PARTICIPACION EN EL DESARROLLO SOCIO-ECONÓMICO

CAD;   atherosclerotic   stroke   relates   to   plaques;   abdominal   aneurysm   due   to   weakening  of   the   vessel;   nontraumatic   amputation  of   lower   extremity   (peripheral   vascular  dz);  mesenteric  angina,  small  bowel  infarction,  renovascular  atherosclerosis   of  the  renal  arteries.    Atherosclerosis  only  involves  muscular  arteries  and  elastic   arteries.    Can  small  vessel,  such  as   arterioles  get  hardened?   Yes.    Example:  look  at   the  spleen  –  hyaline   arteriolar  sclerosis  and  hyperplastic   arteriolar   sclerosis  (onion   skinning).        

1.    Hyaline  arteriosclerosis  is  a  small  vessel  dz;  lumen  is  narrow;  whenever  there   is  a  lot  of  pink  staining  stuff,  this  is  hyaline.    Example:  small  vessel  dz  of  diabetes  and   HTN  –  two  major  dz’s  that  produces  a  small  vessel  dz  with  different  mechanisms:  

a.   Diabetes:  nonenzymatic   glycoslyzation  –   aka   HbA1c;   glycoslyzation   is   glucose   attaching  to   aa   and  protein.   For   HbA,   its   glucose   attaching   to   aa  and  HbA,   and   the   HbA  is  glycosylated.    HbA1c  levels  correlate  with  the  blood  glucose  levels   of  the  last   6-­‐8  weeks,   so   this   is   the   best   way   of   looking   at   long   term   glucose  levels.     All   the   damage  seen  in  diabetes  is  due  to   glucose.    For  a  diabetic,  you  should  be  under  6%,   meaning   that   you   are   in   a   normal   glucose   range.   There   is   nothing   unique   about   diabetes  except  for  a  large  glucose  level,  you  keep  that  normal,  and  it’s  as  if  you  don’t   have   diabetes.     The   only   two   pathologic   processes   are   this:   nonenzymatic   glycosylation  of  small  BV’s  including  capillaries  in  the  kidney,  and  osmotic  damage.    

Those  tissues   that   contain  aldose  reductase  –  lens,   pericytes  in  the   retina,  schwann   cells  –  all  have  aldose  reductase  and  can  convert  glucose  into  sorbitol  and  sorbitol  is   osmotically   active   sucks   water   into   it   and   those   cells   die,   leading   to   cataracts,   microaneurysms  in  the  eye  b/c  the   pericytes  are   destroyed  and  weakened  and  the   retinal  vessels  get  aneurysms,  and  you  get   peripheral  neuropathy  b/c   schwann  cells   are  destroyed.    They  all  related  to  excess  glucose.    So,  tight  glucose  control  =  normal   life.

What   does   nonenzymatic   glycosylation   to   do   the   basement   membrane   of   small   vessels?   Its  renders  them   permeable  to   protein,  so   the  protein  in  the  plasma  leaks   through   the   BM   and   goes   into   the   vessel   wall,   produces   a   hyaline   change   and   narrows  the  lumen.    What   if  there  is   nonenzymatic   glycosylation  of  the  GBM?  It  will   render  it  permeable  to  protein  –  called  microalbuminuria.    This  is  the  5irst  change  to   be   seen   in   diabetic   nephropathy.     So,   what   is   the   mechanism?   Nonenzymatic   glycosylation.    

b.  Hypertension

Does  not  use  nonenzymatic  glycosylation.    It  just  uses  bruit  force  and  drives  (b/c  of   increase  in  diastolic  pressure)  the  proteins  through  the  BM  and  produces  the  effect.    

When  we  look  at  a  kidney  in  HTN,  it  is  shrunken,  has  a  cobblestone  appearance  –  this   is  b/c  there  is  hyaline  arteriolosclerosis  of  the  arterioles   in  the  cortex,  ischemia,  and   is  wasting  away  with  5ibrosis  and  atrophy  of  tissue.      Lacunaer  strokes  (tiny  areas  of   infarction  that   occur   in  the  internal  capsule)  are   a   hyaline  arteriosclerosis   problem   related  to  HTN.  

2.    Hyperplastic  arteriosclerosis

Seen  in  malignant   HTN;   more   common  in  blacks   then   whites,   mainly   b/c   HTN   is   more  common  in  blacks  than  whites.    Mainly  see  this  vessel  dz  in  malignant  HTN  (ie   when  pt  has  BP  of  240/160).

B.    Aneurysm

1.    DeUinition:  area  of  outpouching  of  a  vessel  due  to  weakening  of  the  vessel  wall.    

Atherosclerosis  can  cause  weakening  of  the  abdominal  aorta  leading  to  an  aneurysm.    

What  would  be  the  analogous  lesion  in  the  lungs  with  weakening  and  outpouching?  

