Saleh Mohsen

‫احملقق كوانن‬
 Last​ ​lecture​ ​the​ ​doctor​ ​talked​ ​about​ ​Chemical​ ​Mediators​ ​of-
 Inflammation,​ ​and​ ​their​ ​two​ ​sub-divisions​ ​according​ ​to​ ​their
 source:​ ​Circulating​ ​plasma​ ​proteins,​ ​Cell-derived​ ​ones.​ ​And
 she​ ​discussed​ ​the​ ​Cell​ ​derived​ ​ones​ ​in​ ​details;​​ ​so,​ ​today's
  .lecture​ ​will​ ​be​ ​about​ ​the​ ​circulating​ ​plasma​ ​protein
 …​ ​Let's​ ​start
  -​ ​:Circulating​ ​plasma​ ​protein​ ​→
1. Coagulation​ ​(clotting)​ ​/​ ​fibrinolytic​ ​factors​ ​(both 
names​ ​are​ ​highly​ ​correlated​ ​to​ ​each​ ​other). 
2. Kinin​ ​system. 
3. Complement. 
 
1- Coagulation​ ​(clotting):​ ​-  
 
✓ To​ ​activate​ ​the​ ​coagulative​ ​system,​ ​we​ ​have​ ​two​ ​different 
pathways​ ​according​ ​to​ ​the​ ​type​ ​of​ ​stimulus:  
​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​A)​ ​Intrinsic​ ​Pathway​ ​B)Extrinsic​ ​Pathways. 
These​ ​Pathways​​ ​are:​ ​group​ ​of​ ​activating​ ​factors,​ ​in​ ​which 
activating​ ​one​ ​factor​ ​induces​ ​the​ ​activation​ ​of​ ​other​ ​factors; 
cascade-like​ ​reaction.​ ​The​ ​two​ ​pathways​ ​will​ ​produce​ ​the​ ​same 
product​ ​but​ ​in​ ​different​ ​pathways​ ​depending​ ​on​ ​the​ ​stimulus.​ ​At 
the​ ​end,​ ​they​ ​both​ ​meet​ ​at​ ​the​ ​same​ ​pathway. 
 
✓ In​ ​intrinsic​ ​pathway​​ ​the​ ​first​ ​factor​ ​activated​ ​usually​ ​is 
factor​ ​12(XII)​ ​and​ ​this​ ​is​ ​activated​ ​by 
((High-molecular-weight​ ​kininogen-HMWK),​ ​Prekallikrein 
and​ ​negative​ ​Surface)​ ​→​ ​once​ ​it​ ​gets​ ​activated,​ ​it​ ​activates 
factor​ ​no.​ ​11(XI)​​ ​→​ ​ ​and​ ​then​ ​this​ ​will​ ​activate​ ​factor​ ​no.9(IX) 
→​​ ​then​ ​factor​ ​no.9​ ​in​ ​the​ ​presence​ ​of​ ​(activating​ ​factor​ ​8 
-VIII-)​ ​will​ ​lead​ ​to​ ​the​ ​activation​ ​of​ ​the​ ​most​ ​important​ ​factor 
in​ ​our​ ​series​ ​which​ ​is​ ​factor​ ​no.10(X)​.​ ​→​ ​ ​factor​ ​no.10​ ​in​ ​the 
presence​ ​of​ ​factor​ ​no.5​ ​will​ ​act​ ​on​ ​prothrombin​ ​and​ ​convert​ ​it 
to​ ​thrombin​ ​→​ ​then​ ​thrombin​ ​acts​ ​on​ ​Fibrinogen​ ​and 
converts​ ​it​ ​to​ ​fibrin​.​ ​ ​ ​ ​(P.s:​ ​if​ ​you​ ​didn't​ ​get​ ​it​ ​very​ ​well​ ​see 
the​ ​image​ ​on​ ​the​ ​next​ ​page.)  
 
✓ Fibrin​ ​is​ ​the​ ​most​ ​important​ ​product​ ​for​ ​coagulation​ ​since​ ​it 
is​ ​the​ ​most​ ​important​ ​component​ ​in​ ​clot​ ​formation.​ ​The​ ​clot 
is​ ​formed​ ​from​ ​fibrins​ ​and​ ​platelets​ ​→​ ​then​​ ​fibrin​ ​monomers 
are​ ​cross​ ​linked​ ​by​ ​activating​ ​factor​ ​8​ ​VIII. 
 
✓ B)​ ​Extrinsic​ ​pathway​:​ ​it​ ​starts​ ​with​ ​the​ ​activation​ ​of​ ​factor 
no.7(VII)​ ​(because​ ​of​ ​tissue​ ​trauma)​ ​which​ ​requires​ ​the​ ​tissue 
factor​ ​(TF)​ ​to​ ​initiate​ ​this​ ​process;​ ​by​ ​converting​ ​factor​ ​7 
directly​ ​to​ ​activated​ ​factor​ ​no.​ ​10​​ ​(skipping​ ​all​ ​the​ ​sequences 
that​ ​the​ ​intrinsic​ ​has​ ​to​ ​pass​ ​through)​​ ​→​ ​prothrombin​ ​→ 
thrombin​ ​→​ ​fibrinogen​ ​→​ ​fibrin​.​ ​(the​ ​same​ ​final​ ​product​ ​as 
the​ ​intrinsic​ ​pathway). 
 

