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Todays Quranic verse
And hold fast, all together, by the rope which God
(stretches out for you), and be not divided among
yourselves; and remember with gratitude God'sfavour on you; for ye were enemies and He joined
your hearts in love, so that by His Grace, ye
became brethren; and ye were on the brink of the
pit of Fire, and He saved you from it. Thus dothGod make His Signs clear to you: That ye may be
guided. [003:103]
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If one advances confidently in the direction
of his dreams, he will meet with a successunexpected in common hours
"Shoot for the moon."Shoot for the moon. Even if you missEven if you miss
it, you will land among the stars.!"it, you will land among the stars.!"
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HEMODYNAMIC
DISORDERS
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THROMBOSIS
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DEFINITION:
It is the process of formation of solid mass in circulation
from the constituents of flowing blood (within a blood
vessel or cardiac chamber, in a living organism-always
formed ante-mortem). The mass itself is called Thrombus.
Blood clot: mass of coagulated blood formed in vitro
Hematoma: extravasular accumulation of blood clot into tissues.Hemostatic plugs: simplest form of thrombus formed in healthy individuals at the site of bleeding
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COMPOSITION OFTHROMBUS
Fibrin, Platelets, RBC's(Hemostatic plug formation: endothelial injury, platelet aggregation, fibrin meshwork )
LOCATION OFTHROMBIArteries, veins, heart chambers, heart valves
TYPES OFTHROMBIArterial vs. venous;
bland vs. septic
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PATHOGENESIS OF THROMBOSIS(Predisposing Factors)
Virchows TriadEndothelial injury
Stasis or turbulence of blood flow
Blood hypercoagulability
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Endothelial Injury
Tissue Damage (Surgery, Fractures, Burns)
Atherosclerosis
HypertensionToxic Products (cigarettes, homocysteine etc. )
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Abnormal Blood Flow
Turbulence of Blood Flow Swirls, Eddies and increased pressure are injurious
These changes occur in arteries and the heart
Atherosclerosis, Aneurysms, Myocardial Infarction, Cardiac Valve Lesions
Hyperviscosity Syndromes e.g. Sickle Cell Anemia, Polycythemia
Stasis of Blood Flow More commonly a problem on the venous side leading to Venous Thrombosis
Can occur in the heart (Atrial Fibrillation or Infarction)
Pregnancy, long plane ride, immobility after surgery
Turbulence and Stasis : Disrupt normal laminar flow and bring platelets in contact with endothelium Prevent dilution of activated clotting factors
Retard the inflow of clotting factor inhibitors and permit thrombi build-up
Promote endothelial cell activation
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Hypercoagulability
Any alterations of the coagulation pathways that predispose toThrombosis
Primary (Genetic) or Secondary (Acquired) Disorders
FactorVLeiden mutation is the most common inherited cause ofhypercoagulability, it is resistant to the anti-coagulant effect of Activated
Protein C
Lack of Protein S, Protein C and Antithrombin III, patients present with
venous thrombosis and recurrent thromboembolism in adolescence and early
adulthood Lupus Anticoagulant with Lupus Erythematosus is associated with arterial
and venous thrombosis & recurrent abortion
Smoking, Obesity, Oral Contraceptives (BCP)
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Lupus -Anticoagulant
Called an Anticoagulant because it interferes with a Coagulation Test, artificially
prolonging It.
