Fluid & Hemodynamics Flashcards
1
Q
How do microbes initiate septic shock? What is the effect of endothelial cell activation and injury during septic shock? What are the effects of mediators on the coagulation pathway? What are the consequent effects on tissues?
A
- Microbes initiate septic shock by
- Interacting with innate immune system such as neutrophils, macrophages
- Interacting with humoral element of innate immune system to activate complement and coagulation cascade
- Acts directly on endothelium
- End result is mediator release such as TNF, IL 6, 8, 10, NO, PAF - Effects of endothelial cell activation
- Thrombosis
- Increased vascular permeability
- Vasodilation - Effects on coagulation pathway
- Microvascular thrombosis
- Decreased fibrinolysis
- DIC - Effect on tissues
- Tissue ischaemia
- Multi-organ failure
2
Q
What is DIC?
A
- Thrombo-haemorrhagic disorder or consumptive coagulopathy characterized by
- Intravascular activation of platelet and coagulation cascade by tissue factors
- Formation of thrombi in microcirculation
- Consumptive coagulopathy
- Increases bleeding risk/diathesis
- Presenting with clinical picture of tissue hypoxia/infarction, hemorrhage and multi-organ failure
3
Q
Describe the pathophysiology of DIC
A
- Occurs via 2 mechanism
+ Release of tissue factor into circulation
+ Widespread endothelial cell injury with increased tissue factor expression by TNF - Activation of platelets and coagulation cascade due to tissue factor release
- Decreased fibrinolysis and Protein C
- Formation of thrombus in micro-circulation
- Stasis of blood
- Reduced washout of activated clotting factors
- Formation of multiple fibrin-rich thrombi
- Consumes platelets, fibrin, clotting factors -> Consumptive coagulopathy
- Secondary activation of fibrinolysis
- Increases bleeding risk
4
Q
List some common triggers of DIC. What are the pathological consequences of DIC? In DIC, what would you expect to find on FBC and coagulation profile?
A
- Causes of DIC
- Sepsis
- Trauma
- Burns
- Malignancy: Lung, stomach, pancreas CA
- Obstetrics: Amniotic fluid embolism, fetal death in-utero
- Others: Snake bite - Pathological consequences
- Thrombus in microcirculation leading to ischaemia of vulnerable organs
- Consumptive coagulopathy of platelets, fibrin, clotting factors
- Causing bleeding diathesis - Ix findings
- Low Ho
- Low platelets
- High WCC
- High INR
- High PT and aPTT
- High fibrin degradation products
5
Q
What are the consequences of DIC?
A
- Thrombotic consequences
- Tissue hypoperfusion and ischaemia
- Multi-organ failure
- Microangiopathic haemolytic anaemia - Bleeding consequences
- Hemorrhage
6
Q
What are the risk factors for development of AAA? Describe the pathogenesis of AAA formation. What are the clinical consequences of AAA?
A
- Risk factors for AAA
- Male
- Age > 60yo
- Connective tissue disorder: Marfan’s syndrome
- Smoking
- HTN
- Atherosclerosis
- Diabetes - Pathogenesis of AAA
- Structural or functional compromise of the vascular wall connective tissue
- Can be due to
+ Connective tissue disorder (Marfan’s) with poor intrinsic quality of vessel wall connective tissue
+ Atherosclerosis plaque in intima compressing on media
- Local inflammation
- Collagen degradation by proteolytic enzymes
- Loss of vascular smooth muscle cells
- Inappropriate synthesis of non-elastic non-collagen ECM/cystic medial degeneration - Clinical consequences of AAA
- Rupture -> hemorrhage -> death
- Compression of surrounding tissues/organs
- Thrombus formation -> embolus
- Obstruction of branches -> reduced perfusion/ischaemia of organs
- Asymptomatic
7
Q
What are the morphological features of AAA? What are the risk of rupture of AAA?
