Biochemistry

Question 1

What can changes in plasma potassium cause?

Answer 1

• Response to stimuli of excitable cells, such as nerve and muscle, may be affected
• In the heart the consequences e.g. arrhythmias can be fatal

Question 2

What are the two most important factors that determine potassium excretion?

Answer 2

GFR and the plasma potassium concentration

Question 3

Where is almost all of the body potassium found and as a result what happens when there is tissue damage?

Answer 3

• Within cells (98%)
• If there is significant tissue damage, the contents of cells, including potassium, leak out into the extracellular compartment causing potentially dangerous increases in serum potassium

Question 4

How is severe hyperkalaemia defined and what may be the first manifestation of hyperkalaemia?

Answer 4

• Serum K >7.0mmol/L
• Cardiac arrest may be the first manifestation

Question 5

What are typical ECG changes seen in hyperkalaemia?

Answer 5

• Tall tented T waves
• Widening of the QRS complex

Question 6

What are symptoms of hyperkalaemia?

Answer 6

Muscle weakness and paraesthesiae

Question 7

Renal failure is the most common cause of hyperkalaemia, why does it cause this?

Answer 7

• Reduced glomerular function
• It is exacerbated by the associated metabolic acidosis due to the accumulation of organic ions that would normally be excreted; K and H share an excretory pathway

Question 8

How does hypoaldosteronism cause hyperkalaemia?

Answer 8

• Aldosterone deficiency, antagonism or resistance results in loss of sodium and water, reducing the GFR
• Most often seen with ACE inhibitors, ARBs and spironolactone, all of which are used to treat hypertension

Question 9

Why does metabolic acidosis result in hyperkalaemia?

Answer 9

As the concentration of H ions increases with the development of metabolic acidosis, so K ions inside cells are displaced from the cell by H ions in order to maintain electrochemical neutrality

Question 10

How can rhabdomyolysis cause hyperkalaemia?

Answer 10

• Potassium is released from damaged skeletal muscle cells
• This mechanism can also occur in extensive trauma and tumour lysis syndrome

Question 11

Why can insulin deficiency cause hyperkalaemia?

Answer 11

• Insulin stimulates cellular uptake of potassium
• Where there is insulin deficiency or severe resistance to the actions of insulin as in DKA, hyperkalaemia is an associated feature

Question 12

What is pseudohyperkalaemia?

Answer 12

Hyperkalaemia due to its movement out of cells during or after venesection

Question 13

What is hyperkalaemic periodic paralysis?

Answer 13

Rare autosomal dominant disorder resulting in paralysis after exercise

Question 14

How can hyperkalaemia occur due to increased intake?

Answer 14

• A lot of oral drugs are administered as potassium salts
• Potassium may also be given IV
• Blood products may cause hyperkalaemia (as stored RBCs release K)

Question 15

At what rate should IV potassium be given at?

Answer 15

No faster than 20mmol/hour except in extreme cases

Question 16

How is hyperkalaemia treated?

Answer 16

• Calcium - counteracts the effects on the resting membrane potential of cells
• Insulin - causes K to move into cells along with glucose (glucose is also given to prevent hypoglycaemia)
• Dialysis may be required for refractory hyperkalaemia

Question 17

What can cause pseudohyperkalaemia?

Answer 17

1. Delay in centrifugation separating plasma/serum from the cells/clot, especially if the specimen is cold - very common in primary care
2. In-vitro haemolysis
3. An increase in the platelet and/or white cell count

Question 18

What are the clinical features of hypercalcaemia?

Answer 18

• Neurological and psychiatric features e.g. irritability, depression, confusion, lethargy
• GI problems such as anorexia, abdominal pain, nausea, vomiting and constipation
• Renal features such as polyuria, thirst and renal calculi
• Cardiac arrhythmias

Question 19

What are the most common causes of hypercalcaemia?

Answer 19

Primary hyperparathyroidism and hypercalcaemia of malignancy

Question 20

What causes hyperparathyroidism?

Answer 20

A single parathyroid adenoma which secretes PTH autonomously i.e. not responding to feedback control by plasma calcium

Question 21

If PTH is undetectable in someone with hypercalcaemia, what is the likely cause?