 
 
 
 
From​ ​slides:​ ​-  
❖ Fibrin​ ​clot​ ​at​ ​site​ ​of​ ​injury​ ​helps​ ​in​ ​containing​ ​the​ ​cause. 
❖ Fibrin​ ​clot​ ​provides​ ​a​ ​framework​ ​for​ ​inflammatory​ ​cells; 
kind​ ​of​ ​like​ ​threads​ ​holding​ ​the​ ​inflammatory​ ​cells. 
❖ Xa​ ​(activated​ ​factor​ ​10),​ ​aside​ ​from​ ​its​ ​function​ ​in​ ​converting 
prothrombin​ ​into​ ​thrombin,​ ​it​ ​causes​ ​an​ ​increase​ ​in​ ​vascular 
permeability​ ​and​ ​helps​ ​in​ ​leukocyte​ ​emigration​. 
 
 ❖ Thrombin​ ​causes​ ​leukocytes​​ ​adhesion,​ ​platelets 
aggregation,​ ​generation​ ​of​ ​fibrinopeptides,​ ​and​ ​is​ ​a 
chemotactic​ ​factor​. 
 
❖ Fibrinopeptides​ ​are​ ​chemotactic​ ​&​ ​they​ ​induce 
vasopermeability. 
 
● The​ ​intrinsic​ ​and​ ​extrinsic​ ​pathways​ ​function​ ​is​ ​to​ ​produce​ ​a 
clot,​ ​but​ ​we​ ​don't​ ​want​ ​them​ ​to​ ​be​ ​activated​ ​all​ ​the​ ​time​ ​→ 
because​ ​once​ ​they​ ​are​ ​turned​ ​on​ ​they​ ​need​ ​another​ ​system​ ​to 
turn​ ​them​ ​off;​ ​if​ ​that​ ​didn't​ ​happen​ ​the​ ​body​ ​will​ ​be​ ​in​ ​a​ ​state 
of​​ ​widespread​ ​thrombosis.​ ​So,​ ​in​ ​order​ ​to​ ​prevent​ ​this​ ​from 
happening,​ ​we​ ​use​ ​the​ ​Fibrinolytic​ ​pathway​​ ​which​ ​is 
always​ ​linked​ ​to​ ​the​ ​coagulative​ ​process.​ ​So​ ​briefly​ ​the 
function​ ​of​ ​fibrinolytic​ ​pathway​ ​is​​ ​to​ ​inhibit​ ​the 
coagulation​ ​process.​ ​(negative​ ​feedback​ ​mechanism)  
 ‫ اﺣﻨﺎ ﺑﺪﻧﺎ ﻋﻤﻠﯿﺔ اﻟﺘﺨﺜﺮ و ﺗﻜﻮﯾﻦ اﻟﺨﺜﺮة ﺑﺲ ﺗﺤﺪث ﺑﺎﻟﻤﻨﻄﻘﺔ اﻟﻲ‬- :‫ ﺑﺎﻟﻌﺮﺑﻲ‬o
 ‫ﺑﺘﺤﺪث ﻓﯿﻬﺎ اﻹﺻﺎﺑﺔ أو اﻻﻟﺘﻬﺎب ﻣﺎ ﺑﺪﻧﺎ اﯾﺎﻫﺎ ﺗﺤﺪث وﺗﻀﻞ ﻣﺴﺘﻤﺮة ﺑﺸﻜﻞ ﻛﺒﯿﺮ‬
 ‫ ﻓﻠﻬﯿﻚ اﺣﻨﺎ ﯾﻠﺰﻣﻨﺎ ﻃﺮﯾﻘﺔ ل ﻧﻘﺪر ﻧﻮﻗﻒ ﻋﻤﻠﯿﺔ اﻟﺘﺨﺜﺮ وﻧﻤﻨﻌﻬﺎ ﻣﻦ‬..‫ﺑﺎﻟﺠﺴﻢ‬
   .‫اﻟﺤﺪوث ﺑﻌﺪ اﻟﻤﻨﻄﻘﺔ اﻟﻤﺮادة ف ﻟﻬﯿﻚ ﻟﺰﻣﺘﻨﺎ ﻫﺎي اﻻﻟﯿﺔ‬
 
● In​ ​Fibrinolytic​ ​pathway:​ ​Plasminogen​ ​will​ ​be​ ​activated​ ​by 
kallikrein​ ​to​ ​form​ ​plasmin​ ​→​ ​which​ ​degrades​ ​fibrin.​ ​Not 
only​ ​does​ ​plasmin​ ​function​ ​to​ ​degrade​ ​fibrin,​ ​it​ ​also​ ​activates 
the​ ​complement​ ​system. 
 
● XIIa​ ​also​ ​activates​ ​the​ ​fibrinolytic​​ ​pathway​ ​to​ ​prevent​ ​the 
widespread​ ​thrombosis-​ ​negative​ ​feedback​ ​for​ ​the 
degradation​ ​of​ ​fibrin.  
 