But It Is Not an Anticoagulant. It Is a Procoagulant
HIT syndrome3-5% population
Un-fractionated heparin for therapeutic anticoagulation induces circulating
antibodies resulting in platelet activation & endothelial cell injury ending up
in prothrombotic state
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HEMOSTASIS
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Hemostasis & Thrombosis
Hemostasis is the normal, rapid formation of a
localized plug at the site of vascular injury
Thrombosis is thepathologic formation of a blood
clot within the non-interrupted vascular system ina living person
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Hypercoagulable StatesInherited
Abnormality Approximate Rate
Factor VLeiden - APCR (Caucasion) 15-30%Prothrombin Gene Mutation 8-13%
Protein C Deficiency 5-6%
Protein S Deficiency 5 - 6%
Antithriombin Deficiency < 1%Hyperhomocysteinemia 3 - 5 %
Rogers: Am J Hem 41: 113, 1992
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EFFECTS OFTHROMBI
Stenosis or blockage of arterial lumen
ischemia, infarction
Venous occlusion
local congestion and edema and/or pulmonary embolism (travels)
Left heart valve & chamber thrombi
systemic embolism
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MORPHOLOGY OF THROMBITHROMBI DEVELOP
IN THE CARDIOVASCULAR SYSTEM
Lines of ZahnAlternating Pale Layers of Platelets & Fibrin With Darker Layers of Rbcs
(seen in areas with active blood flow like heart, aorta & large arteries not in veins)
*Postmortem clots are gelatinous with a dark red dependent portion & yellow chicken fatsupernatant, usually not attached to the underlying wall
*Thrombi in heart chamber/aortic lumen are applied to the underlying structure, mural thrombi(non-occlusive)
Arterial thrombi are Occlusive/Non-occlusive, begin at site of endothelial injury and grow alongflow of blood & typically are firmly adherent to the injured arterial wall (atherosclerotic plaque)
Venous thrombi are almost always Occlusive- 85-90% of venous thrombi form in lower extremities
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Atheroma with Thrombosis:Atheroma with Thrombosis:
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Thrombus(Lines of Zahn)
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Layering(Lines of Zahn)
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Cardiac Mural Thrombus
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Cardiac Mural Thrombi
Notice underlying endocardial fibrosis
Right
Left
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Aortic Aneurysm
Mural Thrombus
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CLINICAL SETTING FOR CARDIAC /ARTERIAL
THROMBUS FORMATION
Myocardial Infarction (MI)Rheumatic Heart Disease
Atherosclerosis
Rare large round thrombus obstructing mitral valve is called ball-valve thrombus
Thrombi formed in ventricles just before death composed of mainly fibrin Agonal thrombi
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VENOUS THROMBOSIS
Superficial Veins of the Lower Extremities Cause Pain, Swelling - Rarely Embolize
Associated With Varicosities Abnormally Dilated, Tortuous Veins
Increased Risk of Infections
Increased Risk of Varicose Ulcers
Deep Veins of the Lower Extremities Thrombi in Deep Veins (Popliteal, Femoral, Iliac Veins) More Likely
to Embolize About 50% Are Asymptomatic (Formation of Collaterals)
May Produce Edema, Pain and Tenderness
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PhlebothrombosisIt is due to stasis of blood in un-inflamed veins,
particularly the calf veins.
Thrombophlebitis
It is related to inflammation of the vein walls.
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PHLEBOTHROMBOSIS THROMBOPHLEBITIS
Main cause Stasis Inflammation
Primary thrombus Small Larger-depends on extent
of phlebitis.
Propagated clot Long/poorly anchored Usually none-if presentshort and well-anchored
Emboli Common, may be massive Rare unless infective
Sterile
Site Usually calf veins Anywhere
Clinical Often silent Pain
Signs of inflammation
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CLINCAL SETTING FOR VENOUS
THROMBUS FORMA
TION
Cardiac Failure (CHF)
Trauma
SurgeryBurns
3rd Term Pregnancy and Postpartum
Cancer (migratory thrombophlebitis-Trousseaus Syndrome)
Bed RestImmobilization
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Valvular Thrombi (vegetations)
Infective Endocarditis
Non-bacterial Thrombotic Endocarditis (NBTE)-Seen in patients dying of chronic debilitating diseases- advanced cancer (50% cases) &
other end stage diseases (cachectic, marantic or terminal endocarditis)
Atypical Verrucous Endocarditis (Libman-sacks)-Seen in 50% of acute SLE, Systemic sclerosis, TTP, Collagen diseases
Capillary thrombiMinute thrombi composed mainly of packed red cells in vasculitis & DIC
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FATE OF THROMBOSIS
Resolution (Dissolution)
Recent thrombi can undergo total lysis by activation of fibrinolytic system (mostly small venousthrombi). After the first 2-3 h, thrombi wont undergo lysis.
