Thread by @runthelistpod

Who's ready for another #tweetorial?!

This week on HYPOCALCEMIA 🥺🥛

ICYMI, listen to our "Episode 35: Hypocalcemia" pod: apple.co/2XhpRIU

In the episode, Dr. OP Hamnvik @ohamnvik drops an early pearl & teaches us that the clinical manifestations of hypocalcemia occur depending on:

1) TEMPO

2) DEGREE of hypocalcemia

How quickly did the Ca drop & by how much?

If there's been a gradual⬇️ -> pt can be asymptomatic

Remember from last week, that Ca is tightly regulated in the blood (nl = 8.6-10.2 mg/dL). HypoCa = <8.6 mg/dL; tempo & level matter!

Calcium can be found in:

BONES (99% of body's Ca, stored as hydroxyapatite)

PROTEIN (bound to albumin)

FREE (ionized, regulates PTH level)

[1]

For a quick review of calcium regulation & hypocalcemia check out @OsmosisMed's video 💯:

Also check out our Hypercalcemia #tweetorial in which we cover: 1) calcium homeostasis, 2) PTH regulation, & 3) vitamin D metabolism:

https://twitter.com/runthelistpod/status/1271134213018968068

Recap:

1) LOW free/ionized Ca -> ⬆️ PTH release from the parathyroid gland

2) PTH then ⬆️ Ca levels by:

-Bone resorption ➡️ Ca release
-Ca reabsorption via the kidney
-vit. D activation (1,25(OH)2-vit D = calcitriol) -> Ca reabsorption in GI tract

end result: PTH ⬆️ Ca

[2]

So what happens if calcium levels are LOW?

*Muscular irritability & hyperexcitability*

"CATS go Numb" mnemonic:

1⃣Convulsions (seizures)
2⃣Arrhythmias (prolonged QTc)
3⃣Tetany 💪
4⃣Spasms, Stridor (2/2 laryngospasm)
5⃣Numbness [*perioral*, acral (hands, feet) parasthesias]

These clinical manifestations occur because Ca2+ serves to stabilize the neuronal membrane at rest

With LOW calcium levels -> Na+ channels become unstable -> membrane becomes HYPERexcitable ⬆️💪

This explains tetany (carpopedal), convulsions, GI cramps, tingling/parasthesias

Hypocalcemia EKG changes:

1) PROLONGED QTc interval

➡️can lead to Torsades de Pointes (TdP), although it is *less* common in hypoCa than with hypoK or hypoMg

--

2) ST segment changes

➡️can mimic MI!

[3,4]

How do we identify hypocalcemia on physical exam?

1) CHVOSTEK'S sign

= tap the facial nerve as it runs through the parotid gland -> ipsilateral facial muscles twitch

--
2) TROUSSEAU'S sign

= BP cuff occludes pts brachial artery (>SBP) -> carpal spasm in hand within 3 mins
[5]

1) CHVOSTEK'S sign*

Mechanism: w/ hypoCa nerves are HYPERexcitable, so mechanical tapping of facial nerve ➡️ contraction of the muscles it innervates

WATCH this helpful video:

from @AMLandryMD: nejm.org/doi/full/10.10…

*seen in ~10% of pts w/ normal Ca

2) TROUSSEAU'S sign*

Mechanism: inflation of BP cuff promotes ipsilateral carpal spasm 🦢

WATCH:

further explanation:

*more specific test than Chvostek's sign, although not often used clinically as it's uncomfortable for pts

What are the CAUSES of hypocalcemia?

As with hypercalcemia, @ohamnvik teaches us to think about TWO major buckets:

1⃣PTH-DEPENDENT

2⃣PTH-INDEPENDENT

[6]

1⃣PTH-DEPENDENT

LOW PTH due to:
-Genetic (DiGeorge = lack parathyroids)

-HypoMg (impairs PTH release)

-Iatrogenic [post-surgical (e.g. thyroidectomy), neck radiation]

-Infiltrative disease (TB, amyloidosis, hemochromatosis)

-Autoimmune 🦓 (APS-1, due to AIRE mutation)

[7]

(1⃣PTH-DEPENDENT cont.)

Resistance to PTH:
-PHP (Pseudohypoparathyroidism); type 1a due to mutation in GNAS1 = Gs-alpha subunit of PTH signaling cascade

in PHP there's actually a HIGH PTH level, due to *resistance* to its effect

[8]

2⃣PTH-INDEPENDENT

HIGH PTH due to loss of negative feedback of Ca on CaSR (i.e. hypoCa -> ⬆️ PTH)

Vitamin D-dependent:
-inadequate dietary intake (Rickets)
-malabsorption (Crohn's)
-impaired liver (cirrhosis) or kidney (ESRD) activation
-genetic vit. D metabolism defects

[9]

(2⃣PTH-INDEPENDENT cont.)

Vitamin D-independent:
-"Hungry bone syndrome" = ⬆️ Ca into bone
-Pancreatitis = Ca sequestered by free fatty acids
-Tissue injury = intracellular phosphate release -> complex w/ Ca
-Iatrogenic = meds that impair Ca release (bisphosphonates, Denosumab)

For hypocalcemia management decisions & other @ohamnvik pearls, you'll have to listen to the episode: apple.co/2XhpRIU!

Let's end with a quiz:

What would be the typical lab findings in *iatrogenic/post-surgical hypoparathyroidism* (e.g. thyroidectomy & inadvertent parathyroidectomy)?

If the patient has iatrogenic hypoparathyroidism -> ⬇️ PTH

As a result:
⬇️ Ca due to limited bone resorption, kidney reabsorption, vit. D activation
⬆️ phos (remember "Phosphate-Trashing Hormone")

therefore, with post-surgical hypoparathyroidism: ⬇️PTH, ⬇️Ca, ⬆️phos

[10]

In SUM:

-Hypocalcemia clinical sx depend on 1) tempo & 2) degree

-"CATS go Numb":
Convulsions
Arrhythmias (prolonged QTc)
Tetany (carpopedal)
Spasm/Stridor
Numbness (perioral parasthesias)

-Chvostek's & Trousseau's signs

-PTH-dependent (⬇️PTH), PTH-independent (⬆️PTH) causes

For more practice, check out:

1) "Case 3-2009 — A 9-Month-Old Boy with Seizures" nejm.org/doi/full/10.10…

2) @CPSolvers VMR 51: 45yo F p/w dizziness, numbness in the face & bilateral hands 5d after Crohn's flare
clinicalproblemsolving.com/morning-report…

REFs:

[1]uclahealth.org/endocrine-cent…
[2]resident360.nejm.org/clinical-pearl…
[3]step2.medbullets.com/step2-3-renal/…
[4]healio.com/cardiology/lea…
[5]pediagenosis.com/2018/08/facial…
[6]resident360.nejm.org/rotation-prep/…
[7]mmj.eg.net/article.asp?is…
[8]nature.com/articles/s4157…
[9]
[10]aafp.org/afp/2013/0815/…

@MedTweetorials @CPSolvers @COREIMpodcast @CuriousClinPod @DxRxEdu @rabihmgeha @tony_breu @AvrahamCooperMD @medrants @tmodarressi @RachelBlairMD