28-year-old (female) with muscle cramps

00:02 A 28 year old woman presents to a physician with repeated muscle cramps for the last 2 weeks.

00:08 She mentions she commonly has these in the lower limbs and in her back.

00:12 She also feels that she has become irritable over last month.

00:16 On physical examination, her vitals are stable.

00:19 The Trousseau sign and Chvostek sign are present, and deep tendon reflexes are exaggerated.

00:25 Her serum ionized calcium level is 0.9 mmol/L.

00:29 Which of the following electrophysiolgical mechanisms best explains clinical features of the woman? Answer choice (A) - Stimulation of GABA receptors Answer choice (B) - increased firing threshold for action potentials Answer choice (C) - Reduction of afterhyperpolarization Answer choice (D) - Inhibition of Sodium and calcium currents through the cyclic nucleotide-gated (CNG) channels or answer choice (E) - inhibition of sodium current through the sodium leak channels (NALCN) Now take a moment to come to an answer by yourself before we go through it together.

01:09 Okay let's jump right in to this question.

01:11 First let's talk about the question characteristics.

01:13 Now this is a physiology question.

01:15 What we're looking at a patient in a state in which she has abnormal electrolyte levels and looking about how depolarization of muscles occur.

01:25 This is a 2-step question because we have to find out the cause of her symptoms.

01:29 In here, it's going to be the low calcium and then determine how that correlates physiologically to how her membrane action potential works.

01:37 And the stem is absolutely required because we have to figure out the clinical situation and understand the outright abnormality through the question stem.

01:45 So let's walk through this question.

01:47 First we have to determine the cause of her symptoms.

01:49 She's got muscle cramps, she's irritable and she has a positive Trousseau sign and Chvostek's sign on the exam.

01:55 So we can see that the patient has a serum ionized calcium of 0.9 and this is marked hypocalcemia.

02:02 Now a normal serum ionized calcium level should range from 2.2 to 2.7, so this patient's calcium is very low.

02:09 Now hypocalcemia leads to increased neuronal excitability.

02:14 The Trousseau sign is a reliable clinical sign of latent tetany in patients with hypocalcemia.

02:21 It is often acompanied by exaggerated reflexes, also called hyperreflexia.

02:26 So the cause of this patient's symptoms, even her muscle cramps is due to low calcium levels.

02:33 Now we need to know and determine the mechanisms by which hypocalcemia increases neuronal excitability.

02:41 Now hypocalcemia increases neuronal excitability through a number of mechanisms including increasing the resting membrane potential and decreasing the firing threshold.

02:53 Next it can also inhibit GABA receptors, it can reduce afterhyperpolarization and it can increase currents through the cyclic nucleotide-gated (CNG) and also the sodium leak channels (NALCN).

03:09 Now let's refer to our image to help better understand this.

03:13 Now first we see that we have a threshold.

03:16 We have a resting state of -70 millivolts, and the threshold is after the stimulus occurs and our voltage goes to our threshold limit, then we'll have depolarization-repolarization which is our action potential which will then be followed by refractory period and then back to resting state.

03:34 Now, hypocalcemia can cause as we said through various mechanisms, one of them is what's called 'reducing hyperpolarization'.

03:45 That means you have a decrease in the refractory period.

03:50 So you have less time of resting between action potentials and you actually have increased firing and that's why you have the positive clinical signs - the Trousseau sign and the Chvostek's sign and these tetany because we have smaller refractory period or also called 'reduced afterhyperpolarization' which causes the increased clinical symptoms.

04:11 So in this case, the answer choice is answer choice (C) which is correct, which is reduction of hyperpolarization.

04:18 Now let's go through some high-yield facts regarding hypercalcemia and neuronal excitability.

04:24 Now hypocalcemia can cause increased neuronal excitability which may present with muscle stiffness and cramps, or in severe cases, general tetany.

04:34 And the Trousseau sign is a reliable clinical sign of latent tetany.

04:38 Now hypocalcemia increases neuronal excitability through a number of mechanisms including increasing the resting membrane potential and decreasing the firing threshold, inhibiting GABA receptors, reducing afterhyperpolarization and increasing currents through the cyclic-gated (CNG) and sodium leak channels (NALCN).