Answer 21

Malignancy or rarer cause

Question 22

If PTH is normal or high in a patient with hypercalcaemia, what is the likely diagnosis?

Answer 22

Primary hyperparathyroidism

Question 23

What protein do some tumours secrete which causes hypercalcaemia?

Answer 23

Parathyroid hormone-related peptide (PTHrP) which has PTH like properties and can thus cause hypercalcaemia

Question 24

What are some rarer causes of hypercalcaemia?

Answer 24

Inappropriate dosage of vitamin D, granulomatous diseases e.g. TB., thyrotoxicosis, thiazide therapy, immobilisation, renal disease, calcium therapy

Question 25

What is the name of the condition where high plasma calcium is sensed by he parathyroid glands as normal making them appear to be hyperparathyroid?

Answer 25

• FBH - familial benign hypercalcaemia
• On neck exploration, no parathyroid adenoma is found and it may be discovered that family members also have asymptomatic hypercalcaemia

Question 26

How is FBH diagnosed?

Answer 26

• Urine calcium excretion is inappropriately low for the serum Ca and is usually lower than in primary hyperparathyroidism
• Isotope (sestamibi) scans may be helpful

Question 27

How is hypercalcaemia treated if the serum calcium is >3.5mmol/L?

Answer 27

Urgent IV saline to restore the GFR and promote diuresis

Question 28

How is hypercalaemia of malignancy treated?

Answer 28

Bisphosphonates (zoledronic acid) and denosumab have the best calcium-lowering effects as they inhibit bone resorption

Question 29

How is hypercalcaemia due to primary hyperparathyroidism treated?

Answer 29

• Surgical removal of parathyroid adenoma usually provides cure
• However can become transiently hypocalcaemic so may have to be treated with vitamin D metabolites

Question 30

What can occur in severe primary hyperparathyroidism?

Answer 30

Subperiosteal resorption

Question 31

What are the clinical features of adrenal insufficiency?

Answer 31

• Lethargy, anorexia, pigmentation of hands and mouth, abdominal pain and weight loss
• Acute crisis - hypotension, vomiting, nausea and dehydration

Question 32

Describe the pathogenesis of adrenal insufficiency

Answer 32

• Inability to synthesise steroid hormones (cortisol and aldosterone)
• Lack of mineralocrticoid (aldosterone) activity means that Na cannot be retained in the kidneys and is therefore lost from the ECF (along with water)
• Reduced ECF volume results in dehydration and hypotension with resultant dizziness and lethargy

Question 33

What causes the excess pigmentation seen in adrenal insufficiency?

Answer 33

• Excess ACTH due to reduced negative feedback results in increased melanocyte-stimulating hormone (MSH) being released which acts on skin and mucous membranes
• ONLY seen in primary adrenal insufficiency

Question 34

How is adrenal insufficiency diagnosed?

Answer 34

• Ensure sodium intake is adequate whilst investigations proceed
• Random cortisol - very low or very high result is most useful
• Short syncathen and long synacthen tests

Question 35

Describe the short and long synacthen tests

Answer 35

• Synthetic ACTH is given IV and cortisol is measured at 0, 30 and 60 minutes afterwards.
• Inadequate response to the ACTH may require a long synacthen test to establish whether adrenal insufficiency is primary or secondary due to pituitary or hypothalamic disease
• Normal response to long synacthen test excludes primary adrenal insufficiency

Question 36

What are some causes of adrenal insufficiency?

Answer 36

• Primary adrenal insufficiency = Addison’s disease
• Primary is most often caused by autoimmune disease (developed countries) and TB in developing countries
• Secondary adrenal insufficiency is more common and is usually due to corticosteroid use and results in suppression of the entire HPA axis

Question 37

What is the main hormonal difference between primary and secondary adrenal insufficiency?

Answer 37

Primary there will be increased ACTH where as in secondary there will be decreased ACTH

Question 38

What is relative adrenal insufficiency?

Answer 38

• Inability to mount an adequate cortisol response, usually occurs in acutely ill patients
• Carries a poor prognosis
• Cortisol levels are high but there is a flat response to synacthen

Question 39

How is adrenal insufficiency treated?

Answer 39

Appropriate hormone replacement e.g. fludrocortisone and hydrocortisone + maintenance of sodium intake