● Fibrin​ ​split​ ​products​ ​increase​ ​vascular​ ​permeability.  
 
● Plasmin​ ​cleaves​ ​C3​ ​to​ ​form​ ​C3a,​ ​leading​ ​to​ ​vasodilation​ ​and 
an​ ​increase​ ​in​ ​vascular​ ​permeability.​ ​(C3​ ​and​ ​C3a​ ​are 
anaphylatoxins)-complement​ ​system-. 
 
● Plasmin​ ​activates​ ​XIIa​ ​amplifying​ ​the​ ​entire​ ​process 
As​ ​you​ ​can​ ​see​ ​factor​ ​XII​ ​is​ ​able​ ​to​ ​activate​ ​the​ ​fibrinolytic​ ​system 
and​ ​the​ ​fibrinolytic​ ​system​ ​itself​ ​can​ ​activate​ ​factor​ ​XII​. 
 
● Note:​ ​Thrombin​ ​is​ ​an​ ​important​ ​structure​ ​in​ ​our​ ​body​ ​not 
only​ ​due​ ​to​ ​its​ ​role​ ​in​ ​coagulation​ ​process,​ ​but​ ​it​ ​has​ ​another 
important​ ​role​ ​in​ ​the​ ​inflammatory​ ​process​;it​ ​binds​ ​to​ ​a 
certain​ ​receptor​ ​→​called​​ ​protease-activated.​ ​These​ ​receptors 
are​ ​found​ ​in​ ​platelets,​ ​epithelial​ ​cells​ ​and​ ​even​ ​in​ ​smooth 
muscles​ ​and​ ​this​ ​helps​ ​in​ ​selectin​ ​recognition.   
 
 
Thrombin​ ​as​ ​an​ ​Inflammatory​ ​Mediator:​ ​-  
→​Binds​ ​to​ ​protease-activated​ ​receptors​ ​(PARs),​ ​expressed​ ​on 
platelets,​ ​endothelial​ ​cells​ ​and​ ​sm.​ ​muscles​ ​leading​ ​to: 
 
❖ P-selectin​ ​mobilization. 
❖ Expression​ ​of​ ​integrin​ ​ligands. 
❖ Chemokine​ ​production. 
❖ Prostaglandin​ ​production​ ​by​ ​activating​ ​cyclooxygenase​ ​2 
which​ ​plays​ ​a​ ​role​ ​in​ ​generating​ ​arachidonic​ ​acid 
metabolites. 
❖ Production​ ​of​ ​PAF​ ​(platelet​ ​activating​ ​factor). 
❖ Production​ ​of​ ​NO. 
 
2- Kinin​ ​System: 
 
➔ Leads​ ​to​ ​the​ ​formation​ ​of​ ​bradykinin​ ​from 
HMWK. 
➔ Effects​ ​of​ ​bradykinin: 
✓ Increased​ ​vascular​ ​permeability. 
✓ Arteriolar​ ​dilatation. 
✓ Bronchial​ ​smooth​ ​muscle 
contraction(bronchospasm)*. 
✓ Pain. 
✓ Short​ ​half-life​ ​(inactivated​ ​by​ ​kinases). 
 
 -​Prostaglandin​ ​E2​​ ​and​ b ​ radykinin​ ​are​ ​the​ ​only 
factors​ ​that​ ​cause​ ​pain​ ​. 
-Most​ ​mediators​ ​as​ ​you​ ​can​ ​see​ ​increase​ ​vascular 
permeability. 
*Remember​ ​that​ ​leukotriene​ ​C4​ ​,​ ​D4​ ​and​ ​E4​ ​from​ ​aa 
metabolism​ ​also​ ​cause​ ​bronchospasm​ ​(LTD4,​ ​LTC4, 
LTE4). 
 

→​Interaction​ ​between​ ​the​ ​four​ ​plasma​ ​mediator​ ​systems: 

- Although​ ​each 
system​ ​works 
alone,they​ ​do 
interact​ ​with​ ​each 
other.  
- For​ ​example:​ ​In 
order​ ​to​ ​activate 
factor​ ​no.12, 
Prekallikrein​​ ​will​ ​be 
converted​ ​to​→ 
kallikrein​​ ​which​ ​will 
activate​ ​factor​ ​12.  
- Factor​ ​12​ ​itself​ ​can 
also​ ​once​ ​activated 
convert​ ​prekallikrein​ ​into​ ​kallikrein. 
- At​ ​the​ ​same​ ​time​ ​kallikrein​​ ​can​ ​activate​ ​the​​ ​Fibrinolytic 
pathway​,​ ​by​​ ​producing​ ​plasmin​ ​which​ ​will​ ​activate​ ​the 
complement​ ​system 
(C3)​. 
- Kallikrein​ ​can​ ​convert 
HMWK​ ​to​ ​Bradykinin. 
- *​So​ ​kallikrein​ ​itself​ ​other 
than​ ​activating 
plasminogen​ ​and​ ​the 
clotting​ ​system​ ​causes​ ​the 
formation​ ​of​ ​bradykinin 
from​ ​the​ ​HMWk 
(​High-molecular-weight 
kininogen)​. 
→​Note:​​ ​you​ ​must​ ​know​ ​and​ ​differentiate​ ​between​ ​these​ ​4 
systems​ ​and​ ​how​ ​they​ ​are​ ​connected​ ​to​ ​each​ ​other.​ ​(Coagulation, 
Fibrinolysis,​ ​bradykinin​ ​and​ ​the​ ​complement​ ​systems). 
 
