cancer
Bronchial carcinoid
Weight loss, muscle weakness
What is Bruce protocol exercise testing?
6 minutes of exercise testing
If can’t complete this, have a higher risk of cardiovascular adverse events –> cardiac angiography
What are the different hypolipiproteinaemias associated with?
Type 1: eruptive xanthomas Type 2: tendon xanthomas Type 3: tubo-eruptive xanthomas Type 4: eruptive xanthomas Type 5: similar to type 1 + high VLDL and chylomicrons
How does aprepitant treat chemotherapy induced nausea and vomiting?
Acts via neurokinin receptor, inhibits substance P
What medication can reduce alcohol craving and how?
Acamprosate
Increases GABA actvitity
What is the treatment of toxic alcohol poisoning e.g. ethylene glycol?
IV fomepizole - competitive inhibitor of alcohol dehydrogenase
What is a disadvantage of crystalloid solutions?
Need a relatively large volume to restore intravascular volume
What is a side effect of theophylline?
Agitation and insomnia
What is Brodie’s abscess?
Chronic osteomyelitis of the knee
What is J point depression a physiological response to?
Increase in HR
How is pseudo-Cushing’s differentiated from simple obesity?
Slight rise in urinary free cortisol (from long term alcohol XS)
What is HbcAb indicative of?
Prev hepatitis B infection
What markers are seen in bronchial carcinoid?
Chromogranin A
Neuron specific enolase
What is syringobulbia?
Syringomelia but the lower brainstem is also affected (Xiin nuclei)
How does herceptin cause cardiomyopathy?
Inhibition of erb-b2 receptor
With chest drains what does swinging of the drain mean?
The drain is still in contact with the pleural space
What are the symptoms of cryptogenic pulmonary eosinophilia?
Malaise Weight loss Fever Raised ESR and eosinophils Asthma in 50%
What occurs if EPO therapy is started in CKD patients who also have iron deficiency anaemia?
Causes severe depletion of iron
At what stage of CKD is EPO deficiency expected?
CKD 3
What level of urine sodium suggests renal tubular acidosis (intrinsic renal cause)?
Over 40
Why do basal alveoli demonstrate greater compliance than apical alveoli?
Basal alveoli are compressed by the weight of the lungs
Compliance is volume change per unit pressure change
Therefore ventilation reduced at the bases
What is the cause of Crigler-Najjar syndrome?
Absence (T1 - autosomal recessive) or decrease (type 2 - autosomal recessive with pseudo-dominance) in glucuronyl transferase leading to severe unconjugated hyperbilirubinaemia
What is the blood supply of the liver?
Portal vein - 75%
Hepatic artery - 25%
Why does anaemia occur in lead poisoning?
Inhibition of ferrochelatase, decreased red cell lifespan, and reduced stability of red cell membrane
How can you differentiate proximal LAD occlusion from distal LAD occlusion?
Proximal - STE in septal leads e.g. V1 and V2 - occlusion occurs before the septal branches
What are the symptoms of alkaptonuria?
Urine turns dark on standing
Arthritis
Black/blue pigment layer in cartilage
What is there a deficiency of in McArdle’s disease?
Muscle phosphorylase
Why does hypokalaemia exacerbate digoxin toxicity?
Enhances binding of digoxin to Na/K pump
Which type of renal disease has no immune deposits on renal biopsy?
Granulomatosis with polyangiitis
What are IgA deficiency patients at risk of?
Developing coeliac disease
GI and sinus infections
What is isotype suppression in multiple myeloma?
Normal IgG and IgA levels
What is DNA splicing?
Introduction of additional exons
Which complement deficiency is associated with early development of lupus?
C4
Which vessels do nitrates have the largest effect on?
Large veins
What is seen on ECG in posterior MI and what vessel does this correspond to?
ST depression leads V1-V3, large R wave
Proximal right coronary artery, left circumflex
What is a similar syndrome to Wolf-Parkinson White syndrome?
Lown-Ganong-Levine
Short PR interval only
Which calcium channel blocker is contra-indicated in malignant hypertension?
Nifedipine
What are the indications for permanent pacing?
Complete heart block Mobitz type 2 heart block Drug resistant tachyarrhythmias Persistent AV conduction blocks post MI Sick sinus syndrome
What part of the ECG corresponds with the first heart sound?
R wave
What is the cause of paroxysmal nocturnal dyspnoea?
Increased atrial pressure
What is systolic click-murmur syndrome
MV prolapse
Recurrent non-coronary chest pains
On standing/during Valsalva - ventricular volume gets smaller; midsystolic click and late systolic murmur move earlier in systole
What can bundle branch blocks lead to?
Ventricular dyssynchrony –> heart failure
Where are leads placed in cardiac resynchronization therapy?
Right atrium
Right ventricle
Left ventricle
What is seen on blood film in myelofibrosis?
