chapter 4: hemodynamics Flashcards
edema vs effusion
edema = exudation of transudate or exudate into the interstitial space
effusion = fluid accumulation into potential spaces (body cavities) such as pleural space, peritoneal space (ascites), pericardial space, joint space
plasma transfusion, platelet transfusion, and red blood cell transfusion have are best to treat what defects
plasma
- factor deficiencys
- hypovolemic shock
- promotes coagulation and replenish plasma loss seen in shock from massive loss from burns or hemorrhage
platelet
- platelet dysfunctions (Bernard soulier syndrome)
- low platelet count (thrombocytopenia)
- treat overactive bleeding in these conditions
RBC
- anemia
- replenish after trauma, or surgery
describe the steps of primary hemostasis
*platelet adhesion/ activation/ aggregation = platelet plug
- platelet adhesion to sub endothelial surface by vWF and Gp1b interaction
- platelet activation = shape change to increase surface area, change to negative charge, conformational change of Gp2b-Gp3a complex, and platelet granule secretion of ADP and TXA2 by thrombin and ADP stimulation
- platelet aggregation is initiated by increased TXA2, thrombin conversion of fibrinogen to fibrin, Gp2b–Gp3a complex change to allow bivalent binding of fibrinogen and subsequent cross linking,
list the defects of primary hemostasis (platelet plug defects)
- vWF disease (vWF)
- Bernard Soulier syndrome (Gp1b)
- Glanzman thrombasthenia (Gp2b-3a)
- thrombocytopenia (low platelet count)
dehydration is a _____state
hyper coagulable (i.e. thrombotic)
sickle cell anemia causes what to occur in blood flow
STASIS
what would result in unilateral edema and what are common causes of it?
lymphedema by lymphatic obstruction
- filariasis (Wuchereia helminth infection)
- tumor resection surgery can remove LNs and cause lymphedema (breast cancer patients)
- Differentials: infection, inflammation, trauma, tumor, surgery, malformations
white vs red infarction
white- seen in organs with single blood supply (ex: spleen, heart, kidneys), arterial occlusion, solid organ, platelet rich
red- seen in organs with dual blood supply ( ex: lung), seen with venous occlusion, seen in loose tissue for blood collection, or because repurfusion injury, or because STASIS.
*extensive bleeding can cause brown -hemosiderin residue
defects of primary hemostasis vs secondary, vs small vessel defect manifestations
primary
- petechiae, purpura, mucocutanous bleeding, mentorhaggia, thrombocytopenia
- intercerebral hemorrhage
secondary
-hemearthrosis, bleeding into soft tissue or joints, by factor deficiciencys
small vessels
-ecchymosis, and hematoma
define air embolism and give details
-introduction of air bubbles into circulation causing ischemic injury
-causes:
cardiac catheterization / laparoscopic procedures
deep sea diving
**deep sea diving = decompression illness
Cause: increase in N2 in circulation as increase in pressure during descent; rapid ascent = N2 loss and introduction of air emboli
-bends: joint pain from bubble in muscles and around joints
-chokes: bubbles in lung vasculature cause edema, hemorrhage, and emphysema leading to respiratory distress
- if chronic it will form Caisson disease (decompression sickness)
- bone infarction due to multifocal ischemic necrosis of bone
- usually femoral head, tibia, humorus
DIC affects which PT or aPTT?
both will be abnormal
mechanism, presentation, and complication of the hyper coagulable state by oral contraceptive use
mechanism : increase estrogen levels by the pill causes increased liver production of coagulation factors and decreased anticoagulant factors
complication: increases risk of thrombosis
presentation: stroke / emboli
define amniotic fluid embolism and give details
- amniotic fluid enters mom circulation following delivery and causes allergic reaction
- Sx: sudden dyspnea, cyanosis, neuro change, shock, DIC
- can be lethal but if survives pulmonary edema develops
- **AF causes coagulation
- autopsy findings: squamous cells keratin, fat, mucin, inside moms blood vessels
PT vs aPTT time ? what do you use to assess primary hemostatic defect?