3- Complement​ ​Activation​ ​Pathways:  
(please​ ​in​ ​order​ ​to​ ​understand;​ ​read​ ​this​ ​and​ ​see​ ​the​ ​picture​ ​in 
next​ ​page​) 
✓ It​ ​has​ ​different​ ​pathways​ ​of​ ​activation​ ​according​ ​to​ ​the 
stimulus,​ ​the​ ​most​ ​important​ ​pathway​ ​is​ ​the​ ​Classic 
pathway. 
 
✓ Has​ ​three​ ​different​ ​pathways:​ ​Classic​,​ ​Alternative​​ ​and​ ​the 
last​ ​one​ ​is​ ​Lectin​ ​(​lectins​ ​pathway​ ​usually​ ​depends​ ​on​ ​a 
substance​ ​called​ ​mannose​ ​if​ ​it's​ ​present​ ​on​ ​the​ ​bacterial 
surface​ ​that​ ​will​ ​bind​ ​and​ ​activate​ ​the​ ​lectin​ ​complement 
pathway). 
✓ The​ ​important​ ​pathways​ ​are​ ​Classic​​ ​and​ ​Alternative 
pathways.  
 
✓ Complement​ ​system​ ​is​ ​composed​ ​of​ ​a​ ​group​ ​of​ ​proteins 
called​ ​C​ ​(from​ ​1​ ​until​ ​9). 
 
✓ In​ ​classic​ ​pathway​,​ ​we​ ​have​ ​an​ ​immune​ ​complex​ ​that 
usually​ ​contain​ ​(igG​ ​or​ ​igM)​ ​–​ ​immunoglobulins-​ ​→​ ​they 
will​ ​activate​ ​C​ ​no.1​,​ ​then​ ​C1​ ​will​ ​work​ ​on​ ​to​ ​activate​ ​C2​ ​and 
C4​ ​→​ ​activated​ ​C2,​ ​C4​ ​will​ ​give​ ​→​ ​C3​ ​convertase​​ ​that​ ​will 
work​ ​on​ ​C3​ ​and​ ​cause​ ​cleavage​​ ​of​ ​C3​ ​into​ ​→​ ​C3a​ a​ nd​ ​C3b​. 
 
✓ C3b​ ​will​ ​go​ ​and​ ​give​ ​C5​ ​convertase​ ​→​ ​will​ ​work​ ​on​ ​C5​ ​and 
cleave​ ​it​ ​into​ ​C5a​ ​and​ ​C5b​.  
 
✓ C5b​ ​will​ ​activate​ ​C6,​ ​C7,​ ​C8​​ ​and​ ​C9​ ​→​ ​they​ ​combine​ ​to 
produce​ ​a​ ​membrane-attack​ ​complex​ ​MAC​ ​(a​ ​complex​ ​that 
is​ ​bonded​ ​to​ ​the​ ​membrane​ ​and​ ​attacks​ ​the​ ​microorganism 
causing​ ​lysis​ ​of​ ​the​ ​bacteria,​ ​also​ ​called​ ​(C5-9)​ ​complex). 
 
 ✓ C3a​ ​and​ ​C5a​ ​(​anaphylatoxins​)​ ​are​ ​responsible​ ​for​ ​increasing 
vascular​ ​permeability,​ ​vasodilation,​ ​and​ ​induce​ ​mast​ ​cells​ ​to 
secrete​ ​histamine. 
 
✓ C5a​ ​activates​ ​lipoxygenase​ ​pathway​ ​of​ ​Arachidonic​ ​acid. 
✓ C5a​ ​activates​ ​leukocytes​,​ ​increases​ ​integrin​ ​affinity. 
✓ C5a​ ​is​ ​a​ ​chemotactic​ ​agent. 
✓ C3b​ ​and​ ​iC3b​ ​are​ ​opsonins​ ​that​ ​perform​ ​the​ ​process​ ​of 
opsonization​:​ ​recognition​ ​of​ ​the​ ​microorganism​ ​during 
phagocytosis​. 
✓ Plasmin​ ​and​ ​proteolytic​ ​enzymes​ ​split​ ​C3​ ​and​ ​C5;​ ​leading​ ​to 
complement​ ​system​ ​activation. 
✓ Membrane​ ​attack​ ​complex​ ​(C5-9)​ ​lyse​ ​bacterial​ ​membranes 
 
→​In​ ​the​ ​Alternative​ ​pathway:​ ​ ​It​ ​is​ ​the​ ​same​ ​as​ ​the​ ​classic 
pathway​ ​but​ ​the​ ​start​ ​process​ ​is​ ​different,​ ​we​ ​will​ ​start​ ​with​ ​C3​ ​in 
a​ ​Microbial​ ​surface​ ​or​ ​with​ ​an​ ​immunocomplex​ ​(igA)​​ ​and​ ​will​ ​be 
converted​ ​to​ ​→​ ​C3b​,​ ​then​ ​in​ ​the​ ​presence​ ​of​ ​factor​ ​D​ ​→​ ​it​ ​will 
produce​ ​C3​ ​convertase​ ​which​ ​leads​ ​to​ ​formation​ ​of​ ​C3a 
and​ ​C3b​ ​fragments​,​ ​that​ ​will​ ​continue​ ​with​ ​the​ ​same​ ​sequence 
as​ ​the​ ​Classical​ ​pathway.  