A
- AAA is
- Abnormal dilatation of the abdominal aorta
- Commonly seen in between renal artery and iliac bifurcation
- Atheromatous ulcers and mural thrombus
- Medial thinning and destruction - Risk of rupture
- < 4cm = nil
- 4 - 5cm = 1%
- 5 - 6cm = 11%
- >6cm = 25%
8
Q
Describe the pathogenesis of aortic dissection. How are aortic dissections classified? What are the potential consequences of aortic dissection?
A
- Pathogenesis of aortic dissection
- Medial wall weakness
- Commonly seen in
+ HTN - Medial hypertrophy of vasa vasorum also present
+ Connective tissue disorder
- Starts with intimal tear
- Allows blood to enter medial layer
- Dissects proximally or distally along laminar plane
- Formation of medial hematoma which can eventually rupture - Classification of aortic dissections
- Stanford: Type A (proximal), Type B (distal)
- DeBakey: Type I (asc + desc), Type II (asc), Type III (desc) - Consequences of aortic dissection
- Rupture into intima or through adventitia
- Rupture into pericardium, pleural or peritoneum
- Cardiac tamponade
- MI
- Aortic insufficiency
- Distal organ ischaemia depending on type
+ Type A: CVA
+ Type B: Renal, mesenteric, spinal, lower limb ischaemia
9
Q
What is aortic dissection? What are the major risk factors for aortic dissection?
A
- Aortic dissection is
- Blood dissecting through laminar plane of aortic media
- Usually occurs within 10cm of aortic valve
- Can extend proximally or distally
- Forming medial hematoma which can eventually rupture
- Does not affect aorta that has substantial atherosclerosis - Risk factors
- HTN
- Connective tissue disorder: Marfan’s syndrome
- Males
- Age 40 - 60yo
- Trauma
- Iatrogenic arterial cannulation/catheterisation
10
Q
Define shock/What is shock? Describe the stages of shock. What happens at the cellular and tissue level during the irreversible phase?
A
- Shock is hypotension due to
- Reduce cardiac output
- Reduce effective circulatory blood volume
- Impaired tissue perfusion
- Cellular hypoxia - Stages of shock
A. Non-progressive
- Reflex neurohumoral compensatory mechanisms triggered (baroreceptor reflex, sympathetic nervous system, renin-angiotensin system) -> maintains cardiac output and BP -> maintain perfusion to vital organ
B. Progressive
- Tissue hypoperfusion
- Worsening of circulatory and metabolic imbalance
- Metabolic lactic acidosis
C. Irreversible
- Irreversible cell damage
- Lysosomal enzyme leakage and nitric oxide synthesis
- Leads to death - Irreversible phase
- Mitochondrial swelling
- Lysosomal swelling -> leakage of lysosomes enzymes
- Severe cell damage
- Nitric oxide release -> Decrease myocardial contractility
- Acute tubular necrosis -> Acute renal failure
- Ischaemic gut -> Bacteraemic shock
- Pre-cardiac arrest -> Death
11
Q
Describe the initial clinical presentation of shock. What other types of shocks are there?
A
- Clinical presentation of shock
- Fever
- Hypotension
- Tachycardia
- Tachypnea
- Cool clammy skin
- Altered mental status
- Oliguria
- Narrowed pulse pressure - Types of shock
- Hypovolaemic -> Hemorrhage, burns, GI losses
- Cardiogenic -> AMI, arrhythmia, cardiomyopathy
- Distributive -> Sepsis, anaphylaxis
- Obstructive -> PE, tamponade, PTx
- Neurogenic -> Spinal trauma
12
Q
Describe the process of primary hemostasis. How is the coagulation cascade activated following injury? What does prothrombin time measure?
