Hemodynamics and Shock Flashcards
Hemostasis
formation of blood clot at the site of injury
Conditions that lead to an increase in hydrostatic pressure
Venous obstruction (DVT)
Cirrhosis
CHF
CKD
Pregnancy
Most systemic emboli arise from what type of thrombus?
mural thrombi
An increase in salt retention leads to an increase in water retention; how does this effect the pressures across a blood vessel?
Leads to an increase in hydrostatic pressure and a decrease in oncotic pressure
What is the main goal of the coagulation cascade?
Production of fibrin to solidify the platelet plug
What occurs when there is a derrangement in the balance between hydrostatic and oncotic pressure?
Increased fluid movement out of the vessels and into the tissues
What are the possible mechanisms of edema?
Increased hydrostatic pressure
Decreased oncotic pressure
Increased vascular permeability
Lymphatic obstruction
When does edema occur?
When rate of fluid leakage from vessel exceeds rate of lymph drainage, fluid accumulates in tissues (interstitial space)
Alias for factor IIa?
Thrombin
In the coagulation cascade, thrombin is responsible for?
Converting fibrinogen into fibrin monomers
Activating factor V into factor Va
Activating factor VIII into factor VIIIa
Activates factor XIII to stabilize fibrin
What is the main concern when platelet counts drop to less than 2000/μL
Intracranial bleeding
Diseases associated with sudden massive hemorrhage
Aortic dissection in the setting of Marfan syndrome
AAA
MI
What are possible reasons for a decrease in albumin levels?
Malnutrition
Liver disease
Nephrotic syndrome
Transudates represent what type of edema?
Non-inflammatory edema
What is the goal of primary hemostasis?
To form a weak platelet plug at the site of injury
Where do mural thrombi form?
In the heart chambers
What is the main cause of increased hydrostatic pressure?
Impaired venous return
Pathogenesis of septic shock
TLRs recognize PAMPs
Release of inflammatory mediators (INF-γ, TNF, IL-1, IL-12, IL-18)
Activation of complement
Endothelial cell activation leading to vasodilation and edema
Endothelial dysfunction leading to release of procoagulant factors
Results in HoTN, hypovolemia, thrombosis and decreased tissue oxygenation
What are the high risk secondary or acquired causes of hypercoagulability?
prolonged bed rest or immobilization
MI
A-fib
tissue injury
CA
prosthetic cardiac valves
disseminated intravascular coagulation
heparin induced thrombocytopenia (HIT)
Antiphospholipid Ab syndrome
What cofactor does protein C require in order to inhibit factors Va and VIIIa and thus function as an anticoagulant?
protein S
Signs and symptoms of a DVT
unilateral swelling
pain
warmth and redness
In what direction do venous thrombi tend to grow?
in the direction of blood flow, toward the heart
What underlies the most serious and most common forms of cardiovascular disease?
Thrombosis
Libman-Sacks Endocarditis
A sterile verrucous endocarditis that occurs in the setting of systemic lupus erythematous
A deficiency in factor VIII results in what disease?
Hemophilia A
In what circumstances would there be an alteration in blood flow, from laminar to turbulent?
Normal arterial bifurcation
Dilated vessels (aneurysm, hemorrhoid)
Internal obstruction (atherosclerotic plaque)
External compression
Inadequate heart chamber function (Afib)
Alias for factor II
Prothrombin
Fate of a thrombus
Propagation
Embolization
Dissolution
Organize/recanalize
What factors are responsible for platelet adhesion to the subendothelial surface?
Where are these factors located?
Von Willebrand Factor (released from endothelial cells)
Gp1b (receptor located on platelet)
What is the morphology of a transudative effusion?
Protein poor
Translucent
Straw colored
Manifestations of hypoxic tissue injury
heart failure
HoTN
Renal failure
Lung failure
Coma
Death
Where do arterial thrombi usually occur?
coronary aa
cerebral aa
femoral aa
Chronic congestion can lead to what condition?
Hemosiderosis
How does endothelial activation cause prothrombic events?
Damage to the endothelium exposes vWF and tissue factor which will trigger coagulation
Downregulates thrombomodulin and protein C
Release plasminogen activator inhibitors (to inhibit tPA)
What conditions predispose a patient to formation of mural thrombi?
