physiology/pathology of heart disease Flashcards
what is the haemorrhage, haemostasis, thrombosis?
haemorrhage; bleed from ruptured blood vessel
heamostasis; stopping bleeding
thrombosis; formation of a clot inside a blood vessel
what are the types of haemorrhage and what are the causes of it?
Internal - leaky blood vessels inside body
external - natural opening or break in skin
causes: trauma - different types of injury medical condition - IV; defects in the blood intramural; defects in the vessel walls EV; defects outside blood vessels
what are the risk factors for haemorrhage?
- medication
- age
- trauma
- disease
- infection
what are the classifications of haemorrhage?
Class I; loss of 15% BV and no change in vital signs
Class II; loss of 15-30% BV
Class III; loss of 30-40% BV and decrease in BP and higher HR
Class IV; loss of >40% BV and possible death
what is the grading scale of haemorrhage?
Grade 0; no bleeding Grade 1; petechial bleeding Grade 2; mild blood loss Grade 3; gross blood loss Grade 4; debilitating blood loss, maybe death
what happens when you have a haemorrhage shock?
decreased BV
decreased CO
decreased organ perfusion
what are the clinical and physiological reponses you can have to a haemorrhage?
- stop further blood loss
- vasoconstriction
- haemostasis
- fibrinolysis
- surgery - replace lost blood volume
- volume expanders; crystalloids are aqueous solutions of mineral salts or other water soluble molecules
- blood transfusion
what is a thrombus made up of?
coagulation (fibrin clot) + platelets (haemostatic plug) n
how does tissue damage affect fibrin clot being formed?
it amplifies thrombin so more fibrinogen is turned into fibrin clot and this integrates clot to stabilise it
what is the steps of coagulation initiation and amplification?
tissue damage causes inactive XII to turn into XIIa and this causes XI to form XIa.
XIa is responsible for causing IX to turn into IXa and IXa causes Factor X to become active Xa
Factor Xa causes prothrombin to form thrombin and this thrombin will convert fibrinogen into fibrin and this fibrin causes a fibrin clot
what is thrombin used for?
- coagulation amplification
- vasoconstriction
- platelet activation
- fibrin clot
what are some positive and negative inhibitors that allow platelet activation/inhibition?
activators; increase thrombosis - collagen - thrombin - fibrinogen - VWF inhibitors; increase anti-thrombotic - PGI2 - nitric oxide - ITIM receptors -
what do platelets secrete when activated?
they secrete ADP which is involved in a autocrine pathway to allow platelets to bind together
they secrete TxA2 to allow a loop of platelet activation to occur
how does platelet aggregation occur?
so fibrinogen and integrin is released and they can bind to together to then bind platelets together for them to aggregate
what is the difference between a resting and activated platelet?
resting has - discoid shape - granular - active integrins activated has - shape change to lamellipedia - degranulation - aggregation - adhesion to sub endothelium - spreading
what are some anti-platelet drugs?
- ticagrelor
- clopidogrel
- prasugrel
- tirofiban
- abciximab
what other roles do platelets have apart form thrombosis and haemostasis?
- wound repair
- infection
- immunity
- cancer
- inflammation
- tissue regeneration
what is fibrinolysis?
degradation of a fibrin clot
what degrades fibrin clots?
plasmin; a serine protease which causes fibrin degradation
what can stop fibrin clot degradation?
TAFIa reduced fibrin clot degradation
so there’s an increase clot stability
what are the compensatory mechanism I for a haemorrhage?
when you have blood less -> decrease ABP and altered blood gases
lower ABP causes baroreceptor reflex and gases change causes chemoreceptor reflex to both be activated
so more cardiac stimulation and systemic vasoconstriction; allows flow and volume redistribution so increased CO
what are the compensatory mechanism II for a haemorrhage?
you have activation of RAAS, vasopressin release, and catecholamine release
these all allow vasoconstriction to occur so more blood volume and increased cardiac stimulation
signs and symptoms of hypovolemia?