Thus the use of tPA is only effective in the first 1-3 hours
Organization and recanalizationReplacement by granulation tissue followed by recanalaization or healing totally to leave only a
small fibrousLump as evidence of a previous thrombus
PropagationAccumulation of more platelet & fibrin and obstruction
EmbolizationEarly & infected thrombi may detache from site of origin and may block distal vesseles
Hyalinization & Calcification
(Degraded thrombus with superadded bacterial infection may lead tomycotic aneurysm)
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Thrombus Propagated into the
Inferior Vena Cava
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CLINICAL SIGNIFICANCE:
Obstruction of arteries or veins can cause
ischemia, infarction, or may embolize
Venous thrombi may lead to congestion, poor wound healing, skin ulcers and painful
thrombosed veins
Microthrombi in microcirculation (capillaries) may cause DIC
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DIAGNOSIS:
Clinical signs are unreliable.
Phlebography using a contrast medium.
Radioactive iodine-labelled fibrinogen test.
Doppler ultrasound.
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EMBOLISM
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EMBOLISM
It is the process of carrying an abnormal mass (embolus)
in the blood stream to a point distant from its origin.
*An embolus is a detached intravascularsolid, liquid or gaseous mass that
is carried by the blood to a site distant from its point of origin
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TYPES OF EMBOLI
Gas(air, nitrogen , other gases)
Liquid
(amniotic fluid, radiographic contrast material, fat after soft tissue trauma / fracture, bone marrow )
Solid(thrombus-- most common, foreign body- bullet, catheter; also atheroematous material, tumor cell
clumps, tissue fragments, parasites, bacterial clumps etc.
99% are dislodged thrombusRarely: Bullets, Fat, Air, Atherosclerotic Fragments, TumorFragments, Bone Marrow
Emboli can be Bland (sterile) or Septic (infected)
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ORIGIN & SITES OF EMBOLIZATION:
Venous: Systemic veins Pulmonary arteries
Arterial: Heart or aorta Systemic circulation
Paradoxic: Systemic veins (through septal defect in heart or
AV shunts in lungs) systemic circulation
*Retrograde: Embolus traveling against the flow of blood (metastatic deposits in spine fromcarcinoma prostate due to retrograde embolism through intraspinal veins from large thoracic
& abdominal veins due to increased pressure in body cavities: during coughing or straining)
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EFFECTS OF EMBOLISM
Ischemia
Infarction
Sepsis if infected
(example: pulmonary embolism with pulmonary infarction)
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Thromboembolism
A detached thrombus or part of thrombus constitutes the most
common type of embolism
*Arterial (systemic) thromboembolism(from within heart & arteries)
*Venous thromboembolism Pulmonary thromboembolism
(from veins of lower legs & upper limbs, pelvic vein, cavernous sinus of brain, right side of heart)
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Systemic Thromboembolism
Emboli traveling within the arterial circulation
80% arise from intra-cardiac mural thrombi (myocardial infarction)
Vegetations on the heart valves (mitral/aortic) & prosthetic heart valves mayembolize to the systemic circulation
Infective endocarditis, Cardiomyopathy & CHD may be cause Emboli developing in relation to atherosclerotic plaques, aortic aneurysms,
pulmonary veins and paradoxic emboli
Major site of embolization are lower extremities (75%), brain (10%), intestine,kidney & spleen
Leads to infarction of the affected organs, gangrene, arteritis & mycoticaneurysm, myocardial infarction and sudden death.
