ESA1

Question 1

Define Type 1 diabetes

Answer 1

-An absolute lack of insulin caused by autoimmune destruction of the beta islet cells of the pancreas which results in an inability to utilise glucose and therefore a high blood glucose concentration which can lead to cardiovascular damage

Question 2

Define type 2 diabetes and the associated risk factors for developing it

Answer 2

• A relative lack of insulin caused by increased insulin resistance and pancreatic exhaustion. Leads to an elevated blood glucose which predisposes to cardiovascular damage
• Obesity, physical inactivity, high sugar intake, genetics

Question 3

Describe the typical symptoms of diabetes

Answer 3

-Polyuria, polydipsia, tiredness, blurred vision, thrush, weight loss (type 1)

Question 4

Describe the micro and macrovascular complications of diabetes

Answer 4

• Micro -> neuropathy, retinopathy, nephropathy
• Macro -> MI, Stroke, gangrene, peripheral vascular disease
• Acute -> DKA/HONK, hypoglycaemia, hyperglycaemia

Question 5

What is sickle cell disease? What is a sickle crisis?

Answer 5

• An autosomal recessive condition where there is a point mutation from A->T producing the amino acid valine instead of glutamate in the haemoglobin chain. This produces a hydrophobic sticky pocket due to alteration in the folding of the globin chain. These hydrophobic pockets attract one another, when in deoxy Hb state, leading to polymerisation of Hb and temporary distorting of the cell. After repeated sickling the RBC remains distorted. This leads to increased destruction of RBCs and also possibly damage to small vasculature as the sickled cells can occlude the vessel due to increased membrane rigidity
• Sickle crisis is when there is a high number of RBCs which sickle at the same time and occlude vasculature and can be precipitated by cold, stress etc

Question 6

Describe both a and b thalassaemias

Answer 6

• A-> decreased or absent a-chains resulting in Hb chains made from B-tetramers -> stable tetramer. Symptoms appear before birth as foetal Hb is 2a and 2g chains
• B-Thalassaemia -> decreased or absent b chains but a-chains cannot form stable tetramer. Symptoms appear after birth as a chains become replaced by b chains

Question 7

What is scurvy?

Answer 7

-Vitamin C deficiency which results in an inability for the enzyme propyl hydroxylase leading to weak tropocollagen helices. This produces weak collagen bundles and results in swollen and bleeding gums and joint pain

Question 8

What is down syndrome?

Answer 8

-Genetic alteration whereby there is an extra complete or partial copy of chromosomal 21. This leads to characteristic facial features and mild to moderate intellectual disability.

Question 9

What is turner syndrome?

Answer 9

• Caused by an genetic alteration caused by a sex linked aneuloidy whereby the karyotype is 45,X
• Produces females with short stature, webbed neck, low-set ears, infertility and renal problems

Question 10

What is klinefelters syndrome?

Answer 10

• Genetic alteration caused by a sex linked aneuploidy whereby the karyotype is 47, XXY
• Produces males with gynaecomastia and language and reading impairment

Question 11

What is Marfan’s syndrome?

Answer 11

-Genetic abnormality in fibrillin gene producing an abnormal fibrillin-1-protein which normally coats the outside of elastin. This produces abnormal elastin and leads to tall stature, arachnodactyly and increased susceptibility to aortic dissection

Question 12

What is Elhers-Danlos?

Answer 12

-Deficiency in Type 3 collagen (reticular collagen) leading to weaker collagen structures. Presents with unstable joints, easy bruising, flat feet and stretchy skin

Question 13

What is Vitiligo?

Answer 13

-Autoimmune destruction of melanocytes which leads to skin depigmentation. Can have major psychological effects depending on ethnicity and area affected

Question 14

What is alopecia?

