B2 Flashcards
Define thrombosis
A pathological process which denotes the formation of a blood clot in intact vessels due to inappropriate activation of normal haemostatic process
State the cause of thrombosis
VIRCHOW’s TRIAD :
I) Endothelial injury
- over loss of endothelium exposes subendothelial ECM —> leads to platelet adhesion , release of tissue factor ( factor III , procoagulant ) and reduces local production of PGI2 ( anticoagulant ) and plasminogen activators ( anticoagulants )
- may be induced by hypertension, bacterial products , radiation injury , hypercholesterolemia, homocystinuria , toxins of cigarette smoke.
2) Abnormal blood flow
-turbulence contributes to arterial & cardiac thrombosis by causing endothelial injury or dysfunction
- stasis contributes to development of venous thrombi
- How?
I) turbulence & stasis promotes endothelial cell activation & enhanced procoagulant activity by altering endothelial gene expression
II) stasis allows platelets & WBC to come into contact with endothelium when the flow is sluggish
III) stasis also prevents washout of activated clotting factors & inhibits inflow of clotting factor inhibitors
- example : hyperviscosity syndromes eg polycythemia; sickle cell anemia which cause vascular occlusion resulting in stasis
3) Hypercoagulability
- defined as the alteration of coagulation pathways that predispose affected person to thrombosis
- may be genetic ( example : Factor V mutation , prothrombin gene mutation ) or acquired ( oral contraceptive use , hyperestrogenic state of pregnancy , tumors , smoking & obesity )
Describe the Pathogenesis of arterial & venous thrombosis
Arterial
- due to formation of atheromatous plaque on the intimal surface of any artery —>enlarges —> protrudes into lumen —> causes turbulence in blood flow & loss of intimal endothelial cells ->exposure to subendothelial ECM —> cause fibrin deposition & platelet clumping with RBCs —> thrombus formation
Venous
- occurs at valves which protrude into the vessel lumen & produces a degree of turbulence
- veins can get damaged by trauma , stasis & occlusion
- coralline / laminated growths are seen
Atheromatous —> accumulation of macrophages ( foam cells ) , lipids , debris , calcium and CT
Venous thrombosis are more serious than arterial thrombosis as they can embolize & leads to ( ……………..)
Venous thrombosis are more serious than arterial thrombosis as they can embolize & leads to ( pulmonary infarction & death (pulmonary embolism) )
Compare and contrast arterial & venous thrombosis
Arterial thrombosis
- formed in areas of active blood flow
- caused by atherosclerosis & turbulent blood flow
- appearance : alternating lighter layers of platelets & fibrins with darker red cell rich layer
Venous thrombosis
- formed in areas of sluggish / static blood flow
- caused by venous stasis
- appear dark-red with greater concentration of red cells
- Ill-defined laminations (lines of Zahn )
: lines of Zahn
—> pale : platelets
—> dark red : fibrin , RBCs , Leucocytes
Describe the possible fates of thrombus
1) Propagation
- thrombus grows in size —> expand to obstruct the entire lumen
2) Embolization
- thrombus dislodges to distal sites in the vasculature & form embolus
- arterial thrombus leads to systemic embolism
- venous thrombus leads to pulmonary embolism ( most dangerous )
3) Dissolution
- thrombi is removed by fibrolytic activity , typically occurring within the first day or two
- as the thrombi ages , it becomes more resistant to fibrinolysis due to continued polymerisation
4) Recanalization
- older thrombi get organised by ingrowth of endothelial cells , SMC & fibroblast
- capillary channels form within the old thrombi, creating conduits along the length of the thrombus & reestablishing the continuity of the original lumen .
Describe the clinical effects of thrombi
1) Obstruct arteries & veins
2) Acts as possible source of emboli ( others bring amniotic fluid , gases & fat )
Arterial thrombi
- can embolize & cause tissue infarction
- can also obstruct critical vessels (eg : coronary & cerebral )
Venous thrombi
- most occur in the superficial or deep veins of the leg
- leads to local congestion & swelling predisposing the overlying skin to infection & ulcers
- deep venous thromboses ( DVTs) occur in the larger leg veins above the knee joints ( eg : popliteal, femoral & iliac veins ) — more prone to embolize
- may embolize to lung & cause death ( pulmonary embolism )
Define the term embolus
An embolus is a detached , intravascular solid , liquid or gaseous mass that is carried by blood to a site distant from the point of origin.
