Hemodynamic Disorders PDF

Dr. Maha Akkawi Hemodynamic Disorders · eas Thrombosis and Shock By Eleen Alhaj : Dentistry-122  Edema 60% of body weight is water 2/3 of this fluid is intracellular 1/3 i...

Dr. Maha Akkawi Hemodynamic Disorders · eas Thrombosis and Shock By Eleen Alhaj : Dentistry-122  Edema 60% of body weight is water 2/3 of this fluid is intracellular 1/3 is extracellular, mostly as interstitial fluid 5% of extracellular fluid is in the vascular compartment Edema is increased fluid in the interstitial tissue spaces Collection of fluid in body cavities is named according to place: hydrothorax, hydropericardium, or hydroperitonium Anasarca is severe and generalized edema with profound subcutaneous tissue swelling Edema = %60 a ja (Intracellular 1 +2/31s & , ↑ & Si(Extracellular 41/3a 9 (interstitial finid I Wis -still , 11113 diy * Wi %5 a. Ivascular compartment ( ↑ Edema 11 is - this t will interstitial fluid spacesa - - id dime : * hydropericardium& - ↑ ↑ Hi hydroperitonium : shipus- , Ascites I · Sibling ↑ &Gedema Anasarca : &is d subcutaneous tissue 11.  - The balance between vascular hydrostatic pressure and plasma colloid osmotic pressure is the driving force that maintains movement of fluids between vascular and interstitial spaces - Normally, the exit of fluid into the interstitium at the arteriolar end is almost balanced by inflow of fluid from the interstitium back into the vascular bed at the venular end - A small amount of fluid stays in the interstitium because of little higher hydrostatic pressure to push fluids out - This little amount of fluid is drained back by lymphatics Edi dib vascular hydrostatic pressure I - j) amcolloidosmoticpresentatio 1.. ↑ 114s space - - ~ /T & - interstitial Ho - - is &I - di Vascular Na interstitial his, interstitiala s 1 &Stasy ,a in (interstitial so did, and - 1also in dinterstial s &25. / 95 susmotic pressure It isI hydrostatic pressure - ~ 1 W assists d , hydrostatic pressure 11 - - - ↑ d is mic interstitium - & I s joss drained und l o IS 21 ma · Lis s fluid& is · Endl Shi  /- -I hydrostatic pressure 11 Gi osmotic Plasma colloid pressured ↳ / interstitial stand. osmotic pressures & hydrostatic pressure subclavian vein No Thoracic /. Milymphatic sid - drained is · No edema 58 % &S & &24  - Normal hydrostatic pressure is 32 mm Hg at the arteriolar end of a capillary bed, and 12 mm Hg at the venous end - The mean colloid osmotic pressure of tissue is approximately 25 mm Hg - In inflammation, arteriolar pressure is increased to 50 mm Hg, because of arteriolar dilation - The venous pressure increases to approximately 30 mm Hg - At the same time, osmotic pressure to an average of 20 mm Hg because of protein leakage across the venule - The net result is an excess of extravasated fluid Capillary bed To hydrostapressure sS 32 mm Hg 2S - - (Arterial end (15) 20 p g) : · 25mmtg &13 (ss/ 25y* Tissue 11) Main , colloid osmotic pressure11 &M * -.1. sommtys jg Arteriolar pressure s inflammations mid arteriolar dilation I ↓ sizomaty a 30 , 50 11% ) sommiy sig S - venous pressure 11 & 1 - s / omm ~ - post capillary venule * El leakage · slidj. 20914 Did ↑.. 1 681,↑ and 225 ·isles Des +Has fluid No obj - - · C Dinne 15 & - ·si is bin pie + colloid osmotic pressive & * ↑ 1 /N &(5j/s.. ·St >  w· hydrostatic 11 Gi & pressure - ~ - - -, asiv hydrosfatic pressure o - Plasma colloid osmotic pressures * A , Edema e Na , osmotic pressured Edema · evenue g - - / --  Pathophysiologic Categories of Edema Increased hydrostatic pressure: I-Impaired venous return: 1- Congestive heart failure 2- Constrictive pericarditis 3- Ascites (liver cirrhosis) 4- Venous obstruction or compression: a- Thrombosis b- External pressure (tumor) c- Inactivity of lower limb II- Arteriolar dilation 1- Heat 2- Neurohumoral disturbance Increased hydrostatic pressure - colloid osmotic pressur is i impaired venous return TI : Edema as · se hydrostatic pressure I diss * , Mid 114&I is) - failure & - congestive heart -- 0, Edema ,5 - gi ↑ + - x , (11) pericardium 11 jetll constrictive pericarditise Diastole. j M thick n pericardium 1 , Ets post - - venous return s d king is circulation Ascites lliver cirrhosis) & - ~ ~ & i digi sti liver - I s - portal circulatin it Il stisl as thrombosis; tumor - vein 1 obstruction &Id - - · Edema/d - 88 %, vein I s hydrostatic pressure Arteriolar dilation clajd is his & hydrostatic pressure so ·55 Arteriolar dilations* C. Id Heat 1d hydrostatic pressure 