 
 [Please​ ​read​ ​the​ ​summary​ ​of​ ​effector​ ​functions​ ​from​ ​picture] 

 
Defects​ ​in​ ​the​ ​Complement​ ​System​: 
❖ Defects​ ​could​ ​happen​ ​due​ ​to​ ​a​ ​deficiency​ ​in​ ​the​ ​main 
components​ ​of​ ​the​ ​complement​ ​system​ ​or​ ​in​ ​the​ ​inhibitory 
proteins​ ​that​ ​inhibit​ ​these​ ​components​ ​after​ ​completing​ ​their 
job. 
 
❖ If​ ​we​ ​have​ ​C3​ ​Deficiency,​ ​It’s​ ​really​ ​a​ ​big​ ​problem​ ​because​ ​it 
is​ ​abundant​ ​in​ ​both​ ​pathways​ ​so​ ​its​ ​deficiency​ ​will​ ​block​ ​the 
whole​ ​complement​ ​system.​ ​→​​ i​ ncrease​ ​susceptibility​ ​to 
recurrent​ ​infections. 
 
❖ If​ ​we​ ​have​ ​a​ ​Deficiency​ ​in​ ​C2​ ​and​ ​C4:​ ​that​ ​will​ ​not​ ​affect​ ​the 
two​ ​pathways​ ​→​ ​it​ ​will​ ​only​ ​affect​ ​the​ ​classic​ ​pathway,​ ​so 
they​ ​will​ ​be​ ​more​ ​susceptible​ ​to​ ​SLE​​ ​(​_​systemic​ ​lupus 
erythematosus_)​ ​an​ ​autoimmune​ ​disease​ ​in​ ​which​ ​the​ ​body’s 
immune​ ​system​ ​mistakenly​ ​attacks​ ​healthy​ ​tissue​ ​in​ ​many 
parts​ ​of​ ​the​ ​body​ ​by​ ​the​ ​action​ ​autoantibodies​ ​(antibodies 
that​ ​bind​ ​to​ ​the​ ​contents​ ​of​ ​the​ ​cell​ ​nucleus​ ​i.e:​ ​anti-double 
stranded​ ​DNA​ ​and​ ​all​ ​our​ ​cells​ ​have​ ​DNA​ ​hence​ ​these 
antibodies​ ​cause​ ​injury​ ​to​ ​any​ ​organ). 
 
 
❖ If​ ​we​ ​have​ ​a​ ​Deficiency​ ​in​ ​late​ ​components​ ​(C5​ ​and​ ​later): 
then​ ​we​ ​will​ ​have​ ​a​ ​low​ ​MAC​ ​(membrane​ ​attack​ ​complex)​ ​→ 
so​ ​the​ ​patient​ ​struggles​ ​in​ ​killing​ ​those​ ​microorganisms​ ​→ 
patients​ ​will​ ​have​ ​a​ ​high​ ​susceptibility​ ​to​ ​a​ ​certain​ ​type​ ​of 
infection​ ​which​ ​is​ ​Neisseria​ ​infection​.​ ​That's​ ​Because​ ​this​ ​type 
of​ ​bacteria​ ​needs​ ​MAC​ ​to​ ​be​ ​killed. 
 
❖ A​ ​deficiency​ ​in​ ​the​ ​inhibitors​ ​of​ ​C3​ ​and​ ​C5​ ​convertase​​ ​such 
as​ ​↓​ ​DAF​ ​→​ ​Decay-accelerating​ ​factor,​ ​a​ ​deficiency​ ​in​ ​this 
factor​ ​will​ ​cause​ ​the​ ​complement​ ​system​ ​to​ ​stay​ ​active​ ​→​ ​this 
will​ ​cause​ ​hemolytic​ ​anemia​ ​(lysis​ ​of​ ​RBC's).  
 
❖ A​ ​deficiency​ ​in​ ​C1​ ​inhibitor​​ ​→​ ​angioneurotic​ ​edema​. 
 
 
Morphologic​ ​Appearance​ ​of​ ​Acute​ ​Inflammation  
 
- We​ ​have​ ​different​ ​types​ ​of​ ​Morphologic​ ​Appearance​ ​of 
Acute​ ​Inflammation,​​ ​divided​ ​into: 
 
1) Catarrhal:​​ ​Acute​ ​inflammation​ ​+​ ​mucus​ ​hypersecretion​ ​(e.g. 
common​ ​cold:​ ​runny​ ​nose​ ​and​ ​mucus​ ​hypersecretion)​. 
 