Bronchiectasis   –   due   to   cystic   5ibrosis   with   infection,   destruction  of   elastic   tissue   leading   to   outpouching   and   dilatation   of   the   bronchi.     Example:   what   is   the   GI   aneurysm?   Diverticular   dz   –   have   a   weakening   and   outpouching   of   mucosa   and   submucosa  

2.    Law  of  Laplace  –  the  wall  stress   increases  as  radius  increases.    In  terms  of  this,   once  you  start  dilating  it,  it  doesn’t  stop  b/c  as  you  dilate  something,  you  increase  the   wall  stress  and  eventually  it  ruptures.    So,  in  other  words,  all  aneurysms  will  rupture   –  it’s  just  a  matter  of  when.

3.     Abdominal   Aorta   Aneurysm:   Why   is   the   abdominal   aorta   the   MC   area   of   aneurysm?  B/c  there  is  no  vasa  vasorum  or  blood  supply  to  the  aorta  below  the  renal   arteries.    So,  the  only  way  abd.  aorta  gets  O2  and  nutrients  is  from  the  blood  that’s  in   the  lumen.    So,  part   furthest   from  it  mgets  screwed.    Therefore,  apart  from   the  part   that   is   not   getting   much   O2   and   nutrients,   it   will   be   more   susceptible   to   injury,   therefore   atherosclerosis   leads   to   weakening   of   the   wall   and   aneurysm/injury   occurs.    

a.    MC  complication  abdominal  aortic   aneurysm  =  rupture.    The  triad  of  s/s  are:    a   sudden  onset  of  severe  left  5lank  pain  b/c  the  aorta  is  retroperitoneal  organ  and  so  it   does  not   bleed  into  the  peritoneal  cavity,  but  into  the  peritoneal  tissue.     So,  severe   left  Ulank   pain,   HypoTN,   and  pulsatile   mass  on   PE.     These   are  three  things   that   always   occur   when   there   is   a   ruptured   aortic   abdominal   aneurysm.     MC   complication  of  any  aneurysm  =  rupture

4.     Aneurysm  of  the   arch  of   the   aorta   –  MCC  =  tertiary   syphilis.    Pathology  of   syphilis  is   vasculitis  of  arterioles.  Chancre,  too.    Its  painless  b/c  if  you  section  it,  you   will   see  little   arterioles  surrounded  by  plasma   cells   and  the  lumen   of  the   vessel  is   completely   shut,   so   it   is   ischemic   necrosis.     In  other   words,   it   is   ischemia   of   the   overlying   tissue   undergoing   necrosis.     B/c   nerves   are   next   to   vessels,   they   are   knocked  off,   too,  and  it  is  painless.    All  of  syphilis  is  a   vasculitis.    That  is  what   the   Treponema  infects  –  small  vessels  and  arterioles.    What  are  they  affecting  in  the  arch   of  the  aorta?  The  vasa  vasorum;  the  richest  supply  of  vasa  vasorum  is  in  the  arch,  so   its  logical  that  the  Treponema  will  pick  it  –  leads  to  endarteritis  obliterans  (they  are   obliterating   the   lumen),   ischemia,   weakening   under   systolic   pressures,   leads   to   depression  in  the  arch  of  the  aorta  (looks  like  a  catcher’s  mitt).    What  will  that  do  to   the   aortic   valve   ring?   It   will   stretch   it   –   which   murmur   will   this   lead   to?   Aortic   regurg.    Murmurs  can  occur  b/c  there  is   valvular  damage  or  b/c   the  valvular  ring  is   stretched.    So,  there  can  be  stretching  of  the  ring  and  nothing  wrong  with  the  valves,   and   have   a   murmur,   or   you  can   have   damage   to   the   valves   and   have   a   murmur.    

Syphilis  is  an  example  of  stretching  of  the  aortic  valve  ring  leading  to  a  murmur  and   aortic  regurg.  