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Emboli can arise from--
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Pulmonary Thromboembolism
Generally originate from deep leg veins (popliteal, femoral & iliac)Usually pass through the right heart Into pulmonary vasculature
60% Pulmonary Arterial obstruction usually leads to sudden death, RVF
Most pulmonary emboli (60-80%) are clinically silent because of small size
May occlude main pulmonary artery, across the bifurcation (SaddleEmbolus) or pass into the smaller branching arterioles
Embolic obstruction of medium-sized arteries may result in hemorrhagewithout infarction because of intact bronchial circulation. If bronchialcirculation is compromised as in left heart failure it results in infarction
Emboli obstructing small end-arteriolar pulmonary branches usually result inassociated infarction
Multiple pulmonary emboli over time may cause pulmonary hypertensionand right heart failure
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Thromboembolism
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Pulmonary
Embolus
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Saddle
PulmonaryEmbolus
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Fat embolism syndrome
Microscopic fat globules derived from long bone fractures (fatty marrow) or
rarely from soft tissue trauma and burns
10% of cases show clinical findings
Clinically characterized by
Pulmonary insufficiency, neurologic symptoms, anemia & thrombocytopenia
Symptoms appear 1-3 days after injury
PathogenesisMechanical obstruction in pulmonary & cerebral microcirculation and chemical
injury to endothelium by free fatty acids resulting in skin rash
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Air embolism
Gas bubbles within the circulation can obstruct vascular flow to cause distal
ischemic injury
Air can enter the circulation duringChest wall injury, Operation on neck & head, Obstetrical operation & trauma, Intravenous
infusion, Sudden atmospheric pressure changes in scuba & deep sea divers, underwaterconstruction workers and in individual in unpressurized aircraft in rapid ascent (Decompressionsickness- Caisson disease)
Clinically characterized byBends due to rapid gas bubble formation within skeletal muscle & about joint
Chokes due to respiratory distress caused by edema, hemorrhage, focal atelectasis, emphysema
CNS & CV effects due to focal ischemia
Multiple foci of ischemic necrosis specially in heads of femur, tibia, humerus etc
Clinical effects observed with air in excess of 100 ml
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Amniotic Fluid Embolism
Torn placental membrane- amniotic fluid release
Rupture of uterine veins
Infusion of amniotic fluid into maternal venous circulation
Morphologically characterized by
Lungs show squamous cells, lanugo hair, fat from vernix caseosa & mucin from GIT & RS
pulmonary edema, diffuse alveolar damage, systemic fibrin thrombi
Clinically characterized by
Severe dyspnea, cyanosis, hypotensive shock, seizures, coma & DIC
Mortality rate> 80%
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Disseminated Intravascular Coagulation (DIC) Sudden widespread fibrin deposition in microcirculation
Rapid consumption of platelets and coagulation proteins
Secondary massive fibrinolysis, all the little thrombi dissolve
Clotting Disorder Turns Into a Bleeding Disaster
Sepsis is common cause of DIC (30-50% of patients with gram negative sepsis)
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Disseminated Intravascular Coagulation
Schistocytes
Microthrombi
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Clinical Consequences of DIC
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Tumor Embolism
Tumor EmbolismLymphatics (Carcinoma)
Blood vesseles (Sarcoma)
Common sitesLiver (Carcinoma)
Lung (Carcinoma & Sarcoma)Bone (Prostate, Thyroid, Breast, Kidney, Lung
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INFARCTION
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INFARCTION
An infarct is a localized area of ischemic necrosis caused by
occlusion of either the arterial supply or venous drainage in a
particular tissue
90-99% of all infarcts due to arterial thrombotic or embolic events
Less common causes of infarction are vasospasm, hemorrhage in atheromatous plaque, twisting
of vessel, extrinsic compression or traumatic rupture of blood supply
Coagulative necrosis is characteristic of hypoxic death in all tissues except CNS
All infarcts tend to be wedge-shaped, with the occluded vessel at the apex
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TYPES OF INFARCTS:
Bland vs. Septic
(assumed to be bland unless specified as septic)
Arterial (usually white/pale) vs. Venous (red/hemorrhagic);
Bland and arterial most common
Organs with a single venous outflow channel (testis & ovary) are predisposed to infarction
caused by venous thrombosis
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MORPHOLOGY OF INFARCTS
White/Pale:
Occur with arterial occlusion or in solid organs with single blood supply (ex: kidneys, spleen)
Red/Hemorrhagic:Occur with venous occlusion, in loose tissues, tissues with dual circulation, in tissues previously
congested and when flow is re-established to a site of arterial occlusion & necrosis.
All infarcts are wedge shaped, poorly defined & hemorrhagic in initial stage, later margins are
better defined revealing hyperemia, become pale & sharply defined in solid organs and firmer &
browner in spongy organs
Microscopic evidence is visible after (12-18) hours if patient survives
Characterized by coagulative / liquefactive necrosis surrounded by inflammatory zone, later there
is evidence of regeneration & repair. Most infarcts are ultimately replaced by scars tissue.
