Cardiovascular Pathology Flashcards
1
Q
What is CVD?
A
CVD is an umbrella term used to describe all conditions of the heart and blood vessels. Includes congenital
diseases and acquired conditions like IHD, AF, Heart Failure and Stroke.
Affect heart & blood vessels; includes congenital & acquired.
2
Q
How many people are affected by CVD in the UK?
A
435 people with lose their lives to CVD today & 530 will go to hospital due to a heart attack
42,000 of these deaths every year occur in those under 75 years of age
7 million people living with CVD (3.5 each male & female), 530 will go to hospital for IHD, 190 die from IHD
3
Q
What is Ischaemic heart disease?
A
Definition: generic designation for a group of syndromes resulting from MI
CVD includes IHD
(Ischaemia- imbalance between demand & supply of oxygenated blood to heart)
Aetiology: almost always caused by coronary artery atherosclerosis, sometimes due to hypertrophy
(demand)
4
Q
What are the 4 IHD syndromes?
A
- MI- duration and severity of ischaemia causes myocardial death
- Angina Pectoris- ischaemia is less severe and does not cause myocardial death
o Stable angina- typical angina
o Prinzmetal angina- variant form of angina due to vasospasm of artreies NOT due to atherosclerosis
o Unstable angina- crescendo angina - Chronic IHD with heart failure
- Sudden cardiac death
MI, Unstable angina, sudden cardia death= acute coronary syndrome
5
Q
DUNNO
A
Cancer taking it over
Coronary heart disease is the UKs single biggesst killer
Prevalence of IHD is highest in Northern England and Scotland.
6
Q
What are the medical risk factors for IHD?
A
High blood pressure
Lipid profile abnormalities
High blood cholesterol- now evidence; looking at total LDL not going to give estimate, need to look at
alpha & B lipid subunits (but we can’t do this atm), so we look at ratio of total cholesterol: HDL (higher
ratio- more at risk of developing IHD) or high HDL (better indicator of CVD risk)
Diabetes doubles the risk of developing CVD
7
Q
What are the lifestyle risk factors for IHD?
A
(Alcohol cardio protective in small amounts)
Modifiable risk factors (e.g. smoking, physical inactivity & poor diet)
20,000 cardiovasc deaths per year due to smoking in UK
27% adults in UK obese
20,000 cardiovasc deaths per year due to smoking in
8
Q
What are the therapeutic advances for IHD and why are they effective?
A
Therapeutic advances have allowed earlier, more effective and safer treatments
People now living with rather than just dying from it
Statins- 2ndry prevention (debate about being a primary preventative drug)
Surgeries- coronary artery bypass grafts, percutaneous coronary intervention
9
Q
What is the pathogenesis of IHD?
A
MI is a consequence of reduced blood flow in coronary arteries due to a combination offixed vessel
narrowingandabnormal vascular toneas a result ofatherosclerosisandendothelial dysfunction. This
leads to an imbalance between myocardial oxygen supply and demand
In coronary arteries
o 3 parts (media, intima, adventitia)
o Inflammation to coronary artery- is the trigger
o Cholesterol tries to act as a plaster
o Form an atherosclerotic plaque fibrous cap
o Get typical angina- at rest occlusion of artery but mechanism for vessel to vasodilate to deliver
more blood, but in case where need more oxygen (e.g. climbing stairs) heart needs more O2
angina
o What can then happen;
1.Plaque can continue to grow- after 75% occlusion artery can no longer autoregulate with
vasodilation & heart will undergo changes
2. Erosion of atherosclerotic plaqueplatelet aggregation thrombus unstable angina
If thrombus continues to grow complete
occlusion full transmural occlusion
Acute coronary syndrome- Unstable angina
10
Q
What is MI?
A
Death of cardiac muscle from prolonged ischaemia.
Transmural vs Subendocardial; full thickness vs inner one third of the wall (least well perfused)
Subendocardial- inner 1/3 of heart wall (most vulnerable part of endocardium to infarction)
11
Q
What is the pathophysiology of MI’s?
A
- Stable atherosclerotic plaque
- Acute plaque changes
- Platelet aggregation
- Thrombus formation
- Coronary artery occlusion
12
Q
How is coronary artery thrombus formed?
A
- Can have complete occlusion
- & bleeding into plaque
- Occlusion in 1st 24hrs can’t see changes to naked eye or microscope
- 1st see pale area in subendocardial region then after 2-3 days will be a transmurial infarct
- Then get a transmural infarction
13
Q
What Myocardium changes are shown in MI ? (TIMELINE)
A
Myocardium changes
<24h Normal
1-2dy Pale, oedema, myocyte necrosis, neutrophils
3-4dy Yellow with haemorrhagic edge, myocyte necrosis, macrophages
1-3wk Pale, thin, granulation tissue then fibrosis
3-6wk Dense fibrous scar
• Area supplied by coronary artery oedematous
• Neutrophils (acute inflamm cells) – trying to respond to dead cells
• Macrophages then replace neutrophils- chronicity of condition
• Granulation tissue- remains in place for lifetime
Transverse section- yellow pale area with haemorrhagic edge (3-4 days)
14
Q
What are the complications of MI’s?
