hemodynamic disorders chapter 4 Flashcards
what is edema
accumulation of fluid resulting from net movement of water into extravascular space
What is hemostasis
process of blood clotting preventing excessive bleeding after blood vessel damage
in appropriate hemostasis
1- Thrombosis
2- embolism
3- infraction
–> causing myocardial infraction, pulmonary embolismand stroke
how is edema developed
- the vascular hydrostatic pressure to push water and salts out of capillary is nearly balanced with the tendency of plasma colloid osmotic pressure to pull water and salts back to capillary
2- when there is high Hydrostatic pressure or low colloid osmotic pressure, it will cause leakage out of capillary into interstitial spcae and edema, and if it involved serosal surface, it is called effusion
inflammatory edema
1- protien-rich exudates accumulate due to increase in vascular permeability caused by infalmmatory mediators
Non-inflammatory edema and effusion
poor fluid accumlation called transudates
causes of edema
1impaired venous return increased Hydrostatic pressure
2Arteriolar dialation increasing hydrostatic pressure
3: hypoportienemia causing decreased osmotic pressure
4- lymphatic obstruction
5- sodium retention
6- inflammation
what is the causes of icnreased hydrostatic pressure
caused by impaired venous return, if the impiarment is localized like in Deep venous thrombosisit result in localized edema
- condition increasing venous pressure will cause more widespread edema
causes of reduced plasma osmotic pressure
1: inadequate synthesis or icnrease loss of albumin
in cases like cirrhosis, protien malnutrition, nephrotic syndrome
Causes of Sodium & Water Retention
Primary kidney disorders
Cardiovascular disorders (↓ renal perfusion)
Congestive heart failure (CHF)
Effects of Sodium Retention
✔ ↑ Hydrostatic pressure → Due to increased intravascular fluid
✔ ↓ Colloid osmotic pressure → Due to plasma dilution
Role of the Renin-Angiotensin-Aldosterone System (RAAS)
🛑 Activated in response to ↓ renal perfusion
⚡ Increases sodium & water retention
💧 Leads to fluid overload → edema & effusions
4️⃣ Early vs. Late Heart Failure
🔹 Early Heart Failure
✅ Sodium & water retention helps restore cardiac output & renal perfusion
✅ Increased vascular tone & ADH release support circulation
🔹 Late Heart Failure
❌ Excess fluid retention worsens hydrostatic pressure
❌ Leads to edema & effusions (fluid accumulation in tissues & cavities)
lymphatic obstruction causes
trauma, fibrosis, tumors, infectious agents causing lymphedema
what is filariasis
parasite induce obstructive fibrosis of lymph nodes resulting in edema in external genitalia and lower limbs called elephantiasis
Edema: Gross & Microscopic Features
✅ Clearing & separation of extracellular matrix (ECM)
✅ Subtle cell swelling
Types of Subcutaneous Edema
ypes:
✅ Diffuse or localized (high hydrostatic pressure areas)
✅ Gravity-dependent (dependent edema):
Legs → Standing
Sacrum → Lying down (recumbent position)
✅ Pitting Edema: Finger pressure leaves a depression due to fluid displacement
Edema in Specific Conditions
💧 Renal Dysfunction → Periorbital Edema
Appears in loose connective tissue (e.g., eyelids)
💨 Pulmonary Edema
Lungs 2-3× normal weight
Frothy, blood-tinged fluid (air + edema + RBCs)
🧠 Brain Edema
Narrowed sulci & distended gyri
Compressed by the skull
Types of Effusions (Fluid Accumulation in Body Cavities)
📌 Common Types:
✔ Pleural cavity → Hydrothorax
✔ Pericardial cavity → Hydropericardium
✔ Peritoneal cavity → Hydroperitoneum (Ascites)
📍 Types of Effusions:
🔹 Transudative Effusion (Protein-poor, straw-colored)
🔹 Chylous Effusion (Milky → Lymphatic blockage)
🔹 Exudative Effusion (Protein-rich, cloudy → WBCs present)
what is hyperemia
active processs in which arteriolar dialation happens in SkM or inflammation causing erythemea due to increased delivery of oxygeneated blood
What is congestion
Passive process from reduced venous outflow of blood from tissue and it can be systemic like HF or localized like venous obstruction and it results is cyanosis due to accumulation of deoxygenated hemoglobin
Types of congestion
1Acute pulmonary congestion
2Chronic pulmonary congestion
3Acute Hepatic congestion
4- Chronci passive hepatic congestion
Morphology of acute pulmonary congestion
cute pulmonary congestion: enlarged alveolar capillaries, alveolar septal edemaand focal intraalveolar hemorrhage
morphology of chornci pulmonary congestion
congestive heart failure, septa is thickened and fibrotic and alveoli contain macrophage laden with hemosiderin Heart failure cells from phagocytosed RBCs
acute hepatic congestion
central vein and sinusoids are distended because the centrilobular area is at distal end of hepatic blood supply
the centrilobular hepatocytes udnergo necorsis and the periportal hepatocytes are better oxygenated and may develop only fatty chnage
Morphology of chronic passive hepatic congestion
the centrilobular regions are red-brown and depressed due to cell death and are accentuted against surround zone of uncongested tan liver ( nutmeg liver)
What are the steps of normal hemostasis?