2) Serous:​ ​Abundant​ ​protein-poor​ ​fluid​ ​(​Transudate​)​​ ​with 
low​ ​cellular​ ​content,​ ​e.g.​ ​skin​ ​blisters​ ​(such​ ​as​ ​in​ ​burns) 
and​ ​accumulation​ ​of​ ​transudate​ ​in​ ​body​ ​cavities​ ​(usually 
seen​ ​in​ ​patients​ ​with​ ​heart​ ​failure​ ​and​ ​renal​ ​failure​ ​because 
they​ ​have​ ​increased​ ​hydrostatic​ ​pressure​ ​due​ ​to​ ​increased 
fluids​ ​in​ ​the​ ​body).   
 
3) Fibrinous:​ ​Accumulation​ ​of​ ​a​ ​thick​ ​exudate,​ ​which​ ​is​ ​rich 
in​ ​fibrin,​ ​may​ ​resolve​ ​by​ ​fibrinolysis​ ​or​ ​organize​ ​into​ ​thick 
fibrous​ ​tissue​ ​(e.g.​ ​in​ ​the​ ​cases​ ​of​ ​rheumatic​ ​fever​,​ ​renal 
failure​ ​leading​ ​to​ ​fibrinous​ ​pericarditis​).​ ​-More 
explanation-​→​ ​ ​The​ ​problem​ ​is​ ​that​ ​the​ ​body​ ​can't​ ​get​ ​rid 
of​ ​the​ ​fibrin-rich​ ​fluid​ ​so​ ​it​ ​will​ ​accumulate​ ​in​ ​thick 
 fibrous​​ ​tissue​ ​and​ ​a​ ​problem​ ​appears​ ​when​ ​this​ ​occurs​ ​in 
a​ ​critical​ ​site​. 
➔ ​ ​Remember​ ​that​ ​the​ ​body​ ​needs​ ​to​ ​activate​ ​the​ ​fibrinolytic 
system​ ​to​ ​get​ ​rid​ ​of​ ​the​ ​fibrin​ ​but​ ​sometimes​ ​when​ ​it​ ​is​ ​too 
much​ ​the​ ​system​ ​cannot​ ​cause​ ​fibrinolysis​ ​of​ ​all​ ​this​ ​fibrin 
and​ ​this​ ​ultimately​ ​leads​ ​to​ ​healing​ ​by​ ​fibrosis) 
​ ​For​ ​example​,​ ​if​ ​the​ ​pericardium​ ​of​ ​a​ ​ ​patient​ ​with​ ​lupus​ ​is 
attacked​ ​due​ ​to​ ​the​ ​condition,​ ​the​ ​pericardium​ ​ ​will​ ​form​ ​an 
exudate​ ​of​ ​fibrin​ ​or​ ​fibrous​ ​tissue​ ​or​ ​fluid​ ​that​ ​compress​ ​the 
pericardium​ ​to​ ​the​ ​inside.​ ​This​ ​results​ ​in​ ​constrictive​ ​pericarditis​, 
in​ ​which​ ​the​ ​pericardium​ ​gets​ ​close​ ​to​ ​the​ ​heart​ ​muscle​ ​so​ ​it​ ​will 
not​ ​have​ ​the​ ​ability​ ​to​ ​expand​ ​leading​ ​to​ h ​ eart​ ​failure​.  
➔ Note:​ ​You​ ​need​ ​to​ ​know​ ​that​ ​the​ ​formation​ ​of​ ​fibrinous 
tissue​ ​in​ ​critical​ ​organs​ ​ ​interferes​ ​with​ ​the​ ​patient's​ ​quality 
of​ ​life​ ​and​ ​leads​ ​to​ ​serious​ ​problems(such​ ​as​ ​pericarditis). 
  