Describe thromboembolism ( aetiopathogenesis , clinical effects , consequences )
- may be pulmonary or systemic
Pulmonary thromboembolism’s
I) aetiopathogenesis
- commonly ( 95%) originate from the deep vein of the leg ( DVT ) proximal to the popliteal fossa -> travel to right side of heart —> lodge in main truck of pulmonary artery or the bifurcation of pulmonary arteries ( saddle embolus ) —> pulmonary infarct & death
II) significance
- most emboli are small —> get reorganized
- if >60% pulmonary circulation is blocked , right heart failure & sudden death will occur
- emboli obstruction of medium sized arteries leads to haemorrhage due to anoxia , but will not cause infarction due to dual bronchial circulation
- multiple small emboli can cause pulmonary hypertension with right heart failure ( Cor pulmonale)
II) systemic
- commonly arise from intracardiac mural thrombi ( 80% ) , aortic aneurysm , fragmented valvular vegetations, thrombi overlying ulcerated atherosclerotic plaques ( basically in the arteries )
- lodges anywhere in blood circulation eg lower extremities (75%) , CNS ( 10%) , organs — whereas venous emboli typically lodge in the lungs
Describe air/gas embolisms
I) Aetiopathogenesis
- may be caused by IV infusion of air bubbles , chest wall injuries , obstetric or laparoscopic procedures
- causes gas bubbles to form in the circulation —> coalesce to form frothy masses to obstruct vascular flow
- Examples :
I) Decompression sickness / the bends —> in areas of great pressure examples : underwater , gases dissolved in tissue & fluid . Upon rapid resurfacing , gases expand in the tissue & bubbles out of the solution in the blood to form gas emboli which can lead to tissue ischemia ;
II) Caissons disease —> more chronic form of decompression sickness —> persistence of gas emboli in skeletal system leads to multiple foci of ischemic necrosis , common sites are the femoral heads , tibia & humeri.
Describe amniotic fluid embolism
I) Aetiopathogenesis
- A complication of labor & immediate post-partum period
- ruptured uterine vessels or placental membrane —> causes amniotic fluid to enter into maternal circulation
II) Clinical signs & symptoms
- dyspnoea , cyanosis , seizure , shock & coma
- pulmonary edema & DIC may occur after due to release of thrombogenic substances in amniotic fluid
- diffuse alveolar damage occur later
- squamous cells , hair , fat and mucin may be found in maternal circulation
Describe fat embolism & fat embolism syndrome ( aetiopathogenesis , clinical symptoms )
I) Aetiopathogenesis
- due to trauma to long bones ( eg : vigorous CPR ) , soft tissue crush trauma & burns
- cause release of microscopic fat globules into blood vessels —> leads to mechanical obstruction & biochemical injury of endothelium ( fat embolism syndrome )
I) Mechanical obstruction
- due to presence of fat emboli itself & also associated RBC & platelet aggregation , causing the occlusion of cerebral & pumonary microvasculature
II) biochemical injury
- due to release of fatty acids —> cause local toxic injury to endothelium
- platelet aggregation & granulocytes recruitment ( with release to proteases , ROS & eicosanoids ) —> futher damaged to vascularity.
** usually fat embolism ( 90% ) are cleared away with little clinical manifestations but 10% develop fat embolism syndrome
II) Clinical symptoms
- anemia due to increase in phosphatidase A enzyme & RBC aggregation
- thrombocytopenia
- neurological symptoms
Define infarction
An area of ischemic necrosis caused by occlusion of either arterial supply or venous drainage in a particular tissue
State the causes of infarcts
1) Thromboembolism’s ( 99%)
2) Tumors causing compression of a vessel
3) Twisting of vessel
- eg : testicular , ovarian torsion , bowel volvulus
4) Local vasospams
State the classification of infarcts
1) Based on Color
I) red infarcts
II) white infarcts
2) Based on presence of microorganism
I) bland - No m/o
II) septic - m/o present
Red infarcts commonly occur in :
I) ( …………..)