PT time reflects the extrinsic pathway
aPTT time reflects the intrinsic pathway
- flow cytomtery
- PFA-100 (platelet function assessment for adhesion and aggregation)
manifestations of acute and severe hemorrhage, and chronic blood loss
acute
-asymptomatic
severe
- hypovolemic shock
- increased intracranial pressure (brainstem herniation)
chronic
-iron deficiency anemia
(peptic ulcers, menstrual bleeding)
causes of decreased plasma oncontic pressure
hypoproteinemia by
- malnutrition (kwashiorkor)
- decreased albumin/ protein synthesis (liver failure)
- too much lost (kidney disease/ nephrotic syndrome)
definition of shock; and list the types
low cardiac output or low blood volume leads to decreased oxygen perfusion to tissues
- tissue O2 and nutrient delivery is inadequate to meet the physiologic needs of the body leading to hypoxic injury
- acute = reversible; prolonged = irreversible tissue damage
3 major mechanisms: decreased cardiac ouput, decreased blood volume (hypovolemia), or systemic inflammatory response syndrome causing increased need
types: cardiogenic, hypovolemic, shock associated with systemic inflammation, neurogenic, anaphylactic
origin / pathogenesis of septic shock
- *usually by gram + bacteria
- microbial pathogen recognition and subsequent release of TNF and IL-1 with increase in permeability and vasodilation (decreased vascular resistance and hypovolemia) and endothelial damage/activation (edema, NO release, hypovolemia) and coagulation (increased factor 7, TF, decreased protein C and antithrombin, stasis , and decreased coag factor washout) leading to to multiorgan dysfunction
- hypovolemic shock (hypotension from low BV)
- intravascular coagulation (DIC) [leads to hemorrhage]
- metabolic changes from decreased tissue oxygenation [ decreased ox phos , ATP, causing tissue necrosis and more inflammation, increased lactic acid and decreased pH]
multiorgan disfunction caused by: hypovolemia, hypotension, thrombosis, and subsequent decrease in O2 delivery leading to hypoxic injury
what is factor 2
prothrombin
what is the consequences of pulmonary edema? and clinical presentation associated with its manifestation ?
impedes O2 diffusion/ gas exchange
increases risk of bacterial infection
leads to pulmonary effusion
-seen in left ventricular heart failure
hyperemia vs congestion
hyperemia = too much blood arriving at arteriole end; physiologic and can be controlled by precapillary sphincter
congestion = venous obstruction causing decreased fluid drainage from venule side; pathologic
function of ADP
“platelet recruiter”
-increases activation of platelets by stimulating granule secretion
contributing factors to infarction ? types of infarction ? and what is seen on slide of infected tissue?
- anatomy of vascular supply (single or double or multiple)
- rate of occlusion (faster increases chance of infarction)
- tissue vulnerability to hypoxia
- types: MI, cerebral, pulmonary, bowel, gangrenous necrosis of limbs
- seen wedges shaped hypoxic injury (except brain) followed by acute inflammation
what is the risk of chronic emboli reorganized overtime
increased risk of pulmonary HTN
function of prostacyclin
inhibit platelet aggregation (vs TX A2)
vasodilation
what is the consequences of brain edema?
-can herniate through foramen magnum and compress brainstem blood supply = cause medullary neurologic damage or death
cholesterol cleft in embolus means the source is _____
atherosclerotic plaque
mechanism and clinical examples of of shock type: neurogenic and anaphylactic
neurogenic: anesthetic accident or spinal cord injury causing vasodilation and decreased vascular resistance due to autonomic disruption
anaphylactic : IgE mediated hypersensitivity run causing decreased vascular resistance
*both lead to hypotension and hypo-perfusion
mechanism, presentation, and complication of the hyper coagulable state by protein C and S deficiency and antithrombin 3 deficiency
mechanism: deficiency of protein C and S mean can not induce stopping of coagulation therefore inability to stop bleeding
complication: increased risk of venous thrombi, and recurrent ones
presentation: rare, begins in childhood
define systemic thromboembolism
- thromboembolus = varying level of blood vessel obstruction due to dislodges thrombi that become an emboli
- arterial/venous thrombi usually from cardia (mural) thrombi of left ventricle or vegetation from endocarditis or paradoxical embolism from PFO
- usually travel to LE to brain (or other organs) causing obstruction of blood supply and infarction
2 way renal failure causes transudate edema
- sodium/water retention by RAAS activation (increases hydrostatic pressure)
- nephrotic syndrome causes excess protein loss in urine decreased oncotic pressure)
effects of adrenal insufficiency in septic shock
initial increase in glucorticoids is stopped due to DIC causing hypoxic adrenal injury from low blood perfusion
define septic emboli and give details
-bloodborne infective material that can lead to septic infarction and abscess formation causing increase in inflammatory response
-seen in bacterial endocarditis vegetations break off
sx:
skin microemboli - purpuric
nail bed vascular damage - splinter hemorrhage
retinal microemboli- roth spots
signs of DVT? and what are outcomes of DVTs?