Arrhythmias
Dilated cardiomyopathy
MI
Myocarditis
Endothelial cells release von willebrand factor, where is this factor located within the cells?
Weibel Palade bodies
Three stages of shock
Nonprogressive phase: perfusion remains
Progressive stage: hypoperfusion of organs
irreversible stage: severe tissue injury
What morphological changes are seen with edema?
Clearing and separation of the ECM and subtle cell swelling
Most common trigger of septic shock
Gram-positive bacterial infection
Fibrinolysis limits the size of a clot through the activity of what enzyme?
Plasmin
Endothelial activation is believed to have an important role in triggering what type of event?
Arterial thrombotic event
Hemosiderin-laden macrophages are often termed what because of the condition that causes this?
Heart failure cells
(CHF leads to chronic congestion which leads to hemosiderin-laden macrophages)
Plasmin is tightly controlled by what inhibitory factor?
α2-plasmin
What clinical manifestation can lead a physician to a defect in primary hemostasis?
Mucocutaneous bleeding
Antiphospholipid antibody syndrome
An acquired hypercoagulable condition resulting from Abs against plasma proteins that bind to phospholipids, leading to a prothrombic state
After injury, what is the first thing to occur prior to onset of primary hemostasis? What is the mechanism behind this?
Vasoconstriction
A neurogenic reflex and endothelin
A majority of emboli are
dislodged thrombi
Most common pathogenic feature of shock associated with systemic inflammation is?
Massive outpouring of inflammatory mediators from cells of the innate and adaptive immune system, producing arterial vasodilation, vascular leakage, and venous blood pooling
What type of thrombus underlies the majority of infarctions?
arterial
Septic infarctions are often converted into
Abscesses
Development of DVT is common where?
Lower extremity
What type of edema signals potential underlying cardiac or renal disease?
Subcutaneous edema
What protein is key to maintaining plasma osmotic pressure?
Albumin
Why are amniotic emboli lethal?
Squamous cells, hair, fat and mucin from the fetus enter maternal circulation; mother has an anaphylactic rxn to the material
Purpura and ecchymoses are characteristic of what kinds of disorders?
Systemic disorders that disrupt small blood vessels
Alias for factor VIII
Antihemophilic A factor (AHF)
Dependent edema
The distribution of subcutaneous edema shifts with changes in gravity
i.e. in the legs when standing, in the sacrum when laying recumbent
What typically leads to salt retention?
Kidney disease
Kidney hypoperfusion 2/2 cardiovascular disease
What are common consequences of a PE?
right sided heart failure
pulmonary hemorrhage
pulmonary infarction
sudden death
What is the most common form of thromboembolic disease?
Pulmonary emboli
Chronic congestion differs from acute congestion in that
a chronic increase in blood volume can lead to capillary rupture, releasing blood cells in addition to fluid
Transudate fluid contains
low protein content, few cells
What is the significance of the lines of zahn to a pathologist?
Shows that the clot formed antemortem in flowing blood, rather than postmortem
Types of shock
Cardiogenic
Hypovolemic
Septic
Neurogenic
Anaphylactic
Plasmin is activated from its zymogen form, plasminogen, by what factor?
t-PA
What is the purpose of secondary hemostasis?
Production of fibrin to stabilize the weak clot produced by primary hemostasis
Common effects of a venous thrombus?
Painful congestion and edema distal to obstruction
Can embolize to the lungs
Common location of a superficial venous thrombosis?
Saphenous Vs
What are the characteristics of a postmortem clot?
Gelatinous
Dark red dependent portion of settled RBCs
Yellow fatty upper portion
Not attached to underlying vessel wall
A prothrombin time (PT) assesses the function of what proteins in what pathway?
Factors VII, X, V, II and fibrinogen in the extrinsic pathway
Liver failure results in edema and ascites, what is ascites?
Fluid accumulation in the abdomen
What type of edema typically results from renal dysfunction
Periorbital edema
(edema in areas containing loose CT)
What are the peripheral manifestations of endocarditis?
Purpura (Janeway lesions)
Roth spots in the retina
Splinter hemorrhages in nail bed
What is the dominant histologic characteristic of infarction?
Ischemic coagulative necrosis
Standard of care for treating septic shock?
Abx to treat the underlying infection
Pressors and supplemental O2
IV fluids
What factors help to maintain CO and BP in the nonprogressive phase of septic shock?
