Hypokalemic rhabdomyolysis due to watery diarrhea,
hypokalemia, achlorhydria (WDHA) syndrome caused by vipoma.
Mild hypokalemia is common and encountered in a multitude of
diseases, but severe hypokalemia leading to rhabdomyolysis is relatively rare.
The watery diarrhea, hypokalemia,
achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide
(VIP)-producing tumors, is an extremely rare cause of hypokalemic
rhabdomyolysis and the literature is limited to one case report. We report a
second case of an adult who presented with rhabdomyolysis due to severe
hypokalemia. Further evaluation revealed that he had a VIP-producing pancreatic
neuroendocrine tumor (NET), which was the cause of his hypokalemic
rhabdomyolysis. Although rare in occurrence, a high index of suspicion is of
paramount importance for establishing the correct diagnosis and treatment.http://www.ncbi.nlm.nih.gov/pubmed/19488018
Vasoactive intestinal peptideVasoactive intestinal
peptide also known as the vasoactive intestinal
polypeptide or VIP is a peptide hormone containing 28 amino acid residues. VIP is a neuropeptide that belongs to a
glucagon/secretin superfamily, the ligand of class II G
protein-coupled receptors.[1] VIP
is produced in many tissues of vertebrates including
the gut, pancreas, and suprachiasmatic
nuclei of the hypothalamus in
the brain.[2][3] VIP
stimulates contractility in the heart, causes vasodilation, increasesglycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea,
stomach and gall bladder. In humans, the vasoactive
intestinal peptide is encoded by the VIP gene.[4]
VIP has a half-life (t½)
in the blood of about two minutes.
Function[edit]
VIP has an effect on several tissues:
·
With respect to the digestive system, VIP seems to induce smooth muscle relaxation (lower esophageal
sphincter,stomach, gallbladder), stimulate secretion of water
into pancreatic juice and bile,
and cause inhibition of gastric acid secretion and absorption from the
intestinal lumen.[5] Its
role in the intestine is
to greatly stimulate secretion of water andelectrolytes,[6] as
well as relaxation of enteric smooth muscle, dilating peripheral blood
vessels, stimulating pancreaticbicarbonate secretion,
and inhibiting gastrin-stimulated gastric acid secretion.
These effects work together to increase motility.[7]
·
It also has the function of
stimulating pepsinogen secretion
by chief cells.[8]
·
It is also found in the brain and some autonomic nerves. One region of the brain
includes a specific area of thesuprachiasmatic
nuclei (SCN), the
location of the 'master circadian pacemaker'.
The SCN coordinates daily timekeeping in the body and VIP plays a key role in
communication between individual brain cells within
this region. Further, VIP is also involved in synchronising the timing of SCN
function with the environmental light-dark cycle. Combined, these roles in the
SCN make VIP a crucial component of the mammalian circadian timekeeping
machinery.
·
VIP helps to regulate prolactin secretion;[9] it
stimulates prolactin release in the domestic turkey.
·
It is also found in the heart and has significant effects on the cardiovascular system.
It causes coronary vasodilation[5] as
well as having a positive inotropic and chronotropic effect.
Research is being performed to see if it may have a beneficial role in the
treatment of heart failure.
·
VIP provokes vaginal lubrication in normal women, doubling the total
volume of lubrication produced in one study.[10]
·
The growth-hormone-releasing
hormone (GH-RH) is a
member of the VIP family and stimulates Growth Hormonesecretion in the anterior
pituitary gland.
Pathology[edit]
VIP is overproduced in VIPoma.[5] Can
be associated with Multiple
Endocrine Neoplasia Type 1 (Pituitary,
parathyroid and pancreatic tumors). Symptoms are typically:
·
Profuse non-bloody/non-mucoid
diarrhea (3L+) causing dehydration and the associated electrolyte disturbances
such ashypokalemia and metabolic acidosis.
·
Lethargy and
exhaustion may ensue https://en.wikipedia.org/wiki/VIPoma
1.
Rhabdomyolysis updated
Rhabdomyolysis constitutes a common cause of acute
renal failure and presents .....
Renal insufficiency and acidosis increase the potassium
levels further
on.
2.