A
- Arrhythmias (change in normal sinus rhythm of heart)- either directly or by limited perfusion to the conduction system structures (SA node, AV node etc)- ischemia’s to those critical strucs
- Congestive cardiac failure- contractility dysfunction (with smaller coronary artery branches- specifically ones that supply papillary muscles that control mitral valve affected) or by papillary muscle infarct/ severe MR (mitral regurg) congestive cardiac failure
- Thromboembolism- if have subendocardial region of infarction tissue now vulnerable & can break off- send fragments of tissue (if on R side of heart pulmonary emboli, if on Lstroke)
- Pericarditis- if inflamm intense enough neutrophils can go through endocardium to pericardium- pericarditis (complication of infarction)
- Ventricular aneurysm- wall weakening, rest of wall continues contracting at normal pace weakened area gets pushed aside & causes aneurysm to ventricle
- Cardiac tamponade- full thiockness of myocardium infacted, becomes so weak that blood rushes into pericardial sac & decompresses the heart (e.g. can have large haematoma encasing heart)
- Cardiogenic shock
Mural thrombus- thrombus formation can occur in heart- if no thrombus formation then that area gets pushed out ventricular aneurysm
15
Q
What are the complications of MI’s
A
- Impaired contractility-Ventricular thrombus-Stroke(embolism)
- Impaired contractility-Hypo tension, decreased coronary perfusion, increased ischaemia-Cardiogenic shock
- Tissue Necrosis-papillary muscle infarction-mitral regurgitation-Congestive Heart failure.
- Tissue Necrosis-Ventricular Wall Rupture-Cardiac Tamponade
- Electrical Instabilitty-Arrhythmias
- Pericardial Inflammation-Pericarditis
16
Q
What are the blood markers for IHD?
A
Blood Markers of IHD
• Troponins T & I
o Proteins released by damaged myocytes (any muscle damage not specific to heart)
o detectable 2 – 3h, peaks at 12h, detectable to 7 days
o raised post MI but also in pulmonary embolism, heart failure, & myocarditis.
• Creatinine kinase MB
o detectable 2 – 3h, peaks at 10-24h, detectable to 3 days
o Creatine kinase (or creatine phosphokinase)- enzyme mainly in brain, skel muscles & heart
o Elevated level of creatine kinase in heart attacks, heart muscle damage, or conditions that damage skeletal muscles or brain.
o 3 isoenzymes of creatine kinase (CK)-BB, -MM, and -MB
o MB subtype more concentrated in myocardium (also in skel muscle)
o Increased in Polymyositis, rhabdomyolysis, carbon monoxide poisoning, crush injuries, pulmonary embolism, hypothyroidism & muscular dystrophy.
• Myoglobin
o peak at 2h but also released from damaged skeletal muscle
• Lactate Dehydrogenase Isoenzyme I
o peaks at 3days, detectable to 14days
• Aspartate transaminase
o Also present in liver so less useful as a marker of myocardial damage
• All biomarkers detectable within 2-3 hrs
• But take into account that lactate dehdrog also in liver damage
17
Q
What is hypertension?
A
• Primary (Idiopathic or Essential) and Secondary
• Definition:
o Blood pressure (BP)- a continuously distributed variable, essential hypertension is one extreme of this distribution rather than a distinct disease (at one end extreme of this distribution rather than an actual disease)
o Detrimental effects of raised BP increase continuously as pressure rises
o Hypertension- a sustained diastolic pressure greater than 90 mm Hg or sustained systolic pressure greater than 140 mm Hg.
18
Q
Whats the aetiology of Primary Hypertension?
A
Aetiology of Primary Hypertension
• Majority of patients (90%) have primary essential hypertension of unknown cause
• Assume its; multifactorial, genetics & env
• Environmental;
o Obesity
o Alcohol
o Smoking
o Stress
o Na+ intake (increase salt intake)
• Genetic;
o insulin resistance (metabolic syndrome)
• Metabolic syndrome- combination of diabetes, high BP & obesity;
o Need 3 or more of the symptoms; a certain waist circumference, high triglyceride & low HDL levels in blood, high BP (consistently 140/90mmHg or higher), can’t control blood sugar level (insulin resistance), increased risk of developing blood clots (e.g. DVT), tendancy to develop infalmm
o Risk factors; age (older), race (Asian, African), other conditions (CVD, non-fatty liver disease, polycystic ovary syndrome)
19
Q
Whats the epidemology of Hypertension?
A
- Hypertension prevalence in adults of 16 years or older was 31.5% in men and 29.0% in women (2010)
- WHO estimated over 1 billion people worldwide in 2008
- Vulnerability to complications increases with age
- Africans affected more.
20
Q
How do Hypertrophied Arteries differ from normal?
A
- 3 layers in vessel; endothelial cells, middle bit- smooth muscle component, outside layer
- Abnormal if hypertension; more cigar shaped nuclei & more layers (smooth muscle hypertrophied) & lumen narrowed
21
Q
How is BP regulated?
A
• Aetiology: determined by factors that affect cardiac output & peripheral resistance in BP regulation
22
Q
What is the Renin-Angiotensin Aldosterone system?
A
- Role in regulating blood vol & systemic vasc resistance- both influence cardiac output & arterial pressure
- Renin- released by juxstoglomerular apparatus in kidneys-
- When renin is released into blood, it acts oncirculating angiotensinogen, that undergoes proteolytic cleavage to form the decapeptide angiotensin I.
- Angiotensin 1 ACE (from all endothelium cells especially lungs) converts it to ang 2
- Vascular endothelium, particularly in lungs, has an enzyme, angiotensin converting enzyme (ACE), that cleaves off 2 amino acids to form the octapeptide, angiotensin II (AII), although many other tissues in body (heart, brain, vascular) also can form AII.
- Ang 2; constricts blood vessels (has ang 2 receps), stims Na transport in kidneys (increases BP), stimulates aldosterone to be released from adrenal cortex
- Aldosterone- Na & fluid retention (increases BP) by releasing ADH
23
Q
What is Angiotensin II?
A
- Constricts resistance vessels (via AII [AT1] receps)- increasing systemic vasc resistance & arterial pressure
- Stims sodium transport (reabsorption) at several renal tubular sites- increasing sodium & water retention
- Acts on adrenal cortex to release aldosterone, which acts on kidneys to increase sodium & fluid retention
- Stims release of vasopressin (antidiuretic hormone, ADH) from posterior pituitary- increases fluid retention by kidneys
- Stimulates thirst centers in brain
- Facilitates norepinephrine release from sympathetic nerve endings & inhibits norepinephrine re-uptake by nerve endings, thereby enhancing sympathetic adrenergic function
- Stims cardiac hypertrophy & vascular hypertrophy
- ACE (angiotensin converting enzyme)- benefit of using ACE Inhibitors in hypertension treatment!
