LMP301 2014 Lecture 14.pdf
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Department
Laboratory Medicine and Pathobiology
Course
LMP299Y1
Professor
Kenneth Yip
Semester
Summer

Description
  Lecture  14:  Iron  Metabolism  and  Hemoglobins   Iron  Absorption   -­‐ normal  American  diet  contains  10 -­‐30mg  of  iron  per  day   -­‐ 5-­‐10%  will  be  absorbed  by  the  intestines  (duodenum)   -­‐ dietary  iron  in  the  form  of  Fe2+  (ferric)   o soluble  in  the  stomach  (by  acidic  pH)   o insoluble  in  duodenum  (because  alkaline  pH)  >>>  gastric  acid  converts  it  to  Fe2+   o ascorbic  acid  (now  in  a  lot  of  processed  foods),  sugars  and  amino  acids  increase  absorption     o eggs,  cheese,  milk,  veggies,  tea  decrease  absorption  (chelate  iron  –  removes  iron  from  blood)     Iron  Physiology   -­‐ majority  of  iron  is  from  diet  (0.35mmol/day)   -­‐ then,  iron  is  stored  (50-­‐70  mmol)  –  goes  back  into   circulation  to  cells  who  need  it   o 3  major  components  that  stores  iron?   1) red  blood  cells  (70%  of  total  iron  store)   2) Ferritin  (plasma  protein)  –  20%  storage   3) Myoglobin  (5%)  –  small  protein   -­‐ iron  loss  (excess  we  don’t  utilize)  à  urine  excretion   (mainly),  menstrual  flow  (in  females),  desquamation  (of   the  cells  à  every  time  cells  are  shed  off,  they  have  iron  in   them  and  iron  is  removed  with  cells)     Iron  Transport   -­‐ major  protein  for  moving  protein  (a fter   absorbed  in  the  plasma)  into  the  cell:   transferrin   -­‐ circulates  in  extracellular  space   -­‐ transferrin  will  bind  to  iron  (in  ferric  form)   -­‐ the  transferrin  +  iron  binds  to  transferrin   receptor  (part  of  plasma  membrane)   -­‐ then  move  through  clatharin  coated  vesicles   into  the  cytoplasm  à  then  endosome  (different   pH)   -­‐ iron  is  released  from  transferrin  protein  (where   its  released  back  to  cytoplasm  to  repeat  action)     Iron  Uptake  by  the  Cells   -­‐ transferrin  delivers  iron  to  cell  surface   transferrin  receptors  (TfR)   -­‐ the  Tf-­‐R  complex  is  taken  into  the  cell  by  endocytosis  and  into  a  vesicle   -­‐ release  of  iron  due  the  acidic  pH  of  the  vesicle   -­‐ (Apo-­‐transferrin  because  its  not  about  to  iron  anymore )  transferrin-­‐receptor  return  the  cell  surface  and  repeat   process     Iron  Transport  and  Cell  Uptake   -­‐ each  transferrin  molecule  has  2  binding  sites  for  Fe3+   -­‐ these  sites  are  not  always  occupied  (may  only  have  one  bound)   -­‐ only  25-­‐50%  of  transferrin  is  normally  saturated   -­‐ in  the  past  Total  Iron  Binding  capacity  (TIBC)  was  used  as  an  indirect  measure  of  transferrin   concentration   -­‐ now  we  can  measure  Transferrin  directly     Iron   -­‐ iron  is  an  essential  element   -­‐ free  iron  is  highly  toxic  to  cells   -­‐ iron  is  found  complexed  with  several  proteins   o hemoglobin  (part  of  red  blood  cells)   o myoglobin  (major  protein  for  muscle  tissue)       o cytochromes  (in  the  liver)   -­‐ usually,  binding  of  iron  proteins  occurs  through  heam   o iron  usually  in  the  middle  of  the  protein   o inorganic  molecule     o center  is  iron  bound   o heam  the  inorganic  component  of  the  protein  that    coordinates   binding  of  iron     Iron  and  Hemoglobin   -­‐ RBC:  main  role  to  transfer  oxygen  into  tissues   -­‐ Picks  up  oxygen  from  lungs,  into  various  tissues,  and  go  back  to  the  lungs   -­‐ Hemoglobin  main  goal:  to  transfer  oxygen   Iron  Storage     -­‐ iron  is  utilized  for  heme  synthesis  or  stored  as  ferritin  or  hemosiderin   o Ferritin  is  a  protein  and  can  bind  4500  iron  atoms  thus  protecting   cells  from  free  iron   § High  capacity  for  iron  binding   o Hemosiderin  is  insoluble  ferritin   § Releases  iron  slowly   § High  capacity  of  iron,  but  can  als o  release  iron   -­‐ one  third  of  iron  stores  exist  in  liver,  spleen  and  bone  marrow     Diseases  Associated  with  Iron  Homeostasis   -­‐ iron  deficiency  (anemia)   -­‐ iron  overload  (chronic)   -­‐ iron  poisoning  (chronic)   -­‐ chronic  disease     Clinical  Case  #1   -­‐ A  42  year  old  women  presented  with  a  history  of  increasing  lethargy,  dizziness,  and  breathlessness   -­‐ She  has  brittle  hair  and  nails   -­‐ Complained  of  heart  palpitation  on  exercise  and  reported  particularly  heavy  periods     o Serum  iron  was  low   o Transferrin  saturation  was  low   –  not  enough  iron?  No  point  in  transferrin   o Ferritin  was  low     -­‐ Diagnosis:  Iron  Deficiency  Anemia     Iron  Deficiency   -­‐ common  condition   -­‐ usually  picked  up  when  serum  iron  is  lowered  and  stores  are  beginning  to  be  effected   -­‐ iron  levels  and  iron  stores  are  depleted;  results  in  anemia   -­‐ causes:   o loss  of  blood:  gastrointestinal  or  genitourinary     o inadequate  intake:  often  seen  in  children,  pregnant  women,  older  people  due  to  diet     Iron  Deficiency:  lab  Investigations   -­‐ once  iron  stores  have  been  depleted,  biochemical  tests  of  iron  metabolism  becomes  abnormal   o serum  iron  ↓   o TIBC  ↑   o Iron  saturation  (Fe/Tf  <  15%)  ↓   o Serum  transferrin  ↑  (reflects  responses  of  the  tissue  to  low  iron)   o Serum  ferritin  ↓  (reflects  low  body  iron  stores)       § Very  good  indicator  of  iron  deficiency   § Next:  Hb  ↓  >>>  small  erythrocytes  (microcytic  anemia)  with  low  cytoplasmic  Hb  concentration   (hypochromic  –  light  in  colour)       Iron  Deficiency:  Lab  Investigations   -­‐ erythocytes  are  much  smaller  in  anemia  patients   -­‐ microcytic  anemia:  small  cells     o low  cytoplasmic  hemoglobin  concentration   o much  paler  in  colour  =  not  enough  hemoglobin  in   them   o microcytic  anemia  (because  of  iron  deficiency)     Iron  Deficiency:  Symptoms   -­‐ weakness,  or  fatigue,  general  malaise  and  sometimes  poor  concentration   -­‐ shortness  of  breath  (circulation  of  red  blood  cells  to  try  to  restore  iron)   -­‐ increasing  cardiac  output   -­‐ pale  skin,  mucosal  linings,  and  nail  beds   -­‐ behavioral  disturbances  in  children  and  impaired  neurological  developments  in
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