MOD: pathology of SS, clostridium and EBV, & nutritional/hyperproliferative anemias Flashcards
Types of clostridium and most clinically relevant
non inv abcess, non inv with toxemia, invasive non-necr inflam (eg fascitis), and INVASIVE WITH NECROSIS
Invasive clostridium wtih rapid progression of infxn with non-suppurative tissue necrosis: 2 types
Traumatic, and non-traumatic/spontaneous type
Traumatic invasive clostridium
multiple aerobic-anaerobic orgs, usu C PERFRINGENS GANGRENE OR RHABDOMYOLYSIS
Non-traumatic spontaneous invasive clostridium
single spp, usu C SEPTICUM, SPONT RHABDOMYOLYSIS
Spontaneous clostridial rhabdomyolysis sx
sudden onset of severe pain in area oft extremity without suggestive physical findings
- feeble tachycardia
- swelling and discoloration of skin, bullae, gas formation w/i hours (due to anaer gas prod bacteria)
- avg of 20 hr to death
If spont clostridial rhabdomylysis not treated?
death, renal failure, coagulopathies, CV etc
predisposing factors to clostridial rhabdomyolysis
DM, trauma, operation, CV , immunsuppr tx, chemo, antibios with psuedomembranous colitis, myelo-lymphoprolif disorders, cancer
What do most pts with spont clostridial rhabdomyolysis have in addn?
cecal right side COLON CANCER (bc the clostridium bacterium gain sys access by ulceration)
or myeloprolif disorder
are most clostr rhabdomyolysis caused by perfringens or septicum, and why?
C SEPTICUM (bc more aerotolerant)
what helps clostridium spread
SPORES (tumor env helps with this)
btw they are anaer, gram +
What TOXINS are in C septicum?
Lecithinase disrupt cell membs (incl muscle cells)
Hemolysins cause hemolysis (can cause renal failure etc)
HLA
fibrinolysin
Leukolysins (cause lysis of neutros)
things that allow it to migrate to SKM
THETA and DELTA toxins
What do Theta and Delta toxins in C septicum do?
THETA cause CV failure by reducing mycardial fxn
DELTA cause necrotizing vasculitis causing organ dysfxn
What might clostrial RHABDOMYOLYSIS show on dx?
elevated CPK and LDH and hyperkalemia (incr K+) (no elev CPK would mean hemolytic process)
and red to brown urine (positive hemoglobin dipstick)
and ABSENT NEUTROS
What does elev CPK and LDH
plus + urine dipstick with red to brown urine mean?
CLOSTRIDIAL RHABDOMYOLYSIS!
may also be gram +, spores
What spp might boxcar shaped bacilli suggest?
CLOSTRIDIUM PERFRINGENS!
subterminal spores might be septicum
Tx for clostridial rhabdomyo?
MORTALITY >70%
have to usu amputate, can incl antibios or maybe hyperbaric O2
What genetic mutation is inherited in sickle cell?
GLUTAMIC ACID changes to VALINE!
What primary issues can SS cause?
hemolysis of RBCs, the shapes can cause vascular occlusions and organ dysfxn, ischemia etc
- ANEMIA
- dysfxnl SPLEEN since v young age
issues of SS in kids and adults causing mortaility?
kids-inv of spleen, lungs, brain
adults- nephropathy
what does SCA (sickle cell anemia) increase the risk for?
bacterial infxns such as
Strep pneum, H influenza b, salmonella, klebsiella (partly due to dysfxnl spleen bc its microcirculation is messed up, and ineffective complement activn)
-also parvovirus b-19
-risk of developing PNEUMOCOCCAL MENINGITIS (but most are infants, high mortality)
-strokes
How to test for spleen function
look for pitted red cells in glutaraldehyde, liver spleen scan
What is pancytopenia
def of ALL 3 BLOOD CELLS: WBC, RBC, and platelets!
What is myelophthisic anemia?
anemia that occurs in pts that have their marrow replaced by fibrosis and granulomas
What does rapid elevation of BUN, creatinine, and postassium (with reduction in serum calcium) suggest?
acute renal failure! (can happen as result with clostridum rhabdomyolysis)
What IS rhabdomyolysis
rapid breakdown of SKM
What predisposing factors can put patients at risk for developing secondary infections when they have clostridial rhabdomyo?
pancytopenia
hepatosplenomeg (means lymphoprolif?)
lymphoprolif or myeloprolif or myelophthis
colon carcinoma, DM
what might clostridial rhabdo show re WBCs?
might show lack of WBCs bc of leukolysis (unusual for bacterial infxn)
What might feber, seizures, and nuchal rigidity suggest?
MENINGITIS
What might increased protein and neutros with decreased glucose in CSF suggest?
bacterial meningitis
Most common causes of meningitis in NEONATES INFANTS AND KIDS TEENS ELDERLY
neonates- E COLI, group b strep
infants/kids- strep pneum
adolescents and YA- neisseria meningitis
elderly-strep pneum, then listeria
WHY are patients with sickle cell anemia sus to meningitis and strep pneum etc?
bc they have functional ASPLENISM since early age
(and decr phagocytic and lytic activitiy due to dysfxn activation of complement producing C3b and C5b and low complement lvls), capsule evades lysis by complement C3b etc
What 2 disease states does EBV produce?
lytic: virions produce MONO!
latent: immortalized in B cells, produces burkitt’s lymphoma and nasopharyngeal carcinoma
can be asympto
What 2 cancers does latent EBV cause?