24
Q
What is Secondary Hypertension?
A
Affects 5% of those with hypertension
• Cushing’s – adrenal glands stim cortisol – stimulates the sympathetic nervous system and has an aldosterone like action on the kidneys
• Conn’s disease- adrenal gland directly releases aldosterone into blood (bypassing renin & angiotensin) Na+ and water retention = hypertension (increases BP)
• Pheocytochritoma (medical emergy)- vast amount of catecholamines released by adrenal gland (adrenaline & noradrenaline) sympathetic nervous system stim allowing BP to increase
• Aorta coarctation- congenital narrowing of aorta (BP to kidneys reduced- trigger cascade of events that will increase BP)
• Renal artery stenosis- (BP to kidneys reduced- trigger cascade of events that will increase BP) juxtaglomerular apparatus stimulated to produce renin
25
What is Malignant Hypertension?
• BP >180/120mmHg
• Clinically signs & symptoms of organ damage;
o acute hypertensive encephalopathy
o and/or nephropathy
o with retinal haemorrhages/papilloedema
• Needs urgent treatment to prevent organ damage & preserve organ function
26
What are the complications of Hypertension?
• Hypertensive Renal disease;
o Renal cortical scarring seen at autopsy- “Flea bitten” kidney
o Flea bitten kidney- petechial haemorrhages & microinfarctions on renal cortical surface (typical of malignant hypertension) which are caused by thromboses in certain arteries
• Hypertensive Cerebrovascular disease-subarachnoid haemorrhage 2ndry to berry aneurysm rupture, lacunar infarcts (stroke from occlusion of small penetrating arteries that provide blood to brain’s deep strucs)
27
What is Hypertensive heart disease?
• Systemic (left sided) hypertensive heart disease
• In hypertension, heart hypertrophy- adaptive response to pressure overload, can lead to myocardial dilation, congestive heart failure & sudden death.
• Criteria:
o Left ventricular concentric hypertrophy
o History or pathological evidence for hypertension (3 readings of high BP)
• Concentric hypertrophy of the left side & interventricular septum. Right side compressed.
• L ventricle so expanded reduces R ventricle to a slither
28
What is Cor Pulmonale?
* Pulmonary (right sided) hypertensive heart disease
* Disorders of lung & blood vessels of lung causes R heart failure
* Right ventricular hypertrophy, dilation & potentially heart failure secondary to pulmonary artery hypertension caused by disorders of the lung or pulmonary vasculature.
* Right ventricular hypertrophy secondary to diseases of left side & congenital causes are generally excluded in definition; but pulmonary venous hypertension that follows left sided diseases is quite common.
* Causes;
29
What are Aneurysms?
* Definition: localised abnormal dilation of a blood vessel or the wall of the heart
* True aneurysm- when bounded by arterial wall components or the attenuated wall of the heart (all layers involved)
* False (pseudoaneurysm) aneurysm- breach in vascular wall intravascular hematoma that freely communicates with the intravascular space (pulsating on outer aspect of arterial wall- ‘pulsating haematoma’)
30
What is Dissection?
• Arterial dissection arises when blood enters wall of an artery, as a hematoma dissecting between its layers.
• Dissections may, but do not always, arise in aneurysmal arteries.
• Aneurysms and dissections (most importantly when affecting the aorta) can rupture!
• A false aneurysm is diff to dissection as in a false aneurysm- haematoma outside wall (so diff to dissection)
• True aneurysm (affects all 3 components- intima, media & adventitia) (at top);
o Saccular- affects one side
o Fusiform- affects 360 degrees around artery
• False aneurysm- hematoma outside 3 components (intmia etc) that communicates with inside artery
• Dissection- hematoma makes it’s way THROUGH wall of artery (predominantly in media component of wall)
• Aortic dissections can be divided into type A & B;
o Type A- ascending aorta affected
o Type B- only descending aorta affected
• Double barrelled aorta- dissection starts at break in wall of vessel, continues down, can rebreak at bottom, so get another channel (2ndry passageway) on outer aspect of aorta forming (blood flowing down both of these channels)
31
What causes Aneurysms?
• Aetiology;
o Atherosclerosis
o Cystic medial degeneration- affects media (middle aspect) of artery, cystic degen there allows blood to go through length of vessel
o Trauma
o Congenital defects (can give rise to berry aneurysm in brain)
o Infections (mycotic aneurysms)
• Atherosclerosis and cystic medial degeneration most common cause of AAA.
• Cystic medial degeneration frequently accompanies Marfan syndrome.
• Mycotic aneurysm can be secondary to infective endocarditis
• The obliterative endarteritis characteristic of the tertiary stage of syphilis shows a predilection for small vessels with complications especially in the aorta and nervous system.
Look up:
AAA- localized abdominal aorta enlargement, usually 2cm but can swell to over 5.5cm, most common in men >65yrs, if ruptures internal bleeding (most common symptom of rupture- sudden & severe abdo pain)
Marfan syndrome- connective tissue disorder usually inherited (autosomal dominant)- abnormal fibrillin produc, characteristics; tall, abnormally long slender limbs & fingers & toes, heart defects, lens dislocation
Berry aneurysms- wall weakness causing bulge in blood vessel usually where it branches, usually in abdominal aorta & brain
Mycotic aneurysms (infected aneurysm)- from bacterial infec of arterial wall (common complication of hematogenous spread of bacterial infec classically from the heart), vessel wall can become digested false aneurysm forms
Syphilitic (Leutic) aneurysms- aorta inflamm associated with teritiary stage of syphilis infec (Treponema pallidum) , begins with inflamm of outermost layer of blood vessels aneurysm, coronary artery narrowing, aortic valve insufficiency. Ascending aorta most commonly involved.