sx: unilateral swelling, warmth, redness, pain
outcomes: can lead to PE that
1. small = asymptomatic
2. medium = lodge in artery supply to portion of lung and cause SOB, dyspnea
3. large saddle emboli= lodge in primary arteriole trunk where bifurcation of pulmonary arteries is causing instant death from right heart failure
affects immediately following coumadin (anti-coal) delivery
- increased of coagulation and risk of thrombosis because decreases levels of protein C and S first
- can lead to coumadin induced skin necrosis
- therefore start with another anti-coagulant initially
what hemodynamic changes cause exudate vs transudate
exudate ( high in proteins and WBC and RBCs)
-caused by increased vascular permeability (seen in inflammation) and STASIS blood flow with some increase in interendothelial spaces
transudate (low cellular content)
- increased hydrostatic pressure or decreased oncotic pressure
- heart failure, liver disease, kidney disease
define hypercoagulabiltiy and list primary vs secondary causes
- aka thombrophilia
- disorders of the blood predisposing coagulation and increases risk of thrombis
- *venous thrombi is most common
primary (genetic) *point mutations
- decreased antithrombotic factors
- increased prothromboitic factors (factor 5 disease, prothrombin mutation)
secondary (acquired) *multifactorial
- bed rest (immobility)
- MI
- A-fib
- cancer
- tissue injury from surgery
- proestetic valves
- DIC
- heparin induced thrombocytopenia
- Oral contraceptives
5 functions of thrombin
- fibrinogen converter to fibrin (creation of secondary hemostatic plug and fibrin stabilization)
- PAR cleavage and continued platelet activation/ aggregation by stimulating platelet granule release (Increases TXA2/ ADP for recruitment and aggregation)
- pro inflammatory ( works with histamine to induce release of P-selectins from WP bodies to induce rolling)
- anti-thombotic (binds with thrombomodulin to activate plasmin)
- promoting irreversible platelet contraction (platelet plug stabilizer )
main effected organs in cardiogenic and hypovolemic and septic shock
- brain, heart , lungs, kidneys, adrenals, GI tract
- mimic hypoxic injury
adrenals
-coritcal lipid depletion used for steroid use
kidneys
-acute tubular necrosis
lungs
-not affected in pure hypovolemic shock bc resistant to hypoxic injury, but in septic shock = diffuse alveolar damage
DIC from septic shock causes micro thrombi deposition affected these organs. and lead to petechial hemorrhages on serosal skin
what are heart failure cells
hemosideren laden macrophages seen in hemosiderosis
mechanism of edema by decreased oncontic pressure pressure
loss of fluid equilibrium and osmosis across semi-permeable membrane
what is common in patients under the age of 50 with a stroke
patent foramen ovale causing venous emboli to become arterial and enter cerebral vasculature
what can cause increased capillary hydrostatic pressure and subsequent edema
- increased blood flow (hyperemia)
- venous obstruction (congestion)
- increased salt/water retention (RAAS activation)
- increase blood volume
clinically:
-heart failure
-renal failure
-pregancy
-liver cirrhosis
define hemostasis
stopping blood flow
what is the consequences of pulmonary effusion? and clinical presentation associated with its manifestation ?