11 8. & je Substances , neuroses i blood vessels 11 : Neurohumoral disturbance 11 a ~ on ↳ -516 blood vessels dilation 11 & Neurohumoral Control s bi vasodilation ji Edema d d pressures constriction ·  Reduced plasma osmotic pressure: 1- Protein losing glomerulopathies (nephrotic syn) 2- Liver cirrhosis 3- Malnutrition 4- Protein losing gastroenteropathy Lymphatic obstruction 1-Inflammatory 2- Neoplastic 3- Postsurgical 4- Postirradiation 11 &Ed - l : Plasma colloid osmotic pressures dist ↑ is, , - & I S M ? blood gia. : ilgil as & es.5 z Kidney normally 1 : protein losing glomerulopathies ① 19 Jess is is glomerulas 11 M. ~ job nephrotic , = syndrome disease - *i, edema 64? plasma colloid osmotic pressive is Bl, urine ·Id chronic diarrhea o s 4 , vare : protein losing gastroenteropathy i · : ! si 25 diarrhea Ig liversi J. i liver I d 31 lliver failureI &j Jilgic · , : 3 & - - low Plasma osmotic pressure -9 S. j ↑ -S. edema. d S : -sije malnutrition ⑪ :  C lymph rodemphatic o struction - Ha is↑ localised as drainage 15 do · edema da24164 Lymphatic s drainage by Lymphatic (drainage d i · Simslymph nodes it - ( Neoplastics I His edema lymphatic drainage ~. lymphatic damage as -- m i postsurgical - Did brest cancer surgery I d is 1 breast s Wil 1iaxilas,lymph nodes I s is S E y iinilaxila lymph nades , 11558Tlymphatic cut ↑ Postsurgical Hig wi ~ - Edema jo11 , drainage Maxila lymph nodes Lymphedema * tis Fibrosis lymih 1) : Postirradiation : po · drainage of  Lymphedema in the arm after left mastectomy (Sislis/1) Ho s /1) Elephantiasis: a case of filariasis in Indian Woman breast cancer 11 - mastectomy is Lymphedemast is & Sills/I : edema axillary lymph node g left side 1 I is NEW ! G -- jsig · Ivangisseg inflammation Jus : is ll filaria - parasite in filariasis - - ~ - inguinalymph node 11 s inflammation 5 25 I. - Lymphatic drainage 5 Box's inquinaHlymph nudesi, is infibrosis inflammation Isbe - elephanti d N - : S - & ↑ - filariasis,i elephantasis  Sodium retention: 1- Excessive sodium intake with renal insufficiency 2- Increased tubular absorption of sodium a- Renal hypoperfusion b- Increased renin-angiotensin- aldosterone secretion Inflammation: 1- Acute inflammation 2-Chronic inflammation 3- Angiogenesis 1S : Edema 11.spiads will Sodium retention - So Kidney function s NJ li : Excessive sodium intake with renal in sufficiency i edema so %(2 il 95 A ii. s as)) 99:11 - is Kidney Hi - Madis heart failure · , hypoperfusion 15) millil Kidneys blood supply 11 lig 11 -jij renin 18 renin angiotensin aldosterone Secretion si;dais , & ~ : lung 11 & g Angiotensin I s o Angiotensin 1 &1 Angiotensinogensid as Kiddey /I. ↑ Angiotensing in Angiotensin I 11 -a converting enzyme dis is - blood vessels / is vasoconstriction ~ - & Is Angiotensing Adrenal gland 1 aldosterone 11 jigigs or · Kidneys is ! / & 55 Aldosterone its. · Higedema d *E S : inflammation - edema in fonsili tonsil - is inflammation distil · - edema is inflammations A ·;&"renin ~ 18 : renin angiotensin aldosterone secretion It lung 11 & g. Angiotensin I s o Angiotensin 1 &1 Angiotensinogen sid Kiddey /I as Angiotensing in Angiotensin I 11 -a converting enzyme so s - blood vessels / is vasoconstriction ~ - & Angiotensing Is Adrenal gland 1 aldosterone 11 jigigs or Kidneys is ! / * Es Aldosterone ·. is  Hyperemia and Congestion Hypermemia: - It’s an active process that results from increased blood flow because of arteriolar dilation. - Tissues that have hyperemia means that they have more oxygenated blood and will appear more red Congestion: - It’s a passive process. It may result from impaired venous return from the tissue involved - Tissues will have deoxygenated blood - Causes may be systemic: cardiac or hepatic - Examples: 1- chronic passive congestion of liver within arteries , within veins Mis g Hyperemia and congestion I I arterioles iii dig arteriole / - - I esd Hypermenia - : & s issue 11 flow 11 gist/ active process & &s arteriolar dilation /I S , - stis Big Wijli hyperemia ·tradition has - venous end 5 e9 i i organ w arteriolarend I set : congestion 11-. 