- tachycardia
- rapid breathing
- decrease systolic pressure, confusion
- loss of peripheral pulses so less urine
what are the 3 peaks of death for prognosis of hypovolemia?
minutes - exsanguination
hours - decompensation
days/weeks - sepsis and organ fialure
what can be the treatment for hypovolemia?
- maximise oxygen delivery
- stop bleeding
- replace fluids
- can use pressor agents
what are some haemostatic agents you can use to reduce bleeding?
- recombinant factor VIIa; increases formation of IXa and Xa and so fibrin formation
- desmopressin; stimulates VWF release and increases VIII levels so more fibrin formation
- fibrinogen; causes more fibrin clot formation
what are some antifibrinolytic agents?
- tranexamic acid; stops plasminogen being converted to plasmin so less fibrinolysis so more clot stability
- aprotinin; inhibits plasmin
- epsilon aminocaproic acid; inhibits conversion of plasminogen to plasmin
why does sympathetic activity increase in essential hypertension?
it is due to the increase in descending excitatory activation from spinal cord from pre-motor sympathetic neurones in medulla
when is SN activity increased?
in hypertension, obesity, heart failure, renal failure, metabolic syndrome, sleep apnea
how can you compensate for mild to moderate haemorrhage?
increase heart rate and ventricular contractility
allow vasoconstriction to occur and so retention of water and sodium by kidney
what happens when you have a more severe haemorrhage?
need a blood tranfusion
if ABP falls below cerebral auto regulatory range so less brain blood flow
you can have multiple organ failure so irreversible shock
neutrophils are activated, inflammatory mediators are released so myocardium is depressed as smooth muscle doesn’t constrict so lower ABP so death
how does inspiration effect SV?
inspiration leads to increased venous return to right ventricle so increased right SV so increased left EDV and SV
it also increases heart rate
what neurones and receptors inhibit cardiac vagal neurones? what does this explain as well?
the central respiratory neurones and the pulmonary stretch receptors
this causes heart rate to increase and airways widen and this inhibits vagal activity as well
- they explain respiratory sinus arrhythmia
what mechanisms can cause heart rate to increase when reparation increases?
- voluntary hyperventilation
- mental stress/anxiety
- systemic hypoxia
- exercise
what is the effect of exercise in healthy person?
increase in respiration and increase in heart rate
- vasoconstriction in splanchnic circulation + kidney
- but vasodilation in the exercising muscle
so increased oxygen to working muscles and ABP is maintained and so is cerebral blood flow ( by auto regulation)
there’s an increase in SV and the CO
SV is increased due to sympathetic activity to ventricular muscle increase
EDV increases due to respiratory and muscle pump
where do the pre-motor sympathetic neurones enter?
goes in through afferent fibres and up the spinal chord
increased heart rate
what are the two types of heart failures?
you can have reduced ejection fraction <30%
- systolic dysfunction so dilated ventricle and so impaired contraction
you can have preserved ejection fraction >50%
diastolic dysfunction so stiff ventricular wall and limited filling
what is reduced ejection fraction associated with? what is its characteristics?
with renal failure and atrial fibrillation
- smoking
- MI
- obesity and age
what is preserved ejection fraction associated with? what is its characteristics?
- obesity and ageing
- AF
- women
- renal dysfunction
what is the classification of congestive heart failure?
I; no limitation of physical activity
II; slight limitation of activity. dyspnoea and fatigue
III; marked limitation of activity. dyspnoea with minimal activity
Iv; severe limitation of activity
how can drugs affect heart function?
- directly
- > force of contraction and rate/rhythm
- indirectly
- > vasculature
what is stroke volume determined by?
- preload - left ventricular end diastolic pressure
- afterload; pressure in left ventricle wall during ejection
- inotropy = contractility
what determines contractility?
the contractile machinery of myocardial striated muscle is basically the same as that of voluntary striated muscle
need calcium
what does inotropic mean?
force of heart contraction increase
+ve drugs - increase calcium levels and heart rate
-ve drugs - decrease heart rate e.g. verapamil
what is the MoA for digoxin?