Septic infarction results from embolization of infected vegetation from heart valve or if microbes
seed area of necrosis abscess organization
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FACTORS AFFECTING INFARCTS:
Nature of the vascular supply (dual arterial supply)
Collateral circulation
Rate of development of occlusion
Duration of occlusion
Metabolic needs of the tissue/organ Vulnerability of the tissue to hypoxia
Brain - < 3 minutes
Heart 0.5-2 hours
Kidney 2-3 hours
Skin fibroblasts - < 24 hours
Oxygen content of blood
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Hemorrhagic Lung Infarct Pale Splenic Infarct
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Myocardial Infarction
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MYOCARDIAL INFARCTION
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RENAL INFARCT
ION
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Lung Infarct
Wedge Shape...
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Infarcted Colon
OK Colon
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CLINICAL SIGNIFICANCE OF INFARCTION
Usually causepain;
May cause loss of function (example: myocardial infarct maycause heart failure);
May cause hemorrhage or sepsis (examples: lung infarct causes
hemoptysis, bowel infarct causes GI bleeding or sepsis).
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Marker Initial elevationafter AMIMean time topeak elevation
after AMI
Time to return to baselineafter AMI
Myoglobin 1 - 4 h 6 h 18 - 24 h
CK-MB 3 - 12 h 10 - 24 h 48 - 72 hMB-isoform 1 - 6 h 4 - 12 h 38 h
cTnI 3 - 12 h 10 - 24 h 5 - 10 days
cTnT 3 - 12 h 12 - 24 h 5 - 14 days
DIAGNOSIS OF INFARCTION
Depends on the organ involved
MI (ECG, Serum markers)
Common serum markers used to detect AMI
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SHOCK
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SHOCK
It is defined as systemic hypo-perfusion due to reduction either in
Cardiac Output or Effective Circulating Blood Volume.
The End Results are:
Hypotension, followed by
Impaired Tissue Perfusion and Cellular
Hypoxia
Reversible Cellular Injury Irreversible Tissue Injury Death
Non-Progressive Stage, Progressive Stage, Irreversible Stage
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TYPES OF SHOCK
Three Main Categories:
Cardiogenic,
Hypovolemic, and
Septic
Others:
Neurogenic Shock (anesthetic and spinal cord injury) & Anaphylactic Shock
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CARDIOGENIC SHOCK
Results From Severe Myocardial Failure Due to:
Intrinsic myocardial damage (myocardial infarction, ventricular
rupture, arrhythmia) Extrinsic Compression (cardiac tamponade)
Outflow Obstruction (pulmonary embolism)
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HYPOVOLEMIC SHOCK
Results From Loss of Blood or Plasma Volume:
- Hemorrhage
- Fluid Loss (severe burns, trauma, vomiting, diarrhea etc.)
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SEPTIC (ENDOTOXIC) SHOCK
Most common cause of death in ICUs in the US
Dissemination of infection into the vasculature
Caused by overwhelming systemic microbial infection, mostoften by Gram-negative infection (Endo-toxic Shock) but can
also occur with Gram-positive and fungal infections
Spread & expansion of localized infection (abscess, peritonitis,
pneumonia) into the blood stream.
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Pathogenesis Of Septic Shock
Endotoxins are bacterial wall lipopolysaccharides (LPS) whichconsists of a toxic fatty acid (Lipid A) core and a complexpolysaccharide coat (unique to each species). Gram-positivebacteria and fungi have analogus molecules.
High quantities of LPSp (TNF & IL-1 IL6 & IL8)-Systemic vasodilation (hypotension),
-Diminished cardiac contractility,
-Widespread endothelial injury and activation (SLA, ARDS, DAD),
-Activation of coagulation system (DIC)
Multi-organ system failure and death
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Effects of Shock on Tissues
Brain -- ischemic encephalopathy --> confusion, obtundation;
Heart -- subendocardial ischemia, infarction; contraction band
necrosis --> decreased output
Kidneys -- acute tubular necrosis --> oliguria, anuria and electrolytedisturbances
Lungs -- diffuse alveolar damage (DAD) --> adult respiratory
distress syndrome (ARDS) --> hypoxia
GI tract -- mucosal necrosis, hemorrhages Liver -- central necrosis, fatty change
Coagulation system -- disseminated intravascular coagulation (DIC)
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Morphology
of Shock
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Clinical Course of Shock
Hypotension
Weak, rapid pulse, tachycardia
Rapid shallow respiration Drowsiness, confusion & irritability
Cool, clammy skin
In septic shock the skin is initially warm and flushed
secondary to peripheral vasodilation
Multi-organ failure ensues if shock continues
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EDEMA
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EDEMA
Excess accumulation of fluid in the interstitial tissue spaces.Increased intracellular accumulation (edema) is generally termed as hydropic change.