1- Arteriolar vasoconstriction
2- PRimary hemostasis
3- secondary hemostasis
4- clot stablization and resorptionn
arteriolar vasoconstriction of Normal hemostasis
- occurs immediately and reduces blood flow to injured area
- mediated by reflex neurogenic mechansim and augmented by local secretion of factors like endothelin
Primary hemostasis
- formation of platelet plug
- disruption of endothelim exposes subendothelila Von willebrand Factor (vWF) and collagen promoting paltelet adherence and activation
- the secreted products recruited more platelets adn undergo aggregation to form primary hemostatic plug
what happens upon activation of paltelets
1- shape change to flat palteltes with spiky protrusions ( inc SA)
2- release of secretory granules
Secondary hemostasis ( deposition of fibrin)
1vascular injury exposing tissue factor (procoagulant glycoprotien expressed by subendothelial cells)
2: tissue factor binds and activates factor VII causing thrombin generation
3-Thrombin cleaves fibronegen into fibrincreating fibrin meshwork and also potent activator of plateletsleading to their aggregation (consildation of intitial platelet plug).
4: Clot stabilization and resorption: contraction of polymerized fibriin and platelet aggregates and forming a permanent plug
what is the function of tissue plasminogen activator ( t-PA)
made by endothelial cells are set into otion limiting clotting to the site of injury and leading to clot resorption and tissue repair
Platelet Function in Hemostasis
Primary Plug Formation → Seals vascular defects
Surface for coagulation factors → Enhances clotting
Types of Platelet Granules
α-Granules:
Contain P-selectin (adhesion molecule)
Store fibrinogen, factor V, vWF (coagulation proteins)
Growth factors: PDGF, TGF-β (wound healing)
Dense (δ) Granules:
Contain ADP, ATP, Ca²⁺, serotonin, epinephrine
ADP triggers platelet recruitment
how is adhesion of platelets mediated?
Gp1b binds to vWF
Gp1a/2a binds collagen
vWF deficiency → von Willebrand disease
GpIb deficiency → Bernard-Soulier syndrome
steps of platelet aggregation and plug formation
1- Gp2b/3a binds fibronegn and platelets form bridges
2- Thrombin stabilizes plug
3- platelet contraction consolidates the plug
4- thrombin converts fibrinogen to fibrin
platelet activation steps
1-Thrombin activates PAR-1 (protease-activated receptor) (G-protein receptor)
2ADP recruits more platelets by binding 2 G proteins (P2Y1 and P2Y12)
3-Activated platelets produce thrombaxane A2 (TxA2)which induces platelet aggregation
platelet aggregation steps
- After activation, the conformational change in glycoprotien 2b and 3a that occurs during activation allow binding og fibrinogen which leads to platelet aggregation
2- thrombin converts fibrinogen into insoluble fibrin cemeting the platelets and creating the secondary hemostatic plug
3- RBCs and WBCs are found in the plug due to P selectin expressed on activated platelets
Glanzmann thrombasthenia cause
inherited deficiency of Gp2b-3a causing bleeding disorder
what is the coagulation cascade
series of amplifying enzymatic reaction leading to depostion of insoluble fibrin clot
what does coagulation cascade depend on?