32
What is a Abdominal Aortic Aneurysm?
```
• Need surgery when over 5 ½ cm
• Atheroscelerosis most common cause
• Risk factors;
o Male
o Smoking
o Hypertension
o Advanced age
```
33
What is Heart failure/congestive Cardiac failure?
• Heart can’t pump enough blood needed to meet tissue’s metabolic demands
• R & L ventricles failing
• Occurs insidiously or suddenly;
o Cumulative effects of chronic workload on ventricles (hypertension & valve diseases)- insidious
o Acute heamodynamic stress (fluid overload & large MI)- sudden
34
Pathogenesis of L sided Heart Failure
Pathogenesis of L Sided Heart Failure
• Cells stretch- try to compensate
• Cells increase their size to try to compensate
• If workload persistent ventricles start to fail, try to compensate by other mechanisms;
o Release norepinenphrine to increase heart rate & myocardial contractility
o Reduc in blood flow to kidneys- active RAAS to increase blood flow (as aadjusts fluid vol, but can be counterproductive pul oedema)
o Release natriuretic peptides from R atrium to decrease vol overload on heart (adjusts fluid vol)- reduce blood vol by excreting water & Na
Clinical effects of L sided failure due to;
• Low cardiac output & hypoperfusion of tissues
• Pulmonary congestion
L Heart Failure (Congestion)
• Heart doesn’t pump enough- back pressure in pulmonary system- causes pulmonary oedema
• Lungs; pulmonary congestion & oedema, heart failure cells
• Dyspnea
• Orthopnea (out of breath, relieved when up right)
• PND (paroxysmal Nocturnal Dyspnea)- feel like your drowning
• Blood tinged sputum- RBCs escape vasculature in alveoli
• Cyanosis
• Elevated pulmonary ‘WEDGE’ pressure (PCWP) (nl= 2-5mm Hg)
L Sided Failure (Low Cardiac Output)
• Reduced kidney perfusion
o Pre-renal azotemia- kidney’s can’t excrete waste products like urea & creatinine (pre-renal failure)
o Renin-angiotensin-aldosterone activation; salt & fluid retention (expansion of interstitial & intravascular fluid vol but can be counterproductive pulmonary oedema)
• Advanced cardiac failure can lead to cerebral hypoxia- irritability, restlessness, stupor & coma
35
What is R sided Heart Failure?
R Sided Heart Failure
Etiology
• L heart failure can cause R sided failure
• Cor pulmonale (R heart failure due to primary lung disease)
Symptoms & signs
• Fatigue
• Dependant oedema
• Distension of jugular veins
• Liver enlargement
• Ascites
• Anorexia & complaints of GI distress
• Cyanosis
• Elevation in peripheral venous pressure
Symptoms and signs due to
• (engorgement of systemic and portal venous systems)
• Liver and spleen (portal congestion)
o passive congestion (nutmeg liver)
o congestive splenomegaly
o ascites
o Congestion & oedema of bowel wall (can get malabsorption)
• Pleura/Pericardium (systemic venous congestion)
o pleural and pericardial effusions
o transudates
o Oedema of Peripheral and dependent parts of body
36
What are the cardiac changes in CHF?
* Cardiomegaly
* Chamber Dilatation
* Hypertrophy of myocardial fibers, BOXCAR nuclei
37
Valvular Abnormalities?
* Congenital
| * Acquired
38
What is Valvular Heart disease?
Valvular Heart Disease (VHD)
Opening probs- STENOSIS
• Failure of valve to open completely impeding forward flow
• Leads to pressure overload of heart
• Almost alwayas due to chronic abnormality of valvular leaflet caused by relatively few disorders
• Acquired Aortic stenosis (AS)
o Calcification of a deformed valve (congenitally bicuspid- under more pressure), (50-70y age)
o “Senile” calcific AS- calcification of anatomically normal aortic valve (>70y age group)
o Rheum, Heart Dis.
• Acquired Mitral stenosis (MS)
o Rheumatic Heart Disease
• Both make 70% of all VHD
Closing probs- REGURGITATION or Incompentence or insufficiency
• Faliure of valve to close completely allowing revearse flow
• Leads to vol overload of heart
• Can result from intrinsic diseqase of valve cusps or damage to supporting strucs
• Has many causes & may appear acutely or chronically
39
What is Calcific Aortic Stenosis?
* Most common valvular abnormal (2% prevalence rising with increasing life expec)
* Usually consequence of age- related wear & tear of either normal valve or congenital bicuspid aortic valve (bicuspid AV undergoes more mechanical stress so becomes stenotic earlier)
* Role for hyperlipidaemia, hypertension & inflamm in pathogenesis (factors also implicated n atherosclerosis)
* Mitral valve generally normal but can be involved by extension of calcific deposits (calcification can extend to involve mitral valve)
40
What is Aortic stenosis?
* 2X gradient pressure
* LVH (but no hypertension), ischemia (can produce angina)
* Cardiac decompensation with persistent angina, CHF (congestive heart failure)
* 50% die in 5 years if angina present
* 50% die in 2 years if CHF present
41
What is RHD?
Rheumatic Heart Disease
• Follows a group A strep infection, a few weeks later
• Body responds, but some antibodies cross react with heart tissue causing damage e.g. myocardial inflammation, vegetation, pericarditis
• DECREASE in “developed” countries
• PANCARDITIS (inflammation of the 3 heart carditis layers):
1. Endocarditis
2. Myocarditis
3. Pericarditis
42
What is acute RHD?
* Inflammation
* Aschoff bodies
* Anitschkow cells
* Pancarditis
* Vegetations on chordae tendinae at leaflet junction
43
What is chronic RHD?