11gEs ·. z - venousblood organs venous return zi , tissues :5 dids & Venous blood 110 is - · co2 siblue & %diy passive - process d is & congestions / : Heart failure is Milit insystemic -jos blood sits j so blood a 31 eS / &hearts & venous return Des is vein/ s blood d I Jobs 14 i hepatic as - &jet liver is es Givenous return ,. el - · livers S &d  langst sliver sis congestion se : In chronic passive congestion, there will be: 1- Pooling of poorly oxygenated blood 2- Hypoxia to poor oxygen supply due to impaired circulation 3- Death of the parenchymal cells in that tissue 4- Persistent congestion of the capillaries will cause their rupture, resulting in foci of hemorrhage 5- Red cells fragments and necrotic tissue will be phagocytosed resulting in aggregates of hemosiderin- laden macrophages. pooling of poorly oxygenated bloodI as ·I& chronic congestion 1 00: 51 ~ Is bloody &S ↑ circulation I s Could - O , as venous Wh & arterial blood J i arterial blood& organs? Scapillaries /Is , Sh des hypoxiai Lit ~ -shemorrhage s rupture of capillaries & Sidi's venous bloods- I - : venous blood J15 I 858n , necrotictissue jirbes 1 hemorrhageis Dred cells 11 /RBIS RBCs I aw phagocytosis on macrophages - I g ↑ hemosiderin 1 is #? is chronic congestion s do s I - - rupture of capillaries, necrotictissue , s hemosiderinladen macrophages is Dog S left side failure is - Hail Heart failure / suss & 06s ·↳ organ st :05 right side heart failures 11/14 Lung It's congestion , congestion liver I & Right side heart failure/1.in liver manifestation :· - left side heart failure/18 manifestation i. Lung -  Examples: I- Acute pulmonary congestion: is characterized by - alveolar capillary congestion - alveolar septal edema - focal intra-alveolar hemorrhage II- Chronic pulmonary congestion: - the septa become thickened and fibrotic - alveolar spaces may contain hemosiderin laden macrophages (heart failure cells) ~ & left side of the heart failure or any pulmonary congestion 110 Dig -isj & Glit - pump /10sing bloods ↑ 1 Alsiggigi's · alveolar capillary congestion - alveolar septal edema r focal intra-alveolar hemore, hemorrhage Ed. Capillaries/ a macrophagess lung fibrosis 1 hemorrhage /1 Chronic B , 116* to g - , , ↓ - 1244 RBC /Mas hemorrhage I SIRBC 165% 1 - - hemosiderin heart failure cells hemosiderin st? macrophages& alveali 11 it,  Pulmonary congestion with dilated capillaries and leakage of blood in the alveolar spaces. Note the heart failure cells filled with hemosiderin pigment from the breakdown of RBCs 10 gas jin pulmonary circulations Heart failure is - capillary I i congestion & yel left side of the heart , RBCs / zijj , hemorrhage Jess Micedema - jadalvedi 11 - hemosiderin macrophages11- % Heart failure cells insid Heart failure 1s abnormality 11d dis ? heart failure cell sig in : I alredist it's :gljd hemosiderin laden macrophages 11 He His is I pulmonary edema ·  III- Acute hepatic congestion: is characterized by: - the central vein and sinusoids are distended with blood - there may be central degeneration of hepatocytes - the peripheral hepatocytes suffers lesser degree of hypoxia, but may suffer fatty change distended with blood a a central vein Slacute & liver It's congestion 11 ↑ : hypoxia , degeneration in main did d hepatocytes Joe disease sigil &11 %. Peripheral is 5 severe 05 hepotocytes 114 & 9. liver 11 ik is gon venous return gestion hepatic congestions failureJo.Not "A blood&S1- & heart - pumping - II as 99 ja venous return - livers is mainly g congestion - -- : s sign u es livers it's central veins and sinusoids it's - [ * 15 Scentral. veins10 sheart 111 drainage My i bleedings = central vein 11 s rupturescis oxygenated bloodJe got hemosiderin laden , macrophages ---- · ↑ , · iss hypoxia Ms /, liver 11 go centrilobular ng · zone three t Wil veins ~ ↳%15 zone one s arteviole 1 Id Edw  III- Chronic passive congestion of liver: - the centrilobular areas are congested and look red-brown in color - There will be hepatic cell necrosis and cell drop out - There will be hemosiderin laden macrophages - There may be evidence of fibrosis in long standing cases (cardiac cirrhosis) - In cases of shock (reduced blood perfusion) the centrilobular areas are the first to suffer chronic passive congestion a hepatic congestion sidy rupture of capillarywasus congested centrilobular , jes /gla · hemosidrein) JRBCs May red-brown color blood , By se] i hepatocyte is necrosis ses hypoxia Bes De aygenetedi hemosiderin-laden macrophage sci chardiac cirrhosis Se fibrosis " long standing It is a Nutmegpatter I &j'52 Minds reduced blood perfusion 2 shock & a centrilobular areas  congestionstun liversin ·is &N Nutmeg liver ↑ I a red brown d Nutmeg/ isidid s bleeding  Hemorrhage - Hemorrhage simply means bleeding - - Bleeding may occur due to clotting disorders, or from trauma - Capillary bleeding