1- depends on Calcium which binds y-carboxylated glutamic acid residues present on factor 2, 7, 9 and 10 and use Vitamin K to produce y-carboxylated glutamic acid
what are types of cogulation cascade
1- extrinsic. (PT)
2- intrinsic. (PTT)
extrinsic pathway of cogulation cascade
1- the prothrombin time (PT) assa assess function of extrinsic pathway protiens
2- tissue factor, phospholipids and calcium are added to plasma and time for a fibrin clot to form is recorded
extrinsic protiens
Factors 7, 10, 5 and 2 ( prothrombin) and fibrinogen
partial thromboplastin time (PTT) function
- screens function of protines in intrinsinc pathway
- Clotting clotting og plasma is initiated by adding negative charged particles that activate factor 12 ( Hageman factor) together with phospholipids and calcium and time to fibrin clot to form
intrinsic protiens
factors 12, factor 11, factor 9, factor 10, factor 5, factor 2 and fibrinogen
what will deficiencies in factor 5, 7, 8, 9 and 10 cause
moderate to severe bleeding disorders
what will factor 9 deficincy cause and factor 12 deficiency
mild bleeding only –>9
dont bleed and susceptible to thrombosis.
what is the most important factor invivo
factor 7a tissue factor complex because is teh most important activator of factor 9 and factor 9a and factor 8a complex is the most important activator of factor 10
thrombin activities
1- conversing fibrinogen to fibrin, which polymerize into fibril and amplifies coagulation process by activating factor 11, 5, and 8, and also stabilizing secondary hemostatic plug by activating factor 9
2Platelet activation by activating PAR1
3Proinflammatory effects by activating PARs, which mediate inflammation and contribute to tissue repair and angiogensis
4: Anticoagulant effects
Factors limiting cogulation
1- Dilution by blood flow and coagulation factors are removed by the liver
2- Negative charged phospholipids from platelets which are actvated by contact with subendothelial matrix
3- Plasmin
Mechanism of fibrinlysis by plasmin
1- Plasminogen is turned to plasmin by factor 12 depndent pathway or by plasmingen activators (t-PA)
2- plasmin is actiavted once bound to fibrin and it breaks down fibrin and interfers with its polymerization
3- inhibtied by alpha2-plasmin inhibtor
platelet inhibitory effects by endothelium
1- it serves as barrier sheilding plateletes from subendothelila vWF and collagen
2- release of inhibitor molecules like PGI2 and NO and ADPase
what is the source of PGI2
produced by COX1 which is epressed by healthy endothelium with normal flow
What is the source of NO
by endothelial nitric oxide synthase
Anticogulant effects of endothelium
1- thrombomodulin
2- protien C recepetor
3- heparin like molecules
4- tissue factor pathway inhibitor
mechansim of thrombomodulin and protien C in anticogulation
1- Thrombomodulin bind to thrombin and causes it to lose it ability to activiate cogulation factors and platelets and it activates protien C
2- Protien C which is VitK dependent protease binds to it cofactor Protien S and form a complex and it inhibits Factor 5a and 7a
Mechanism of heparin like molcuels in coagulation
1- it activate antithrombin 3 which inhibit thrombin and factor 9a, 10a, 11a, 12a,
mechansim od tissue factor pathway inhibitor (TFPI)
requires protien S as a cofactor and inhibts factor/Factor 7a compexes
fibronyltic activites of endothelium
1- Secretion of t-PA
causes of abnormal bleeding
1- Defect in primary hemostasis ( platelet defect or von willebrand disease)
2- Defect f secondary hemostasis ( coagulation factor defects)
3- generalized fects involving small vessels
consequence of defect in primary homostasis
1- it appears as small bleeds i skin or mucocsal membrane
on skin it is petechiae, minute and 1-2 mm or purapura 3mm or more
it is due that small vessels on skin are prone to rupture by trauma but are fixed immediaately
2- mucosal bleeding like epistaxis, gastrointstinal bleed and excessive menstruation
3- Thrombocytopenia increases risk of intracerebral hemorrhage
Consequence. of defect of secondary hemostasis
1- bleeds to soft tissues ( muscle) and joints ( Hemarthrosis) following minor trauma ( Hemophilia)
consequence of defect involving small vessels
1- palpanle purapura
2- ecchymoses ( brusises) (1 to 2 cm)
- both of them can cause hematoma
- caused by vasculitis, amyloidosis and scurvy
causes of thrombosis
1- endothelila injury
2- stasis or turbulent blood flow
3- Hypercoagulbility of blood ( Virchow triad)
How does endothelila injury induce thrombosis
1severe injury will expose vWF and tissue factors
