Agnihotri, AK

Aruoma, OI

Bahorun, T

Dawka, S

English

AJOL - African Journals Online

Published	  by	  iambr.info/AMBR	  Open	  Access Editorial	  	  Aruoma.	  Arch	  Med	  Biomed	  Res.	  2014;1:92-­‐95.	   	  	  92	  Metabolic	   Homeostasis,	   Biomarkers	  and	  Medical	  Education	  Assessment	  	  	  Okezie	   I	   Aruoma1,	   Theeshan	   Bahorun2,	   Arun	   K	   Agnihotri3,	  Sushil	  Dawka3	  	  The	   maintenance	   of	   metabolic	   homeostasis	   is	   of	   paramount	  importance	   for	   critically	   ill	   patients	   and	   electrolyte	   disorders,	  which	   are	   common	   homeostatic	   disbalances	   in	   adult	   patients	   in	  Intensive	  Care	  Units	  (ICU),	  have	  been	  increasingly	  associated	  with	  a	  rise	  in	  morbidity	  and	  mortality,	  as	  has	  been	  improper	  treatment	  of	  electrolyte	  disorders.1,2	  Given	  the	  disorders	  (e.g.	  severe	  burns,	  trauma,	  sepsis,	  brain	  damage,	  malignancies	  and	  heart	  failure)	  are	  associated	  with	   the	  disturbances	   in	  electrolyte	  homeostasis,	   it	   is	  of	   critical	   importance	   to	   institute	   a	   proficient	  management	   in	   a	  hospital	   intensive	   care	   setting/environment.	   Hyponatremia	   (the	  most	   common	   electrolyte	   disorder)	   generally	   alludes	   to	   a	  condition	  where	   sodium	   level	   in	   the	   blood	   is	   abnormally	   low.	   It	  interesting	   that	   the	   release	   of	   anti-­‐diuretic	   hormone	   and	   hence	  the	  impairment	  of	  water	  excretion	  are	  so	  frequent	  in	  hospitalized	  patients,	   that	   virtually	   all	   patients	   are	   at	   risk	   of	   hyponatremia.	  Many	   cases	   of	   dysnatremia	   are	   acquired	   after	   a	   patient	   is	  admitted	   to	   the	   ICU,	   and	   the	   presence	   of	   dysnatremia	   is	  associated	  with	   poor	   prognosis.	   Interestingly,	   limited	   number	   of	  prospective,	  randomized,	  controlled	  studies	  have	  been	  conducted	  to	   evaluate	   the	   optimal	   treatment	   of	   electrolyte	   disorders.	  Magnesium,	   calcium	   and	   phosphorus	   are	   important	   electrolytes	  involved	   in	   the	   regulation	   of	   homeostasis.	   Intituting	   a	   robust	  strategy	  for	  the	  treatment	  of	  “hyponatremia	  and	  hypernatremia”,	  “hypokalemia	   and	   hyperkalemia”,	   “hypophosphatemia	   and	  hyperphosphatemia”,	   “hypocalcemia	   and	   hypercalcemia”,	   and	  “hypomagnesemia	  and	  hypermagnesemia”	   is	   therefore	  of	  critical	  	  importance.	   The	   actual	   electrolyte	   correction	   requires	   individual	  adjustment	  based	  on	  the	  patient's	  clinical	  condition	  and	  response	  to	  therapy.	  However	  the	  utility	   in	  monitoring	  them	  in	  critically	   ill	  patients	  is	  still	  unclear.	  	  This	  issue	  of	  Archives	  of	  Medical	  and	  Biomedical	  Research	  reports	  the	   outcome	   of	   a	   prospective,	   non-­‐interventional,	   single	   center	  study	   in	   the	   intensive	   care	   unit	   of	   a	   tertiary	   care	   hospital	   to	  determine	  the	   incidence	  and	  clinical	  presentation	  of	  magnesium,	  phosphorus,	   and	   calcium	   abnormalities	   in	   patients	   admitted	   to	  the	  ICU.	  Calcium	  and	  phosphorus	  are	  recognized	  to	  be	  responsible	  for	  much	  of	  the	  structural	  integrity	  of	  the	  bony	  skeleton	  and	  also	  to	   participate	   in	   several	   diverse	   processes,	   such	   as	   enzyme	  activation,	   cell	   division,	   blood	   coagulation,	   and	   membrane	  stability.	   Hypocalcemia	   caused	   by	   critical	   illness	   is	   usually	  	  	  To	   cite:	  Aruoma	  OI,	  Bahorun	  T,	   Agnihotri	   AK,	   Dawka	   S.	  Metabolic	   Homeostasis,	  Biomarkers	   and	   Medical	  Education	   Assessment.	   Arch	  Med	   Biomed	   Res.	  2014;1(3):92-­‐95.	  	  