Chem Path

Question 1

Formula to calculate osmolarity (mmol/l)

Answer 1

2(Na + K) + urea + glucose

Question 2

A 75 year old man with a long history of heart failure comes into hospital with confusion. O/E there are bibasal crackles in his lungs on auscultation. His sodium is 128mmol/l. What is the diagnosis?

Answer 2

Hypervolemic hyponatraemia associated with fluid overload from heart failure.

Increased secretion of ADH leads to increased reabsorption of water is disproportionate to the slight increase that also occurs in sodium. Therefore the serum sodium shows hyponatremia.

Question 3

A 30 year old with severe diarrhoea and vomiting after food poisoning presents to A&E with a seizure. She is not epileptic. Her partner reports that she has not been able to eat or drink anything for days and has told him she has been ‘feeling dizzy’. Her HR is elevated at 105bpm. What is the likely electrolyte imbalance?

Answer 3

Hypovolemic hyponatremia

Extrarenal cause due to severe fluid loss without adequate replacement. Patients present with dehydration - increased HR, postural hypotension, decreased skin turgor, decreased urine output - and eventually may present with confusion (<131mmol/l), seizures (<125mmol/l) and coma (<117mmol/l).

Renal causes of hypovolemia hyponatraemia are Addison’s (salt losing nephropathy, CAH and diuretics.

Question 4

An 80 year old man comes to A&E with a 1 week history of a cough and fever. He has been feeling increasingly unwell and now complains of feeling lethargic and sleepy. Investigations show that he has a decreased plasma osmolality with and increased urine osmolality. A CXR confirms the underlying diagnosis. How should this man be managed?

Answer 4

This man has a history consistent with pneumonia with associated SIADH. This gives a euvolemic hyponatremia, which gives a combination of high plasma osmolality and low urine osmolality. Other causes of SIADH include meningoencephalitis, TB, small cell lung cancer, SSRIs, PPIs and carbamazepine.

Treatment is with fluid restriction, demclocycline, which decreased the collecting duct cell response to ADH (monitoring of U&Es needed) and tolvaptan, which blocks V2 receptors. He also needs investigations to determine the cause of the pneumonia and treatment with antibiotics.

Question 5

A 35 year old woman goes to her GP complaining of increasing tiredness over the past 3 months. She is miserable and says this is because she has also gained 6 kg of weight in that time. The GP does blood tests and tells her to come back in a week.

During that time, the woman becomes confused and her partner brings her to A&E. The junior doctor notices that she is hyponatremic and starts her on a rapid infusion of saline to correct this. 2 hours later she becomes unable to move, loses consciousness and dies. What happened?

Answer 5

This lady had an underlying diagnosis of hypothyroidism. This can cause a euvolemic hyponatremia, which can then cause confusion once the serum sodium levels begin to dip. The association between hypothyroidism and hyponatremia is thought to be due to inappropriate ADH release or decreased GFR.

Her sodium was rapidly corrected by the saline infusion, causing central pontine myelinolysis. This is osmotic demyelination leading to paraparesis, dysarthria, seizures, coma and eventually death.

Sodium should therefore only be corrected by 1mmol/l per hour and not more than 8-10mmol/l in the first 24h if there is severe hyponatremia.

Question 6

Name 2 causes of:

a) Hypovolemia hypernatremia
b) Euvolemic hypernatremia
c) Hypervolemic hypernatremia

Answer 6

a) Extensive burns, loop diuretics
b) Increased respiratory rate, diabetes insipidus, dehydration
c) Conn’s, hypertonic saline (iatrogenic)

Question 7

How do you use investigations to distinguish between nephrogenic and cranial diabetes insipidus?

Answer 7

8hr fluid deprivation test

• nephrogenic: when given desmopressin there will be no concentration of the urine
• cranial: desmopressin will increase urine concentration
• both: before desmopressin, passing large volumes of dilute urine (urine osmolality <2)

Question 8

Causes of:

a) Nephrogenic DI
b) Cranial DI

Answer 8

a) Defect in the receptor for ADH secondary to an inherited cause, lithium or chronic renal failure
b) A decrease in or absence of ADH release, secondary to head trauma, a tumour or surgery

Question 9

Name 3 causes of redistribution of potassium which cause hypokalemia.