 ‫ ﻗﺪ ﺗﺘﺤﻠﻞ ﻋﻦ ﻃﺮﯾﻖ اﻧﺤﻼل اﻟﻔﯿﺒﺮﯾﻦ أو ﺗﻨﻈﻢ‬،‫ﺗﺮاﻛﻢ اﻻﻓﺮازات اﻟﺴﻤﯿﻜﺔ اﻟﻐﻨﯿﺔ ﺑﺎﻟﻔﯿﺒﺮﯾﻦ‬
 - ‫ ﻣﺰﯾﺪ ﻣﻦ اﻟﺘﻮﺿﯿﺢ‬- .(‫ﻓﻲ اﻧﺴﺠﺔ ﻟﯿﻔﯿﺔ ﺳﻤﯿﻜﺔ )ﻋﻠﻰ ﺳﺒﯿﻞ اﻟﻤﺜﺎل اﻟﺘﻬﺎب اﻟﺘﺎﻣﻮر اﻟﺤﺎد‬
 ‫اﻟﻤﺸﻜﻠﺔ ﻫﻲ أن اﻟﺠﺴﻢ )ﻧﻈﺎم ﻓﺒﺮﯾﻨﻮﻟﯿﺘﯿﻚ( ﻻ ﯾﻤﻜﻦ اﻟﺘﺨﻠﺺ ﻣﻦ اﻟﺴﻮاﺋﻞ اﻟﻐﻨﯿﺔ ﻓﻲ‬
 ،‫ ﻋﻠﻰ ﺳﺒﯿﻞ اﻟﻤﺜﺎل‬.‫ﺑﺎﻟﻔﯿﺒﺮﯾﻦ ﻟﺬﻟﻚ ﺳﻮف ﺗﺘﺮاﻛﻢ ﻓﻲ اﻷﻧﺴﺠﺔ اﻟﻠﯿﻔﯿﺔ ﻓﻲ ﻣﻮﻗﻊ ﻏﯿﺮ ﻣﺮادة‬
 ،(pericardium)‫ وﻫﺬا ﯾﻀﻐﻂ ﻋﻠﻰ اﻟﺘﺎﻣﻮر‬،lupus ‫إذا ﻛﺎن اﻟﻤﺮﯾﺾ ﻣﺼﺎب ﺑﺎل‬
 ‫ﺑﺤﯿﺚ ﯾﻜﻮن ﻟﺪﯾﻪ ﺗﺮاﻛﻤﺎت اﻻﻓﺮازات أو اﻷﻧﺴﺠﺔ اﻟﻠﯿﻔﯿﺔ أو اﻟﺴﻮاﺋﻞ اﻟﺘﻲ ﻣﻦ ﺷﺄﻧﻬﺎ ﺿﻐﻂ‬
 ‫ اﻟﺘﻬﺎب اﻟﺘﺎﻣﻮر ﻓﺈﻧﻪ ﯾﺠﻌﻞ اﻟﺘﺎﻣﻮر ﻗﺮﯾﺒﺔ ﻣﻦ ﻋﻀﻠﺔ اﻟﻘﻠﺐ أي‬:‫اﻟﺘﺎﻣﻮر إﻟﻰ اﻟﺪاﺧﻞ ﯾﺴﻤﻰ‬
 .‫أﻧﻪ ﻟﻦ ﯾﻜﻮن ﻟﺪﯾﻬﺎ اﻟﻘﺪرة ﻋﻠﻰ ﺗﻤﺪﯾﺪ‬
 
4) ​ ​Suppurative​ ​(purulent):  
- accumulation​ ​of​ ​Pus:​ ​Creamy​ ​yellow​ ​or​ ​blood-stained​ ​fluid 
consisting​ ​of​ ​neutrophils,​ ​microorganisms​ ​&​ ​tissue​ ​debris 
e.g.​ ​acute​ ​appendicitis​ ​(when​ ​you​ ​open​ ​the​ ​cavity).​ ​ ​‫ﺣﺐ اﻟﺸﺒﺎب‬ 
acne​ ​‫ﻣﺜﻼ‬. 
- Abscess:​ ​focal​ ​localized​ ​collection​ ​of​ ​pus​ ​(it​ ​accumulates​ ​in 
subcutaneous​ ​tissue​ ​or​ ​in​ ​any​ ​organ).  
- Empyema:​ ​A​ ​collection​ ​of​ ​pus​ ​within​ ​a​ ​hollow​ ​organ(e.g: 
gall​ ​bladder). 
 
5) Ulcers:​ ​ ​happens​ ​in​ ​the​ ​epithelial​ ​surface.​ ​(‫)ﺗﻘﺮح‬ 
- Defect​ ​of​ ​the​ ​surface​ ​lining​ ​of​ ​an​ ​organ​ ​or​ ​tissue. 
- Mostly​ ​occurs​ ​in​ ​the​ ​GI​ ​tract​ ​or​ ​on​ ​skin. 
 ​ ​Note:​ ​you​ ​will​ ​study​ ​these​ ​pictures​ ​in​ ​full​ ​details​ ​in​ ​the​ ​lab,​ ​so​ ​just 
distinguish​ ​between​ ​them​ ​now​ ​and​ ​later​ ​on​ ​you​ ​will​ ​know​ ​the​ ​details. 

Subcutaneous​ ​Abscess​ ​full 

of​ ​pus-​ ​suppurative 
(purulent)  
 

Cavity​ ​in​ ​the 

lung​ ​containing 
neutrophils​ ​and 
necrotic​ ​debris- 
lung​ ​abscess. 
Many 
neutrophils​ ​are 
viewed​ ​under 
the​ ​microscope. 

Fibrinous​ ​Pericarditis-​ ​this​ ​is 

the​ ​case​ ​of​ ​a​ ​patient​ ​with 
rheumatic​ ​fever.​ ​In​ ​this 
picture,​ ​the​ ​pericardium​ ​is 
open​ ​and​ ​fibrinous​ ​exudate 
is​ ​observed   
 Gastric​ ​ulcer-​ ​normal​ ​epithelial​ ​is 
lost​ ​and​ ​the​ ​dark​ ​brown​ ​color​ ​is 
due​ ​to​ ​bleeding  

 
Foot​ ​Ulcer-​ ​commonly​ ​occurs​ ​in 
patients​ ​with​ ​diabetes​ ​or​ ​ischemia​ ​to 
limbs;​ ​decreased​ ​blood​ ​flow​ ​causes 
loss​ ​of​ ​epithelium​ ​and​ ​ulceration 

Serous​ ​Inflammation:​ ​burn​ ​blisters

 
 
 
 
 
 