can occur because of ~ - congestion, tissue injury from trauma, or inflammation - - Bleeding may be external or internal, within the tissues - Collection of blood within a tissue is called hematoma. Large hematomas can be fatal - Bruise is a type of insignificant hematoma RBCs nextravasation is bleeding : Hemorrhage & · is est , In ii S blood vessels a Clotting disorder tranmas one bleeding - - - , not's clut jaw is ↳ Si , rupture % glbi in jis longestion & bliltuyd-ll Capillary S. ~ - - ~ & soss I blood vessels or inflammations bleeding o frauma is bleeding , b leeding Skin Basi Urine Il , Vaginally stool 11, W :II pr Now - circulations Shock & , s) Stay disblsblhematoma slid organis i lik & & is jos, , - Sijjaisbal sabain hematoma - & insignificant hematoma-Bruise I  Significance of bleeding stems from the amount and the place where bleeding occurs. Small amounts of bleeding in the cranial cavity may be fatal, whereas, 1.5 liters of blood in the stomach may pass unnoticed by the patient. Rapid bleeding of up to 20% of total body blood may be compensated for by the body and does not cause serious clinical manifestations Slow bleeding may result in iron deficiency anemia. This is very important point to keep in mind particularly in elderly people significant of bleedings % significant postbleedings's , , used ? ·piis bleeding ·pleindia: amount of blood losed. ignificant a S inSi ii, significant - ~ Eineda ar wil agl place - S : of where bleeding occurs a - Stomach Lig diningL , N :⑤ location of bleeding 1 , : 2 significant Issu/it , neck, I brain does jes · je rateslo, dini 2 is digitis bleeding si j : fatalinas 15. Grate 04 s Migh · bleedingsto = dis van was iron deficiency anemia t a aldis n , - slow bleeding I I +340549 S 8· & - Stool /1 Jigyds colon cancer & Isid. - -. jijijs elderly enemial 1 Sibli , anemiaripidest ·Bi sg, mis deficiency d animal 2 iron : , YicanceroI So i /Bill &  - Small hemorrhages of 1-2 mm into the skin or mucous membranes are called petechiae - Petechiae are caused because of: 1- increased intravascular pressure 2- low platelet count 3- defective platelet function & 4- clotting factor deficiency morphology of hemorrhages o is I mucous membrane jo ,112 & very small in size - hemorrhage It's Blisslips &gloral cavity - ↑ 1 / , be gas 1-2 mm e dat petechiae bleeding - · petechiae Nic intravascular pressure ↓Ssj -1 -gdj&1155 - - /13 · it 41s 19 4 , & -  -Purpuras: larger hemorrhages: 3-5 mm - these hemorrhages can happen because of the same reasons as in the case of petechiae, plus: - vascular inflammation (vasculitis), and increased vascular fragility purpursal si bleeding Gy 3-Emm - jus larger hemorrage & purpuras Jo abnormal platelets , low platelets function Is By 10, blood J /1 blood vessels It's inflammation al vasculitisis just - = blood g blood vessels soft ifragility its  - Ecchymosis: are subcutaneous hematomas or bruises 1- They are 1-2 cm in area 2- the erythrocytes in these hemorrhages are phagocytosed and degraded. 3- Their hemoglobin, red-blue in color will be converted to bilirubin, which is blue green in color 4- Eventually, bilirubin will be converted to hemosiderin, a golden-brown colored material substaneous tissue 11. %s bruises ,I hematoma 8. : Echymosis 11-2mm) 558 D ↑ ssvs I fresh its hematoma 1 iboi - I venous blood is in Gij &Wh slis blood Vessels s , ↳did bilirubin ~ - &2 - ins I #: & echmois1 # golden-brown ed hemosidering bilirubin b - _ 3 · Session  · d - Larger accumulations of blood: 1- hemothorax: blood in the pleural cavity 2- hemopericardium: blood in the pericardial cavity 3- hemoarthrosis: blood in the joint Wapists hemophilia 11 · 4- hemoperitoneum: blood in the peritoneal cavity  - Hemostasis: the process by which the blood is kept in the clot free fluid condition within the blood vessels - Thrombosis on the other hand, is the opposite of hemostasis. It’s the formation of a thrombus (blood clot) in intact vessels or after a minor injury pa a within the circulation o joi on 7 so& &as , T 7 Hemostasis i descriptions Is Hemostasis /:: clut / Swimdis & : · · Physiological s & I break blood vessels s hemostasis (850. Thrombosis s pathological · ·. 