Answer 9

Insulin, beta agonists e.g. salbutamol, metabolic alkalosis - exchange of H+ and K+ leads to greater excretion of potassium as H+ ions are reabsorbed to correct the alkalosis.

Question 10

In what ways can diabetes mellitus lead to hypokalemia?

Answer 10

1) Treatment with insulin (particularly in DKA) can cause intracellular shift of K and therefore hypokalemia
2) Can cause an osmotic diuresis causing extra potassium loss via the kidneys
3) Can have a coexistent hypomagnesemia (related to poor dietary intake, poor absorption or osmotic diuresis)

Question 11

How can Addison’s disease cause hyperkalemia?

Answer 11

Primary adrenal insufficiency leads to a lack of aldosterone being produced. Aldosterone causes the excretion of potassium and reabsorption of Na. Therefore, if it is absent there will be a hyperkalemia due to less potassium excretion with coexisting hyponatremia due to greater sodium losses.

Question 12

How do you calculate the anion gap?

Answer 12

(Na + K) - (Cl + HCO3) = the concentration of unmeasures anions in the plasma e.g. albumin.
Normal is 14-18mmol/l

Question 13

Name 4 things that can cause an increase in the anion gap.

Answer 13

Ketoacidosis - secondary to starvation, DKA or alcohol
Lactic acidosis
Uraemia - secondary to renal failure
Toxins - ethylene glycol, methanol, paraldehyde, salicylates

Question 14

What ratio of AST to ALT would you expect in alcoholic hepatitis vs. viral liver disease?

Answer 14

AST:ALT in alcoholic liver disease is usually a ratio of 2:1

In viral, ratio is <1:1

Question 15

What is the relevance of gamma GT in liver function tests?

Answer 15

Confirms a hepatic source of a high ALP. Increased with chronic alcohol disease, bile duct disease and metastases.

Question 16

Outline the different factors involved in the regulation of calcium levels.

Answer 16

Vitamin D - conversion of 7-dehydrocholesterol by exposure to sunlight creates D3. D3 is converted in the liver to 25-OH D3 and then by 1-alpha hydroxylsase to 1,25-(OH)2D3 which is the active form, causing increased absorption of calcium and phosphate in the intestines.

PTH release is increased when plasma Ca levels are low. PTH causes an increase in 1-alpha hydroxylase (for conversion of 25-OH D3) but also increased bone resorption by osteoclasts and kidney resorption of calcium.

Question 17

Give 2 signs of osteomalacia and 2 signs of rickets.

Answer 17

Osteomalacia - bone and muscle pain, increased fracture risk, Looser’s zones i.e. pseudofractures.
Rickets - bowed legs, costochondral swelling, widened epiphyses in the wrists and myopathy.
Both - decreased serum Ca and PO4 with increased PTH and ALP.

Question 18

Name the condition:

High Ca, normal/high PO4, low PTH, normal ALP

a) Osteomalacia
b) Osteoporosis
c) Paget’s disease
d) Primary hyperparathyroidism
e) Sarcoidosis
f) Multiple myeloma
g) Secondary hyperparathyroidism
h) Tertiary hyperparathyroidism
i) Hypoparathyroidism
j) Osteopenia

Answer 18

f) Multiple myeloma

Question 19

Name the condition:

Normal Ca, normal PO4, normal PTH, normal ALP, DEXA T score 2.2

a) Osteomalacia
b) Osteoporosis
c) Paget’s disease
d) Primary hyperparathyroidism
e) Sarcoidosis
f) Multiple myeloma
g) Secondary hyperparathyroidism
h) Tertiary hyperparathyroidism
i) Hypoparathyroidism
j) Osteopenia

Answer 19

j) Osteopenia

Loss of bone mass after menopause or with age leads to defective anabolism or excessive catabolism (seen with endocrine dysregulation).

Bone demineralisation with thin trabeculae and herniation of nucleus pulposus are the findings on imaging.