Open	  Access	  This	  is	  an	  Open	  Access	  article	  distributed	   in	   accordance	  with	   the	   Creative	   Commons	  Attribution	   Non	   Commercial	  (CC	  BY-­‐NC	  3.0)	  license,	  which	  permits	   others	   to	   distribute,	  remix,	  adapt,	  build	  upon	  this	  work	   non-­‐commercially,	   and	  license	  their	  derivative	  works	  on	   different	   terms,	   provided	  the	   original	   work	   is	   properly	  cited	   and	   the	   use	   is	   non-­‐commercial.	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  	  Correspondence	  to	  Okezie	  I	  Aruoma;	  oaruoma@auhs.edu	  	  Published	  by	  iambr.info/AMBR	  Open	  Access Editorial	  	  Aruoma.	  Arch	  Med	  Biomed	  Res.	  2014;1:92-­‐95.	   	  	  93	  multifactorial	   (e.g.	   hypoalbuminemia,	  metabolic	   or	   respiratory	   acidosis,	  hypomagnesemia,	   renal	   failure,	   massive	  blood	   transfusions)	   although	   calcium	   loss	  due	   to	   increased	   tissue	   sequestration	   of	  calcium	   may	   be	   the	   predominant	   cause	   in	  patients	   with	   pancreatitis,	   septicemia,	  burns,	   or	   toxic	   shock.	   Tetany	   is	   the	  commonest	   symptom	   associated	   with	   an	  acute	   reduction	   in	   plasma	   ionized	   calcium.	  The	   characteristic	   clinical	   features	   of	   these	  electrolyte	   disorders	   present	   as	  neurological	  and	  cardiac	  manifestations.	  Ionized	   calcium,	   serum	   calcium,	  magnesium,	   and	   phosphorus	   along	   with	  arterial	   blood	   gases	   (ABG)	   were	   measured	  on	  admission	  with	  clinical	  features	  recorded	  in	   an	   approved	   format	   in	   300	   consecutive	  patients	   admitted	   to	   the	   ICU	  over	   a	  period	  of	   two	   years.	   Thereafter,	   ionized	   calcium,	  serum	  phosphorus,	   serum	  magnesium,	  and	  ABG	   were	   monitored	   every	   alternate	   day.	  Hypocalcemia	   was	   the	   commonest	  electrolyte	   abnormality	   seen	   in	   165	   (55%)	  patients	   followed	   by	   hyperphosphatemia	  seen	  in	  74	  (24.67%)	  and	  hypophosphatemia	  seen	   in	   72	   (24%)	   patients.	   Hypocalcemia	  with	   renal	   failure	   was	   seen	   in	   52	   (31%)	  patients	   (p	   =	   0.009).	   Hypophosphatemia	  and	  hypomagnesemia	  were	  commoner	  with	  respiratory	   failure	   i.e.	   23	   (31.95%)	   and	   13	  (27.66%)	   patients,	   respectively.	   An	  association	   of	   liver	   disease	   with	  hypomagnesemia	  was	  noted	  in	  the	  study	  (p	  <	   0.05).	   Arrhythmias	   associated	   with	  electrolyte	   abnormalities	   were	   the	   most	  common	   clinical	   observation,	   seen	   in	   69	  (41.81%)	   patients	   with	   hypocalcemia,	   20	  (42.55%)	   with	   hypomagnesemia,	   and	   29	  (40.27%)	   with	   hypophosphatemia.	   The	  abnormalities	   reported	   may	   be	   associated	  with	   arrhythmias,	   blood	   transfusions,	   and	  diuretic	  use	  and	  may	  have	  a	  bearing	  on	  the	  clinical	  outcome.	  The	   comments	   from	  Balci	  et	  al3	   is	  noteworthy	  –	  “Hypomagnesemia	   is	  known	   to	   have	   a	   high	   prevalence	   rate,	   but	  its	   diagnosis	   may	   be	   intrigued	   by	   some	  factors:	   it	   has	   nonspecific	   manifestations	  that	  are	  frequently	  overlooked;	  magnesium	  level	   is	   not	   examined	   “routinely”	   in	   blood	  test	  and	  patients	  may	  be	  hypomagnesemic,	  even	  with	  a	  normal	  serum	  magnesium	  level.	  Thus	   magnesium	   deficiencies	   are	   generally	  masked	   by	   other	   electrolyte	   deficiencies.	  Clearly	   a	   multi-­‐centered	   study	   with	  stringent	  patient	  selection	  and	  longer	  follow	  up	  will	   possibly	   serve	   in	   understanding	   the	  role	  of	  these	  electrolytes	  and	  this	  has	  global	  health	   implications.	   