II) (………….)
III) (…….)
White infarcts commonly occur in :
I) (…………….)
Red infarcts commonly occur in :
I) ( venous occlusion ( testicular , ovarian torsions ) )
II) ( loose tissue ( lungs ) , in which blood can collect in infarcted zones )
III) ( tissue with dual circulation ( lungs , SI ) )
White infarcts commonly occur in :
I) ( arterial occlusion in solid organs ( heart , kidney , spleen ) in which the tissue density limits the seepage of blood from adjacent patent vascular beds )
Describe the morphology of an infarct
( applies to both red and white infarct )
1) Gross
- wedges shape with the occluded vessel located at the apex and serosal surface of the organ forming the base.
- serosal surface may have overlying fibrinous exudates
- margins of the infarct defined by a narrow rim of hyperaemia
2) Histological
- coagulative necrosis
- areas of inflammation ( IF cells , edema ) followed by tissue repair ( granulation tissue ) which is ultimately replaced by scar tissue
- neutrophils present within 12 hrs, followed by macrophages within 3 days then fibroblasts & scar tissue formation by 1st week
- in brain it is liquefactive necrosis
Describe the factor that influence infarct development
1) Nature of blood supply to the organ
- organs with dual blood supply are less susceptible to infarcts ( lungs , pulmonary & bronchial arteries ; liver hepatic artery & portal vein; hand & forearm , radial & ulnar arteries )
2) Rate of occlusion
- slowly developing occlusion are less likely to cause infarction as there is enough time for development of collateral blood supplies
- example : small interarteriolar anastamoses that interconnect the 3 major coronary arteries, if 1 major artery is slowly occluded ( eg : encroaching atherosclerosis plaque ) , blood flows is increased in the collateral sufficient to prevent infarction
3) Vulnerability of tissue to ischemia
- how long the tissue can withstand a lack of blood supply
- neurons —> more susceptible to infarction when deprived of blood supply ( 3-4 min )
- myocardial cells - die after 20-30 mins of ishchemia
- fibroblasts within myocardium — remains viable after many hours of ischemia
4) O2 content of blood
- conditions like cyanosis , hypoxia , anemia increases likelihood of infarction , especially if blood flow is occluded.
Define shock
A state of systemic tissue hypoperfusion resulting from decreased cardiac output and or decreased effective circulating blood volume
Classify the types of shock
1) Hypovolemic
- due to decrease blood or plasma volume
- ex: massive haemorrhage , burns , vomiting , diarrhea
2) Cardiogenic
- due to decreased cardiac output
- ex: myocardial infarction , cardiac tamponade , cardiac arrhythmia , pulmonary embolism
3) Septic
- sepsis cause the massive outpouring of inflammatory mediators
- systemic vasodilation and pooling of the blood is seen
- flushing of the skin is seen — in all other forms of shock vasoconstriction ( pallor ) is seen so as to preserve blood supply to vital organs.