Answer 14

-Autoimmune condition which leads to hair loss in varying locations

Question 15

What is psoriasis? Name the layers of the skin

Answer 15

• Disorder of epidermal growth and differentiation of unknown cause. Suspected to have a genetic association. Produces excessive proliferation of all layers of the skin and results in scaling
• Stratum basale, stratum spinosum, stratum granulosum and stratum corneum

Question 16

What is osteogenesis imperfecta and why is it of medicolegal importance?

Answer 16

• Autosomal dominant defect in the production of type 1 collagen which produces a spectrum depending on the severity of the defect
• Can range from being incompatible with life to having fragile long bones and bone deformities
• Can often be confused for non-accidental injury

Question 17

What is osteoporosis. Give its major risk factors

Answer 17

• Decrease in bone density increasing chance of fractures either due to a increased osteoclast activity or an attenuated osteoblast activity
• Menopause (decrease in oestrogen decreases inhibition of osteoclasts)
• Age (decreased osteoblast activity)
• Long term corticosteroids use
• Low immobility

Question 18

What is osteomalacia? What is rickets?

Answer 18

• Softening of the bones due to calcium deficiency in adults, most commonly secondary to vitamin D deficiency due to lack in diet or sun exposure leading to fragility and fractures
• Softening of bones due to calcium deficiency in children leading to poor bone matrix and distorted epiphyseal growth plates leading to slow growth and deformed bones

Question 19

What is achondroplasia?

Answer 19

-Genetic abnormality in FGFR3 gene which results in abnormal epiphyseal growth plates producing short limed dwarfism

Question 20

What is pituitary dwarfism?

Answer 20

-Deficiency of GH due to a problem with the pituitary producing dwarfism with normal proportions

Question 21

What is acromegaly?

Answer 21

-Excessive GH in an adult producing widening of bones by periosteal growth

Question 22

What is cretinism and how can it be treated?

Answer 22

• Hypothyroidism in the neonate which has not been detected and produced mental retardation
• If caught early enough can be treated with thyroxine to prevent mental retardation and promote normal growth

Question 23

What is myasthenia gravis?

Answer 23

• Autoimmune destruction of NMJ end plates which results in widening of the synaptic cleft and Ach receptor loss
• Symptoms include ptosis, fatigue and double vision. Can be come fatal if affects resp muscles.
• Treated with pyridostgmine (AchE inhibitor)

Question 24

What is botulism?

Answer 24

-Toxin which blocks release of Ach from pre-synaptic bulb. Prevents muscle contraction

Question 25

What is organophosphate poisoning?

Answer 25

-Irevesible inhibition of Ach-esterase resulting in a prolonged state of muscle contraction (tetani)

Question 26

What is muscular dystrophy?

Answer 26

-Recessive x-linked disease resulting in decreased or absent production of the dytropin protein. Spectrum from beckers to duchennes. Duchennes is a total loss leading to muscle fibres tearing them selves apart upon contraction leading to necrosis of cells due to excessive Ca entry and fibrous scar tissue formation

Question 27

What is malignant hyperthermia? How is it treated?

Answer 27

- Autosomal dominant condition which becomes apparent during exposure to genral anaesthesia. Leads to a drastic and uncontrolled increase in oxidative metabolism in skeletal muscle which overwhelms the bodys capacity to supply o2/remove co2 and regulate body temp. Quickly leads to circulatory collapse - Treated with dantrolene (muscle relaxant)

Question 28

What is marasmus and kwashiokor?

Answer 28

- Marasmus is protein-energy malnutrition resulting in muscle wasting, loss of body fat, no oedema - Kwashiorkor is protein deficiency producing oedema, ascites, fatty liver and anorexia

Question 29

What is lactose intolerance?

Answer 29

- Intrinsic low activity of lactase enzyme | - Bacteria break down lactose in the gut producing flatulence, diarrhoea and stomach cramps

Question 30

What is galactosaemia? How does it cause cirrhosis and cataracts

Answer 30

- Lack of galactokinase or galactose-1-P uridyl transferase - Kinase deficiency is rare, transferase is more common and serious due to both galactose and galactose-1-P build up due to saturation of both enzymes. - Galactose-1-P is toxic to liver and galactose becomes reduced to galactitol in the eye using NADPH and aldose reductase. This causes oxidative damage to occur leading to cataracts

Question 31

What is G6PD deficiency?