Outcome​ ​of​ ​acute​ ​inflammation:  
1) Complete​ ​resolution​ ​(back​ ​to​ ​normal)​ ​→​ ​removes​ ​the​ ​bad 
agent.  
Conditions: 
• Clearance​ ​of​ ​injurious​ ​stimuli. 
 • Removal​ ​of​ ​the​ ​exudate,​ ​fibrin​ ​&​ ​debris.  
• Reversal​ ​of​ ​the​ ​changes​ ​in​ ​the​ ​microvasculature. 
• Replacement​ ​of​ ​lost​ ​cells​ ​(regeneration). 
→​If​ ​we​ ​don’t​ ​have​ ​a​ ​complete​ ​resolution​ ​with​ ​its​ ​full 
steps,​ ​then​ ​we​ ​will​ ​skip​ ​to​ ​healing. 
 
2) Healing​ ​by​ ​fibrosis: 
• Organization​ ​by​ ​fibrosis​ ​through​ ​formation​ ​of 
Granulation​ ​tissue​ ​(​a​ ​collection​ ​of​ ​fibroblasts​ ​and 
blood​ ​vessel​ ​formation)​→​collagen,​ ​and​ ​that​ ​happens 
in​​ ​the​ ​following​ ​cases:   
✓ Substantial​ ​tissue​ ​destruction​ ​affects​ ​the​ ​frame 
and​ ​it​ ​can't​ ​get​ ​back​ ​to​ ​normal. 
✓ Tissue​ ​cannot​ ​regenerate​ ​such​ ​as​ ​heart​ ​myocytes 
and​ ​neurons. 
✓ Extensive​ ​fibrinous​ ​exudates. 
3) Abscess​ ​formation​ ​(if​ ​the​ ​microorganism​ ​was​ ​very​ ​virulent). 
(‫ﻣﻜﺎن اﻟﺠﺮح ﻟﻔﺘﺮة ﻃﻮﯾﻠﺔ ﻋﺸﺎن ﺻﺎر ﻓﻲ ﻓﯿﺮوﺳﺎت )ﻋﺸﺎن ﻫﯿﻚ ﻟﻤﺎ ﺗﻨﺼﺎب ﻣﺮات ﺑﻀﻞ ﻣﺒﯿﻦ‬ 
  
4) Progression​ ​to​ ​chronic 
inflammation:​ ​if​ ​it​ ​was 
too​ ​extreme​ ​it​ ​will 
develop​ ​to​ ​a​ ​chronic 
one​ ​and​ ​also​ ​if​ ​the 
acute​ ​one​ ​failed​ ​to 
destroy​ ​it. 
*​ ​All​ ​outcomes​ ​will 
eventually​ ​lead​ ​to​ ​fibrosis 
Role​ ​of​ ​Lymphatic​ ​System
in​ ​inflammation
 If​ ​ihe​ ​local​ ​-
  inflammatory
  reaction​ ​failed​ ​in​ ​containing​ ​the​ ​injurious​ ​agent,​ ​we​ ​have
 another​ ​defensive​ ​mechanism:​​ ​Secondary​ ​lines​ ​of​ ​defense
1. Lymphatic​ ​system:  
• Lymphatic​ ​vessels​​ ​drain​ ​offending​ ​agents, 
edema​ ​fluid​ ​&​ ​cellular​ ​debris,​ ​and​ ​may​ ​become 
inflamed​ ​(LYMPHANGITIS). 
• Lymph​ ​nodes​​ ​may​ ​become​ ​ ​inflamed 
(LYMPHADENITIS).   
• Secondary​ ​lines​ ​of​ ​defense​ ​may​ ​fail​ ​to​ ​contain 
infections,​ ​or​ ​may​ ​be​ ​overwhelmed​ ​(meaning 
that​ ​this​ ​defense​ ​system​ ​will​ ​fail)​ ​resulting​ ​in 
BACTEREMIA​ ‫​ ​ﺗﺴﻤﻢ اﻟﺪ ​م‬or​ ​toxemia.-​ ​which 
requires​ ​the​ ​third​ ​line​ ​of​ ​defence​ ​(MPS)  
2. MPS​ ​(mononuclear​ ​phagocyte​ ​system):   
• Phagocytic​ ​cells​ ​of​ ​spleen,​ ​liver​ ​&​ ​BM.  
• In​ ​massive​ ​infections,​ ​bacterial​ ​seeding​ ​may​ ​occur​ ​in​ ​distant 
tissues.​ ​(Virulent​ ​types​ ​of​ ​bacteria​ ​may​ ​overcome​ ​all​ ​these​ ​lines​ ​of 
defences​ ​and​ ​eventually​ ​lead​ ​to​ ​septicemia,​ ​which​ ​can​ ​be​ ​fatal 
especially​ ​in​ ​immunocompromised​ ​patients),​ ​the​ ​bacteria​ ​would​ ​be 
able​ ​to​ ​go​ ​to​ ​anywhere​ ​through​ ​the​ ​bloodstream​ ​and​ ​cause 
inflammation​ ​in​ ​any​ ​organs​ ​it​ ​reaches.​ ​Hence​ ​if​ ​not​ ​controlled​ ​this 
condition​ ​can​ ​be 
fatal).