- comprise O2 diffusion and gas exchange
- seen as progression of pulmonary edema from left ventricular heart failure
define fat/marrow embolism and give details
- bone marrow introduced into circulation and lodges into lungs
- from bone fracture or soft tissue trauma (i.e. resuscitation)
- sx: [usually asymptomatic] respiratory distress (dyspnea), and petechiae on chest, anemia, thrombocytopenia (platelet adhesion to fat globulins)
- *fat embolism syndrome: respiratory distress, mental status change, stroke anemia,thrombocytopenia (platelet adhesion to fat globulins)
*will see them in post mortem findings due to resuscitation before death
mechanism, presentation, and complication of the hyper coagulable state by heparin induced thrombocytopenia (HIT)
mechanism: pt given unfractioned heparin which binds to circulating P4F. heparin-P4F complex is recognized by IgG ab, and is then cross linked to the platelet FC receptor which causes platelet activation and aggregation. induced clotting and increases risk of thrombi
complication: decreases platelet levels in blood causing hemorrhage and thrombi
presentation: black fingers and toes and hands
what is factor 1
Fibrinogen
model the intrinsic pathway/ extrinsic pathway/ common pathway and factors needed
intrinsic
12–>11–>9 + 8 –> 10 + 5 –> thrombin –> fibrin
extrinstic
TF(3)–>7–>10 + 5 –> thrombin (2) –> fibrin (1)
common
10 and on
10 + 5a needs calcium and lipids for thrombin activation
mechanism and clinical examples of of shock type: cardiogenic
mechanism
-failure of myocardial pump (decreased cardiac output) resulting from intrinsic myocardial damage, extrinsic compression, or obstruction to outflow
example
-MI , ventricular rupture, compression, arrhythmia, pulmonary embolism, cardiac tamponade
Pt sx: hypotension, tachypnea, weak/ rapid pulse, cool/ pale skin
what is the main molecule responsible for platelet plug stabilization in primary and secondary hemostasis
thrombin
role of complement in septic shock
- microbial activation (alternative pathway) or C3b from plasmin release
- increases inflammatory response and endothelial damage
mechanism and clinical examples of of shock type: systemic inflammation mediated shock
mechanism:
activation of innate and adaptive immunity and inflammation leading to vasodilation (initial warmth), venous blood pooling, increased vascular permeability (leakage), endothelial injury and activation, DIC, and leukocyte mediated damage
ex:
overwhelming microbial infection
superantigens (toxic shock syndrome)
trauma, burn, pancreatitis
function of a2 - antiplasmin
binds and inhibits plasmin as a regulator
what makes thromboxane A2? what is is effect? what opposes it endogenously and exogenously?
- made by COX
- it increases platelet aggregation
- opposed by prostacyclin (PGI2)
- inhibited by aspirin
what factor deficiencys cause no bleeding? mild bleeding? severe bleeding? incompatible with life?
none- 12
mild-11
severe- 5, 7, 8, 9, 10
incompatible = 2 (prothrombin def)
myocardial cells vs myocardial fibroblasts during ischemic injury
- myocardial cells = Permanent tissue and will necrosis with no regeneration after ischemic damage
- myocardial fibroblasts = will remain viable after ischemic damage and have some regenerative properties
what is virchows triad?
- assessment of risk of thrombosis (coagulation)
1. endothelial injury (hypercholesteremia, inflammation)
2. abnormal blood flow (STASIS, turbulence)
3. hypercoagability (inherited, or acquired like cancer)
mechanism and clinical examples of of shock type: hypovolemic
mechanism: inadequate blood or plasma volume from extreme fluid loss (leading to decreased C.O.)
ex:
hemorrhage, vommitting, diarrhea, burns, trauma
Pt sx: hypotension, tachypnea, weak/ rapid pulse, cool/ pale skin
*this type of shock has the best prognosis if treated quickly
define disseminated intravascular coagulation (DIC) and describe the mechanism of pathology and clinical manifestation seen in the disorder
- widespread thrombi formation in microcirculation which can impede blood flow and damage organs
-due to increased thrombin systemic activation
-uses up platelets and coag factors and develops into coagulation factor deficiency and thrombocytopenia (hemorrhage disorders) which results in bleeding/hemorrhaging and ultimately hemorrhagic stroke or hypovolemic shock
*non-specific disease caused by complications of many diseases associated with systemic thrombin activation
(Sepsis, surgery/trauma, cancer, severe pregnancy complications)
manefestation: chest pain or sob (if seen with pulmonary blood clots); DVT symptoms if DVT associated; headaches and neuro symptoms if stroke,
effects: internal bleeding inside body, external bleeding of skin or mucosa (mucocutaneous bleeding), stroke, organ failure second to heart failure, possible death
- impairs mainly: Brain, lungs, heart kidneys
sx: blood in urine/stool, headaches, double vision seizure, purpura, petechiae, bruising, prolonged bleeding, heavy periods
what is the consequences of subcutaneous edema? and clinical presentation associated with its manifestation ?