Further,	   while	   the	  kidney	   is	  a	  principally	  responsible	  organ	  for	  retention	   and	   excretion	  of	   electrolytes	   and	  fluid	  in	  healthy	  individuals,	  pathophysiologic	  mechanisms	   and	   hormonal	   interactions	   of	  anti-­‐diuretic	   hormone,	   aldosterone,	   and	  parathyroid	   hormone,	   and	   other	   factors	  such	   as	   physiological	   stress	   also	   play	  important	   roles	   in	   regulating	   fluid	   and	  electrolyte	  balance	  in	  the	  organism1-­‐4.	  Metabolites	   are	   obvious	   candidates	   for	  biomarker	   screening	   because	   they	  represent	  the	  downstream	  effect	  of	  enzyme	  catalysis	   and	   other	   biotransformations	   and	  are	   smaller	   in	   number	   than	   the	   proteome.	  Metabolism,	   which	   is	   mainly	   an	   anabolic	  process	   in	   the	   growing	   stage,	   may	  sometimes	   change	   due	   to	   either	   over-­‐nutrition	   or	   starving	   conditions,	   leading	   to	  many	   abnormalities	   and	   giving	   rise	   to	  metabolic	   disorder	   based	   diseases.	   Many	  simple	   intermediate	   compounds	   are	  generated	  during	  the	  process	  of	  metabolism	  leading	   to	   the	   production	   of	   ATP.	   	   Thus	  metabolomics	  (the	  systems	  biology	  of	  small	  molecules)	   is	   a	   new	   approach	   for	   the	  untargeted	   identification	   of	   potential	  biomarkers.	   A	   particular	   advantage	   of	  metabolomics	   over	   targeted	   metabolite	  measurement	   is	   in	   hypothesis	   generation:	  the	   discovery	   of	   changes	   in	  molecules	   that	  were	   not	   already	   associated	   with	   a	  biological	   phenomenon.	   The	   ability	   of	  metabolomics	   to	   determine	   high-­‐throughput	   system-­‐wide	   physiological	  phenotypes	   gives	   it	   immense	   power	   in	   the	  Published	  by	  iambr.info/AMBR	  Open	  Access Editorial	  	  Aruoma.	  Arch	  Med	  Biomed	  Res.	  2014;1:92-­‐95.	   	  	  94	  field	   of	   tumor	   biology	   and	   the	   cancer	  macro-­‐environment/micro-­‐environment	   for	  further	  understanding	  of	  factors	  responsible	  for	   the	   incidence	   of	   various	   types	   of	  diseases	   including	   cancer,	   diabetes	   and	  diseases	  of	  overt	  inflammation5-­‐7.	  Interestingly,	   normal	   cells	   use	   a	   controlled	  mechanism	  during	  their	  whole	  life	  span	  and	  consume	  different	  metabolites	  in	  a	  guarded	  way	   according	   to	   their	   requirement	   from	  the	   available	   pool	   of	   metabolites	  surrounding	   the	   cell	   microenvironment.	  However,	  cancerous	  cells	  do	  not	   follow	  the	  normal	  controlled	  mechanisms	  due	  to	  their	  metabolic	   disorders,	   leading	   to	   the	   genesis	  of	   metabolic	   markers.	   Cancer	   cells	   use	  metabolites	   in	   an	   uncontrolled	   and	  inappropriate	   manner	   from	   the	  surroundings.	   For	   example,	   receptors	   used	  for	   the	   transport	   of	   metabolites	   such	   as	  glucose	   (which	   is	   transported	   by	   glucose	  transporter,	   GLUT)	   do	   not	   work	   in	  cancerous	   cells	   the	  way	   they	   do	   in	   normal	  cells.	   This	  mechanism	  supports	   the	   survival	  of	  cancerous	  cells	  while	  impacting	  adversely	  on	  the	  survival	  of	  neighboring	  normal	  cells.	  The	   myokines	   (cytokines	   changing	   the	  environment	   both	   inside	   and	   outside	   the	  cells	   and	   tissues	   leading	   to	   the	   genesis	   of	  metabolic	   based	   diseases)	   are	   the	   same	  proteins	   as	   cytokines,	   which	   are	   of	   low	  molecular	   weight	   and	   are	   responsible	   for	  metabolic	   disorders	   related	   to	   obesity	   and	  type	  2	  diabetes.	  