Rhabdomyolysis - Wikipedia, the free encyclopedia
Urine from a
person with rhabdomyolysis showing the characteristic
brown ..... is uncertain.
High potassium
levels tend
to be a feature of severe rhabdomyolysis.
The first goal of treatment is to correct dehydration. Fluids
are often given through a vein (intravenous fluids) to replace fluids lost in
diarrhea.
The next goal is to slow the diarrhea. Some medications
can help control diarrhea. Octreotide, which is a human-made form of the
natural hormone somatostatin, blocks the action of VIP.
The best chance for a cure is surgery to remove the tumor.
If the tumor has not spread to other organs, surgery can often cure the
condition.
For metastatic disease, peptide receptor radionuclide
therapy (PRRT) can be highly effective. This treatment involves attaching a
radioactive molecular (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a
novel way to deliver high doses of beta radiation to kill tumours.
Some people seem to respond to a combination chemo called
capecitabine and temozolomide but there is no report that it totally cured
people from vipoma. https://en.wikipedia.org/wiki/VIPoma
www.ncbi.nlm.nih.gov/pubmed/2182997 - Similar
Parathyroid hormone (PTH) impairs extrarenal disposal of potassium in
both acute ... Since patients with chronic renal failure have elevated blood
levels of PTH, ..
Often, a report
of high blood potassium isn't true hyperkalemia. Instead, it may be caused by
the rupture of blood cells in the blood sample during or shortly after the
blood draw. The ruptured cells leak their potassium into the sample. This
falsely raises the amount of potassium in the blood sample, even though the
potassium level in your body is actually normal. When this is suspected, a
repeat blood sample is done.
The most common
cause of genuinely high potassium (hyperkalemia) is related to your kidneys,
such as:
Other causes of
hyperkalemia include:
·
Addison's
disease (adrenal failure)
·
Alcoholism or
heavy drug use that causes rhabdomyolysis, a breakdown of muscle fibers that
results in the release of potassium into the bloodstream
·
Angiotensin II
receptor blockers (ARBs)
·
Destruction of
red blood cells due to severe injury or burns
·
Excessive use
of potassium supplements
Causes sho
Effect of the
parasympathetic system on secretion of parathyroid hormone. This study evaluated the effect of parasympathetic
agonists and antagonists on immunoreactive (i) PTH secretion in vitro and on
serum iPTH in vivo in rats. In in vitro studies pilocarpine or bethanechol
significantly inhibited PTH secretion. This inhibition was blocked by the
simultaneous addition of atropine to the incubation medium. In in vivo studies,
the cholinergic agonists pilocarpine and bethanechol and the cholinergic
antagonist atropine were administered to rats by IV infusion. Blood was obtained
before and again after two hours of infusion for analysis of iPTH. Pilocarpine
or bethanechol significantly decreased serum iPTH. This inhibition by either
agent was blocked by the simultaneous administration of atropine.
Administration of atropine alone significantly increased serum iPTH above
baseline. This stimulation of basal serum iPTH by parasympathetic blockade
suggests that even basal PTH secretion may be influenced by endogenous
parasympathetic tone. Therefore, the following conclusions were reached: (1)
parasympathetic influences inhibit PTH secretion, and (2) endogenous
parasympathetic tone may be an inhibitory modulator of basal secretion of PTH.
http://www.ncbi.nlm.nih.gov/pubmed/2861555
Administration of intravenous vitamin C in hemodialysis
patients noticeably decreased level of PTH, but its effect gradually diminished. http://www.ncbi.nlm.nih.gov/pubmed/22057074
Effect of
restricted potassium intake on its excretion and on physiological responses
during heat stress. The effect of low potassium (K+) intake on its
excretion, concentration in sweat and on physiological responses during heat
stress was evaluated on eight Indian male soldiers in winter months at Delhi.