* THICKENED VALVES
* COMMISURAL FUSION
* THICK, SHORT, CHORDAE TENDINAE
Mitral valve always involved
MV affected alone in 70% cases, both MV & aortic valve in 25%
TV (tricuspid valve) infreq involved
PV only rarely
44
What are the clinical features of Acute RF?
```
Clinical Features of Acute Rheumatic Fever
Jones Criteria
• Evidence of preceding streptococcal infec
• +2 major manifestations
• Or 1 major + 2 minor
Major manifestations
• Migratory polyarthritis
• Pancarditis- pericardial friction rub, weak heart sound, arrhythmias
• Subcutaneous nodules
• Erythema marginatum of skin
• Sydenham chorea
Minor manifestations
• Fever
• Arthralgia (pain in a joint)
• Elevated acute phase proteins in blood
```
45
What are the Clinical features of chronic RHD?
* Appears years after initial rheumatic fever episode
* Depends on which cardiac valve involved
* Cardiac murmurs
* Cardiac hypertrophy & dilation
* Arrhythmias
* Cardiac failure
* Thromboembolic complications
* Infective endocarditis
46
What are Regurgitations (two types) ?
```
Regurgitations
AR (Aortic Regurg)
• Rheumatic
• Infectious
• Causes of aortic dilatations;
o Syphilis
o Rheumatoid Arthritis
o Marfan
MR (Mitral regurg)
• MVP (mirtal valve prolapse)
• Infectious
• Fen-Phen (anti-obesity drug)
• Papillary muscles, chordae tendinae (damage to MV strucs also causes MR)
• Calcification of mitral ring (annulus)
```
47
What is Mitral Valve Prolapse?
```
• MYXOMATOUS degeneration of the mitral valve
• Cause unknown in most cases, associated with connective tissue disorders (marfan syndrome)
• “Floppy” valve
• 3% incidence, F>>M
• Easily seen on echocardiogram
Clinical Features
• Usually asymptomatic
• Mid-systolic “click”
• Holosystolic murmur if regurg. present
• Occasional chest pain, dyspnea
• 97% NO untoward effects (no problems)
• 3% Infective endocarditis, mitral valve insufficiency, arrhythmias, sudden death
```
48
What is Mitral Annular calcification?
* Degenerative calcification of the mitral “skeleton” (annulus)
* F (>60y)>>M
* Usually NO dysfunction
* Regurgitation usually, but Stenosis possible
* Arrhythmias & sudden death; deep penetration of calcium deposits impinging on atrioventricular conduction system
* Increased risk of infective endocarditis & embolic stroke from dislodged overlying thrombi
49
What is the meaning of congenital heart defects?
* Abnormalities of the heart & great vessels present from birth
* May not be evident until adult life (Coarctation, ASD)
* Faulty embryogenesis (week 3-8)
* Usually MONO-morphic (i.e., SINGLE lesion) (ASD, VSD, hypo-RV, hypo-LV)
* Overall incidence 1% of births
50
What are common malformations of congenital heart defects?
```
Highlighted D = LR shunt, T= R to L shunt (cyanosis, or “blue” babies)
• Ventricaular septal Defect (42% per million live births)
• Atrial Septal Defect (10%)
• Pulmonary stenosis (8%)
• Patent Ductus arteriosus (7%)
• Tetralogy of fallot (5%)
• Coarctation of aorta (5%)
• Atrioventricular septal Defect (4%)
• Aortic stenosis (4%)
• Transposition of great arteries (4%)
• Truncus arteriosus (1%)
• Total anomaluous pulmonary venous connection (1%)
• Tricuspid atresia
```
51
What are Sporadic Genetic Abnormalities in congenital heart diseases?
* Main known causes of congenital heart diseases
* Gene abnormalities in only 10% of CHD
* Trisomies 21 (Down), 13, 15, 18 & monosomy; XO (Turners syndrome)
* Mutations of genes which encode for transcription factors; TBX5= ASD, VSD, NKX2.5= ASD
* Deletion of Chr 22q11.2(chromosome 22 important in heart development)=conotruncus, abnormal development of thymus & parathyroid (DiGeorge syndrome)
52
What are environmental factors in congenital heart diseases?
* RUBELLA (congenital rubella syndrome) (in early preg)
* Gestational diabetes
* TERATOGENS
53
What is the stages in heart development?
* Heart formed by cells from lateral mesoderm
* Migrate in 2 waves
* By day 21 2nd wave of cells
* Heart properly formed by day 50
Atrial septal defect=
• Pressure moves from R to L
• Ventric septal defect L to R
• All increase pulmonary pressure= damage pulmonary arterioles
• When pul pressure high enough, blood moves from R to L – Eisenmenger syndrome
54
What are the 3 groups of Congenital Heart Disease?
1. L to R SHUNTS: all “D’s” in their names
• NO cyanosis
• Pulmonary hypertension
• SIGNIFICANT pulmonary hypertension is IRREVERSIBLE
ASD, VSD, AVSD, PDA
2. R to L SHUNTS: all “T’s” in their names
• CYANOSIS (i.e., “blue” babies)- pressure on R exceeds pressure on L; deoxygenated blood in systemic circ
• VENOUS EMBOLI become SYSTEMIC “paradoxical” emboli
Tetralogy of fallot , Transposition of great arteries, Truncus arteriosus , Total anomalous pulmonary venous connection , Tricuspid atresia
3. OBSTRUCTIONS:
• Coarctation of aorta or aortic/ pulmonary valve stenosis
55
What is ASD?