2infalmmation will shift gene expression on endothelium to prothrombotic (endothelial activation or dysfunction)
3physical injury, infectious agents, abnormal blood flow, metabolic abnormalities (hypercholesterolemia or homocystinemia)and toxins from smoking
what prothrombotic alteration causes
1- procoagulant changes: when endothelial cells are activated by cytokines, it downregulat thrombomodulin and enhcanes procoagulant and proinflammatory of thrombin
- it also downregulates protien C and tissue factor inhibitor
2antifibrinolytic: activated endothelial cells secrete plasminogen activator inhibitors (PAIs), which downregulate t-PA
what alteration in blood flow will cause to thrombosis
1- promote endothelila activation enhancing procoagulant activity and leukocyte adhesion
2- disrupting laminar flow causing platelets into contact with endothelium
3- preventing washout of clotting factors
what diseases with altered blood flow cause thrombosis
1ulcerated atherosclerosis (exposing vWF and factors)
2- aeurysms
3-acute myocardial interaction, which promotes formation of cardial mural thrombi
40 theumatic mitral valve stensosi causing left atrial dialation and atrial fibrialtion, which is a site for stasis and thrombosis
5hyperviscosity (polycythemia vera) increasing resistance of flow causing small vessel stasis
6- sickle cell aemia impeding blood flow, causing thrombosis
what is hypercoagubility
abnormal high tendency to blood to clot by alteration of coagulation factors
what are the types of hypercoaguility
1primary (genetic)
2Secondary (acquired)
what mutations causes hypercoagubility
1- point mutation in factor 5
2- mutation in prothrombin gene
mutation in factor 5 leiden
1- single nucelotide mutation in factor 5
render factor 5 resistant to cleavage and inactivation by protien C causing loss of antithrombotic pathway
2- autosomal dominant
Prothrombin gene mutation
1- singel nucelotide change in prothrombin gene ( G20210A)
2- mutation in 3-untranslated region of prothrombin
- elevated prothrombin and cause 3 fold increased risk in venous thrombosis
other causes of primary hypercoagubility
1- deficncy in antithrombin ( 3, protienC and protien S
- patient present with venous thrombosis and recurennt thromboembolism
Homocytinemia causes accquired and genetic
- elevated homcystein may be inherited or acquired caused by deficincy of cystathione beta synthase
- acquired causes include deficncy in vitB6 and vitB12 and folic acid
causes of acquired hypercoagibility
1- acquiredthrombophilia
2- oral contraceptive
3- pregnancy by increased hepatic synthesis of coagulation factors and reduced anticoagulant synthesis
4- Cancer producing procoagulants
5- age due to reduced PGI2
6- smoking and obesity
Heparin-induced thrombocytopenia syndrome (HIT syndrome)
1- autoimmune disorder by formation of antibodies recognizing heparin and PF4 on actiavted platelets
2- PF4-IgG complex formation and links to Fc receptor on platelet causing recruit of extra PF4 creating more target for HIT antibodies
3- binding og HIT ab to platleltes actiavted macrophage to clear them ( thrombocytopenia)
4- causes necrosis of skin, gangrene of limbs, stroke and myocardial infraction
diagnosis of HIT syndrome
1- anti-PF4 heparin antibodies
2- low molecular weight heparin preparations induce HIT less frequency
3- direct inhibitors of factor X and thrombin remeove risk
Pathogensis of APS
the aPL antibodies are directed against anionic membrane phospholipids or protiens assocaiteed with PL
- anti-Beta2-glycoprotien anitbodies are suscpeted to have major role in APS by activated endothelial cells, monocytes and platelets
- it causes complete activated and inhibition of fibrinolytic processes whihc favorprothrombotic state
Antiphosphlipid anitbody syndrome (APS)
autoimune disease which may come alone ( primary) or with other autoimmune disease mostly SLE ( secondary) ( Lupus anticoagulant syndrome )
- symptoms include recurrent thromboses, repeated miscarrigaed, cardiac valve vegeations and thrombocytopenia
- presentation include pulmonary embolism ( after lower extermity venous thrombosis) , pulmonary hypertension ( from recurrent subclinical pulmonary emboli), valvular heart disease, stroke, bowel infraction or renovascular hypertension
protiens involved in APS
1- cardiolipid
2- beta2-glycoprotien 1
complication of APS
1- pregnancy morbidity
2-venous or arterial thromboses
3- pregancny complciations
Fetal loss caused by APS
not caused by thrombosis but anitbody-mediated interferance with growht and differeenaton of trophoblasts leading to failure of placentation
Venous thrombosis ( phlebothrombosis)