DEXA T score between 1 and 2.5 indicates osteopenia whereas >2.5 indicates osteoporosis.

Question 20

Name the condition:

High Ca, low PO4, high PTH and normal/high ALP

a) Osteomalacia
b) Osteoporosis
c) Paget’s disease
d) Primary hyperparathyroidism
e) Sarcoidosis
f) Multiple myeloma
g) Secondary hyperparathyroidism
h) Tertiary hyperparathyroidism
i) Hypoparathyroidism
j) Osteopenia

Answer 20

h) Tertiary hyperparathyroidism

Found when there is autonomous high PTH release e.g. in patients with CKD after a kidney transplant.

Question 21

Name the condition:

High Ca, normal PO4, normal PTH and high ALP.

a) Osteomalacia
b) Osteoporosis
c) Paget’s disease
d) Primary hyperparathyroidism
e) Sarcoidosis
f) Multiple myeloma
g) Secondary hyperparathyroidism
h) Tertiary hyperparathyroidism
i) Hypoparathyroidism
j) Osteopenia

Answer 21

e) Sarcoidosis

Hydroxylation of vitamin D can occur outside of the kidneys (e.g. in granulomas formed by the disease) leading to high levels of 1,25 (OH)2 D3. This is also related to high levels of IFN gamma due to activated lymphocytes and macrophages.

Question 22

Name the condition:

Normal Ca, normal PO4, normal PTH, raised ALP.

a) Osteomalacia
b) Osteoporosis
c) Paget’s disease
d) Primary hyperparathyroidism
e) Sarcoidosis
f) Multiple myeloma
g) Secondary hyperparathyroidism
h) Tertiary hyperparathyroidism
i) Hypoparathyroidism
j) Osteopenia

Answer 22

c) Paget’s disease

Disorder of bone remodelling leads to increased osteoblastic and osteoclastic activity and ‘mosaic bone’ appearance.

Presents with focal pain, warmth, deformity, fractures, cardiac failure and spinal cord compression.

Question 23

Name 4 symptoms of hypocalcaemia.

Answer 23

Neuromuscular excitability - hyperreflexia, convulsions, laryngeal spasm
Paraesthesias
Muscle cramps
Depression and memory loss
Chvostek’s - twitching of facial muscles in response to tapping over the distribution of the facial nerve
Trousseau - carpal spasm when upper arm is compressed e.g. by tourniquet

Question 24

A patient with DiGeorge syndrome has surgery on his thyroid gland and ends up with hypoparathyroidism. What will his investigations show?

Answer 24

Low PTH leads to low Ca and high PO4. ALP may be low or normal.

Question 25

What are the management options for hypocalcemia?

Answer 25

Calcium replacement
Alfacalcidol (if CKD)
10% calcium gluconate IV

Question 26

What type of porphyria is presented below?

Autosomal dominant condition which presents with skin lesions, neurovisceral symptoms such as abdominal pain and autonomic instability. Porphyrins are found in the faeces and urine.

a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Erythropoietic protoporphyria
d) Porphyria cutanea tarda
e) Variegate porphyria
f) Congenital erythropoietic porphyria

Answer 26

b) Hereditary coproporphyria

Reduction in coproporphyrinogen oxidase leads to build up of coproporphyrinogen III.

Question 27

What type of porphyria is presented below?

A non acute porphyria which only present with skin lesions, causing photosensitivity, burning, itching and oedema when exposed to the sun.

a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Erythropoietic protoporphyria
d) Porphyria cutanea tarda
e) Variegate porphyria
f) Congenital erythropoietic porphyria

Answer 27

c) Erythropoietic protoporphyria

Reduction in ferrochetalase leads to an increase in protoporphyrin IX.

Question 28

What type of porphyria is presented below?

An autosomal dominant deficiency in hydroxymethylbilane synthase which leads to neurovisceral symptoms, such as abdominal pain and psychiatric disturbances, but no cutaneous symptoms.

a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Erythropoietic protoporphyria
d) Congenital erythropoietic porphyria
e) Variegate porphyria
f) Porphyria cutanea tarda

Answer 28

a) Acute intermittent porphyria

Symptoms - abdominal pain, N&V, increased HR and BP, constipation, seizures, psych disturbances, sensory loss, muscle weakness.

