Lecture 6: Disturbances of potassium homeostasis in poisoning Flashcards
What is homeostasis
maintenance of metabolic equilibrium
What regulates the total body K+ levels
Kidneys
What controls distribution of K+ between ICF and ECF
non-renal mechanisms
What transporter is responsible for active uptake of K+
Na+/K+ ATPase
What is the normal intracellular concentration of K+
~140 mmol/L
How is K+ passively lost through cells
Through K+ channels
How does disturbing K+ balance affect cells
disrupts stability of excitable cells as they need rapid changes in membrane potential to function
What is the normal range for [K+]
3.3 - 5.1 mmol/L
What are the two non-renal mechanisms resonsible for [K+] disturbances in poisoning
- Na+/K+ ATPase
- K+ channels
What is hypokalaemia and what potassium concentration would you find
Low potassium levels
[K+] < 3.3 mmol/L
Name 3 mechanisms for hypokalaemia
- Increased Na+/K+ ATPase activity
- Competitive blockade of K+ channels
- Gastrointestinal losses of potassium
- Renal losses of potassium
- Systemic alkalosis leading to shift in K+ from ECF to ICF
How does increased Na+/K+ ATPase activity lead to hypokalaemia
- greater cAMP production
- increased affinity for intracellular Na+
- increased affinity for Na by Na+/K+ ATPase
Clinical features of hypokalaemia
- weakness of limbs in skeletal muscle
- paralytic ileus (no movement of gut muscle)
- cardiac muscle impairment leading to arrythmia and ECG changes
What ECG changes would you see in someone with hypokalaemia
- Flat or inverted R waves
- Extra abnormal U wave
- ST segment depression
How does Salbutamol increase hypokalaemia
- Salbutamol is a beta2 receptor agonist
- Beta2 receptors are coupled to adenylyl cyclase
- stimulation of beta2 receptors increases intracellular cAMP
- increase Na+/K+ ATPase activity
How does the dose of Salbutamol affect hypokalaemia
More salbutamol = more ATPase upregulation = more hypokalaemia
Are soluble barium salts toxic if ingested
Yes
Are insoluble barium salts toxic if ingested and why
No- they are not absorbed
How does Barium cause hypokalaemia
- Vomiting and diarrhea add to K+ loss
- Barium reversibly blocks K+ channels
- Passive K+ loss reduced, Na+/K+ ATPase continues to pump into cell
- ICF [K+] rises and ECF [K+] falls
- As ECF [K+] falls, Na+/K+ ATPase declines steeply reducing cellular K+ uptake
Management of hypokalaemia
- reduce/ remove exposure
- respiratory support
- IV potassium
Name 3 indirect mechanisms of hyperkalaemia
- Inhibition of Na+/K+ ATPase activity
- Depletion of cellular inhibition of cytochrome oxidases
- Activation of Ca2+ dependent K+ channels
- Ingestion of K+ salt
- systemic alkalosis shifting K+ from ICF to ECF
- rhabdomyolysis
Direct mechanisms of hyperkalaemia (3)
- Unconsciousness (muscle hypoxia due to lack of blood supply)
- Seizure (vigorous muscle activity)
- Acute renal failure (impaired excretion of potassium)
Clinical features of hyperkalaemia
- pain in smooth and skeletal muscle (not paralysis)
- arrhythmia
- ECG changes
What ECG changes are seen in hyperkalaemia
- Tall, peaked T waves
- ST segment depression
- Prolonged PR interval
- Widening of QRS wave
T wave difference in hypokalaemia and hyperkalaemia
Hypo = low K+ = low/ upside down T waves
Hyper = high K+ = high T waves
Management of Hyperkalaemia
- Digoxin-specific antibody fragments
- Antidotes for cyanide
- Insulin and dextrose
Why are insulin and dextrose given together in treatment for hyperkalaemia
- insulin shuts down Na+/K+ ATPase, reducing K+ conc
- needs to give sugar as well otherwise patient will develop hypoglycemia
