Extra HF notes Flashcards
Which drugs are used to chronically manage a patient with HF?
- Beta blockers
- Aldosterone receptor antagonists
- ACE inhibitors
How do you acutely treat a patient with HF?
- Sit them upright
- Give oxygen (if saturation <94%)
- Pain relief
- Frusemide (works on the loop of Henle)
What part of the kidney tubule does frusemide work on? Where do thiazide diuretics work?
Na/K/Cl co-ransporters of the loop of Henle
Thiazide diuretics - distal tubule
Define heart failure.
Heart fails to pump blood (CO) at a rate equal to the requirements of the metabolising tissues, or heart can only do so with an elevated filling pressure.
- Can be left sided, right sided, or both(i.e.congestive)
- Can be low output or high output(working hard e.g. in septic shock/haemorrhage)
- Acute or chronic
What controls cardiac output? What is the equation?
How does the heart respond to increased demand, in an adaptive and non-adaptive model?
Physiologically: exercise–> increased HR/contractility
Morphologically:
Adaptive modelling = COMPENSATION i.e. normal changes e.g. in an athelete
- Increased heart size and mass - cell hypertrophy and increased protein synthesis
- Physiological hypertrophy does not show abnormal morphological changes.
Non-adaptive remodelling = DECOMPENSATION i.e. heart failure.
What are some causes of heart failure?
What are the commonest causes of heart failure?
- Ischaemic heart disease
- High BP
- Valve disease - mitral and aortic
- Shock
What are the pathological changes in heart failure? What are the molecular changes?
Pathological changes to stress: relatively non-specific features but may also have specific feaures of cause e.g. amyloidosis, inflammation, haemochromatosis etc.
Molecular changes: fetal genes, ab protein sythesis, cytokines, gf, neurohormones. These have destructive atocrine and paracrine effects on myocytes.
Describe the changes in myocardial remodelling in heart failure.
It is unknown whether this abnormal myocardial remodelling is the CAUSE or EFFECT of heart failure
- Cell hypertrophy(–> thick ventricular wall) and lengthening (associated with ventricular dilation and more advanced disease)
- Changes in ECM around myocytes e.g. fibrosis (triggered by AgII and aldosterone) - alter the way forces are transmitted through myocardium
- Myocyte death - apoptosis (triggered by SNS, AgII and other local factors in HF)
MACROSCOPICALLY…
- Globular heart with spherical shape can form –> poor mechanics (increased end-diastolic wall stress) and papillary muscles of the mitral/tricuspid valves can get pulled apart
What would you see in an autopsy of heart failure? What would you see histologically?
Histologically you might see evidence of non-specific microscopic change (interstitial fibrosis and cell hypertrophy) or specific ( infective agents, amyloid, iron overload)
True or false?
In a patient with left or right heart failure the feedback will eventually lead to biventricular heart failure.
In the response to stress, the switch from beta-myosin to alpha-myosin allows the heart to cope better.
True
False - under stress, genes switch to producing fetal types of proteins, such as beta-myosin.
List some intrinsic diseases of the heart causing heart failure.
The most common is ISCHAEMIC HEART DISEASE.
What are the main 3 patterns of cardiomyopathy? Which is most common?
- Dilated pattern (flabby heart) e.g. inflammation, post infarction, muscle dystrophies, idiopathic. - MOST COMMON
- Hypertrophic pattern (gym bunny heart) - HOCM
- Restrictive pattern (straight jacket heart) e.g. amyloid, idiopathic.
Describe what is meant by dilated cardiomyopathy. Name some macro and microscopic features.
MOST common type of cardiomyopathy - increased MASS, THIN walls as ventricular chamber dilates.
- MACRO - globular shape
- MICRO- myocyte hypertrophy, fibrosis (non-specific)
What are the causes of dilated cardiomyopathy?
- Idiopathic -
- 33% of cases are inherited (mutation in myocyte structural proteins)
- Late stage of inflammatory myocarditis - local paracrine loops inducing chronic myocardial damage including infectious and autoimmune causes.
Other:
- Genetic - muscular dystrophies
- Toxic - chemotherapy, alcohol, vitamin deficiencies
- Metabolic - iron overload syndromes
- Pregnancy -
What are the causes of dilated cardiomyopathy due to inflammation?
- Infection - viral (e.g. Coxsackie), bacterial(rare), protozoal (trypanosome)
- Drug hypersensitivity reaction
- Systemic disease e.g. sarcoid, SLE
- Idiopathuc - giant cell myocarditis
What is HOCM? How does it present? What are the macro/micro pathological changes.
