LMP301 2014 Lecture 14.pdf

5 Pages
Unlock Document

Laboratory Medicine and Pathobiology
Kenneth Yip

  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
More Less

Related notes for LMP299Y1

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.