What does this result in?
Baroreceptors, catecholamines, RAAS, ADH
Results in tachycardia, peripheral vasoconstriction, renal conservation of fluid
What is a major cause of arterial thromboses?
Atherosclerosis
Pulmonary edema occurs 2/2
Left ventricular failure (mainly)
Renal failure
ARDS
Functional role of thrombin im primary hemostasis?
initiation of the release factors from platelet granules
What conditions predispose a patient to formation of aortic thrombi?
Ulcerated atherosclerotic plaques
Dilated aneurysms
What are the two types of platelet adhesion disorders discussed in the lecture?
Von Willebrand disease
Bernard Soulier syndrome
What occurs in Kwashiorkor?
Malnutrition leads to protein deficiency which then leads to development of edema
What clinical manifestation is seen with thrombocytopenia but not usually seen with qualitative disorders?
Petechiae
In what condition are septic emboli common?
Endocarditis
Main effect of an arterial thrombus?
Occlusion of a critical vessel (coronary or cerebral A)
IWhat renal condition leads to a loss of albumin into the urine, leading to a decrease in oncotic pressure and thus edema?
Nephrotic syndrome
What are the most common inherited causes of hypercoagulability (thrombophilia)?
Point mutation in factor V (most common)
Prothrombin gene mutation
Common cause of fat emboli seen postmortem?
CPR
What do venous thrombi contain that distinguish them from postmortem clots?
Lines of Zahn
How does Renal failure contribute to the production of edema?
Renal failure leads to the retention of salt and water, increasing blood volume and leading to edema
What is the most common cause of renal hypoperfusion?
CHF
Bleeding time was often a method used by physicians to determine if there was a defect in platelets, what is the normal bleeding time?
2-7 minutes
What steps are involved in platelet aggregation?
The conformational change in the GpIIb-IIIa receptor complex allows for fibrinogen to bind with higher affinity, these fibrinogen molecules cross-link to form aggregates
The nutmeg appearance of the liver results from what condition?
CHF or local thrombus which results in chronic passive congestion of the central vein
Types of granules within platelets
α-granules
δ-granulse (dense)
Factor XI deficiency
Leads to mild bleeding due to thrombin’s ability to positively feedback on XI to amplify the cascade.
What factors are dependent on vitamin K?
Factors II, VII, IX, X
Protein C and protein S
When do arterial thrombi usually occur?
When there is turbulent blood flow or endothelial injury
What is the major contributor to the formation of venous thrombi?
Stasis
Venous thrombi are termed stasis thrombi for what reason?
Thet form in the sluggish venous circulation and contain more enmeshed RBCs
Effusion
When rate of fluid leakage from vessel exceeds rate of lymph drainage, fluid accumulates in body cavities
What type of infarct occurs when there is collateral supply to an organ, like the lung?
Red infarct
What disorder is characterized by the loss or impaired production of platelets?
Thrombocytopenia
Vitamin K is antagonized by what drug?
Coumadin
Hyperemia
increase blood volumes arriving to a tissue; a physiologic process that occurs 2/2 arterial dilation during exercise
what factors influence the development of an infarct?
Anatomy of vascular supply (one vs dual)
Rate of occlusion
Tissue vulnerability to hypoxia
What leads to ascites?
Decreased production of albumin 2/2 liver failure
Portal HTN leading to congestion
Cardiogenic shock
Low cardiac output 2/2 inability of the heart to pump properly
What do hyperemia and congestion have in common? What differentiates them?
They both involve an increase in blood volume within tissues, but they differ in the mechanism for which this occurs
Morphology of acute pulmonary congestion
Engorged alveolar capillaries, alveolar septal edema and focal intraalveolar hemorrhage
In what direction do arterial thrombi tend to grow?
Retrograde, toward the heart
Pulmonary emboli typically originate from?
DVTs
What obstetric thrombotic complications occur with antiphospholipid antibody sydrome?
unexplained miscarriage or stillbirth
Characteristics of an amniotic embolism
sudden severe dyspnea
cyanosis
shock
If patient survives: pulmonary edema develops
What conditions lead to an increase in capillary permeability?
Sepsis
Inflammation
Burns
Glanzmann thrombasthenia results from a defect in what factor of hemostasis?