HOCM = familial hypertropic cardiomyopathy
One of the causes of sudden death in young people
- Genetic disorder - autosomal dominant inheritance. 75% caused by one of 5 genes.
- Typical clinical picture - young people, recurrent syncope, SOB, sudden death due to arrhythmia.
- MACRO pathology - Mainly left ventricle and septal hypertrophy which impairs normal myocardial function.
- MICRO pathology - myocyte disarray(not lined up) and fibrosis.
Describe the genetic component of HCM.
75% caused by one of five genes - mutations being in contractile proteins or associated regulatory proteins in myocytes:
- Most common - mutation in beta-myosin heavy chain - Chr14
- Others - troponin T, myosin binding protein C
Different protein mutations cause different phenotypes e.g. troponin T mutations cause much less striking hypertrophy and disarray compared to mutations in beta-myosin heavy chain. Some subgroups only appear in old age (s less aggresive phenotype)
What is restrictive cardiomyopathy?
Failure of the left ventricle to RELAX –> failure to fill properly in diastole.
Causes can be myocardial (e.g. amyloid) or endocardial and pericardial disease (e.g. fibrosis)
What causes senile atrial amyloid? What causes systemic amyloid?
Senile atrial amyloid - derived from ANF (atrial natriuretic factor) and is part of normal ageing process.
Systemic amyloid - usually in patients who have myeloma or other haematological malignancies–> AL amyloid production. In chronic inflammatory disease –> AA amyloid production (these deposit in tissue and impair normal tissue function)
Endocardial diseases: Endomyocardial fibrosis - what are the two types?
Dense fibrous layer lines pappillary muscles of endocardium and ventricular wall and this stops ventricle contracting properly.
Two types:
Non-tropical conditions - acute disease assoc with EOSINOPHILIA syndromes, UC; damage to endocardium by proteins released by eosinophils.
Tropical conditions- chronic disease, dense white firbosis. ?relationship to eosinophilia, AI response secodary to malaria, abnormal response to streptococcal infection.
What are the causes of pericardial disease?
- Pericardial disease usually follows on from some form of previous suppurative, caseous or haemorrhagic pericarditis may or may not be present.
- Heart is encased in dense fibrous tissue and sometimes cacified.
Which valve diseases can cause heart failure? State why.
- Mitral valve disease:
- Mitral regurgitation - from volume overload
- Aortic valve disease:
- Aortic stenosis - pressure overload
- Aortic regurgitation - volume overload
These can cause valve changes and ventricular hypertrophy and/or dilatation.
Which types of heart failure do patients with congenital heart disease get? (e.g. in ventriculoseptal defect in Down syndrome)
Right ventricular hypertrophy
High pressure on the left ventricle forces blood through defect and raises pressure in thin walled right ventricle –> right heart failure.
List two extrinsic diseases which cause heart failure.
Systemic hypertension –> left sided HF
Pulmonary hypertension –> right sided
Pathological changes are NON-specific e.g. hypertrophy, dilatation later on, myocyte hypertrophy and interstitial fibrosis.
What are the causes of pulmonary hypertension?
Chronic obstruction of pulmonary vessels e.g. PE –> smaller vascular bed
Destruction of pulmonary vessels e.g. in fibrotic disease
Chronic hypoxia e.g. COPD/lung fibrosis/CF–> pulmonary bed constriction
–> right ventricular failure because high pressure.
What are the complications of heart failure? (local and systemic)
Local -
- ARRHYTHMIAS–> sudden cardiac death;
- further myocardial ISCHAEMIA.
Systemic -
- LEFT sided:
- FORWARD failure –> hypoperfusion of kidneys, GIT(malabsorption across mucosa) and brain
- BACKWARD failure –> pulmonary congestion and oedema
- RIGHT sided:
- FORWARD failure - minor
- BACKWARD failure –> organ congestion(e.g. liver) and systemic oedema
How does systemic hypoperfusion of the kidney lead to oedema?
hypoperfusion –> retains water and sodium –> increased plasma volume –> oedema
What is the effect of right sided heart failure on the production of clotting factors and the metabolism of drugs?
Decreased:
RHF, liver congestion would occur and you would get a typical “nutmeg liver”, with impaired liver function as a consequence, and hence decreased production of clotting factors and impaired drug metabolism.