occlusive with thrombus fomring long luminat cast because thrombi form in sluggish venous circulation they tend to contain more enmeshed red cells ( red thrombi or stasis)
morphology of thrombi
1- lines of Zahn which are pale platelet and fibrin deposits
2- Mural thrombi in heart indicating arrthymias, dialted cardiomyopathy and myocardial infraction or myocarditis or catheter trauma
3- ulcerated atherosclerotic plaque and aneurysmal dialtion –> aortic thrombi
arterial thrombi
oxxlusive to cornary then cerebral then femoral arteries
thrombi on heart valves
1- vegetations which may be infected or sterile
blood-brone bacteria or fungi can adhere to damadged valve ( rehuamtic heart disease) or may cause valve damage directly and it can cause large thromboti mases ( infective endocarditis)
- sterile vegeations can develop on noninfected valves in persons with hypercoaguble states called nonbacterial thrombotic endocarditis
- SLE can cause libman-sacks endocarditis
Postmorten clots
sometimes mistaken of antemorten venous thrombi
- clots formed after death and have dark red protion with red cells settled by gravity and yellow chicken fat upper portion
Fate of thrombosis
1- propagation: thrombi accumlate additonal plateltes and fibrin
2- embolization: thrombi dislodge and travel in vasculture
3- Dissolution by fibrinlysis causing rapdid shrinkage and total disappearnce of
(RECENT) thrombi
4- Organization and recanalization: older thrombi organized by ingrowth of endothelial cells and smooth muscle cells and fibroblasts
recanalization may convert thrombus into a smaller mass of CT becoming incorportaed into vesel wall and with remodeling and contraction of mesenchymal elemnts only a fibrous lump may remain amrk of original thrombus
What happens when thrombi obstruct arteries or veins?
They cause occlusion or embolization, leading to clinical symptoms.
What symptoms do venous thrombi cause?
Painful congestion & edema distal to obstruction.
➡️ Main risk: Embolization to lungs (pulmonary embolism).
What symptoms do arterial thrombi cause?
Main risk: Occlusion of critical vessels (e.g., coronary or cerebral arteries).
➡️ Can lead to stroke, heart attack, or tissue infarction.
Why are venous thrombi dangerous?
➡️ They can break off and travel to the lungs, causing a pulmonary embolism.
Why are arterial thrombi dangerous?
They can block blood flow to vital organs, leading to serious or fatal consequences.
Venous thrombosis types
1- superficial which typically occurs in varucisutues whihc cause local congestion, swelling, pain and tenderness but the edma and impaired venous drainge predispose infection and ulcers ( varicose ulcers)
2- Deep vein thrombosis involve leg large veins at or above knee ( popliteal, femoral and iliac) it can emobolize and cause pulmonary infraction
Lower extermity DVT causes
1- bed rest and immoblziation
2- congestive heart failure
3- trauma
4-surgery
5-burns
6- vascular insults and procoagulatn release from injured tissues
6- increased heaptic syntehsis of coagulation factors and decreased t-PA
contributions to thromboitc diathesis
1- preganacy
2- decreaed venous return from leg veins and systemic hypercoagulability with hormonal change of pregnancy
3- turmor assocaited infalmmation and coagulation factors
4- procoagulants ( mucin) from tumor cells increased thrmoboembolism in disseminated cancers ( migratory thrombophlebitis or trousseau syndrome )
causes of arterial and cardiac thrombosis
1- atherosclerosis due to loss of endothelial integrity with abnormal blood flow
2- myocardial infraction whihc can rpedispose to cardiac mural thrombi by causing dyskinetic myocardial contraction and endocardial injury
3- rheumatic heat disease whihc can cause atrial mural thrombi
Disseminated intravascular coagulation (DIC)
1- widespread thrombosis within microcirculation that may be sudden or insidious
2- complcation from other diseases involved in activation of thrombin
3- can cause circulatory insufficiency and organ dysfunction ( brain, lungs, kidney and hearts)
4– it uses up plateltes and coagulation factors ( consumptive coagulopathy) and acitvates fibrinolytic mechnasim
5- it can cause hemorrhagic stroke, bleeding, hypovolemic shock
what is an emobolism
is a detached intravascuar solid, liquid or gas mass that is carried by blood from its point of orgin to distant site which may cause dysfunction or infraction
types of emboli
1- thromboembolsim by enlodged thrombi
2- nitrogen bubbles
3- fat droplets
4- atherosclerotic debris ( cholesterol emboli)
5- tumor fragments
6- BM
7- Foreign bodies
what does the clincal consequence of embolism depend on
1- size
