Haemostasis, haemorrhage and shock Flashcards
What is the state of impaired nutrient delivery to cells and a fall in BP due to decreased blood volume called?
shock
What is the aim of the immediate physiological response to blood loss?
stop the bleeding
What is the aim of the short term physiological response to blood loss?
restore blood pressure
What is the aim of the medium term physiological response to blood loss?
restore fluid volume
What is the aim of the long term physiological response to blood loss?
replace blood constituents
Which 3 responses are involved in the immediate response to blood loss (to stop blood loss)?
vascular response, platelet response, plasma response (coagulation)
What structures are involved in the vascular response of haemostasis?
smooth muscle and endothelium
What action is undertaken by smooth muscle during the vascular response due to blood loss?
myogenic response
What happens during the myogenic response?
smooth muscle undergoes vasoconstriction
What substances promote vasoconstriction?
humoral factors
What role does the endothelium play in the immediate response to blood loss?
allows platelet adhesion and aggregation, and participates in anticlotting and fibrinolysis
What causes the platelets to aggregate in the platelet response?
damaged blood vessels mean a turbulent flow causing platelets to come into contact with the vessel wall (containing exposed collagen). Results in platelets adhering
How does a platelet plug form?
aggregated platelets release chemicals that cause further aggregation via positive feedback
Example of a chemical released by platelets during aggregation
thromboxane A2, ADP
What is the effect of thromboxane A2?
vasoconstriction which promotes aggregation as it reduces blood flow to the injury site
Which compound combines with activated platelets to form a blood clot?
fibrin
Which plasma factor system is involved in blood clot formation?
coagulation system
What is the precursor to fibrin?
fibrinogen
What is the umbrella term for substances required to convert fibrin into fibrinogen?
clotting factors
Where are many clotting factors synthesised?
liver
Which vitamin is required for the synthesis of several clotting factors?
vitamin K
How are clotting factors activated?
in an enzymatic cascade where one activated factor activates the next one in the sequence
How many blood clotting factors exist?
12 (I-XIII except there is no factor VI)
Examples of blood clotting factors
I = fibrinogen, II = prothrombin, IV = Ca2+ ions, XII = Hageman factor
Describe the sequence of events in the common pathway of coagulation that leads to the formation of fibrin
prothrombin is converted to thrombin by clotting factors (Factor Xa with aid of Ca2+, factor V and phsopholipid). Thrombin converts fibrinogen to soluble fibrin, and also activates factor XIII. Factor XIIIa converts soluble fibrin into insoluble fibrin
How is prothrombin converted to thrombin?
via clotting factors - factor Xa with the aid of Ca2+, phospholipids, factor V
What substance converts fibrinogen into soluble fibrin?
thrombin
What are the actions of thrombin?
converts fibrinogen into soluble fibrin and activates factor XIII -> factor XIIIa
What substance converts soluble fibrin into insoluble fibrin?
factor XIIIa
What are the 2 pathways in the coagulation system?
intrinsic and extrinsic pathways (converge to the common pathway to form blood clot)
How is the intrinsic pathway activated?
interval vasculature damage
How is the extrinsic pathway initiated?
external injury/tissue damage leading to bleeding
How are clotting factors activated in the intrinsic pathway?
the clotting factors come into contact with abnormal surfaces (exposed collagen)
Which clotting factors are involved in the intrinsic pathway?
XII (Hageman factor), XI, IX, VIII
How are clotting factors activated in the extrinsic pathway?
tissue factors (factor III, tissue thromboplastin) are released
Which clotting factors are involved in the extrinsic pathway?
tissue factors (III) and factor VII
Which factor initiates the common pathway?
factor Xa
How is factor Xa activated in the extrinsic/intrinsic cascade?
phospholipid and Ca2+ ions convert factor X -> Xa
What is the term used to describe blood clot formation within an intact blood vessel?
thrombosis
Which coagulation pathway may play a role in thrombosis?
intrinsic pathway
Which plasma factor system is involved in breaking down blood clots?
fibrinolytic system
Which enzyme undertakes fibrinolysis?
plasmin
What is the precursor to plasmin?
plasminogen
Which substances are plasminogen activators (convert plasminogen into plasmin)?
Hageman factor (XII) and kallikrein
What is the function of plasmin?
breaks fibrin down into soluble fibrin fragments
Which structures trigger compensatory mechanisms to increase BP during the short term response to blood loss?
arterial baroreceptors
Which nerves mediate the baroreceptor reflex to increase BP?
sympathetic nerves
Which hormones are released in the short term response?
adrenaline, angiotensin II, vasopressin (ADH)
Describe the series of events in baroreceptor reflexes
reduced blood volume reduces BP which decreases baroreceptor firing to the CVS in brainstem. As a result, there’s an increased sympathetic NS activity which increases heart rate, ventricular contraction, venous constriction and arterial constriction. This increases stroke volume, cardiac output and peripheral resistance. Therefore mean arterial BP increases.
What is the immediate effect of haemorrhage on stroke volume?
decreases stroke volume
What is the immediate effect of haemorrhage on cardiac output?
decreases cardiac output because stroke volume decreases (CO = SV x HR)
What equation can be used to calculate the mean arterial pressure?