- if significant it can impair wound healing and infection clearing
- seen in heart failure or renal disease
what mediates the neurogenic vasoconstriction reflex seen in the first step of hemostasis
endothelin in the endothelium that is exposed when damage occurs
what the 2 types of platelet granules and their contents
alpha granules
- have P-selectins on membrane
- contain coagulation factors: fibrinogen, factor 5, vWF,
- contain wound healing factors: fibronectin, platelet factor 4, PDGF, TGF-B
Dense (delta) granules
-contain: ADP, ATP, calcium, serotonin, and epinephrine
(functions are platelet recruiter and activator)
***TXA2 is inside platelets not in granules
what is a big cause of ascites
portal hypertension
what are weibel palade bodies? and why are they important for hemostasis ?
found in endothelial cells
- contain vWF (and P-selectins)
- vWF is activated during damage to promote platelet adhesion to the Gp1b receptor
- **LOOK LIKE CUCUMBERS ON HISTO SLIDE
what are 2 clinical signs of liver failure associated with hemodynamics
ankle edema (decreased albumin production decreases oncotic pressure) ascites (increased portal pressure/portal hypertension from liver cirrhosis causes congestion and fluid leakage into peritoneal space)
*transudate edema
arterial thrombi vs venous thrombi (color, cause, common site, effects)
arterial (white thrombi)
- causes occlusion –>ischemic infarction
- platelet rich
- occur in high shear stress (turbulence) i.e atherosclerotic plaque and vasculitis
- common at cerebral, coronary, and femoral arteries
venous (red)
- RBC rich ; firmer
- occurs in response to STASIS seen in inflammation
- common in the LE (DVT)
- attached to vessel walls in veins
what occurs in heart failure that causes transudate edema
- increased hydrostatic pressure by decreased pump activity and subsequent congestion
- low perfusion and decreased renal blood flow (causes RAAS activation and sodium water retention –> increased dilute blood volume)
* decreased renal blood flow also causes renal failure (causes increased protein losses and decreased oncotic pressure)
what is a platelet aggregation disorder
Glanzman thrombasthenia
- deficiency of Gp2b-3a complex
- decreases ability of fibrinogen cross links to form and results in platelet plug defects
what are the 4 main steps of hemostasis
- neurogenic (reflex vasoconstriction of damaged blood vessel to decrease surface area and blood flow to area)
- primary hemostasis (platleg plug formation)
- secondary hemostasis ( fibrin deposition and the coagulation cascade)
- clot stabilization and resorption
mechanism, presentation, and complication of the hyper coagulable state by antiphospholipid antibody syndrome (Lupus coagulant)
in vivo:
Ab bind to plasma proteins (B2-glycoprotein I) and induce hypercoaguble state
in vitro: Abs against plasma proteins that bind to phospholipids and inhibit coagulation
complications: present with thombotic complications
- aterial or venous thrombosis (DVT, PE)
- miscarriages
- cardiac valve vegetations
- thombocytopenia
- necrotic digits (digital gangrene)
- renal failure (micgroangiopathy)
presentation:
- symphilis false positive
- secondary form = lupus pts with symptpms and autoimmune disorder
- primary form = symptoms without autoimmune disorder
- antibodies present in normal people therefore not only dx of disease
mechanism, presentation, and complication of the hyper coagulable state by Factor V Leiden mutation
mechanism : point mutation of glutamine –> arginine causes factor 5 to be immune to protein C inhibition and chronically active
presentation: DVT/PE at young age with low risk factors and high family history
complication: DVTs and PE
Test: genetic testing, APCR test (assessment of clotting time before and after APC administered and + is no change)
what increases your risk of bleeding disorders
thrombocytopenia
factor deficiencys
**causes visceral and intercranial bleeding
non stop flight increases risk of ___ because of ____
thrombosis because of abnormal blood flow due to STASIS
what is a normal platelet count
> 150,000
[20-50,000 = petechiae / ecchymoses ]
[<10,000 = increased risk of intracranial hemorrhage or spontaneous mucocutaenous bleed]
[<2000 = widespread bruising, retinal hemorrhages, intracranial bleeding ]
manifestations of chronic congestion
- exudate edema by congestion
- hemosiderosis (hemosidereon laden Macrophages seen with chronic congestion in heart failure)
- tissue damage
function of t-PA
*fibrinolysis
convert plasminogen to plasmin to degrade the fibrin clot
most common cause of infarction ? lesser common cause and examples of when it could occur?