2- positon of the embolus
3- vascular bed that is impacted
Pulmonary embolism
mostly originate from DVT from the leg
it is carried through progressively larger veins and the right side of heart beore going to pulmonary arteries
- it can occlude main pulmonary artery, stradddle the pulmonary artery bifurcation or pass to branching arteries depending on it size
- the patient who had one PE is at high risk of more
consequece of PE
1- most of them are silent and are incorporated into vascular wall and sometimes it leaves a fibrous web
2- sudden daeth and acute heart faiulre or Cardiovascular collapse
3- Embolic obstruction of medium size arteries and vascular rupture resulting in pulmonary hemorrhage
4- emobolic obstruction of small end arteriolar pulmonary branches whihc produce hemorrhage or infraction
5- multiple emboli over time cause pulmonayr hypertension and right ventricuar failure
why doesnt PE doesnt cause pulmonary infraction in some cases
because lung is supplies by pulmonary artieres and bronchial arteries and intact bronchial circulation
Systemic thromboembolism
1- arise from intracadial mural thrombi
2- 2/3 are assocaited with left ventricular wall infraction and 1/4 from left artial dialtion and febrilation and reminder from aortic aneurysms, atherosclerotic plaques, valvularr vegeations or venous thrombi
3- the embolsim arrest in lower estermities, brain and other tissues depending on the source of the embolism and relative amout of blood flow that tissue recieves
4- the conequence of systemic emboli depend on vulnerbality of affected tissue to ischemia, caliber of occluded vessel adn whether collateral blood supply exisists
Fat embolism
presence of microscobic fat globules assoacited with heamtopoietic bones marrow
seen after fractures of long bones or soft tissue trauma and burns
it rupture vascular sinusoids in marrow and small venules allwoing marrow or adipose tissue to herniate and travel to lung
Fat embolism syndrome
charchterized y pulmonary insufficiency, neurologic symptoms, anemia and thrombocytopenia
- sympotms include sudden onset of tachypnea, dyspnea and tachycardia and can progress to delirium or coma and diffuse petechial rash due to thrombocytopenia
pathogensis of Fat embolism syndrome
involve both mechnical obstruction and biochemical injury
- fat embolism is assaociated with red cell and platelet aggregates which can occlude pulmonary and cerebral microvasculture
Air embolism
it is due gas bubbles that obstruct vascular flow causing distal ischemic injury
- see in neurosurgery in sittiing positon due to gravity
- endovascular and interventional procedures
- mechnical ventilation
- at least 100mL is necessary to produce clincal affect in pulomnary crculation
- it induces intesne infalmmatory response that may injure alveoli, and bubbles in CNS can cause mental impairment and sudden coma
- seen in decompression sicknes
decompression sickness
- due to nitrogen bubbles disssolved in blood it causes the bends ( pain in muscle and supporting tissues)
- it also causes edema, hemorrhage, focal atelectasis or emphysema leading to respiratory dsitress called the chokes
- chronic form is called Caisson disease whihc leads to multiple foci of ischemic necrosis most common in femroal heads, tibia and humeri
Amniotic fluid embolism
1- 5th most cmmon cause o materanl mortality
2- sudden severe dyspnea, caynosis adn shock and neurologic impairment from headaches to seizures and coma and by DIC
- caused bby biochemcial activation of coagulation factors , component of innate immune system and relase of vasoacitve substances which casue acute pulmonary hypertension adn right heart failure, pulmonary edam adn diffuse alveolar damge
3- ifnusion of amniotic flid or fetal tissue into amternal circules via tear of placental membrane or rupture of uterine veins
diagnosis of Amnitoic fluid embolism
1- presnec eof squamous cells shed from fetal skin
2- lanugo hair
3- fat from vernix caseosa
4- mucin derived from fetal RS and GI in matenrnal pulmonary micorvasculture
Infraction
caused by occlusion of either the arterial supply or venous drainage and it most common outcome is ocngestion
caused mostly by arterial thrombosis or arterial embolism
can be caused too by local vasospasm, hemorrhage into atheromatous plaque or extrinsic vessel compression by tumors
- testicular torsion or bowel volvulus
- traumatic vascular rupture or vascular compromise by edema or by entrapment in a hernia sac
Factors influencing infract
1- avalibility of alternative blood supply whihc determine damage
( lungs, liver, hand and forearm)