Presents with port wine urine.

Can be precipitated by ALA synthase inducers e.g. steroid, alcohol and barbiturates, stress and endocrine problems.

Mx - avoid factors above, analgesia, IV carb/haem arginate

Question 29

What type of porphyria is presented below?

Can be inherited or acquired and presents with crusted vesicles and pigmented and superficial scarring on sun exposed sites.

a) Acute intermittent porphyria
b) Hereditary coproporphyria
c) Erythropoietic protoporphyria
d) Congenital erythropoietic porphyria
e) Variegate porphyria
f) Porphyria cutanea tarda

Answer 29

f) Porphyria cutanea tarda

Secondary to uroporphyrinogen decarboxylase deficiency, leading to skin lesions.

Ix - increased urinary uroporphyrins and coproporphyrins and increased ferritin

Mx - avoid precipitants e.g. alcohol and hepatic compromise, phlebotomy

Question 30

Normal levels for TSH, free T4 and free T3.

Answer 30

TSH 0.33-4.5 mU/L
Free T4 10.2-22.0 pmol/L
Free T3 3.2-6.5 pmol/L

Question 31

A 23 year old woman presents to her GP with a 1 month history of muscle weakness, tremor and heat intolerance. An isotope scan shows a single hot nodule. Her thyroid blood tests show a high free T3 and T4 with a low TSH. What is the diagnosis?

Answer 31

Toxic adenoma

5% of the cases of high uptake hyperthyroidism.

Question 32

How does subacute DeQuervains thyroiditis present?

Answer 32

Self-limiting subacute painful thyroiditis (subacute granulomatous thyroiditis) which has a triphasic course of hyperthyroidism, hypothyroidism then a return to normal thyroid hormone levels. Patients may only notic one phase and may have a diffusely tender thyroid with shifting pain. Recovery usually occurs in weeks to months.

Associated with upper respiratory infections with falling postconvalescent viral titers of various viruses, including influenza, adenovirus, mumps, and coxsackievirus. It is unclear whether damage to the thyroid is caused by the virus or the immune system reaction to the virus.

Fine needle aspiration biopsy of the thyroid gland will show multinucleated giant cell granulomas. Development associated with HLA-B35.

Question 33

Three different causes of hypothyroidism.

Answer 33

1) Primary atrophic hypothyroidism - diffuse lymphocytic infiltration and atrophy, without a goitre and spontaneous presentation with age
2) Hashimoto’s thyroiditis - plasma cell infiltration and goitre which is more common in elderly females. Increased level of autoantibodies e.g. TPO, TG, TSH-R
3) Other causes - iodine deficiency, post thyroidectomy, radioiodine, secondary to lithium or amiodarone treatment

Question 34

Treatment of high uptake hyperthyroidism.

Answer 34

Beta blockers and carbimazole or propylthiouracil (risk of aplastic anaemia). May also use radioiodine or surgery depending on the cause.

Question 35

Name the type of thyroid neoplasia:

A 45 year old woman presents with a well-differentiated thyroid tumour and early lymph node involvement.

a) Anaplastic
b) Follicular
c) Papillary
d) Medullary
e) Lymphoma

Answer 35

b) Follicular (25% of thyroid neoplasias)

Treatment is with surgery, radioiodine and then thyroxine replacement

Question 36

Name the type of thyroid neoplasia:

A thyroid neoplasia that arises from the parafollicular cells. It may be associated with tumours of the parathyroid and adrenal glands.

a) Anaplastic
b) Follicular
c) Papillary
d) Medullary
e) Lymphoma

Answer 36

d) Medullary (5% of cases)

Associated with multiple endocrine neoplasia syndrome type 2, which presents with thyroid, parathyroid and adrenal tumours. It causes a raised plasma calcitonin level because there is hyperplasia of the C cells within the thyroid that produce the hormone.