CO x TPR (cardiac output x total peripheral resistance)
What is the immediate effect of haemorrhage on mean arterial pressure?
decreases mean arterial BP
What is the effect of baroreceptor reflex compensations on stroke volume, heart rate and cardiac output?
increase
What is the effect of baroreceptor reflexes on total peripheral resistance?
increase TPR
What is the effect of baroreceptor reflexes on mean arterial pressure?
increase mean arterial pressure (as both CO and TPR increase)
How is blood volume restored in the medium term response?
interstitial fluid shifted back into blood vessels, decreased fluid loss in kidney, increased fluid intake
What is the name of the forces used to explain the fluid movement between capillaries and the interstitium?
Starling’s forces
What are the 2 major forces that make up the Starling’s forces?
hydrostatic pressure and oncotic pressure
What drives the hydrostatic pressure?
ventricular contraction (BP)
What drives the oncotic pressure?
plasma proteins
Describe and explain the movement of fluid in the arteriole end of capillaries under normal conditions
HP>OP therefore fluid is forced out of the capillaries into the interstitium (net filtration)
Describe and explain the movement of fluid in the venule end of capillaries under normal conditions
OP>HP therefore there is net reabsorption of fluid from the interstitium into the capillary
What is the relationship between filtration and reabsorption in capillary beds under normal circumstances?
filtration approximately equals reabsorption
Describe the alteration of Starling’s forces during haemorrhage
HP is decreased
Why is hydrostatic pressure decreased during haemorrhage?
(decreased blood volume, decreased BP). Arterioles vasoconstrict which increases TPR and decreases capillary BP
What is the effect of reduced hydrostatic pressure (haemorrhage) on fluid exchange in the capillaries?
reabsorption > filtration (more fluid is drawn back into the capillaries by oncotic pressure)
What is the effect of haemorrhage on glomerular filtration rate?
GFR decreases
Which hormones are released in response to a decreased GFR?
renin-angiotensin-aldosterone and anti-diuretic hormone
What is the effect of renin-angiotensin-aldosterone and ADH?
increase reabsorption of Na+ and H2O, and also vasoconstriction
What is the stimulus for the renin-angiotensin-aldosterone system (RAAS)?
increased GFR
Describe the action of aldosterone
increase Na+ and H2O reabsorption in DCT and cortical collecting ducts
Describe the sequence of events in the renin-angiotensin-aldosterone system
juxta-glomerular apparatus releases renin which converts angiotensinogen to angiotensin I. ACE converts angiotensin I into angiotensin II which triggers the release of aldosterone from the adrenal cortex.
How is angiotensinogen converted to angiotensin I?
by renin
How is angiotensin I converted to angiotensin II?
by angiotensin converting enzyme (ACE)
What 2 stimuli can trigger antidiuretic hormone secretion?
decreased plasma volume or increased plasma osmolarity (unrelated to haemorrhage)
What receptor detects decreased plasma volume?
decreased baroreceptor distension
What receptor detects increased plasma osmolarity?
osmoreceptor (increased activation)
Where is ADH secreted from?
posterior pituitary gland (neurohypophysis)
What is the function of ADH?
increases water permeability of collecting ducts (insert aquaporins, increases water reabsorption)
Which area of the brain controls thirst?
hypothalamus
What are 3 possible stimuli for thirst?
increased plasma osmolarity / decreased ECF volume, angiotensin II, dry mouth
Effect of stretch receptors in the stomach on drinking
suppress drinking via ‘feed forward’ regulation
Which blood constituents are replaced in the long term response to haemorrhage?
plasma proteins and blood cells (especially erythrocytes)
How are plasma proteins restored?
plasma proteins are released from the liver
How long does it take for plasma proteins to be restored following haemorrhage?
3-4 days
What is the term for red blood cell production?
erythropoiesis
Which hormone regulates erythropoiesis?
erythropoietin (EPO)
Where is erythropoietin produced?
Kidney
Function of erythropoietin
stimulates red blood cell production in red bone marrow
How long does it take for RBC count to return to normal following blood loss?
2-3 months
What stimulates the kidney to release erythropoietin?
reduced RBC count which reduces oxygen delivery
Shock definition
inadequate blood flow to tissues
What features are associated with shock?
decreased cardiac output, decreased blood/ECF volume
Shock can be reversible or irreversible. What is the usual outcome of irreversible shock?
death
What are the different types of shock?
hypovolaemic shock, low resistance (/distributive) shock, cardiogenic shock
What is hypovolaemic shock?
decreased ECF volume (hypo - low, volaemic - volume)
What are the potential causes of hypovolaemic shock?
haemorrhage, sweating, diarrhoea, burns
What is low resistance (or distributive) shock?
decreased peripheral resistance
What are the potential causes of low resistance (or distributive) shock?
widespread vasodilation e.g. anaphylactic shock
What is cardiogenic shock?
heart fails as a pump
What is a cause of cardiogenic shock?
myocardial infarction
