Week 2 Flashcards
Haemostasis
The arrest of bleeding and
the maintenance of vascular patency
Components of Normal Haemostatic System
1) Formation of platelet plug = Primary Haemostasis
2) Formation of fibrin clot = Secondary Haemostasis
3) Fibrinolysis
4) Anticoagulant Defences
How are platelets formed?
Platelets are formed in the bone marrow by ‘budding’ from megakaryocytes
Platelet structure
Platelets are small anucleate discs with a mean life-span of 7-10 days.
Platelet function
Endothelial damage exposes collagen and releases Von Willebrand Factor (VWF), and other proteins to which platelets have receptors – platelet adhesion at the site of injury.
There is then secretion of various chemicals from the platelets, which leads to aggregation of platelets at the site of injury.
Failure of Platelet Plug Formation - causes
Vascular
Platelets - Reduced number (thrombocytopenia)/Reduced function
Von Willebrand Factor
Consequences of failure of Platelet Plug Formation
Spontaneous Bruising and Purpura
Mucosal Bleeding
Intracranial haemorrhage
Retinal haemorrhages
Mucosal bleeding types
Epistaxes
Gastrointestinal
Conjunctival
Menorrhagia
Hemostasis includes three steps that occur in a rapid sequence: what are they?
(1) vascular spasm, or vasoconstriction, a brief and intense contraction of blood vessels; (2) formation of a platelet plug; and (3) blood clotting or coagulation, which reinforces the platelet plug with fibrin mesh that acts as a glue to hold the clot together.
What are platelets made up of?
Fibrin - can be broken own by fibrinolytic drugs
Platelets contain granules that they release to attract more platelets (aggregation of platelets) at site of injury; what are the chemicals released?
ADP (adenosine diphosphate), serotonin, and thromboxane A2 (which activates other platelets).
Steps of the coagulation cascade (3rd step of haemostasis)
First, blood changes from a liquid to a gel.. Damaged vessels and nearby platelets are stimulated to release prothrombin activator, which in turn activates the conversion of prothrombin into thrombin. This reaction requires calcium ions.
Thrombin facilitates the conversion of fibrinogen into long, insoluble fibers or threads of the protein, fibrin. Fibrin threads wind around the platelet plug at the damaged area of the blood vessel, forming an interlocking network of fibers and a framework for the clot.
This net of fibers traps and helps hold platelets, blood cells, and other molecules tight to the site of injury, functioning as the initial clot.
What are the main components of the coagulation cascade?
Prothrombin, thrombin, and fibrinogen are the main factors involved in the outcome of the coagulation cascade.
Where are Prothrombin and fibrinogen produced?
Prothrombin and fibrinogen are proteins that are produced and deposited in the blood by the liver.
What kind of molecule is thrombin?
Enzyme that converts fibrinogen to fibrin.
Function of pro-thrombin activator?
Activates the conversion of prothrombin, a plasma protein, into an enzyme called thrombin.
Function of fibrin
Fibrin threads wind around the platelet plug at the damaged area of the blood vessel, forming an interlocking network of fibers and a framework for the clot. This net of fibers traps and helps hold platelets, blood cells, and other molecules tight to the site of injury, functioning as the initial clot. This temporary fibrin clot can form in less than a minute and slows blood flow before platelets attach.
How do healthy undamaged vessels prevent abnormal haemostasis and clotting reactions?
The endothelial cells of intact vessels prevent clotting by expressing a fibrinolytic heparin molecule and thrombomodulin, which prevents platelet aggregation and stops the coagulation cascade with nitric oxide and prostacyclin.