- inhibits cell membrane for sodium and potassium ATPase which means reversal of Na+/Ca2+ exchange
more Ca exchange level means higher level intracellularly so stronger contraction; +ve inotropism
affects electrical physiology of the heart blocking AV conduction and reducing heart rate
what is digoxin used for?
used for AF with a fast ventricular rate
should be used for first line treatment for AF and heart failure patients
what is digoxins toxicity and what are signs and symptoms of it?
has a low therapeutic index
patients should be reviewed for clinical signs
signs are bradycardia and arrhythmia and nausea with vomiting
what should digoxins dose be?
for AF patients a high initial loading dose should be given
dose of 15mcg/kg of lean body weight should be given
maintenance dose is a fraction of the effective dose; changed for renal function looking at creatinine clearance
what monitoring is needed for digoxin?
monitor for toxicity and monitor creatinine clearance
U&Es should be monitored; annually if stable but more if not
what are some examples of sympathomimetics?
dopamine - increased force of contraction - has alpha effects causing peripheral vasoconstriction dobutamine - acts on B1 - causes less tachycardia - increased force of contraction
what does adrenaline do?
acts on alpha and B1 and B2
causes peripheral vasoconstriction and strong positive chronotropia
e.g noradrenaline is an alpha adrenoreceptor that has a vasoconstrictor action
why are phsophodiesterase inhibitors used rarely?
used rarely due to increased risk of mortality and used only in severe heart failure
e.g. enoximone
what is heart failure?
a condition caused by heart failing to pump enough blood around body at right pressure
What are the types of heart failure?
- heart failure caused by ventricular systolic dysfunction (LVSD)
- heart failure with preserved ejection fraction (HFPEF)
- heart failure caused by damaged heart valves
what are symptoms of HF?
- rapid weight gain
- shortness of breath
- increased swelling in lower body
- trouble sleeping
- loss of appetite
what are the general principles for treatment for heart failure?
- medicines adherence
- multidisciplinary approach to care
- comorbidities
first line treatment for HF and reduced ejection fraction?
ACE inhibitors for patients with HF and reduced ejection fraction
start at a low dose and titrate upwards in short intervals until max dose is reached
- measure serum Na and K and assess renal function
what’s the counselling for ACE inhibitors?
take first dose at night to avoid dizziness caused low BP
report if you have a persistent cough
what is first line treatment for HF patients with left ventricular systolic dysfunction?
can have beta blockers which are licensed for heart failure with heart failure due to left ventricular systolic dysfunction
start at low dose and increase slowly
assess HR and BP and clinical status after each titration
what’s the counselling for beta blockers?
dont stop taking unless advised
- you may experience side effects such as fatigue, dizziness
- must have regular check ups
what’s an alternative to ACE inhibitors for HF patients due to left ventricular systolic dysfunction?
can have an ARB as an alternative
seek specialist advice for considering hydralazine in combination with nitrate
what treatment should be given to patients with reduced ejection failure and HF?
add a mineralocorticoid receptor antagonist with there ACE inhibitor or ARB
what counselling points are needed for ivabradine?
- avoid grapefruit juice
- may cause temporary luminous visual phenomena
- be careful when driving or using machines
- might get effects like fatigue, irregular heartbeat
what is ivabradine?
- drug that inhibit the If channel in the sinus node
- slows HR with patients in sinus rhythm
- less contraction
- reduces CV death
- improves left ventricular function
if toxicity is suspected what should you do with digoxin?
measure serum digoxin every 8-12 of last dose
what is sacubitril valsartan?
used for treating symptomatic chronic heart failure with reduced ejection fraction
- must be started by a specialist
only in people
- with class II to IV symptoms
- with left ventricular ejection fraction of <35%