5 ] Hemostasis 11 4 & Thrombosis 11 :  Normal Hemostasis Sequence of hemostasis: I- Vasoconstriction - Immediately after injury there is an initial vasoconstriction. - This is stimulated by the release of endothelin from the endothelial cells. - The endothelin is an important vasoconstrictor · · : Homostasis gen i * - & EP blood vesselsing CapillarySis⑤ &slv : si jiji Normal hemostasis/I , i n - & ↑ j * - & - jls, normal - hemostasis - i - & initial vasoconstriction - Calli ↑ : vasoconstraction T J vasoconstriction / 9 S , o jd blood vessels, EN 1 & as vasoconstriction s so endothelin Its jigh endothelial cell /1st blood vessels & t blood vessels/12 lumens s i ? Vasoconstriction 10 - ! blood - 5 * 18 S Endothelin 119  mainly collagen idEcMomisnblood rese line endothelial Sel - ja S I cells is & ~ --- · -  II- Primary hemostasis 1- Activation of platelets after getting in contact ECM which is a potent thrombogenic factor 2- Activated platelets undergo shape change and secrete granules to recruit more platelets · I I platelets di des primary & : hemostasis (2) activated platelet 1,50 - injury it's sit , ! ↑ 11 ↑ =81 granuleslejigs damage - 5I & Sithromboxin -. recruit more platelets -Sin Al ADD ,. , ,g n granules ~ · lls Weis ECM s a bj Platelet M got EA5 high ability , Von Willebrand factor VWF s ECM / bj is s &splatelets/ , ECM 11 918 al - s. / , +4) !. j 4 binds - · Platelets JI  · begi # a S $15 AA platelets adhesion. 0 flat i CADP , TXAt id granule Ji. recruit more platelets ? Granules ⑪ (pimary plug) : s Slig AggregationM s Platelet /15. platelets /I 28 willing time Bets / primary hemoltasis /18 · · secondary hemostasis /s lis  III- Secondary hemostasis This process is brought about by the tissue factor which has the following characteristics: - is a procoagulant factor - synthesized by endothelium - is released at the site of injury Along with activated platelets, tissue factor stimulates the coagulation cascade that culminates in the formation of a meshwork of insoluble fibrin clot i. : dplatelet /1000 : Secondry hemostasis 1 ? it coagulation cascades o is endothelial cell slog V : 55d tissue factor 1 -Bill S origins ~ 24 procoagulant factor ins - / = stimulation - I - activated issuefactorsi - - platelets /I j fibrin /As 1811-918 endothelial cell 11 hemostasis J% 5 & 13 factor i coagulation cascade &3 coagulation factor 12 $11 stabilization & 13s- jej) primary hemostasis / &3050 platelets 11. & I rufas receptor · as I extrinsic pathway, I intrinsic pathway fibrins/ as receptor yes & % secondary hemostasis /18 its · fibrin /16 & Pos jual , tissue factor o And, 15%  IV- Antithrombotic counter regulation: - anticoagulation mechanism is triggered after the formation of permanent clot by polymerization of fibrin and aggregation of platelets - tissue plasminogen activator (t-PA) is activated to prevent further expansion of the clot - 20 ends adjustin &sil n & : ]/ · jijl is thrumbus Antithrombotic counter regulationa e W - plasminogen s1*i /T-pAltissue plasminogen activator - S Bid & block coagulation cascade - Insid fibrin /I n fibrinolysis - plasmin I 1) S25/1 i j - / clot &d coagulation cascade  Endothelium - The endothelial cells normally posses antiplatelet, anticoagulation, and fibrinolytic properties. - If the endothelial cells are injured or activated, they develop procoagulant functions - Example of such activators: IL-1 and TNF. These cytokines increase procoagulant activity, and decrease anticoagulant activity - Endothelial cells are stimulated by: 1- cytokines: IL-1 and TNF 2- plasma mediators 3- infectious agents - The balance between anticoagulant and the procoagulant processes will determine whether thrombosis or containment of the coagulation process will take place and when clut ' platelets & S i Endothelium a & · ECM /lg zjgjls gl : jipoj Injury 15001 p ! I - clot &s s bis in coagulation factors i AnticoagulationQ ↑ · /li Antiplatelets ② degradation j o fibrin l fibrinolytic properties & · wwI : jjs +, 180 injury vasoconstriction s - enduthilen s i l i procoagulant ~ primary hemostasis 11 Platelets I & &. 