- ex: bacterial infections
4) Neurogenic
- loss of vascular tone
- due to anaesthesia, spinal cord injury
5) Anaphylactic
- due by IgE mediated hypersensitivity reactions
- causes systemic vasodilation & increased vascular permaebility
Describe the pathogensis of shock
1) Initial , non progressive stage
- reflex compensatory (neurohormonal ) mechanism are activated to increase BV & BP ( eg baroreceptor reflex, ADH release , sympathetic stimulation, release of catecholamine, activation of RAAS system )
- blood is routed to vital organs ( brain , kidneys , heart )
- net effect : tachycardia, peripheral vasoconstriction leading to pallor , renal conservation of fluid
2) Progressive stage
- tissue experience significant hypoxia —> ATP depletion —> anaerobic respiration takes over —> lactic acid buildup —> pH of blood decrease & impairs vasomotor responses —> causes vasodilation & pooling of the blood
- this leads to decreased effective circulatory blood volume & favours anoxic injury to endothelial cells , leading to DIC
- can be reversed by proper treatment
- effects : oliguria , mental confusion
3) Irreversible stage
- occurs following severe cellular & tissue injury
- death usually occur even if hemodynamic defects are corrected
- widespread cell injury —> leakage of lysozymes leads to necrosis —> multi organ failure
Describe the organ changes in shock ( morphology )
** hypoxic tissue injury is seen due to lack of perfusion to tissue
1) Kidney
- gross :
I) Cortex : enlarged , pale & widened
II) medulla : red congested & cyanotic
iii) Corticosteroids-medullary junction : well defined
- histology : necrosis of tubular epithelial cell are seen ( ischemic acute tubular necrosis )
2) Brain
- gross :
I) overall it become enlarged , swollen , with muddy discolouration
II) Gyri are widened , sulci are narrowed
III) demarcation between gray & white matter are I’ll defined in cut section
3) Heart
- subendothelial haemorrhage & necrosis is seen
4) Lungs
- gross : heavy , firm , red , boggy
- histology : accumulation of pale pink fluid in alveolar space , fibrin deposition , presence of alveolar hyaline membrane ( composed of fibrin & necrotic epithelial cells )
5) Adrenal gland
- cortical cell lipid depletion
6) GIT
- Petechial haemorrhage on serosal surface is seen
Define edema
Abnormal accumulation of fluid in the tissue space (edema ) or body cavities ( effusion )
Describe the Pathogenesis of edema
4 reasons :
1) Due to increased hydrostatic pressure
- results from impaired venous return (CCF , constrictive pericarditis , venous thrombosis , lower extremity inactivity ) and arteriolar dilation ( heat , neurohumoral dysregulation )
- for ex : in CCF , CO is reduced —> renal hypoperfusion —> RAAS system activated to increase salt & H2O retention —> but CO does not increase to compensate for extra blood volume in CCF —> lead to severe edema
2) Due to decreased colloidal oncotic ( osmotic ) pressure
- plasma proteins ( albumin ) responsible for colloidal oncotic pressure
- loss of plasma protein eg : glomerulopathies , malnutrition , liver cirrhosis , protein-losing gastroenteropathy leads to edema
3) Due to decreased lymphatic drainage
- lymphoedema occur due to localised obstruction of lymphatic drainage which can be caused by neoplasia , inflammation or radiation therapy
4) Due to salt & H2O retention
- excessive retention of salt by activation of RAAS system leads to edema as hydrostatic pressure in vessel increase ( due to increased BV ) and also reduced plasma oncotic pressure
- sodium retention occurs in scenarios like m renal hypoperfusion ( activates RAAS system ) , excessive salt intake with renal insufficiency , increased tubular reabsorption of sodium
Classify edema
Local edema
1) Acute inflammatory edema
2) Hypersensitivity (allergic ) edema
3) Edema of venous obstruction
4) Lymphatic edema
Generalised edema
1) Cardiac edema
2) Renal edema
3) Nutritional edema
4) Hepatic edema
Describe the clinical features of renal edema & its possible causes
1) Periorbital edema
2) Pitting edema
Causes
1) Acute chronic glomerulonephritis
2) Nephrotic syndrome
Describe the causes & morphology of pulmonary edema
Causes
- left ventricular failure
- renal failure
- ARDS
- Pulmonary infection
- Hypersensitivity reaction
Morphology - Gross : I) lungs 2-3 times larger II) edema confined to lower lobes III) upon section , escape of frothy , serosanguinous fluid presenting a mixture of air , edema fluid & extravasated red cells
- Histology :
I) accumulation of fluid about the septal arteries with widening of septa
II) granular pink coagulate ( proteinaceous fluid ) within the alveolar spaces
Papilledema refers to the swelling of the ( ………. )
It is a sign of increased ( ……….. )
(………… ) problem may arise , including ( ………………………………………………………………..)
Papilledema refers to the swelling of the ( optic disc )
It is a sign of increased ( intracranial pressure )
( Vision )problem may arise , including ( short flickers of gray vision , blurred or double vision , decreased FOV or ability to see colors )