The GpIIb-IIIa receptor complex
Common causes of air emboli
Cardiac catheterization
Decompression sickness (the bends, caisson dz)
What must be considered in patients < 50 y/o who present with thrombosis, even if acquired risk factors are present?
Inherited causes of hypercoagulability
Bernard Soulier syndrome involves a defect in what factor?
Gp1b receptor on platelets
Exudative fluid components?
What is an exudate indicative of?
High protein, some RBC or WBC
Inflammation
Shock
A state in which dimished cardiac output or reduced efective circulating blood vlume impairs tissue perfusion and leads to cellular hypoxia
Edema is most commonly seen in what tissues?
Subcutaneous tissues
Lungs
Brain
Mutations in prothrombin gene leads to increased risk of thrombus formation how?
What mutation occurs?
Leads to elevated prothrombin levels
Single nucleotide change in the 3’ untranslated region (G20210A)
What vascular thrombotic complications occur with antiphospholipid antibody sydrome?
arterial or venous thrombosis
Where does fluid accumulate in pulmonary edema?
Within the alveolar spaces
Do the disorders involved in platelet adhesion, Von Willebrand and Bernard Soulier, have a defect in platelet aggregation as well?
No
What are the primary abnormalities that lead to thrombosis?
what are these termed?
Endothelial injury
Abnormal blood flow
Hypercoagulability
(Virchow Triad)
What are the other genetic causes of hypercoagulability, that are less common?
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
What type of embolism is a major cause of maternal mortality?
Amniotic fluid embolism
Air embolism
introduction of air into closed circulation
What is the most common cause of morbidity and mortality in Western society?
Cardiovascular disease
What factors are released from endothelial cells that inhibit platelet activation and aggregation?
PGI2
NO
ADPase
In septic shock, disseminated intravascular coagulation leads to a widespread deposition of what substances?
In what locations?
Fibrin-rich microthrombi
Brain, heart, lungs, kidney, adreanl glands and GI tract
Septic emboli result from
bloodborne infective material
What test is performed clinically to assess markers of thrombotic states?
D-dimer
alias for factor I
fibrinogen
Fat emboli result from
fracture or soft tissue trauma that leads to bone marrow being introduced into circulation
Filariasis
A parasitic infection (Wuchereria) in which the organism induces obstructive fibrosis of lymphatic channels and lymph nodes, leading to lymphedema
Fat embolism syndrome is characterized by
respiratory distress
mental status change
anemia
thrombocytopenia
(can be fatal)
What is the mechanism that leads to hepatic congestion
Obstruction of the central vein
A patient with breast CA that had lymph nodes removed would develop what type of fluid accumulation:
edema, effusion, lymphedema?
lymphedema
What complex is the most important activator of factor IX?
factor VIIa/Tissue factor complex
What are the steps involved in primary hemostasis?
- Adhesion
- Activation
- Aggregation
Hemosiderosis
abnormal accumulation of iron as hemosiderin in alveolar macrophages
Thromboxane A2 is a potent promoter of platelet aggregation, what inhibits formation of TxA2?
Aspirin
Lymphedema results from
a disruption in the lymphatic vessels causing an impairment in the clearance of interstitial fluid
What bacterial proteins are the underlying cause of toxic shock syndrome?
Superantigens
What triggers platelet activation?
ADP and Thrombin
Platelet activation occurs after platelets have adhered to the subendothelial layer, what steps occur during activation?
A conformational change in the platelets increasing the surface area
Negatively charge phospholipids translocate to the surface to bind calcium
Conformational change in the GpIIb-IIIa receptor complex to increase it’s affinity for fibringoen
Release of granular contents (ADP and TxA2)
Endothelial cells express multiple factors that oppose coagulation, these factors include
thrombomodulin
endothelial protein C receptor
How is the definitive secondary hemostatic plug formed?
Thrombin converts fibrinogen into fibrin, cementing the aggregated platelets from primary hemostasis in place
Explain the nutmeg liver appearance
Alterations of light and dark areas, dark areas are dying hepatocytes
An exudate represents what type of edema?
Inflammatory edema, caused by an increase in vascular permeability 2/2 release of inflammatory mediators
What type of infarct results when the organ is dependent on one vessel, like the spleen?
White infarct
What disorder is commonly associated with hemophilia?
hemarthrosis, bleeding into the joints
What are the low risk secondary or acquired causes of hypercoagulability?
Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy, postpartum)
OCP
sickle cell anemia
smoking
Morphology of an exudative effusion
Protein rich
Cloudy d/t presence of WBCs
what cells produce tPA?
Endothelial cells
Thrombi often contain lines of Zahn, what defines this?
pale platelet and fibrin deposits alternating with darker red cell-rich laters
Septic infarctions result when?
Cardiac valve vegetations embolize or when microbes seed necrotic tissue
What normally balances the fluid and solutes within blood?
Hydrostatic pressure pushing water and salts out
Colloid osmotic pressure pulling water and salts in
What differentiates transudate from exudate in terms of endothelial changes?
Exudate results from inflammation and inflammation leads to an increased interendothelial space, which does not occur in fluid leakage of a transudate
What are the dermatologic manifestations of defects in homeostasis, most commonly platelet dysfunctions?
Petechiae (small, < 3 mm)
Purpura (larger)
Ecchymosis (palpable)
What things contribute endothelial activation?
physical injury
infectious agents
abnormal blood flow
inflammatory mediators
toxins
metabolic abnormalities
What complex is the most important activator of factor X?
factor IXa/factor VIIIa complex
Localized edema 2/2 infection, inflammation, trauma, tumors, surgery or malformations is characterized as?
Lymphedema
Hypovolemic shock
Low cardiac output d/t low blood volume, likely resulting for massive hemorrhage
Coagulation involves the assembly of reaction complexes that depend on Calcium binding to what on factors II, VII, IX and X?
γ-carboxylated glutamic acid
How does turbulent blood flow contribute to the prothrombotic state?
Activates endothelium
Pushes platelets toward the periphery, in closer contact to the endothelium
Prevents washout of clotting factors which typically occurs with laminar blood flow
Of the coagulation factors, which is the most important due to its various roles in hemostasis?
Thrombin
What is the most common cause of hepatic congestion
Right heart failure
Infarcts are classified according to color and the presense or absence of infarction, what are the classifications?
White infarct: arterial, platelet-rich infarcts occurring in high shear stress
Red infarct: venous, red cell rich, occur in stasis typically in LE
Factor V Leiden
Mutation leading to a glutamine for arginine substitution that renders factor V resistent to inactivation by protein C, increasing risk of developing a thrombus
what occurs with the organization of a thrombus?
There is ingrowth of endothelial cells, smooth muscle cells, and fibroblasts
Histologically, one can determine Bernard Soulier syndrome based on what changes in the platelets?
They appear larger
Reactions that produce γ-carboxylated glutamic acide are dependent on what co-factor?
Vitamin K
A saddle emolism results in instantaneous death for what reason?
emolism leads to right heart failure
Conditions that lead to decreased oncotic pressure
Malabsorption
Nephrotic Syndrome
Liver failure
Malnutrition
A partial thromboplastin time (PTT) assesses the function of what proteins in what pathway?
Factors XII, XI, IX, VIII, X, V, II, fibrinogen in the intrinsic pathway
Most common cause of mild bleeding tendencies
inherited defects in vWF
Aspirin
Uremia
Congestion
Reduced flow of blood from a tissue often pathologic in origin
why do patients in septic shock exhibit insulin resistence and hyperglycemia?
IL-1 and TNF drive gluconeogenesis and impair the surface expression of GLUT4 transporters
What is the mechanism behind Heparin-induced Thrombocytopenia (HIT) syndrome?
Occurs after administration of unfractionated heparin, which causes Ab production against platelet factor 4-heparin complexes, leads to a prothrombic state 2/2 activation and aggregation of platelets
The clinical significance of hemorrhage depends on what?
Volume of blood loss
Rate
Location
Due to the decrease in outflow of blood from congestion, what typically develops?
Edema
Secondary antiphospholipid antibody syndrome occurs in what type of individual?
One with a well-defined autoimmune disease, often systemic lupus erythematosus
In patients with thrombocytopenia, are the functions of the platelets intact?
Yes
Heparin-like molecules are present on the surface of endothelial cells, these molecules bind and activate what molecule that in turn inhibits factors IXa, Xa, thrombin
Antithrombin III
What factors limit coagulation?
Blood flow by washing away the factors that activate clotting
Loss of factors on platelet d/t fibrin coat
Plasmin
Most common cause of DVT formation
Immobilization