Question 37

Name the type of thyroid neoplasia:

A 36 year old man presents with a nodule in the centre of his neck. When he was 20 years old, he had radiotherapy to treat a Hodgkin’s lymphoma in his neck. Imaging of the lump shows an irregular mixed solid and cystic mass in the parenchyma of the thyroid gland.

a) Anaplastic
b) Follicular
c) Papillary
d) Medullary
e) Lymphoma

Answer 37

c) Papillary (over 60% of cases)

Usually presents in 30-40 year olds as an irregular solid or cystic mass in the parenchyma, with or without associated symptoms. Treatment is with surgery with/without radioiodine therapy and replacement thyroxine.

Features of papillary cancer on FNA include: enlarged, often overlapping nuclei with fine, dusty or powdery chromatin, intranuclear cytoplasmic inclusions; and linear chromatin ridges with irregular nuclear outlines.

Question 38

What are the criteria for the diagnosis of Addison’s disease on a SynACTHen test?

Answer 38

ACTH injection will cause cortisol to less than double with lower than expected aldosterone. Normal is rise of at least 200nmol/L in 30 mins.

Question 39

What is the difference in hormone levels between primary and secondary Conn’s syndrome?

Answer 39

Primary - high aldosterone, low renin, normal cortisol

Secondary - high aldosterone, high renin (increase in RAAS)

Question 40

What is the mechanism behind homeostasis of plasma sodium concentration and blood pressure?

Answer 40

Controlled by the renin-aldosterone-angiotensin system.
Reduction in renal blood flow with low BP/plasma sodium concentration leads to conversion of prorenin to renin in the juxtaglomerular cells. Renin controls the conversion of angiotensinogen to angiotensin I. Conversion of AI to AII by ACE in endothelial cells of capillaries leads to vasoconstriction and stimulates the secretion of aldosterone from the adrenal cortex.

Aldosterone enters the distal convoluted tubule cells to increase the number of Na channels on the luminal membrane and Na/K pumps on the basement membrane, allowing Na to enter cells from the lumen and then be exchanged at the BM for potassium. The increase in potassium in the cell then causes a diffusion gradient into the lumen and therefore excretion of potassium.

Question 41

Drug monitoring:

Monitor peak and trough levels and control with single daily dosing.

a) Phenytoin
b) Digoxin
c) Lithium
d) Gentamicin
e) Theophylline

Answer 41

d) Gentamicin

S/E include tinnitus, nystagmus and renal failure.

Question 42

Drug monitoring:

Levels need to be adjusted for smokers and those with liver disease. Can also be increased by erythromycin, cimetidine and phenytoin.

a) Phenytoin
b) Digoxin
c) Lithium
d) Gentamicin
e) Theophylline

Answer 42

e) Theophylline

Excess leads to arrythmias, anxiety, tremor and convulsions.

Question 43

Drug monitoring:

Levels of this drug are increased in hypokalemia. Symptoms of toxicity may be the same as undertreatment.

a) Phenytoin
b) Digoxin
c) Lithium
d) Gentamicin
e) Theophylline

Answer 43

b) Digoxin

The dose should be decreased for those with renal failure or for the elderly. Excess can be treated with Digibind. Toxicity leads to arrythmias, heart block, confusion and xanthopsia.

Question 44

Which conditions cause ALP to be raised to:

a) more than 5 times the upper limit of normal
b) less than 5 times the upper limit of normal?

Answer 44

a) Paget’s disease, osteomalacia, cholestasis, cirrhosis

b) Bone tumours, fractures, osteomyelitis, infiltrative disease, hepatitis

Question 45

Name the appropriate investigation:

A 50 year old alcoholic man presenting with confusion, ataxia and nystagmus.

a) RBC transketolase
b) RBC AST activation
c) RBC glutathione reductase
d) Serum B12
e) RBC folate
f) Caeruloplasmin
g) PTT

Answer 45

a) RBC transketolase - investigation for Wernicke’s encephalopathy, caused by thiamine (B1) deficiency

Question 46

Name the appropriate investigation:

A 33 year old woman who was diagnosed with Crohn’s disease 5 years ago and has recently started taking sulfasalazine.

a) RBC transketolase
b) RBC AST activation
c) RBC glutathione reductase
d) Serum B12
e) RBC folate
f) Caeruloplasmin
g) PTT

Answer 46

e) RBC folate

Folate deficiency may be secondary to B12 deficiency (malabsorptive conditions) or may occur in some inflammatory conditions and with the medications used to treat them e.g. sulfasalazine, methotrexate.