Failure of Fibrin Clot Formation - causes
Single clotting factor deficiency eg Haemophilia
Multiple clotting factor deficiencies, usually acquired eg Disseminated Intravascular Coagulation
Increased fibrinolysis - usually part of complex coagulopathy
Thrombophilia
Deficiency of naturally occuring anticoagulants - may be hereditary
Increased tendency to develop venous thrombosis (deep vein thrombosis/pulmonary embolism)
Common Pathway
In the final common pathway, prothrombin is converted to thrombin. When factor X is activated by either the intrinsic or extrinsic pathways, it activates prothrombin (also called factor II) and converts it into thrombin using factor V. Thrombin then cleaves fibrinogen into fibrin, which forms the mesh that binds to and strengthens the platelet plug, finishing coagulation and thus hemostasis.
Extrinsic pathway
The main role of the extrinsic (tissue factor) pathway is to generate a “thrombin burst,” a process by which large amounts of thrombin, the final component that cleaves fibrinogen into fibrin, is released instantly. The extrinsic pathway occurs during tissue damage when damaged cells release tissue factor III. Tissue factor III acts on tissue factor VII in circulation and feeds into the final step of the common pathway, in which factor X causes thrombin to be created from prothrombin.
Intrinsic pathway
The intrinsic pathway (contact activation pathway) occurs during exposure to negatively charged molecules, such as molecules on bacteria and various types of lipids. It begins with formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and factor XII (Hageman factor). This initiates a cascade in which factor XII is activated, which then activates factor XI, which activated factor IX, which along with factor VIII activates factor X in the common pathway.
What are the three pathways present in secondary haemostasis (coagulation cascade)?
Intrinsic
Extrinsic
Common
What are the 5 types of shock?
Hypovolaemic Cardiogenic Distributive Obstructive (Endocrine)
What is shock?
Shock is a critical condition brought on by the sudden drop in blood flow through the body. Shock may result from trauma, heatstroke, blood loss, an allergic reaction, severe infection, poisoning, severe burns or other causes. When a person is in shock, his or her organs aren’t getting enough blood or oxygen.
Hypovolaemic shock
Most commonly due to acute blood loss - but other causes occur
Volume depletion > reduced SVR > vasoconstriction > reduced preload > reduced CO
Cardiogenic shock
Cardiogenic shock is a life-threatening condition in which your heart suddenly can’t pump enough blood to meet your body’s needs. The condition is most often caused by a severe heart attack, but not everyone who has a heart attack has cardiogenic shock. Cardiogenic shock is rare.
Obstructive shock
Mechanical obstruction to normal cardiac output in an otherwise normal heart = Direct obstruction to cardiac output (PE, Air/Fat/Amniotic fluid-embolism)
Restriction of cardiac filling (Tamponade, Tension pneumothorax)
Distributive (Vasoplegic) shock
- Hot” Shock
- Septic, anaphylaxis, acute liver failure, spinal cord injuries
- Due to disruption of normal vascular autoregulation, and profound vasodilatation.
- Poor perfusion – despite increased cardiac output
- Regional perfusion differences
- Alteration of oxygen extraction
Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body’s tissues and organs.
Endocrine shock
Severe uncorrected hypothyroidism, Addisonian crisis – both reduced CO and vasodilation
Paradoxically – thyrotoxicosis
Neuroendocrine response to shock
Release of pituitary hormones – ACTH, ADH, endogenous opioids
Release of cortisol – fluid retention, and antagonises insulin
Release of glucagon
Haemodynamic Changes in shock
Vascular abnormalities – Vasodilatation, or constriction
Maldistribution of blood flow
Microcirculatory abnormalities – AV shunting, “stop-flow” or “no-flow” capillary beds, failure of capillary recruitment, increased capillary permeability.
Inappropriate activation of coagulation system.
The classes of hypovolaemia
Class I - monitor Class II (mild) - possibly need blood Class III (Moderate) - Needs blood Class IV (Severe) - Massive transfusion protocol
Monitoring of shock
Examination – Pale, cold skin, prolonged capillary refill.