28 , VWFD secondary hemostasis /Is tissue factor Its fissue plasminogen activator slits endothelial cell11 ,silin, cytokines 12.1 TNFV : 3 procoagulants , plasma mediator infections agent thrombosis y procoagulationS anticoagulation 1 1% : blance on endothelial cell 11 thrombosis J anticoagulations & procoagulations tile  Endothelial cells synthesize:  Endothelin: vasoconstrictor  Tissue factor: activate the coagulation cascade, the extrinsic pathway  PGI2 and Nitric oxide: vasodilators and inhibit platelet aggregation  Adenosine diphosphatase that degrades ADP and further inhibits platelet aggregation  Heparin like molecules: allow antithrombin to inactivate thrombin, factor Xa, and other caogulation factors  Thrombomodulin: convert thrombin from procoagulant to anticoagulant  T-PA promotes fibrinolysis of the fibrin clot  Secrete plasminogen activator inhibitors which depress fibrinolysis  vWF that helps bind platelets to collagen 7i s + Jendothelial Cell Big procoagulant : clots % - clots jeis anti it big ne · procoagulants Sl , anticoagulant Bird Anticoagulation procoagulant Sj & vasoconstrictor - Endothelin- vasodilator : PE12 and Nitric oxide-coagulation cascades& Tissuefactor - platelets 11:1S extrinsic pathway nis & &.: (ADPase) Adenosine diphosphate - · Platelets 5 - ADP 11 & platelets 69. Es UWF- Fibrinolysis & ↑ : T-AP- collagen 11 · T-AP/1 ↑ : plasminogen activator inhibitor - · Na factor,11 5S: Hipariu like molecule thrombin - & % still thrombin 116gs Thrombodulin- : Anticoagulant i procoagulant n  - [ ~ & factor D - s - se 155s · ⑰  Antithrombotic properties of endothelium ①  Antiplatelet effects: normal endothelium does not allow platelets to adhere to its surface If endothelial surface is injured and ECM is exposed, this activates platelets and stimulates adhesion. The reason is that ECM is highly thrombogenic PGI2 and nitric oxide inhibit platelet aggregation, and inhibit platelet adhesion to uninjured neighboring endothelium. Synthesis of these two potent vasodilators (PGI2, Nitric oxide) is stimulated by thrombin and other cytokines Endothelial cells secretes adenosine diphosphatase which degrades ADP and further inhibits platelet aggregation i b antiplatelets 5 endothelial cell/ 560 / Antplatelets effect-1 : platelets ne 8. ECM 12 exposure dis is i j ' platelets adhesion s 11 jis & enclothelium si. platelets / vasodilator Nitric Oxide , PEL2 ① platelets 119 34. ADP N &: (ADPase) Adenosie diphosphate ②  ② Anticoagulant properties:  Endothelium prevents coagulation by two receptors that are present on its surface: 1- Heparin like molecules: act indirectly as a cofactor to allow antithrombin III to inactivate thrombin, active factor Xa, and some other coagulation factors 2- Thrombomodulin: binds to thrombin, and convert it from procoagulant to anticoagulant, that activates protein C (an anticoagulant). Activated protein C inhibits clotting by cleaving factor Va and factor IIIa. This step requires protein S as a cofactor. Protein S is produced by the endothelial surface : two receptor th oil s anticoagulat i endothelia cell/· 2."In antithrombin N2 heparin / 00 Heparin like molecule ① % : - some other coagulation factor s factor Xa N inactivate , thrombin /15 -thrombin /1 Jjs is thrombin. /155 receptor 1 ,8 : Thromboduling As & b , lon thrombin 11/AnticoagulantI procoagulant sands I cleaving factor s Anticoagulant was protein scofactor protein - I protein, S , is clearing It is - i Proteins Mendothelial 1). %  ③ Fibrinolytic pathway: the mechanism by which an already formed clot can be remodeled and removed during the course of vascular repair  Plasminogen (produced by liver) is activated by plasminogen activators (produced by endothelial cells) to plasmin. This step is downregulated by plasminogen activator inhibitor-1 (produced by the endothelial cells and platelets)  Plasmin, a serine proteinase, degrades the fibrin clot to fibrin split products, D-dimers. This step is downregulated by alpha- 2 plasmin inhibitor (produced by the liver) ↑ I removel &1, remodeled isdiginsis Fibrinolytic pathway ⑤ : vascular repairdis *** (permenant clot 2) already formed clot , plasminogen activator 115 activateds Vliver /1 so i Plasminogen Q : plasminogen & 18 plasmin 51js lendothelial cell 11. / activated inhibitor -si- /08, (D-dimers) split product 1 fibrin /1 B Plasmin : & Alpha 2-plasmin inhibitor  Prothrombotic properties: this property is triggered whenever endothelial cells are activated or injured  Platelets adhere to the exposed collagen in the endothelial surface. This is facilitated by vWF secreted by endothelial cells  Endothelial cells also secrete tissue factor which activates the extrinsic pathway  Endothelium also secretes plasminogen activator inhibitors which slows down fibrinolysis activated Gas endothelial prothrombotic properities/ : /D : of J Ed ig14m platelets Id 11 is I prothrombotic factor a fissue factor jig Ms. endothelial cell 11. extrinsic pathway Fibrolysis Add's plasminogen activator inhibitor;i Ms. endothelial 114  Platelets Platelets contain two types of granules: I- Alpha granules: these granules contain the