Question 47

Name the appropriate investigation:

Glossitis and angular cheilosis in a pregnant woman who is lactose intolerant. Her obstetrician states that her baby may be at risk of palate deformities and congenital heart defects.

a) RBC transketolase
b) RBC AST activation
c) RBC glutathione reductase
d) Serum B12
e) RBC folate
f) Caeruloplasmin
g) PTT

Answer 47

c) RBC glutathione reductase - for investigation of riboflavin (B2) deficiency, otherwise known as ariboflavinosis.

This is more commonly found in pregnant women. It has also been associated with phototherapy in newborn infants and in some people with chronic diseases like IBD. B2 is found in dairy products.

Deficiency in pregnancy can cause deformities in the fetus.

Question 48

Name the appropriate investigation:

Seborrheic dermatitis and glossitis in a 15 year old boy who has been on isoniazid for 5 months to treat tuberculosis.

a) RBC transketolase
b) RBC AST activation
c) RBC glutathione reductase
d) Serum B12
e) RBC folate
f) Caeruloplasmin
g) PTT

Answer 48

b) RBC AST activation

Certain drugs such as isoniazid inactivate pyridoxine, leading to vitamin B6 (pyridoxine) deficiency. Symptoms are similar to pellagra (dermatitis and dementia) and may cause seizures in adults.

Question 49

Mutations in familial hypercholesterolemia.

Answer 49

Dominant - LDLR, apoB, PCSK9
Recessive - LDLRAP1

PCSK9 - binds to LDLR to increase degradation; mutation leads to a loss of function

Question 50

Causes of increased triglycerides

Answer 50

Deficiency in lipoprotein lipase or apoC II
Increased production of triglycerides (exogenous from small intestine, endogenous in liver)
Deficiency in apoA V

Question 51

Causes of hypolipidaemia

Answer 51

A-beta lipoproteinaemia - deficiency in mitochondrial trifunctional protein (MTP)
Decrease in beta-lipoprotein - truncated apoB
Tangier - deficiency in HDL
Decrease in alpha-lipoprotein - apoA-I mutation

Question 52

What is the function of chylomicrons and VLDL?

Answer 52

Triglyceride-rich - chylomicrons are synthesized by enterocytes from lipids absorbed in the small intestine.
VLDL is synthesized in the liver.

The function of these lipoproteins is to deliver energy-rich triacylglycerol (TAG) to cells in the body. TAG is stripped from chylomicrons and VLDL through the action of lipoprotein lipase, found on the surface of endothelial cells. This enzyme digests the TAG to fatty acids and monoglycerides, which can then diffuse into the cell to be oxidized, or in the case of an adipose cell, to be re-synthesized into TAG and stored in the cell.

Question 53

What symptoms do metabolic disorders of the urea cycle lead to?

Answer 53

Recessive metabolic disorders (except omithine transcarbamylase deficiency which is X-linked). Leads to excess in circulating ammonia.

Causes vomiting, respiratory alkalosis (due to increase in ammonia) and encephalopathy.

Question 54

How do organic acidurias present in neonates?

Answer 54

Organic acidurias are due to the disruption of amino acid metabolism, especially leucine, isoleucine and valine.

In neonates, they present with babies with unusual odour who look lethargic and have poor feeding. On examination they may have truncal hypotonia with limb hypertonia and myoclonic jerks.

Ix show increased ammonia with a metabolic acidosis (unlike respiratory alkalosis of urea cycle disorders), hypocalcemia, low WCC and pancytopenia.

Question 55

What is Reye syndrome?

Answer 55

Recurrent episodes of ketoacidotic coma and cerebral abnormalities due to a disorder of fatty acid oxidation.