• Abnormal fixed opening in atrial septum caused by incomplete tissue formation- allows communic of blood between L & R atria
• NOT patent foramen ovale (which is a flap like tissue that lets blood flow from R to L in foetus, closes after birth as pressure from R decreases & L increases when pulmonary circ starts working)
• Usually asymptomatic until adulthood
• 3 types of AD;
o SECUNDUM (90%): Defective fossa ovalis (not well formed), is near center of atrial septum
o PRIMUM (5%): Next to AV valves, mitral cleft
o SINUS VENOSUS (5%): Next to SVC entrance with anomalous pulmonary veins draining to SVC or RA
• Usually asymptomatic until adulthood
• Mortality low following repair
56
What is VSD?
• Most common CHD defect
• Only 30% are isolated
• Often with TETRALOGY of FALLOT
• Classified according to size & location;
o 90% involve the membranous septum (membranous VSD)
o 10% involve muscualr septum or lie below pulmonary valve (infundibular VSD)
• If muscular septum is involved, can have multiple holes (“swiss-cheese”septum)
• SMALL ones often close spontaneously
• LARGE ones progress to pulmonary hypertension
57
What is Tetralogy of Fallot ?
Most COMMON
1. VSD, large
2. OBSTRUCTION to RV outflow tract (subpulmonary stenosis)
3. Aorta OVERRIDES the VSD
4. RVH
• Due to anterosuperior displacement of infundibular septum during embryogenesis
• SURVIVAL DEPENDS on SEVERITY of SUBPULMONIC STENOSIS
• Classical TOF is a cyanotic congenital heart disease
• Can be a “PINK” (not cyanotic) tetralogy if subpulmonic obstruction is small, but the greater the obstruction, the greater is the R to L shunt
58
What is Obstructive CHD ?
Pulmonary stenosis/atresia
-Aortic stenosis/atresia
-COARCTATION of aorta*
• M>F (2:1)
• But females with Turner’s syndrome (XO) frequently have it
• 2 classical forms;
o INFANTILE FORM (proximal to PDA- patent ductus arteriosus) (SERIOUS)
Shunting of deoxygenated blood via PDA produces cyanosis in lower half of body
o ADULT FORM (CLOSED DUCTUS, i.e. NO PDA)
Typically hypertension in upper extremities & hypotension & weak pulses in lower extremities & features of atrial insufficiency (caludication & coldness)
Development of collateral circ between pre-coarctation arterial branches & post-coarctation arteries through enlarged intercostal & internal mammary arteries causing visible erosions (notching) of undersurface of ribs
• Bicuspid aortic valve 50% of the time
59
What are Abnormalities affecting the pump ?
o Myocarditis
o Pericarditis (not umcommon)
o & rheumatic fever (rare)
60
What is Peripheral Vascular Disease?
* Distal foot discoloured- as further you go vessels smaller- more prone to PVD
* Definition: narrowing of blood vessels (usually arteries) that restricts blood flow (mostly in legs, but sometimes seen in arms)
61
What is the epidemiology Peripheral Vascular Disease?
```
o Common
o Smokers
o Obese, Diabetes
o Hypertension
o Hyperchlesterolaemia
o Age - increase with age (usually 40+)
o Sex – more in men and postmenopausal women (oestrogen protective effect until menopause)
o Genetic Factors
o Developed world
```
62
What is the aetiology of Peripheral Vascular Disease?
Agents in blood that can damage the endothelium (that lead to atherosclerosis & can trigger thrombosis- narrows vessels, can flick off & narrow smaller vessel more distally)
o Smoking (Toxic Effects)
o Hypertension (Haemodynamic Effects)
o Diabetes (Raised serum glucose levels? Toxic?immune effects)
o Hypercholesterolaemic conditions
o Could be damaged by trauma
63
What is the pathogenesis of Peripheral Vascular Disease?
o Causative agents DAMAGE the endothelium= trigger cellular events=eccentric wall thickening by atheroma +/- thrombosis (KNOW VIRCHOW’S TRIAD)
o +/- embolism= narrow lumen= reduced blood flow
o ie NARROWS ARTERY –> ISCHAEMIA –> CELL DAMAGE
o All the symptoms & consequences of peripheral vasc disease are related to restricted blood flow
64
What are the clinical features of Peripheral Vascular Disease?
o Progressive disease leading to increasing levels of tissue hypoxia
o Narrowed lumen – decrease perfusion (6 P’s; pain, cold, pale peripheries, loss of function, eventually can be cell death - gangrene)
o Ruptured plaque - sudden increase in narrowing or emboli from plaque or thrombus (acute onset peripheral pallor, pain & loss of function=gangrene)
o Wall destruction – dilatation (aneurysm) (symptomless until ruptures or decrease function due to side branch occlusion or thrombotic occlusion)
o Plaque rupture= MI
65
What are the 6 Ps of Acute Ischaemia?
1. Pale
2. Pulseless
3. Painful
4. Paralysed
5. Paraesthetic
6. Perishing Cold
66
What are the Clinical Consequences of Chronic Peripheral Vascular Disease?
Stage 1: Reduced pulses
Stage 2: Intermittent claudication
Stage 3: Pain even when resting (critical limb ischemia)
Stage 4: Ulcers
67
What is Giant Cell Arteritis?
* In head (also called temporal arteritis)- can affect ophthalmic artery= blindness, or can get stroke form damage to other arteries
* Definition: chronic granulomatous inflamm of large to small sized arteries, principally in the head
* Classification based on vessel size
* Aetiology: exact cause unknown but broadly speaking, end stage probs are immune mediated
* Epidemiology: most common form of vasculitis- older individuals in US (>50yrs old)
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What is the pathogenesis of Giant Cell Arteritis?
Chronic granulomatous inflamm= narrows artery= ischaemia= CELL DAMAGE (sound familiar)
o Esp. in head (e.g. temporal arteries – AKA temporal arteritis)
o Also vertebral and ophthalmic arteries- permanent blindness, giant-cell arteritis is a medical emerg need prompt recognition & treatment – early recognition VITAL!
o Also occurs in other vessels e.g. aorta (giant-cell aortitis)
69
What is features of treatment of Giant Cell Arteritis?