following proteins 1- P-selectins 2- Fibrinogen 3- Fibronectin 4- Factors V and VIII 5- PDGF 6- TGF alpha II- Delta granules which contain: 1- ADP 2- ATP 3- Ionized calcium 4- histamine, serotonin, and epinephrine I primary homeostatic clot & ↑ side-platelets He Pathological thrombosis 1, Jos I, bleedingit i! two type ofgranules Wes , 9. enucleated cell is i platelets I --- Alpha granules Delta granules a Pr selectins (inflammation 1000:2) & ADD more platelets & Fibrinogen a , fibrin sisd1, coagulation factures ↑ ATP · clot / is insoluble a Fibronectin secondary hemostasis) & lonized calcium & factors 5 and 8 a histamine , serotonin * PDEF epinephrine & TEF Alpha  At injury site, platelets come in contact with ECM and they undergo some changes like: 1- adhesion and shape change 2- secretion 3- aggregation ECMydy platelets i is endothelium/s injury 11 s , mainly collagenc is Shapes v & VWF is in platelets a ADD i secretion Ill ~ · thromboxin Az /l, aggregation for more platelets + ~ ↑ · d  MMM - - · En widely j is Platelet adhesion:  Adhesion of platelets with collagen in the ECM at the time of injury is facilitated by vWF.  vWF act as a bridge between platelet surface receptors Ib protein and the exposed collagen Secretion: This involves secretion of both types of granules Platelet aggregation:  TXA2 (secreted by platelets) is a potent stimulus for platelet aggregation. This is the primary hemostatic plug and is reversible  Thrombin which is formed in the coagulation cascade, binds to platelet surface and with ADP and TXA2 causes further platelet aggregation , followed by platelet contraction and becoming irreversible. This is the secondary hemostatic plug  Thrombin convert fribrinogen to fibrin that adds to cementing of the plug platelets adhesion When & - *lis - /54 , platelets a jat : ) ~ is exposed , platelets , Ub protein n i, unf , J (ADP TXAz) granules 11. , sili , secretion as % Platelets/1 platelets aggregation mes - platelets /Jojig TxAc platelets aggregation ↑ / : coagulation cascadesii i, reversibles primary hemostasis plug I & 55&. platelets 17 & b5-coagulation cascades is - % : Thrombin plateletsi Is platelets aggregation , 2 3 TAs ADD/ & I - ↑ secondary hemostasis plugs No s irreversible zos · N komenting plug fibrin si fibrinogenside Thrombing  GpIIb-IIIa:  Is another important glycoprotein receptor present on the platelet surface.  This gylcoprotein is activated by ADP to bind to fibrinogen.  Fibrinogen then becomes the bridge that connects several platelets together : EPIb-Ia /I platelets in fibrinogens e bis , ADDI activation a platelets Is platelets / %.S. bridge fibrinogen  = 51 & - Sprin & glycoprotein - Ib 10 VWFJI plateletssis EPIba a platelets , platelets d. bisa EPIba13sPlatelets bla · receptor /1st giss VWFS es 45 , platektisivonWillebrand dise ab Epib sid : Brenard-soviler syndrome EPIb-a 11 S Flanzman thrombosthenia bleeding , :  -1 - X Coagulation Cascade It’s composed of two pathways:  The intrinsic pathway initiated by the activation of Hageman factor  The extrinsic pathway which is activated by the tissue factor It’s a series of reactions in which inactive proenzymes are converted into active enzymes This results in the formation of thrombin, that converts the soluble fibrinogen into insoluble fibrin Clotting is regulated in a way to be confined to the site of injury by two mechanisms: 11.3& I coagulation cascades jsd clot st Wr fibrin six - ~ hi is n factor is de coagulation factor : two pathways & coagulation cascades factor 8 common pathway18 eg 5.. 9 11 12 : intrinsic , , pathway - tissue factors Do factor 7 bs@ extrinsic pathway common pathways es 69.s :. - common pathways so -j jajly , , : coagulation cascades no factor a d fibrinogens des thrombing 8%, Factor 2 ad , , thrombing biss. I fibrin 51 · a clut / 81 s insoluble so fibrin Jes X Antithrombins: (antithrombin III).  It inhibits the activity of thrombin, factor IXa, Xa, XIa, and XIIa  Antithrombin is activated by binding to heparin like molecules on endothelial cells Protein C and S:  They are two vitamin K dependent proteins  They inactivate cofactors Va and VIIIa : antithrombosis 5 S1GI's. ↑ thrombin/J& - ↑ : antithrombin T enclothelial / ye & Heparinlike molecules & &4 jis. vitamink dependent protein :,gd : protein cands - factor 5. 