Nucleated red blood cells
Tear drop cells
What are the main causes of aplastic anaemia (acquired and congenital)?
Congenital: Fanconi anaemia
Acquired: Cancer Tx, parvovirus B19, PNH, pregnancy, drugs (indomethacin, carbamazepine, phenytoin, chloramphenicol, propylthiouracil), SLE
What is the criteria for severe and very severe aplastic anaemia, versus non severe aplastic anaemia?
Non severe: marrow cellularity <25%
Severe: 2 or more of: absolute neutrophil count (ANC) <0.5, platelets <20, reticulocytes <20 (peripheral)
Very severe: the above, and ANC<0.2
What is the treatment of aplastic anaemia?
Non severe: Monitoring, blood transfusion + immunosuppressants e.g. anti-thymocyte globulin, lymphocyte globulin, ciclosporin
Severe: BM Tx if under 50 or immunosuppressants as above, eltrombopag (oral thrombopoietin receptor agonist)
What suggests hyperviscosity on fundoscopy?
Papilloedema with distended retinal vasculature
Which antigen is involved in the entry of plasmodium vivax into cells?
Duffy
What antibodies are found in HIT?
Anti PF4 heparin antibodies
What pathways of the coagulation cascade are represented by PT, APTT, and TT?
PT: extrinsic and final common
APTT: intrinsic and final common
TT: final common
Which coagulation factors are part of the intrinsic pathway of the coagulation cascade?
VIII, IX, XI, XII
What is clinically important bleeding in ITP?
Oral mucosal blood blisters
Intracerebral haemorrhage
Severe nosebleeds that do not stop with local measures
Severe menorrhagia that requires hormonal intervention
What are the features of post-partum thyroiditis?
Triphasic pattern of thyrotoxicosis 1-6 months post partum, hypothyroidism, return to euthyroidism at 9-12 months post partum.
What are the associations of polyglandular syndrome type 1?
Hypoparathyroidism Mucocutaneous candidiasis Adrenal insufficiency Primary gonadal failure Primary hypothyroidism Autosomal recessive
What are the associations of polyglandular syndrome type 2?
Adrenal insufficiency (100%)
Hypothyroidism
T1DM
Gonadal failure
How is carcinoid syndrome diagnosed?
Urinary 5-HIAA collection
How does glucagon resolve bradycardia in beta-blocker overdose?
Promotes formation of cyclic AMP
How does cryptosporidium diarrhoea present in HIV patients?
Diarrhoea
No abdo pain or fever
What is the 2nd most common malignancy in patients with FAP?
Duodenal adenoma with malignant transformation
What antibodies are found in autoimmune hepatitis?
Type 1: ANA, anti-smooth muscle
Type 2: Anti-liver, kidney microsomal antibodies
Which type of neuro-endocrine tumour is usually benign?
Insulinoma
What are the features of carcinoid tumours?
Excessive 5-HT (serotonin) causing:
- Flushing
- Diarrhoea and abdo pain
- Wheezing
- Oedema
What type of drug is terlipressin?
Prodrug of lysine vasopressin
What is the significance of e antigen/antibody in hepatitis B?
Marker of infectivity:
- E antigen +ve: high infectivity
- E antibody +ve: low infectivity
E antigen always negative in people with pre-core mutations (false negative)
What are the features of pseudohypoparathyroidism?
Hypocalcaemia –> seizures
Basal ganglia calcification
Round face, short stature, and shortening of 4th and 5th metacarpals
What hormone levels are seen in PCOS?
High LH Normal FSH Normal oestrogen High testosterone Low sex hormone binding globulin (due to insulin resistance)
When does secondary syphilis occur?
4-12 weeks after primary infection
What are the features of secondary syphilis?
Pale pink symmetrical maculopapular rash on palms/soles/trunk
Condyloma lata - confluent plaques in flexures
Generalised lymphadenopathy
Muscle and joint pains
What are the features of Darier’s disease?
Warty plaques in seborrhoeic areas
Palmar pits
Nail dystrophy
Autosomal dominant
What is seen on biopsy in granuloma inguinale?
Donovan bodies
What is seen on MRI in subacute degeneration of the cord?
Increased T2 weighted signal in the posterior columns
When is carotid endarterectomy indicated?
Stenosis >50%
What is the commonest cause of 6th nerve palsy?
Microvascular nerve palsy
What is the difference between medical and surgical 3rd nerve palsy?
Medical = pupil sparing - caused by diabetes/ischaemia Surgical = pupil involvement - compression of the nerve e.g. posterior communicating artery aneurysm
How is tuberculous meningitis diagnosed?
CSF PCR
What are the features of spinal bulbar muscular atrophy aka Kennedy syndrome
Perioral fasciculations
Androgen insensitivity
Proximal weakness and cramps