2- Rate of occlusion as slow occlusions are less likely to cause infraction as they provid etime for collateral pathway to perfuse
3- tissuse vulnerability to hypoxia
4- hypoxemia incerased likehood and extent of infraction
Morphology of infraction
1- red infracts due venous occlusion ( testicular torsion), loos psongy tissue ( lungs), in tissues with dua circulation, tissue prevoisuly congested by sluggish venous outflow and when flow is reestablished to site of prevous arterial occlusion and necrosis
2- White infracts: due to arterial occlusion in solid organs with end arterial circulation and where tisssue density limits the seepage of blood from adjoining capillary beds into the necrotsis tissue
3- ischemica coagulative necrosis except in brain it is liquefactive necrosis
Septic infractions
septic infractions occurs when infectted caddiac valve vegation embolize when microbes see dnecrotic tissue
Shock
state of circulatory failure that impairs tissue perfusion leading to hypoxia
types of shock
1- cardigoenic due to low cardiac output due to myocardial pump failure due to infraction or cardiac tamponade or outflow obstruction
2- hypovolemic shock from low cardiac output due to low blood volume
3- sepsis, septic shock and systemic inflammatory response syndrome
4- neurogenic shock due to spinal injury or IgE mediated hypersenstivity ( anaphylactic shock)
What is sepsis
life threating organ dysnfunction by dysregulated host response to infection
what is septic shock
1- subset of sepsis in which specfic circulatory, cellular or metabolic abnormalities ar assoaicted with a greater risk than sepsis alone
Systemic inflammatory response syndrome (SIRS)
sepsis like condition assocaited with systemic inflmmation by microbial insults like burns, truama and pancreatitis
- innate and adaptiev immune response cause vasodialtion and vascular leakage and venous blood pooling
- it causes hypoperfusion, celular hyoxia and metabolic derrangmetns that lead to organ dysfunction and if severe failure and death
Pathogensis of septic shcok
mostly triggered by gram negative bacteria and fungi which initaie infalmmatory and counter infalmmatory response that interact in complex
factors of developing septic shock
1- infalmmatory and proinfalmmatry response
2- endothelial activation and injury
3-induction of procogulant state
4- metablic abnormalities
5- organ dysfunction
infalmmatory response in sepsis
the infalmmation is done by TLR which recgonize PAMPS and DAMPS and G proteic coubled receptor that detect C-type lectin receptor like dectin
this leads to expression of infalmmatory mediators by NF-kB which icnrease secertion of TNF, IL1, IL12, IL18 and IFNy and HMGB1
there will be also increase in ROS and prostaglandins and paltelet activating factor-
all of this induce endothelial cells to upregulate adhesion molecule expression and stimualte more cytokine and it will cause activation of complement cascade prodcing anaphylotxoins C3a and C5a, chemotactic fragments C5a and opsnosnis C3b
it can also activate coagulation directly through factor 12 and indirect by altered endothelial function
counter infalmmatory response in shock
the hyperinflammation triggers immunosuppression which involve inante and adaptive immune cells which include TH1 ( inflm), Th2 ( antiinflm) and production of anti inflmamtory mediators like soluble TNF receptor and IL1R anatgonist and IL10 which induce apoptosis and cellular anergy
Endothelial acitvation and injury
the proinflammatory state and endothelial cell activation assocaied with sepciss causes vascular leakage adn edema
- inflammtory cytokine loosen endothelial cell tight junction making the vessel leaky and edema is resulted inbody
- endothelium also upregulates vasoactive inflm C3a, C5a and PAF which cause Smooth muscle relaxtion and hypotension
- autoregulation of flow based on metabolic needs is lost
What is a serious complication of sepsis related to coagulation?
Disseminated Intravascular Coagulation (DIC) occurs in up to 50% of septic patients.
How does sepsis promote coagulation?
Pro-inflammatory cytokines increase tissue factor (TF) production by monocytes & endothelial cells.
➡️ They reduce anticoagulant factors, such as TF pathway inhibitor, thrombomodulin, and protein C.
How does sepsis impair fibrinolysis?
Increased PAI-1 (plasminogen activator inhibitor-1) expression inhibits fibrinolysis, promoting clot formation.
What is the role of neutrophil extracellular traps (NETs) in coagulation?
NETs stimulate both intrinsic & extrinsic pathways, promoting a procoagulant state.
How does sepsis-induced vascular leak contribute to thrombosis?
