Biochemistry Flashcards
What can changes in plasma potassium cause?
- 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
What are the two most important factors that determine potassium excretion?
GFR and the plasma potassium concentration
Where is almost all of the body potassium found and as a result what happens when there is tissue damage?
- 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
How is severe hyperkalaemia defined and what may be the first manifestation of hyperkalaemia?
- Serum K >7.0mmol/L
- Cardiac arrest may be the first manifestation
What are typical ECG changes seen in hyperkalaemia?
- Tall tented T waves
- Widening of the QRS complex
What are symptoms of hyperkalaemia?
Muscle weakness and paraesthesiae
Renal failure is the most common cause of hyperkalaemia, why does it cause this?
- 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
How does hypoaldosteronism cause hyperkalaemia?
- 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
Why does metabolic acidosis result in hyperkalaemia?
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
How can rhabdomyolysis cause hyperkalaemia?
- Potassium is released from damaged skeletal muscle cells
- This mechanism can also occur in extensive trauma and tumour lysis syndrome
Why can insulin deficiency cause hyperkalaemia?
- 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
What is pseudohyperkalaemia?
Hyperkalaemia due to its movement out of cells during or after venesection
What is hyperkalaemic periodic paralysis?
Rare autosomal dominant disorder resulting in paralysis after exercise
How can hyperkalaemia occur due to increased intake?
- 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)
At what rate should IV potassium be given at?
No faster than 20mmol/hour except in extreme cases
How is hyperkalaemia treated?
- 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
What can cause pseudohyperkalaemia?
- Delay in centrifugation separating plasma/serum from the cells/clot, especially if the specimen is cold - very common in primary care
- In-vitro haemolysis
- An increase in the platelet and/or white cell count
What are the clinical features of hypercalcaemia?
- 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
What are the most common causes of hypercalcaemia?
Primary hyperparathyroidism and hypercalcaemia of malignancy
What causes hyperparathyroidism?
A single parathyroid adenoma which secretes PTH autonomously i.e. not responding to feedback control by plasma calcium
If PTH is undetectable in someone with hypercalcaemia, what is the likely cause?
Malignancy or rarer cause
If PTH is normal or high in a patient with hypercalcaemia, what is the likely diagnosis?
Primary hyperparathyroidism
What protein do some tumours secrete which causes hypercalcaemia?
Parathyroid hormone-related peptide (PTHrP) which has PTH like properties and can thus cause hypercalcaemia
What are some rarer causes of hypercalcaemia?
Inappropriate dosage of vitamin D, granulomatous diseases e.g. TB., thyrotoxicosis, thiazide therapy, immobilisation, renal disease, calcium therapy
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?
- FBH - familial benign hypercalcaemia
- On neck exploration, no parathyroid adenoma is found and it may be discovered that family members also have asymptomatic hypercalcaemia
How is FBH diagnosed?
- Urine calcium excretion is inappropriately low for the serum Ca and is usually lower than in primary hyperparathyroidism
- Isotope (sestamibi) scans may be helpful
How is hypercalcaemia treated if the serum calcium is >3.5mmol/L?
Urgent IV saline to restore the GFR and promote diuresis
How is hypercalaemia of malignancy treated?
Bisphosphonates (zoledronic acid) and denosumab have the best calcium-lowering effects as they inhibit bone resorption
How is hypercalcaemia due to primary hyperparathyroidism treated?
- Surgical removal of parathyroid adenoma usually provides cure
- However can become transiently hypocalcaemic so may have to be treated with vitamin D metabolites
What can occur in severe primary hyperparathyroidism?
Subperiosteal resorption
What are the clinical features of adrenal insufficiency?
- Lethargy, anorexia, pigmentation of hands and mouth, abdominal pain and weight loss
- Acute crisis - hypotension, vomiting, nausea and dehydration
Describe the pathogenesis of adrenal insufficiency
- 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
What causes the excess pigmentation seen in adrenal insufficiency?
- 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
How is adrenal insufficiency diagnosed?
- 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
Describe the short and long synacthen tests
- 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
What are some causes of adrenal insufficiency?
- 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
What is the main hormonal difference between primary and secondary adrenal insufficiency?
Primary there will be increased ACTH where as in secondary there will be decreased ACTH
What is relative adrenal insufficiency?
- 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
How is adrenal insufficiency treated?
Appropriate hormone replacement e.g. fludrocortisone and hydrocortisone + maintenance of sodium intake