Edema Fluid can be
A transudate (protein-poor fluid -specific gravity 1.020)
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SPECIAL TYPES OF EDEMA
Pleural effusion (hydro-thorax)
Pericardial effusion (hydro-pericardium) Ascites (edema in peritoneal cavity)
Anasarca (widespread edema)
Cerebral edema (in brain, intra- and extracellular)
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Normal Microcirculation
Capillary Arterial Venous
Hydrostatic Pressure + 36 + 16
Oncotic Pressure - 26 - 26
Net filtration Pressure + 10 mmHg - 9 mm Hg(leak-out) (Reabsorb)
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Homeostasis is maintained by the opposing effects of vascular
hydrostatic pressure and plasma colloid osmotic pressure
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Pathophysiologic Categories of Edema
I. Increased Hydrostatic Pressure
II. Reduced Plasma Osmotic PressureIII. Lymphatic Obstruction
IV. Sodium Retention
V. Inflammation
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Increased Hydrostatic Pressure
A. Congestive Heart Failure
B. Portal Hypertension
C. Venous Thrombosis
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Congestive Heart FailureInability ofHeart to Pump blood in systemic circulation
Blood backing up into the lungs
Blood backing up into the venous circulation
Increasing Central Venous Pressure (CVP)
Increased capillary pressure (Hydrostatic Pressure)
Edema
Cardiac Output Decreased Arterial blood volume Decrease Renal perfusion
Activates the Renal Defense Mechanisms
Renin-Angiotensin-Aldosterone Axis, Renal Vasoconstriction, Increased ADH
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Congestive Heart FailureRenin-Angiotensin-Aldosterone Axis
Renin AldosteroneRenal Na
reabsorption
Renal retention of
Na + H2O
Plasma volume
Transudation EDEMA
Decreased Renal Perfusion
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Congestive Heart FailureRenal Vasoconstriction
RenalVasoconstriction
GlomerularFiltrationRate (GFR)
Tubularreabsorption of
Na + H2O
Plasma volume
Transudation EDEMA
Decreased Renal Perfusion
Renal retention of
Na + H2O
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Congestive Heart FailureAnti-Diuretic Hormone
Anti-DiureticHormone (ADH)
Renal retention ofH2O
Plasma volume
Transudation EDEMA
Decreased Renal Perfusion
Renal retention of
Na + H2O
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Central
Venous
Pressure
Renal
Perfusion
Renin Renal
Vasoconstriction
ADH
Congestive Heart Failure
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Clinically initially cardiac edema can be demonstrated in legs or sacrum
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Portal Hypertension
Portal Hypertension is Increased resistance to portal blood flow The most common cause of Portal Hypertension is CIRRHOSIS
Results in Ascites
Pathogenesis of Ascites is complex Increased Portal Pressure (hydrostatic pressure) leads to increased liver sinusoidal
hypertension. Fluid moves into the Space of Disse then into lymphatics
The hepatic lymph percolates into the peritoneal cavity Normal thoracic duct lymph = 1 Liter/d
In cirrhosis, hepatic lymph flow far exceeds Thoracic duct capacity
Cirrhosis hypoalbuminemia decrease in plasma osmotic pressure ascites decrease in blood volume decreased renal perfusion secondary hyperaldosteronism(increased renin etc.)
AscitesAscites
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AscitesAscites
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Portal Hypertension
SinusoidalHypertension
Renal
Perfusion
Hepatic Lymph OverwhelmsThoracic Duct
Aldosterone
ASCITES
Cirrhosis
SerumAlbumin
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Venous Thrombosis
Impaired venous outflow increases hydrostatic pressure
Reduced Plasma Osmotic Pressure
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Reduced Plasma Osmotic Pressure
Albumin is the serum protein MOST responsible for the maintenance ofcolloid osmotic pressure.