As	  cytokines	  are	  known	  to	  influence	   immunological	   changes,	   similarly	  myokines	  are	  considered	  key	  molecules	  that	  cause	   changes	   in	   the	   local	   environment	   to	  initiate	   the	   development	   of	   metabolic	  disorders	  e.g.	  type-­‐2-­‐diabetes	  and	  cancer.	  There	  continues	  to	  be	  worldwide	  growth	  in	  the	   numbers	   of	   medical,	   pharmacy	   and	  biomedical	   sciences	   schools	   and	   programs.	  The	   modality	   for	   assessing	   the	   academic	  programs	  has	  an	   impact	  on	  their	  success8,9.	  Innovative	   methods	   of	   teaching	   are	   a	   goal	  of	   many	   educators	   to	   deliver	   innovative	  curriculum.	   Teaching	   students	   in	  ways	   that	  keep	   them	   engaged	   and	   interested	   in	   the	  content	   is	   a	   challenge	   to	   any	   educator.	  Learning	  is	  a	  lifelong	  process	  and	  in	  order	  to	  achieve	  this	  goal,	  students	  should	  always	  be	  competitive	   and	   focused	   in	   their	   learning.	  Students	   actively	   learn	   by	   observing	   and	  performing	   activities,	   the	   process	   of	  learning	   is	   far	   more	   accelerated	   when	   a	  practical	   implementation	   is	   associated	   and	  the	   learner	   is	   benefited	   with	   the	   applied	  knowledge	   and	   skills	   and	   it	   also	   involves	  trial	   and	   error	   at	   times	   during	   self-­‐exploration.	   Studies	   have	   shown	   that	  medical	   quizzes	   improve	   students’	  comprehension	  and	  enhance	   interest	   levels	  in	   the	   subject.	   These	   however	   have	   been	  mostly	   based	   on	   single	   subject	   quizzes,	  delimited	  by	   the	   curriculum	  and	   traditional	  assessment.	   Studies	   comparing	   traditional	  test	  scores	  before	  and	  after	  a	  quiz-­‐exercise	  show	  irregular	  improvement	  in	  scores.	  Quiz	  competitions	   as	   teaching	   learning	  methodology	   has	   a	   statistically	   significant	  improvement	   in	   their	   performance.	   In	   a	  study	   that	   explored	   which	   aspects	   of	   the	  mediquiz	   students	   find	   “the	   most	   useful”	  and	  which	  is	  the	  “the	  most	  interesting”,	  and	  what	   would	   be	   the	   ideal	   balance	   between	  the	   two,	   not	   presuming	   that	   they	   are	  mutually	   exclusive,	   there	   appears	   to	   be	   a	  moderate	   preference	   for	   ‘interesting’	  questions	  provided	   that	   the	  answers	   linked	  back	   meaningfully	   with	   the	   subject.	   	   The	  rationale	   conclusion	   is	   that	   a	   fast-­‐paced	  interactive	   and	   stimulating	   quiz	   game	   can	  be	   utilized	   to	   provide	   a	   formative	  assessment	   and	   feedback	   to	   both	   learners	  and	  teachers.	  There	  is	  a	  potential	  to	  engage	  in	   a	   collaborative	   skills	   and	   academic	  performance	   development	   to	   enhance	  students	   learning	   in	   medical	   schools	   and	  schools	   of	   biomedical	   sciences	   embracing	  pharmacology,	   pathophysiology	   and	  integrative	  pharmacotherapy.	  	  Author	  affiliations	  1School	   of	   Pharmacy,	   American	   University	   of	  Health	  Sciences,	  Signal	  Hill,	  USA	  Published	  by	  iambr.info/AMBR	  Open	  Access Editorial	  	  Aruoma.	  Arch	  Med	  Biomed	  Res.	  2014;1:92-­‐95.	   	  	  95	  2ANDI	   Center	   of	   Excellence	   for	   Biomedical	   and	  Biomaterials	   Research,	   MSIRI	   Building,	  University	  of	  Mauritius,	  Republic	  of	  Mauritius	  3SSR	   Medical	   College,	   Belle	   Rive,	   Republic	   of	  Mauritius	  	  REFERENCES	  1. 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Metabolic Homeostasis, Biomarkers and Medical Education Assessment

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Metabolic Homeostasis, Biomarkers and Medical Education Assessment

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