Answer 31

-X-linked recessive point mutation producing a defecting glucose-6-phosphate dehydrogenase enzyme. G6PD is involved in PPP, an essential pathway in the RBC for supplying reducing power. PPP maintains the supply of NADPH which in turn maintains the supply of reduced glutathione. Glutathione is the RBCs main source of mopping up free radicals to prevent oxidative damage. In times of oxidative stress such as infection or exposure to anti-malarials, haemolytic anaemia can occur due to increased exposure to oxidative damage producing heinz bodies (cross linking of Hb) causing an increased clearance by the spleen

Question 32

What is PKU?

Answer 32

-Autosomal recessive condition in which there is a defect in the enzyme phenyl hydroxylase. This causes an inability to convert phenylalanine to tyrosine. This results in a decrease in dopamine concentrations and an increase in phenylalanine. PA gets converted to phenylpyruvate as it accumulates in the tissues and it is excreted in the urine. PP also competes with pyruvate for uptake across bbb and results in mental retardation

Question 33

What is homocystinuria?

Answer 33

-Autosomal recessive condition caused by a deficiency in cystathionine-b-synthase. Usually converts homocysteine to cystathionine which converts to cysteine. Instead homocysteine gets converted to methionine or oxidised to homocystine. methionine and disrupts protein structures and leads to disorders of CT. Homocystine is damaging to CNS and CV

Question 34

What is addisons disease? How is it diagnosed?

Answer 34

- Autoimmune destruction of the adrenal glands via the production of antibodies which results in weight loss, tiredness, hypoglycaemia, hypotension, increased pigmentation - Diagnosed by Synacthen. If it was positive for addisons disease there would be no change in cortisol production, if cortisol increases then not addisons

Question 35

Give 3 causes of secondary adrenal insufficiency

Answer 35

- Pituitary microadenoma - Shehans - Ectopic steroids

Question 36

What is cushings disease/syndrome? How does it present?

Answer 36

- Disease is a problem with the pituitary eg adenoma which causes increased acth which causes an increased cortisol - Syndrome is a problem outside of the pituitary such as with the adrenals itself or ectopic acth - moon face, buffalo hump, proximal limb wasting, central adiposity, striae, acne, thin skin, dry hair, hyperglycaemia, hypertension

Question 37

How is cushings disease/syndrome diagnosed?

Answer 37

-Dexamethosone supression test. Pituitary adenoma will respond to the potent glucocorticoid dexamethosone and acth production will decrease and thus cortisol will decrease. In pituitary syndrome there will be no change in cortisol levels

Question 38

Give 3 causes of cushings syndrome

Answer 38

- adrenal adenoma - Ectopic acth from small cell lung cancer - Iatrogenic steroids

Question 39

What are the symptoms of hypothyroidism and give 3 causes. Describe the t3/4 and tsh results. what is the main treatment

Answer 39

- Cold intolerance, weight gain, menorrhagia, lethargy, dry skin, thinning of hair, decreased appetite constipation, low mood, bradycardia, carpal tunnel - Hasimotos/atrophic thyroiditis (anti-tpo - cannot oxidise iodide to finish t3/t4 production) - Iodine deficiency - thyroidectomy - Low t3/4 high tsh - Oral thyroxine

Question 40

What are the signs and symptoms of hyperthrroidism and give 3 causes, describe the t3/4 and tsh results. what is the main treatment

Answer 40

- heat intolerance, weight loss, diarrhoea, increased appetite, irritability, amenorrhoea, tachycardia - Graves disease (anti-tsh) - Toxic multinodular goitre - overtreatment with thyroxine - High t3/4, low tsh - Carbimazole

Question 41

Give 3 drugs which cause hypothyroidism

Answer 41

- Amiodarone - Carbimazepine - Lithium