A decrease in osmotic pressure can result from increased protein loss ordecreased protein synthesis
Increased albumin Loss: Nephrotic Syndrome
Increased protein permeability of the glomerular basement membrane
Protein losing gastroentropathy
Reduced albumin synthesis Cirrhosis
Protein malnutrition
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Inflammation
Both Acute and Chronic Inflammation are associated with Edema
Generalized edema in systemic infections, poisoning, certain drugs
& chemicals, anaphylactic reactions and anoxia
Localized edema in infections, allergic reactions, insect bite,
irritant drugs & chemical and Angioneurotic edema*
*It involves skin of face & trunk and may involve lips, larynx, pharynx, lung etc
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Angioedema
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Angioedema
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Elephantiasis
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Elephantiasis (filariasis)
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peau dorange appearance in breast cancer
S di & W t R t ti
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Sodium & Water Retention
Contributory factors in several forms of edema
Salt retention may be primary cause of edema
Post-streptococcal glomerulonephritis & Acute Renal failure
Increased salt with accompanying water cause increase hydrostatic pressure
and decreased vascular colloid osmotic pressure leading to edema
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EDEMA
INCREASED
HYDROSTATIC
PRESSURE
Congestive Heart Failure
Portal hypertension (Ascites)
Venous Obstruction
HEART
LIVER
KIDNEY
INFLAMMATION
Increased permeability
DECREASED
ONCOTIC
PRESSURE
Nephrotic SyndromeCirrhosis (Ascites)
Protein Malnutrition
LYMPHATICOBSTRUCTION
Inflammatory
NeoplasticSALT & WATER RETENTION
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GENERALIZED EDEMA
HEART
LIVER
KIDNEY
Edema Morphology
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Edema Morphology
Edema of the Subcutaneous Tissue is most easily detected Grossly (notmicroscopically)
Push your finger into it and a depression remains (pitting)
Swelling and wetness of the tissues
Subtle cell swelling with clearing and separation of extracellular elements
Dependent Edema is a prominent feature of Congestive Heart Failure (legs instanding & sacrum in recumbent position)
Periorbital edema is often the initial manifestation of Nephrotic Syndrome,later affecting all parts of body
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Pitting edema
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Pulmonary Edema
Pulmonary Edema is most frequently seen in Congestive Heart Failure (LVF)
May also be present in Mitral Stenosis, Cardiac Surgery, Renal failure,Adult Respiratory Distress Syndrome (ARDS), Pulmonary Infections,Inhalation of toxic substances, Aspiration, Radiation injury, Shock, Uremia,High altitude edema and Hypersensitivity reactions.
The Lungs are typically 2-3 times normal weight
Cross sectioning causes an outpouring of frothy, sometimes blood-tinged fluidrepresenting mixture of air, edema fluid & extravasated red cells
Microscopically alveolar capillaries are congested and there is collection ofeosinophilic, granular and pink proteinaceous material (edematous fluid) ininterstitial and alveolar spaces
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Pulmonary Edema
P l EdN l L
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Pulmonary EdemaNormal Lung
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Pulmonary Congestion
and Edema
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Edema of the Brain
Localized: Abscess, Neoplasm
Generalized: Encephalitis, Hypertensive crises, Obstruction of
venous outflow, Trauma
In Generalized edema brain is grossly swollen with narrowed
sulci and distended gyri showing flattening against skull
Vasogenic & Cytotoxic edema
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Brain edema
C i i C i
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Clinical Correlation
Subcutaneous Edema-Annoying but Points to Underlying Disease
However, it can impair wound healing or clearance of Infection
Pulmonary Edema-May cause death by interfering with Oxygen
and Carbon Dioxide exchange & Creates a favorable environmentforinfection
Edema of Brain-The big problem is: There is no place for the fluid togo! Herniation into the foramen magnum will kill or brain stemvascular supply can be compressed and damage vital centers
i & C i
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Hyperemia & Congestion
Increased volume of blood in an area compared to normal
HyperemiaH
yperemia is an active process resulting from augmented tissue inflowdue to arteriolar dilation (e.g. Acute inflammation, Exercising muscles,
Blushing, Sexual arousal)
Congestion
Congestion is a passive process resulting from impaired outflows from atissue (cardiac failure-systemic or venous obstruction-local)
Both can be Local or Diffuse
MORPHOLOGY OF HYPEREMIA &
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MORPHOLOGY OF HYPEREMIA &
CONGESTION
Hyperemia: tissue is red or purple, engorged with oxygenated blood,
swollen, often edematous. Examples- Lungs.