arterial thrombi occlusion
(can be red or white infarct leading to ischemic necrosis)
- can be caused by venous thrombi in an organ with single vein drain i.e. testes and ovaries
- normally venous thrombi just cause congestion and edema
what is the mechanism of effect by warfarin/coumadin
inhibits active form of vitamin K so vitamin K can’t bind calcium. therefore inhibits coagulation factors 2, 7, 9, 10, C, S
**anticoagulant
thrombus vs thrombosis
thrombus = blood clot thrombosis = clotting of blood by coagulation
what is nutmeg liver? and what causes it ?
chronic hepatic congestion due to central vein obstruction or flow reduction
-central lobular necrosis (cosseting necrosis of granulation inflammatio) resulting in alternating light/dark pattern of hepatic lobules
cause of ascites (peritoneal effusion) vs central hepatic lobule necrosis (nutmeg liver)
ascites
- caused by portal HTN /liver cirrhosis
- *increased risk of infection
nutmeg liver
-caused by central vein congestion/decreased blood flow due to chronic heart failure
role of platelets in hemostasis
- form the platelet plug that initial seal vascular defects
- provides a surface that binds and concentrates coagulation factors
- release granules that induce coagulation cascade, wound healing, and continued platelet activation and recruitment
what factor deficiency is associated with bleeding into joints (hemathrosis )
seen in hemophiliacs (factor 8 aka AHF)
what are the four fates of a thrombus
- propagation : platelet aggregation and fibrin clotting
- embolization : dislodging and travel to distal site
- dissolution: spontaneous shrinkage/ dissapperance by fibrinolysis [seen in new thrombi not older ones]
- organization/ recanalization: thrombi grow into endothelium, reopening of vessel, small remaining fibrous lump pf thrombi
prothomrbotic roles of endothelium
damage to endothelium activates it to:
- decrease thrombomodulin and protein C
- increase PAI (plasminogen activator inhibitor; inhibits t-PA)
- decrease VO to cause vasoconstriction
- increased exposure of adhesion molecules
signs that a large pulmonary embolism resulted in pulmonary infarction
- red infarct bc dual blood supply and venous thrombi
- wedged shape necrosis of hemorrhagic infarction area
- V/Q mismatch bc abnormal perfusion
- elevated D-dimers
- spiral CT shows vascular filling defect in lungs
- sx: SOB, hemoptysis, chest pain, pleural effusion
sites of blood alteration (turbulence and stasis) that lead to endothelial injury
- normal bifurcation (increases turbulence)
- dilated vessels (aneurysm or hemorrhoids cause stasis and TF respectively)
- internal obstruction (plaque)
- external compression (non contractile myocardium)
- inadequate heart chamber function (A-fib)
- hypervisocity
effects of elevated homocysteine levels
- prothomrobitc agent that causes linkage of fibronogen
- leads to arterial and venous thrombi and development of atherosclerosis
what disorders are associated with platelet adhesion defects? and what is their distinct difference in manifestation ?