Burkitt’s lymphoma, and nasopharyngeal carcinoma
What does EBV have affinity for
herpesvirus that has affinity for B CELLS, when viral antigens form in B cells it enters latent phase, and makes host a carrier (type 1 EBV more effective at immortaliztion)
what does “tropism” or tropic mean
affinity for… (eg a certain organ or cell, eg lymphotropic)
Transmission of EBV?
resp route, eg kissing (saliva and oropharyngeal epith cells)
What cells does EBV infect
infects mucosal b cells, causes stim, produces heterophile ab’s
sx of EBV in organs
tonsil lymph and spleen enlargement
What viral antigens does EBV produce
EBNA (epstein barr nuclear antigen) LYDMA (lymphocyte detected membrane ag) MA (memb antigen) EA (early ag) VCA (viral capsid ag)
Immune cell response to EBV
Interferon rel by B cells and T cells and controls EBV induced B cell prolif, prevents it and boosts NK cells
NK cells from interferon act synergistically to protect against EBBV
CYTOTOXIC CD8+ CELLS (most impt factor in controlling ebv induced B cell prolif) since EBV normally activates suppressor T cells
DOWNEY cells are atypical T cells in blood
AB-dep cell mediated cytotoxicity
Humoral ab production (cold aggl, IgM rheum factor, ANA, paul-bunnel heterphil ab, can screen)
what is the most important cell in controlling EBV-induced B-cell prolif
Cytotoxic (CD8+) cells!
What TESTS diagnose Infectious Mononucleosis (in EBV)?
HETEROPHIL AB TEST: agll will occur when u add horse RBC, remove forssmans ab’s via guinea pig ags– but not all pts develop heterophil ab’s so can then use VCA-IgM to dx acute infxn
MONOSPOT TEST: use cow RBC, rapid single step screen
(specific but not sens)
What are downey cells
weird shaped lymphos (kinda gooey)
Other AB tests for MONO?
VLA (viral capsid ag for EBV)
IgG always elev
diffuse and restricted early antigens
EBNA
What are diffuse and restricted early antigens assoc with?
in MONO from EBV
EA-D- assoc with nasopharyngeal carcinoma
EA-R- assoc with burkitt’s lymphoma
Antigen levels and EBV in: subclin prim infxn acute IM past infxn react burkitts nasophar
subclin 1- abs to VCA (igm and igg) acute IM- heterophil ab's, vca igm/g, EA past- vca igg only, EBNA react- vca igg, EA-D, ebna (iggs) burkitt- EA-R, vca, ebna etc nasophar-like burkitt but EA-D instead immunodef pts may lack ab's to ebna
If pt is heterophil ab negative with mono sx, AND vca-IgM ab negative, what may this indicate?
other virus like toxo, HHV6, CMV etc
mono sx in YA
sore throat, fever, chills, fatigue, enlarged lymph nodes
RED thraot, hepatosplenomeg, rashes maybe petchiae etc
usu self limiting
What may heterophil ab’s and DOWNEY CELLS indicate? (also may be slightly elev ALT/AST)
mono! from ebv
-cyto vacuoles, scalloping, cytoplasm indented by RBCs
Hematologic and other complications of mono?
hemolytic anemia, aplastic anemia, RBC aplasia, thrombocytopenia
-lots of other issues with liver spleen joints heart kidneys etc
Burkitt’s lymphoma
malig tumor children involving jaw and viscera (endemic areas of malaria), dev EA-R ab’s
Nasopharyngeal carcinoma
aka lymphoepith carcinoma
chinese males, EA-D ab’s
What other tumors can often contain EBV
HODGKINS LYMPHOMA and AIDS-related CNS lymphomas
Mono EBV can often cause what in transplant pts?
post-transplant lymphoproliferative disorders
- sx can include bloody stools etc
- from impaired immune surv by immunosuppr drugs which can lead to cancer, transplant rjxn or antigen stimulation
3 types of post transplant lymphoprolif disorders
1) Polymorphous B cell hyperplasia
2) B cell lymphoma with atypical immunoblasts
3) Immunoblastic lymphoma
What percent of patients with acute mono (eg in college kids) dont produce heterophil ab’s
30%
another thing EBV can lead to
guillan-barre
can also test for EBV with
PCR, genetic tests to det clonality or prolif
young ale from africa presents with swelling in maxilla, what tests would you look for?
EBV blood studies for VCA-IgG, EBNA, and EA-R
biopsy with starry sky pattern from EBV may mean
Burkitt’s lymphoma!
If burkitts tumor is in an area with endemic malaria vs nonendemic, where would the location be?
endemic (eg africa)- jaw
nonendemic-extranodal sites