8 Jo 1 Is congulation cascade 1b 68 /it Y  ↓ At the same time coagulation cascade is initiated, along the same path, the fibrinolytic process is put into action for the purpose of restricting clotting to the site of injury This is achieved by the activation of plasmin Plasmin is obtained from the precursor plasminogen either by IIXa or by plasminogen activators( the most important is tissue plasminogen activator (t-PA) which is synthesized by endothelial cells Plasmin breaks down fibrin producing fibrin split products Free plasmin is inactivated by alpha 2 antiplasmin to control its action Fibrinolysis is blocked by Plasminogen activator inhibitors hemostasis 11: %Di od , fibrinolysis in ~ coagulations - I i ~ - blood vessels/ is il is to - (2mm & Clot /semm will - Fibrinolysis/t-5% d s thrombosis S , gold 49 · plasmin , bioplasmin/1d ? Filerin 11 s Fibrinolysis E tissue plasminogen activator/ 1) > &sendothelial /rjig sid · plasmin plasminogen ID dimer) fibrin split product = j &1 fibrin s plasmin/in - - alphazantipasmin din inactivation is plasmin  Thrombosis The most important factors that trigger thrombosis are: 1- Endothelial injury 2- Stasis or turbulance of blood flow 3- Blood hypercoagulability ⑰ I- The endothelial cell injury: as may happen in atherosclerotic plaques - Loss of endotheliumleads to exposure of ECM, adherence of platelets, release of tissue factor, local depletion of PGI2 and t-PA - Injured endothelium may elaborate adhesion molecules to bind to platelets, and PA inhibitors · Tis y : thrombosis Clinically * (Pathological) in - s - &13 1 thrombosis 1 zis · JECMs I. J; s endothelial injury G I S -just i jg injury 4Dis abnormal Soy abnormal blood flow ② : thrombosis S1 · is JS-Sy 8,5/1/ Dis - &I coagulation / Dis : Hypercoagulability thrombosis 116s Is' % : , jigly -51j atherosderotic plaques /1. %25 : Endothelial cell injury T I (ECM) &. exposure didng loss of endothelial - Sigj4g , Intimas -- I obstruction of lumen d is platelets & His - Bit · produce adhesion molecule and 6 loss of endothelial cell 1 PA inhibitors. Exposure of ECM-2 Adherance of platelets > tissue factor Release of 4 PEI2 (vasodilator) and T-PAlfibrinolysis) 5 5582m 3 · - , X Mis.  - Sometimes, endothelium may cause thrombosis without being atherosclerosed or injured. It may become dysfunctional due to: hypertension: bacterial endotoxins Radiation hypercholesterolemia homocystinuria Toxic substances from cigarette smoke endotheliams & damage thrombosis in we give 4 girl : endothelial injury i , is hypertension ① vasculitis It sad bacterial encotoxins ② Lis Ding thrombosis /10 & Radiation ③ : 9. ,. s heparin Hypercholestrolemia just is &S abnormal protein Homocystinuria & : Atherosclerosis /I & &1 & : Toxic substances &  ② Alteration in normal blood flow: - Flow of platelets in the blood current is laminar - Turbulance or stasis will result in the following effects: a- disturb platelets and bring them closer to the endothelium 10 b- retard flow of clotting factors c- promote cell activation and leukocyte adhesion / Od- delay the arrival of clotting factors · East Si ↑ : Alteration in normal blood flow ③ · i wis S o 8 S, stasis , &D ↑ d Turbulance sm - : & Je S. 98 &jw/14/4 , bring them clocer to the endothelimg & cloting factor G I : GN - 10 and activation leukocyte / - · thrombosis 5 d , 151 thrombous , & ) Embolis &165in thrombous 11 8 - (ii D , · Embolism s assistin  Examples: 1- Arterial aneurysms are preferred sites for thrombosis because of slowing of circulation in these areas 2- Dilated left atrium due to stenosed mitral valve is a favored site for stasis and turbulance. With atrial fibrillation chances are higher : thrombus o sym nenrymArterialaneuya I ↑ I : - - -I ↑ S , - 1 aneurysms /Jess will &H W & thrombosis I atrium is ↑ mitral spirosis Dilated left a trium value : 2 - & s ventricle Jig glas atrium / 51 is is ventric is & - , thrombus 5 is is disy's stasis , Satrium /Ess ~ ~ Digi & - fibrillations jiji l thrombuss O - - ↑ · emboli & thrombus II  ③ Hypercoagulability: I- primary causes 1- Factor V mutations 2- prothrombin mutations 3- Antithrombin III deficiency 4- protein C and S deficiency coagulation cascade list ; & : Hypercoagulability ↳ 5 coagulation cascadeJ eg /, --- secondary causes (primary 1 commons. 8) primary causes -- common jejtjn L - 1 1/14) factor mutations High risk prothrombin I mutations & Fre bed vets Antithrombin I deficiency a prolonged I 1554 14] protein cand s deficiency ④ , , 8= /188 & infarction T 2-mycocardial - 3 -995 o - 3 Tissue damage -5 In thrombosis Es Mis low risk 4-cancer NI Sslyl s · I wo 5 prosthetic cardiac values