A
- Primary hemostasis is the formation of a platelet plug
- Endothelial injury exposing ECM (collagen, vWF)
- Platelets adhere via G1b protein to vWF
- Platelets activated
- Platelets change shape from flat to round
- Platelets secrete Thromboxane A2 (TXA2) and adenosine phosphate (ADP) which attract more platelet
- Platelets bind to each other via G2b-3a to form platelet plug - Coagulation cascade activated due to release of TF with endothelial injury
- TF activates extrinsic pathway of coagulation cascade
- Activates Factor 7 -> 7a
- Activates Factor 10 -> 10a
- Activates Factor 2 -> 2a (Thrombin)
- Activates Factor 1 -> 1a (Fibrin)
- Fibrin cross-link with platelets to form fibrin clot making up the secondary hemostatic plug - Prothrombin time measures
- Extrinsic and common coagulation pathway
- Factor 7, 10, 5, 2, 1
13
Q
What is the sequence of events that occur to produce hemostasis after a vascular injury? What laboratory tests are used to assess the function of the different pathway of the coagulation cascade? What factors restrict clot to site of vascular injury?
A
- Sequence of events leading to hemostasis
- Transient vasoconstriction
+ Mediated by neurogenic reflex and local factors (endothelin)
- Primary hemostasis
+ Endothelial injury exposes ECM -> Platelets activated and adheres -> Platelet plug formed
- Secondary hemostasis
+ Endothelial injury releases TF -> Activates coagulation cascade -> Thrombin and fibrin generated
+ Fibrin polymerises to form permanent plug with platelets
- Anti-thrombin effect
+ Counter-regulatory mechanism to limit plug to site of injury -> Endogenous anticoagulants, fibrinolytic cascade pathway activation - Laboratory test to assess coagulation cascade
- PT: Assess extrinsic and common coagulation pathway including Vit K dependent factors (10, 7, 2)
- aPTT: Assess intrinsic and common coagulation pathway - Clot limited to site of vascular injury by 2 mechanisms
- Endogenous anticoagulants
+ Antithrombins -> Antithrombin III inactivate thrombin, Factor 10, 9, 11, 12
+ Protein C + S -> Inactivates Factor 5, 8
+ Tissue factor pathway inhibitor (TFPI)
- Fibrinolytic cascade pathway activation
+ Tissue plasminogen activator (tPA) activates plasminogen
+ Plasminogen converted to plasmin -> Acts to degrade fibrin
14
Q
In the normal coagulation cascade, what happens after Factor 10 is activated? Describe the process of fibrinolysis.
A
- Factor 10 activation is the commencement of common clotting pathway
- Activates Factor 2 (Prothrombin) -> 2a (Thrombin)
- Thrombin activates Factor 1 (Fibrinogen) -> 1a (Fibrin)
- Thrombin also activates Factor 8 -> 8a in the presence of Ca
- Causes cross-linkage of fibrin to form permanent plug - Fibrinolysis occurs with the activation of fibrinolytic cascade
- Activated by Factor 7a or plasminogen activators
- Plasminogen activators are tPA and urokinase
- Activates plasminogen to secrete plasmin
- Plasmin acts to degrade fibrin to fibrin-degradation products (FDP)
- Plasmin is inactivated by alpha-2 plasmin inhibitor
15
Q
What is edema? What are some of the causes of edema? What is the difference in composition of fluid between inflammatory and non-inflammatory edema. What factors govern the movement between vascular and interstitial spaces? What is the pathogenesis of cardiogenic edema?
A
- Edema is
- Increase fluid in the interstitial space/3rd space - Causes of edema
- Inflammatory -> Infection, tissue necrosis
- Non-inflammatory -> Increase hydrostatic pressure (fluid overload, CCF), reduce oncotic pressure (hypoalbuminaemia), venous obstruction (DVT)
- Lymphatic obstruction (tumor, radiation, surgery)
- Na and water retention (increase Na intake, renal insufficiency) - Inflammatory vs non-inflammatory fluid
- Inflammatory: Exudate, high protein concentration
- Non-inflammatory: Transudate, low protein concentration - Factors influencing movement of fluid between vascular and interstitial space
- Hydrostatic pressure
- Oncotic pressure
- Permeability of capillary walls - Pathogenesis of cardiogenic edema
- Cardiac failure -> Reduce cardiac output -> Reduce kidney perfusion -> Activates renin-angiontension-aldosterone system -> Increase Na + H20 retention -> Increase hydrostatic pressure -> Peripheral edema