• Key clinical features:
o Rare < 50 years, vague symptoms e.g. fatigue, weight loss
o Facial pain or headache; superficial temporal artery (painful to palpation), jaw claudication
• Diagnosis: biopsy & histologic; segmental disease, 2-3cm length of artery
• Treatment: corticosteroids, anti-TNF therapy in refectory cases
70
What is the Morphology of Giant Cell Arteritis?
* Intimal thickening- reduces lumenal diameter
* Med. granulomatous inflammation -elastic lamina fragmentation
* Multinucleated giant cells- 75% of adequately biopsied
71
What is Endocarditis?
* Chorda tendini- stop heart valves going backwards, keep them intact
* These valves will be damaged- if valves don’t close properly giving heart extra work
* Definition: Endocardium inflammation- lining of heart inflamed (mainly involves valves)
* Typical lesion= vegetation on valves
* Got abnormal flow around structural abnormalities= damage to endothelium (VIRCHOWS triad)
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What are the two forms of Endocarditis?
• 2 main forms;
o INFECTIVE ENDOCARDITIS- clinically important
o Non-infective endocarditis- not covered in lecture
o Nonbacterial thrombotic endocarditis (NBTE)
o Endocarditis of SLE (Libman-Sacks Disease))
73
What is the epidemiology and prognosis of Endocarditis?
• Epidemiology: can occur in normal heart with highly virulent organisms (=acute, aggressive)- poor survival. More common on background of Structural abnormality of valves or myocardium
• With organisms of lower virulence (=subacute infective endocarditis= not so nasty) including;
o Rheumatic heart disease was major cause
o More common causes now…..- if you’ve already got a valvualr abnormality;
MV prolapse
Valvular stenosis (calcification etc)
Artificial (prosthetic) valves
Unrepaired and
74
What is the aetiology of Endocarditis?
See lecture table
75
What is the pathogenesis of Endocarditis?
• Pathogenesis (Clinically serious infection!!!):
o Colonization / invasion of heart valves or heart chamber endocardium by a microbe
o Inflamm cells- make substances that damage cells
o Too much destruc of vasc tissue can get aneurysms etc
o Vegetations made of thrombus & organisms= destroy underlying heart/ vasc tissues (eg aorta)
aneurysmal sacs
abscesses local and distant (emboli)
Septic infarcts or mycotic aneurysms
o Most cases bacterial (fungi / other classes can also cause)
76
What are the clinical features of Endocarditis?
o FEVER- most consistent sign, rapidly developing fever, chills, weakness, can be slight or absent (particularly in elderly)
o NON-SPECIFIC SYMPTOMS- may be only presentation, loss of weight/ flu-like syndrome
o MURMERS- 90% patients with L sided IE, new valvular defect or represent a pre-existing abnormality (if already have a valvular defect need to know it’s changed)
77
What are the clinical manifestation of Endocarditis?
o Splinter (lines on nails) / subungual hemorrhages
o Janeway lesions- erythematous or haemorrhagic non-tender lesions on the palms or soles
o Osler’s nodes- subcutaneous nodules in the pulp of the digits
o Roth spots- retinal haemorrhages in the eyes
o (Little haemorrhages flicking off causing haemorrhages elsewhere)
• Mneunomic: FROM JANE (Fever, Roth spots, Osler’s nodes, Murmers, Janeway lesions, Anaemia, Nail (splinter) haemorrhages, Emboli (septic))
78
What are the complications of Endocarditis?
immunologically mediated conditions e.g. glomerulonephritis
79
How do infections get into the heart?
* Any route of bacteria into the blood stream e.g. dental abnormalities, IVDU, wounds, bowel cancer
* Streptococcus viridans from mouth- endocarditis in native but damaged / abnormal valves (50-60%) cases
* S. aureus from the skin- 10% to 20% of cases overall esp. IVDU
* Coagulase-negative staphylococci (e.g. S. epidermidis)- commonly infect prosthetic heart valves
80
What is Rheumatic Fever?
* Definition: acute immunologically mediated, multi-system inflammatory disease, following group A streptococcal pharyngitis
* Organism causes cross reacting immune response; body tries to get rid of strep A but reacts with antigens on heart valves (DIFF to rheumatoid disease)
81
What is the epidemiology and aetiology of Rheumatic Fever?
• Epidemiology:
o Typically children aged 5-15 yrs old
o Rare in developed world (improved diagnosis/ treatment), 15 million in developing countries (Afric, Middle East & far East)/ poor Western pops
• Aetiology: group A streptococcal pharyngitis
82
What are the pathological features of Rheumatic Fever?
o Vegetations (veruccae)
o Mitral valve changes classical;
Virtually only cause of MITRAL STENOSIS
Leaflet thickening
Virtually always involved in chronic disease (MV only in most cases, aortic valve in 25% cases, tricuspid valve/ pulmonary valves- uncommon)
o Fibrous bridging of valvular commissures & calcification (FISH MOUTH valve/ buttonhole stenosis)- as mouth can’t open- lot of extra work on LV
83
What is the pathogenesis of Rheumatic Fever?
o Due to hypersensitivity reactions- combined antibody & T-cell mediated response to self antigens in heart
o Group A strep (pharyngitis) =antibodies AND T cells (which make cytokines that activate macrophages (e.g. Aschoff bodies)= cross react with self proteins in heart
o See lots of macrophages (from cytokines by T cells)
84
What are the clinical features of Rheumatic Fever?
o Left atrium dilates = mural thrombi form = embolise
o Right ventricular hypertrophy
o Diagnosis by Jones Criteria;
85
What is Pericarditis?
inflammation of pericardial sac
86
What is the aetiology of Pericarditis?