Urine output – Sensitive indicator of renal perfusion
Neurological – Disturbed consciousness a good indicator of cerebral hypoperfusion
Biochemical – Acidosis, lactate levels
Clinical features of shock
The main symptom of shock is low blood pressure. Other symptoms include rapid, shallow breathing; cold, clammy skin; rapid, weak pulse; dizziness, fainting, or weakness.
Monitoring cardiac output in shock
Gold standard – Thermodilution with a PA catheter
Pulse contour analysis
Doppler ultrasonography
General management of all types of shock
Prompt diagnosis, and treatment critical
ABC approach
Establishment of reliable, wide bore IV access and resuscitate while investigating
Identify – and treat – underlying cause
DO2 equation for oxygen delivery in shock
DO2 = CO x (1.39 x Hb x SpO2) + (PaO2 x 0.003)
What is DO2?
Global oxygen delivery (DO2) is the total amount of oxygen delivered to the tissues per minute irrespective of the distribution of blood flow.
Fluid management in shock
Increase pre-load
Rapid fluid replacement (minutes)
Balance between rapid volume replacement, and risk of fluid overload.
Shocked patients more susceptible to pulmonary oedema due to microvascular dysfunction.
The fluid challenge volumes to use
Typically – 300-500ml over 10-20 mins.
Have a target in mind: Increased MAP, Decreased H/r, increased urine output
Fluid choices in shock
Crystalloids – Convenient, cheap, safe But: Rapidly lost from circulation to extravascular spaces, need significantly larger volumes than loss.
Colloids – Cheap(ish), reduce volumes required But: Can cause anaphylaxis, no evidence of benefit
Blood – oxygen carrying capacity, will stay in circulation. But: a scarce resource, and multiple risks
Hypovolaemic shock features
Patients are normally tachycardic and peripherally ‘shut down’. This refers to cool peripheries and a prolonged capillary refill secondary to vasoconstriction. Both the increased heart rate and peripheral vasoconstriction are compensatory responses to reduced blood volume.
Hemorrhagic shock
Is a type of hypovolaemic shock. Caused by volume loss due to acute blood loss. Causes include trauma, self harm, acute GI bleed, obstetric haemorrhage, aneurysm rupture and post-operative bleeding.
Non-hemorrhagic shock
Another type of hypovolaemic shock
Non-haemorrhagic shock occurs due to reduced volume from increased fluid losses or reduced intake. Examples include DKA, severe burns and severe diarrhoea and vomiting.
Neurogenic shock
Brain and spinal cord injuries can cause failure of normal autonomic pathways. If caused by a spinal cord injury these tend to be above T6. A failure of sympathetic tone and unopposed vagal tone results in vasodilation, reduced venous return and a fall in cardiac output. Bradycardia may also play a role.
Type I hemorrhagic shock
Volume of blood loss (ml): <750 Percentage blood loss (%): <15 Heart rate (beats/min): <100 Blood pressure: normal Pulse pressure: normal/increased Respiratory rate (breaths/min): 14-20 Urine output (ml/hour): >30 Mental state: slightly anxious
Type I hemorrhagic shock
Volume of blood loss (ml): <750
Percentage blood loss (%): <15
Urine output (ml/hour): >30
Mental state: slightly anxious
Type II hemorrhagic shock
Volume of blood loss (ml): 750-1500
Percentage blood loss (%): 15-30
Urine output (ml/hour): 20-30
Mental state: mildly anxious
Type III hemorrhagic shock
Volume of blood loss (ml): 1500-2000
Percentage blood loss (%): 30-40
Urine output (ml/hour): 5-15
Mental state: anxious, confused
Type IV hemorrhagic shock
Volume of blood loss (ml): >2000
Percentage blood loss (%): >40
Urine output (ml/hour): negligible
Mental state: confused, lethargic
anaphylactic shock management
Adrenaline 0.5 mg intramuscular (IM)
Cardiac tamponade shock management
Pericardiocentesis and thoracotomy
Septic shock management
IV antibiotics