Edema & decreased blood flow in small vessels cause stasis, reducing the washout of activated coagulation factors.
What metabolic abnormalities occur in sepsis?
Insulin resistance & hyperglycemia due to:
TNF & IL-1
Stress hormones (glucagon, GH, glucocorticoids)
Catecholamines
What happens in full-blown DIC?
➡️ Massive thrombin activation → Fibrin-rich thrombi throughout small vessels → Tissue ischemia
➡️ Platelets & clotting factors are consumed, leading to bleeding & hemorrhage.
How do pro-inflammatory cytokines affect insulin?
Suppress insulin release
➡️ Increase insulin resistance by reducing GLUT-4 expression in liver & tissues
Why is hyperglycemia harmful in sepsis?
Reduces neutrophil function → Impairs bactericidal activity
➡️ Increases adhesion molecule expression → Promotes endothelial dysfunction
What happens to glucocorticoid levels in sepsis?
Early phase: Acute glucocorticoid surge
➡️ Later phase: Adrenal insufficiency due to:
Depressed adrenal function
Adrenal necrosis (Waterhouse-Friderichsen syndrome) from DIC
What causes lactic acidosis in sepsis?
Cellular hypoxia → Impaired oxidative phosphorylation → Increased lactate production
What factors contribute to organ dysfunction in sepsis?
Systemic hypotension
➡️ Interstitial edema & microvascular dysfunction
➡️ Small vessel thrombosis
Why do tissues fail in sepsis despite oxygen delivery?
Mitochondrial damage from oxidative stress → Impaired oxygen utilization
What are the effects of high cytokine levels in sepsis?
Decreased myocardial contractility & cardiac output
➡️ Endothelial injury & vascular permeability → Acute Respiratory Distress Syndrome (ARDS)
Which organs are most affected by sepsis-induced failure?
Kidneys, liver, lungs, and heart → Can lead to death
what is supraantigen and their correlation to septic shock
polyclonal T lymphocyte activators that induce release of high levels of cytoinees causing diffuse rash to vasodialtion hypotension shock adn death
and causes toxic shock syndrome
stages of shock development
1- intial nonprogressive during which compensatory mechanims is working
2- progressive in whihc tissue hypoperfusion and onset of worsenign circulatory adn metabolic derrangments like acidosis
3- irreversible stage in whihc cellular and itssue injury is severe that even if hemodynamic problem is fixed patient will die
What compensatory mechanisms help maintain blood pressure in early (nonprogressive) shock?
Baroreceptor reflexes
✅ Catecholamine release (epinephrine & norepinephrine)
✅ Antidiuretic hormone (ADH) secretion
✅ Renin-angiotensin-aldosterone system (RAAS) activation
✅ Sympathetic nervous system (SNS) stimulation
🡆 Result: 🔺 Tachycardia, vasoconstriction, & renal fluid retention
What are the clinical signs of early (nonprogressive) shock?
✅ Cool, pale, clammy skin due to cutaneous vasoconstriction
✅ Tachycardia (increased heart rate)
✅ Decreased urine output (due to RAAS activation)
✅ Blood shunting to vital organs (heart & brain)
🔴 Exception: Septic shock may initially cause vasodilation, leading to warm, flushed skin.
What happens in progressive (decompensated) shock?
🚨 Tissue hypoxia develops due to inadequate perfusion.
🚨 Anaerobic metabolism replaces aerobic respiration → Lactic acid accumulates → Metabolic acidosis
🚨 Acidosis blunts vasoconstriction, leading to:
Arterial vasodilation
Blood pooling in microcirculation
Worsened cardiac output
Increased risk of endothelial anoxic injury → DIC
🔴 Vital organs begin to fail!
What occurs in irreversible shock?
🚨 Massive cellular injury & organ failure due to:
✅ Lysosomal enzyme leakage → Tissue damage worsens
✅ Myocardial contractility declines (due to excessive nitric oxide [NO] production)
✅ Bacterial translocation from ischemic bowel → Bacteremia & septic shock
✅ Renal failure (due to acute tubular necrosis from prolonged ischemia)
❌ Despite treatment, this phase leads to death.
What are the key interventions for shock?
✅ Identify & treat the underlying cause!
✅ Fluids & vasopressors to restore circulation
✅ Oxygen therapy to combat hypoxia
✅ Correct acid-base imbalances (e.g., metabolic acidosis)
✅ Treat infections aggressively in septic shock