After a stabilization period of 3 days on each diet, i.e., 85 mEq of K+/d (diet
I, normal), 55 mEq of K+/d (diet II), and 45 mEq of K+/d (diet III), the
physiological responses and the sodium and potassium concentrations in sweat,
plasma, RBC, and urine were measured when the subjects were exposed to heat for
3 h daily in a climatic chamber maintained at 40 degrees C DB and 32 degrees C
WB. The subjects worked in the chamber at the rate of 465 W/h for 20 min
periods with 40 min rest between each period of exercise. The whole body sweat
was collected after the spell of work and was analysed for sodium and potassium
levels. Throughout the study the subjects remained on positive sodium balance
except on day 4 in diet III. Fluid balance also remained positive while
potassium balance was negative in subjects on diet II and diet III. There was
no significant change in heart rate, sweat volume, oral temperature, sodium,
and potassium concentrations in plasma and RBC during the entire period of the
study. Even in the subjects with negative potassium balance there was no change
in the sodium and potassium concentrations in sweat during exercise in heat.
The only evidence of potassium conservation was a reduced excretion in urine.
Out of the eight subjects, in one subject there was a flattening of the 'T'
wave in the ECG and reduction in amplitude of the 'T' wave in two more
subjects. As there is no reduction in sweat potassium concentration and the
urine volume is low, the marginal level of reduced excretion of potassium in
urine with a high rate of sweating (7-81) in subjects doing work in the
tropics, there is every likelihood of potassium deficiency if a liberal intake
is not ensured. In our earlier studies (Malhotra et al. 1976) we found that the
concentration of potassium (K+) in sweat is much higher than in plasma even in
acclimatised subjects. A large amount of K+ is therefore likely to be lost in
sweat during exposure to heat. In that study there was no evidence of a
reduction in K+ concentration in the sweat or urine upon repeated exposure of
the subjects to heat, indicative of a compensatory mechanism for conservation
of K+ losses. However, these earlier studies were done on subjects who were on
a normal diet which contained 75-80 mEq of K+ per day. Since a compensatory
mechanism may be triggered only when the body K+ becomes dificient and not
earlier, as is the case with sodium (Malhotra et al. 1959), we have now
investigated the effects of a sequential reduction of reduced dietary K+ on the
dermal and urinary losses of K+. The effects of K+ deficiency on the physiological
responses to heat have also been studied. The results of these studies are
reported here. http://www.ncbi.nlm.nih.gov/pubmed/7197217
Muscarine modulates Ca2+ channel currents in rat sensorimotor pyramidal cells via two distinct pathways.
We used the whole cell patch-clamp technique and single-cell reverse transcription-polymerase chain reaction (RT-PCR) to study the muscarinic receptor-mediated modulation of calcium channel currents in both acutely isolated and cultured pyramidal neurons from rat sensorimotor cortex. Single-cell RT-PCR profiling for muscarinic receptor mRNAs revealed the expression of m1, m2, m3, and m4 subtypes in these cells. Muscarine reversibly reduced Ca2+ currents in a dose-dependent manner. The modulation was blocked by the muscarinic antagonist atropine. When the internal recording solution included 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA) or 10 mM bis-(o-aminophenoxy)-N,N,N', N'-tetraacetic acid (BAPTA), the modulation was rapid (tauonset approximately 1.2 s). Under conditions where intracellular calcium levels were less controlled (0.0-0.1 mM BAPTA), a slowly developing component of the modulation also was observed (tauonset approximately 17 s). Both fast and slow components also were observed in recordings with 10 mM EGTA or 20 mM BAPTA when Ca2+ was added to elevate internal [Ca2+] ( approximately 150 nM). The fast component was due to a reduction in both N- and P-type calcium currents, whereas the slow component involved L-type current. N-ethylmaleimide blocked the fast component but not the slow component of the modulation. Preincubation of cultured neurons with pertussis toxin (PTX) also greatly reduced the fast portion of the modulation. These results suggest a role for both PTX-sensitive G proteins as well as PTX-insensitive G proteins in the muscarinic modulation. The fast component of the modulation was reversed by strong depolarization, whereas the slow component was not. Reblock of the calcium channels by G proteins (at -90 mV) occurred with a median tau of 68 ms. We conclude that activation of muscarinic receptors results in modulation of N- and P-type channels by a rapid, voltage-dependent pathway and of L-type current by a slow, voltage-independent pathway.http://www.ncbi.nlm.nih.gov/pubmed/9914268
Parathyroid cells express Ca(2+)-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration approximately equal to 10(-8) M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution (+)-Muscarine enhanced the adenosine 3',5'-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed > 90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.http://www.ncbi.nlm.nih.gov/pubmed/9374672
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