Congestion: tissue is blue-red in color due to accumulation of
deoxygenated hemoglobin in the affected tissues. Later on tissue becomes
brownish (iron deposition) & indurated (fibrosis).
Examples Liver, Legs, Lungs
PULMONARY CONGESTION
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Acute Pulmonary Congestion: engorged alveolar capillaries, alveolar septal edema, focal
minute intra-alveolar hemorrhage Chronic Pulmonary Congestion: thickened & fibrotic septa along with presence of
numerous hemosidrinladen macrophages (Heart Failure Cells)
HEPATIC CONGESTION
Acute Hepatic Congestion: central vein and sinusoids are distended with blood, centralhepatocytes may show degeneration & peripheral hepatocytes may develop fatty change
Chronic Passive Congestion of Liver: central regions of hepatic lobules are grossly red-brown, slightly depressed & surrounding uncongested zones reveal fatty change (nutmeg
liver). Microscopically there is centrilobular necrosis with hepatocyte drop out andhemorrhage & hemosidrin containing macrophages. Hepatic fibrosis (cardiac cirrhosis) may
be seen in heart failure.
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Hyperemia in Pneumonia
Hyperemia
Infection
(Pneumonia)
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Liver - Chronic Passive Congestion
Nutmeg Liver
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Nutmeg Liver
Cross Section of a NutmegNutmeg Liver
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Chronic Passive Congestion
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SIGNIFICANCE OF CONGESTION
If diffuse, usually indicates Heart failure;
If local, usually indicates a blockage upstream toward theheart;
Cirrhosis can cause Varices in esophagus
HEMORRHAGE
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HEMORRHAGE
Extravasation of blood due to rupture of blood vessels
Rupture of a large vessel: Trauma, Atherosclerosis, Inflammatory orNeoplastic Erosion
Rupture of small vessels: hemorrhagic diathesis
Hematoma is blood enclosed within tissue (red-blue blue-green golden brown)
Petechiae are minute (1-2 mm) hemorrhages into skin, mucous membranes
or serosal surfaces
Purpuras are larger (3-5 mm) hemorrhages
Ecchymoses are larger (1-2 cm) subcutaneous hematomas (bruises)
Hemothorax, Hemopericardium, Hemoperitonium and Hemoarthrosis are bleeding in one
or other body cavities.Hematochezia- bright red blood per rectum, Melena - dark black blood per rectum
Hematuria - blood, gross or microscopic in urine
Hemoptysis - coughing up of blood , Hematemesis - vomiting up of blood
CAUSES OF HEMORRHAGE
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CAUSES OF HEMORRHAGE
Trauma
Vascular diseases with rupture (atherosclerosis, arteritis,
aneurysms, etc.).
Low platelets (below 10-15,000/cu mm)
Coagulopathy (factors less than 10% activity)
Ulcers, tumors, coagulation factors, infarcts,
MORPHOLOGY OF HEMORRHAGE
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MORPHOLOGY OF HEMORRHAGE
Acute
Red or purple collection of blood in tissue
Chronic or old
Brown or maroon pasty material
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HemorrhageWhy do bruises change color
as they Resolve?
The RBCs in a hemorrhage are broken down:hemoglobin (red)pbilirubin (blue-green)p
hemosiderin (golden-brown)
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Clinical Effects of Hemorrhage
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Clinical Effects of Hemorrhage
20% blood loss hemorrhagic shock
Bleeding into the brainstem is fatal while same blood loss from a
finger cut is trivial
Chronic recurrent bleeding can lead iron deficiency anemia!
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Anemia from Blood Loss
This may be the only hint of Occult Cancer
Carcinoma of the Colon
Gastric Carcinoma (less common)