- vWF disease
- loss of vWF - Bernard soulier syndrome
- loss of Gp1b receptor
*in BSS you can see giant platelets on microscopic slide
compare and contrast turbulence and stasis of blood flow
turbulence - caused by arterial/cardiac thrombi
stasis - venous thrombi
both- pro inflammatory activators of endothelium by injury , disrupt laminar flow, prevent washout of clotting factors
what is the antiothrombotic effects of endothelium and mechanisms of influence
- healthy endothelium covers TF and no clotting occurs
- platelet inhibition by PGI2, ADPase, and NO
- anticoagulant by thrombomodulin and thrombin coactivaiton of protein C and S) to degrade factors 5 and 8
- fibrinolytic by release of t-pa
- heparin like molecule which inactivates thrombin and factors 9 and 10
what is a key indicator of primary hemostatic defect
- mucocutaneous bleeding
- nose bleeds / gum bleeds
- petechiae
- purpura
- echymoses
- wound bleeding episodes following surgery or trauma
- rare: hemotypis (coughing blood) , GI bleeds, hematuria
basics of the fibrinolytic cascade
- arrest of clot formation (increased blood flow to wash away factors, thrombomodulin)
- clot resorption (t-pa and plasmin)
- tissue repair
petechiae vs purpura vs. ecchymosis common in platelet dysfunction
petechiae = small purpura = medium size ecchymosis = larger and palpable
mechanism of edema by increased capillary hydrostatic pressure
forces fluid out of capillary into interstitial space
antemortem vs post mortem clots
antemortem (embolus occurring during active blood flow)
* lines of zahn present (alternating pale areas of platelet/ fibrin from clot and red bread from RBCs)
postmortem clot (embolus occurring after death and stopping of blood flow)
- no lines of zahn
- looks gelatinous dark and red like jelly
histologic manifestation of infarction by time of onset and tissue type
min- hours before death : no sign
>4-12 hours before death: microscopic necrosis evidence of wedges shape infarct
cause of portal HTN vs central vein HTN
portal HTN
-vascular congestion of portal vein because of liver disease primarily. then leads to HTN bc of fibrosis and blocked blood flow
central vein HTN
-central vein congestion caused by heart failure and decreased vascular outflow primarily then leading to CV occlusion/ congestion and livers disease
define vegetation and endocarditis (including clinical presentation) and contrast 1. infected endocardial thrombi/vegetation vs. 2. nonbacterial thrombotic endocarditis vs 3. Libman-Sacks endocarditis
vegetation: large thrombi on heart valve
endocarditis : heart valve vegetation break off and manifestation
-skin micro emboli (purpuric)
-retinal microemboli (roth spots)
-nail bed damage ( splinter hemorrhage)
- bacterial or fungi adhere to damaged heart valves and cause endothelial injury and subsequent large thrombi (vegetation) formation. can lead to septic emboli formation and septic infarction (abscess formation and increased inflammatory response)
- vegetations made on non-infected heart valves due to hypercoaguable state
- vegetation formation seen in Lupus
function of D-dimers
fibrin breakdown product that is measured clinically to help diagnostic testing (particularly elevated in pulmonary infarction following Pulmonary embolism and effusion)
how does hyperglycemia and insulin resistance form in DIC ? what is the side effect of hyperglycemia ?
TNF and IL-1 release of stress hormones (glucagon and cortisol) causes increases BG levels and impair GLUT 4 in liver which increases insulin resistance
-hyperglycemia deactivates neutrophils and increases bacterial damage and infection risk
acute heart failure is associated with what other clinical manifestations? chronic?
soft tissue and pulmonary edema leading to pleural effusion
-left ventricle failure to pump causes congestion to occur in the pulmonary venous circulation and causes leaking of fluid into alveolar spaces(edema) and pleural space (effusion)
chronic congestion by hart failure
= hemosderosis (w/ hemosideren laden MOs)
= hepatic congestion (central vein obstruction and nutmeg liver)
what is the cause of instant death in a large saddle emboli coming from a DVT
right heart failure (because the heart can not pump past the obstruction)
what protein blocks the coagulation cascade from further coagulation
throbomodulin
what are the 5 causes of edema
- increased capillary hydrostatic pressure
- decreased oncotic pressure
- increased vascular permeability
- lymphatic obstruction
- sodium and water retention
stages of shock
*shock is a progressive disorder if not treated will lead to death
- initial non progressive phase: cutaneous reflex of vasoconstriction activated, organ perfusion maintained. affects baroreceptors, ADH, RAAS, and sympthaetics but not cerebral or coronary blood flow
sx: tachycardia, skin pallor and coolness, renal fluid conservation - progressive stage: widespread tissue hypoxia and tissue hypo-perfusion and onset of worsening hemostatic and metabolic balance. organs affected and begin to fail.
sx: increased lactic acidosis, low pH, arteriole dilation, and blood pooling, stasis leading to injury and DIC - irreversible stage: severe injury to organs resulting in no possible survival
sx: lysosomal enzyme leakage
resulting immunosuppression in septic shock
cycling between hyper inflammatory and immunosuppressive state by:
TH1 –>TH2 t cell shift
-activates anti-inflammatory effects of M2 MO
-lymphocycte apoptosis by attempted clearing and healing