Leads to vomiting, lethargy, confusion, seizures, decerebration and respiratory arrest which may be triggered by use of salicylates, antiemetics or valproate.

Question 56

What is galactosaemia?

Answer 56

Disorder of carbohydrate metabolism - most severe is galactose-1-phosphate uridylyltransferase deficiency. An increase in galactose-1-PUT leads to liver and kidney disease, which presents with diarrhoea and vomiting, conjugated hyperbilirubinaemia, hepatomegaly , hypoglycaemia and sepsis in neonates.

Question 57

What is the enzyme deficiency present in von Gierke’s disease?

Answer 57

Glucose 6-phosphatase deficiency. Causes hypoglycaemia, hyperuricaemia and excessive lactic acid generation in babies.

Question 58

Investigations for lysosomal storage disorders

Answer 58

Urine mucopolysaccharides/oligosaccharides and leucocyte enzyme activity

Question 59

Examples of lysosomal storage disorders.

Answer 59

Batten disease - accumulation of lipopigment in the brain which causes rapidly progressing optic atrophy and neurological disturbances; more common in Northern European populations

Fabry disease - severe burning pain in hands and feet plus decreased sweat production; presents in children/adolescents

Gaucher disease - easy bruising, chronic fatigue and hepatosplenomegaly

Infantile Tay Sachs disease - symptoms typically first appear between three and five months of age. These may include feeding problems, lethargy and an exaggerated startle reflex in response to sudden loud noises. Motor delays and mental deterioration are progressive.

Question 60

What are peroxisomal disorders and how do they present in neonates?

Answer 60

Disorder in very long chain fatty acids and biosynthesis of complex phospholipids.

Neonate - severe muscular hypotonia, seizures, hepatic dysfunction, mixed hyperbilirubinaemia and dysmorphoc signs.

Question 61

Name 3 different mitochondrial disorders.

Answer 61

Barth syndrome - cardiomyopathy, neutropenia and myopathy; presents at birth.

MELAS - mitochondrial encephalopathy, lactic acidosis and stroke like episdoes; presents between 5 and 15 years old.

Kearns-Sayre - retinopathy, deafness, ataxia and chronic progressive external opthalmoplegia; presents in 12-30 year olds.

Question 62

How are diabetes and impaired glucose tolerance diagnosed on investigations?

Answer 62

Diabetes - symptoms with one of fasting glucose > 7, OGTT >11.1 or random glucose >11.1 (or two tests with no symptoms).

Impaired glucose tolerance - 7.8

Question 63

What are the potential causes of a reduced C-peptide alongside reduced insulin in neonates?

Answer 63

Increase in free fatty acids with or without ketones:
Ketones present - causes include prematurity and IUGR
Ketones absent - caused by inherited metabolic disorders

Question 64

Name 5 conditions in neonates that are associated with prematurity.

Answer 64

• Respiratory distress syndrome
• Retinopathy of prematurity
• Intraventricular haemorrhage
• Patent ductus arteriosus
• Necrotising enterocolitis

Question 65

How is clearance calculated?

Answer 65

Clearance = Urine concentration x urine flow (ml/min)/plasma concentration

Clearance using inulin = GFR

Question 66

Name 3 exogenous toxins that can cause direct tubular injury in the kidney.

Answer 66

Amphotericin, acyclovir, aminoglycosides

Question 67

Liver function test results with paracetamol poisoning.

Answer 67

Disrupts everything: very high AST and ALT (>1000), slight increase in GGT and ALP, metabolic acidosis, low glucose

Question 68

What is Dublin Johnson syndrome?

Answer 68

Autosomal recessive disorder with decreased secretion of conjugated bilirubin into bile, therefore causing raised serum conjugated BR.

Question 69

What is maple syrup urine disease?

Answer 69

Due to mutations in BCKDHA, BCKDHB and DBT.

Inability to metabolise amino acids, valine, leucine and isoleucine, which leads to sweet smelling urine, poor feeding, vomiting and lethargy. If untreated, leads to seizures, coma and death.