Aorta   should  be   closing  during  diastole  –   as   you  pump  the   blood  out,   and   the   SV   goes  down,  and  b/c  the  aortic  cannot  close  properly,  only  some  of  the  blood  will  drip   back  in.    So  you  will  have  more  volume  of  blood  in  the  left  ventricle  in  someone  with   aortic   regurg.    Frank-­‐starling  forces  will  be  working.    As  you  stretch  cardiac  muscle,   you  increase  the  force  of  contraction.    Normally,  you  have  a  120  ml’s  of  blood  and  get   out  80,  so  the  EF  is  80/120  =66%.    Lets  say  you  have  200  mls  of  blood  in  the  LV  b/c   blood  is   dripping  back   in,  and  frank-­‐starling   force  gets   out  100  mls   of  blood,  which   has   an  EF   of   50%.     So   this   isn’t   as   ef5icient.   Therefore,   frank-­‐starling   occurs   in   a   pathologic   condition.     If  you  have  100  mls  of   blood  coming  out   of  your  aorta,  that’s   not   good  b/c   their  head  is   wobbling,   and  when  they  open  their   mouth  you  can  see   uvula   pulsating,   can   take   their   nail   and   lift   it   up   and   see  pulsations   of   the   vessels   under  the  nail,  Water-­‐hammer  pulse,  and  when  listening  with  the  stethoscope  of  the   femoral  artery   you  can   hear  Durasane’s   sign.     This   is   all  due   to   the  increase   in  SV   coming   out   related   to   the   fact   that   there   is   more   blood   in   the   LV.     syphilitic   aneurysms   of   the   abdominal   aorta   is   the   classic   example   of   this.     Anatomy   correlation:  the  Left  Recurrent  Laryngeal  Nerve  wraps  around  the  arch  and  therefore   can  get  hoarseness.    Again  the  MC  complication  is  rupture.

5.    Dissecting  aortic  aneurysm:    

a.   Key  factor  that  causes  a  tear  in  the   aorta  is  HTN  b/c   it   imposes  stress  on  the   wall   of   the   vessel.     There   must   be   weakening   the   elastic   artery   and  is   caused   by   elastic   tissue   fragmentation.   Cystic   medial   necrosis:   that’s   where   the   GAG’s   mix   together  and  there’s  mucinous  material  w/in,  and  walls  of  aorta  rub  upon  itself,  and   when  adding  a  little  bit  of  HTN  leads  to  a  tear.    Wherever  the  area  of  weakness  in  the   elastic   artery   is   where   the   blood   will   dissect   and   tear   –   blood   can   go   to   the   pericardial  sac,  leading  to  cardiac  tamponade.    This  is   called  the  proximal  dissection   (MC).    Most  of  the  tears  up  in  the  arch;  therefore  you  would  think  the  pt  may  have  an   absent   pulse;   this   is   very   common   in   pts   with   tears   that   are   proximal.     When   it   dissects,  it   closes   lumen  to  subclavian  artery   and  it   usually   dissects   on  the  left  and   causes  an  absent  pulse  on  left.

b.   Chest   pain   in   MI  is   diff   than  the  chest   pain  in  a   dissecting  aneurysm.    MI   has   chest   tightness   radiating  to   left  arm   and  jaw;  in  aortic   dissection,  there  is   a  tearing   pain  radiates   to   the  back;  and  is  a  retrosternal  pain.    Pulse  on  left   is  diminished  vs.  

the  one  on  the  right.    On  chest  x-­‐ray,  widening  of  the  aortic  knob.    With  blood  there,   diameter  of  aorta  will  be  enlarged,  as   seen  on  x-­‐ray,  and  this   test  is  85%  sensitive  in   detecting  it,  therefore  it  is  the  screening  test  of  choice;  see  widening  of  the  proximal   aortic  knob.    To  prove,  do  transesophageal  ultrasound  or  angiography  to  con5irm  dx.

c.  Many  dz’s  can  predispose  to  aortic  dissections:

(1)  Marfan  syndrome  (eunochoid  proportions  –  ht  of  pelvic   brim  to  feet  is  greater   than  from  pelvic  brim  to  the  head.  Also,  another  de5inition  is  that  arm  span  is  greater   than  the  height.  AD  inheritance,  c’some  15,  defect  in  5ibrillin,  which  is  a  component  in   elastic  tissue.  Due  to  the  defect  in  5ibrillin,  the  elastic  tissue  is  weak  –  this  is  why  they   have  dislocated  lenses   and  have  dissected  aortic  aneurysms  (MCC  death  in  marfans   is  MVP).    

(2)  Ehler  Danlos  has  a  collagen  defect,  MCC  of  death

(3)   Pregnant   women   are   susceptible   to   dissecting   aortic   aneurysms   b/c   in   pregnancy   they   have   twice   the   amount   of   plasma   vol  vs.   a   non-­‐pregnant   woman.    

There   is   an   increase   of   plasma   vol   by   2  and  RBC  mass   by   1,   so   it’s   a   2:1   ratio   of   increasing   plasma   vol  to  RBC  mass;   which  decreases   the   Hb   concentration.    That’s   why   all   pregnant   women   have  decreased  hemoglobin;  usually  around  11.5  is   their   cutoff  for  anemia  and  the  cutoff  is   12.5  for   normal  women.    This  is  b/c  of  dilutional   effect   with   excess   in   plasma   vol.     Apparently   in   some   women,   the   excess   plasma   volume   for   9   months   can   cause   weakening   of   the   aorta   and   thereby   causing   an   aneurysm.    

V.    Venous  Disorders:

A.  Superior  vena  cava  lung  syndrome  in  a  smoker  with  primary  lung  cancer,  now