• Infections- Viruses (Coxsackie B), bacteria, TB, fungi, parasites
• Autoimmune-
o Rheumatic fever, SLE, scleroderma, post-cardiotomy,
o Late post-MI = Dressler’s, drug hypersensitivity
• Miscellaneous-
o Post-MI (early), uraemia, cardiac surgery, neoplasia (tumour cells growing into it & causing inflamm response)
o Trauma, radiation
87
What is the pathogenesis of Pericarditis
• Acute pericarditis (inflamed=fluid/extra material accumul)
o Serous
o Serofibrinous / fibrinous
o Purulent / suppurative
o Haemorrhagic (e.g. caused by a tumour)
o Caseous (caused by TB)
• Chronic pericarditis (stuck down)
o Adhesive
o Adhesive mediastinopericarditis
o Constrictive pericarditis
o More chance fibrosis & scaring, more chance pericardium gets stuck down constrictive pericardium (can cause heart failure)
• Inflamm causes clear ‘serous’ fluid accumul
• Caused by non-infectious aetiologies (generally);
o Inflammation in adjacent structures can cause pericardial reaction
o Rarely by viral pericarditis (Coxsackie B / echovirus)
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What are the clinical features of Pericarditis
• Sharp central chest pain;
o Exacerbated by : movement, respiration, laying flat
o Relieved : sitting forwards
o Radiating : shoulders / neck
o Differentials : angina, pleurisy
• Pericardial friction rub
• Fever, leucocytosis, lymphocytosis, pericardial effusion
• Complications- pericardial effusion/ cardiac tamponade
89
What is Serofibrinous/ Fibrinous Pericarditis?
• Serous fluid &/or fibrinous exudate in pericardial sac (most common form of pericarditis!)
• Common causes
o Acute MI, Dressler’s syndrome
o Uraemia, radiation, rheumatic fever, SLE, trauma, surgery
• Features of fibrinous pericarditis (without fluid)
o Dry, granular, roughened surface
o More intense inflammatory response =sero-fibrinous
90
What is Purulent/ Suppurative Pericarditis?
* Caused by infections
* Features; red, granular, exudate i.e. pus (can be up to 500mls)
* Inflamm can extend causing mediastino-pericarditis
* Outcome- complete resolution rare; organisation by scarring=restrictive pericarditis (SERIOUS
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What is Haemorrhagic Pericarditis?
• Blood mixed with serous (watery) or suppurative (pus) effusion
• Common causes;
o Neoplasia (malignant cells in effusion)
o Infections (inc TB)
o Following cardiac surgery = cardiac tamponade
• Caseous (cheesy) pericarditis- TB or fungal
92
What is Chronic Pericarditis (Adhesive/ Constrictive Pericarditis)?
(After Acute Often Comes) Chronic Pericarditis (Adhesive/ Constrictive Pericarditis)
• Fibrosis / stringy adhesions obliterates pericardial cavity
• Heart can become encased in fibrous scar – limits cardiac function
• Treated by surgery to remove ‘shell’ around heart
93
What are the four types of Cardiomyopathies?
• Definition: heart muscle disease, mostly uncertain cause
• 4 main types (classified by morphology of the heart);
o Dilated- thick L ventricle
o Hypertrophic- thick doesn’t dilate properly
o Restrictive- not thick but doesn’t dilate proplerly
o Arrythmogenic right ventricular cardiomyopathy (dysplasia)- cause of sudden death
• Epidemiology: depends on subtypes
• Aetiology: unknown (there is a genetic component in many really)- need exclusion of commoner causes of myocardial failure (hypertension, IHD, valvular & congenital HD)
94
What is the pathogenesis of Cardiomyopathies?
• Pathogenesis: main way pathological abnormality causes signs & symptoms;
o Heart Failure (abnormal heart muscle cannot cope with workload)
o Emboli (It’s that Virchow’s Triad again…)- abnormal flow in heart chamber (Most serious acute emboli- to brain (stroke) but can go anywhere e.g. kidneys)
o Arrhythmias (disruption of electrical conduction pathways)
95
What is Dilated Cardiomyopathy?
• Progressive dilation = contractile (systolic) dysfunction
• Heart enlarged, heavy, flabby (dilation of chambers)
• Myocyte hypertrophy with fibrosis
• Arrhythmias- will affect how conduct elec signals, and how well contracts & relaxes
• Associations;
o Genetic (20 – 50% cases)- autosomal dominant (mainly), cytoskeletal proteins gene mutation
o Alcohol (10-20%) and other toxins e.g. chemotherapy
o Others- SLE, scleroderma, thiamine def., acromegaly, thyrotoxicosis, diabetes
• Clinical features;
o Any age but commonly 20 – 50
o Slow progressive signs / symptoms of CCF- SoB, fatigue, and poor exertional capacity
o 5 year survival = ~ 25% (like the ejection fraction…); death due to CCF, arrhythmia / embolism (intra-cardiac thrombus)
o Treatment; cardiac transplantation , long-term ventricular assist (can induce regression)
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What is Hypertrophic Cardiomyopathy?
• Myocardial hypertrophy
• Thick-walled, heavy, poorly compliant L ventricular myocardium- stiff ventricle that doesn’t fill properly;
o Diastolic dysfunction with preserved systolic function
o Intermittent ventricular outflow obstruction (1/3 cases)
• If LVH, NO hypertension, NO valve disease
• 100% genetic cause; mutations sarcomeric proteins, can be sporadic
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What are the clinical features of Hypertrophic Cardiomyopathy?
o ↓ stroke vol- impaired diastolic filling - reduced chamber size / hypertrophied L ventricle compliance
o Obstruction to left ventricular outflow (can cause progression then if concentric)- 25% of patients
o Exertional dyspnoea due to above
o Systolic ejection murmur; ventricular outflow obstruction, anterior mitral leaflet moves toward ventricular septum during systole.
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What are the complications of Hypertrophic Cardiomyopathy?
o Atrial fibrillation
o Mural thrombus formation = embolization / stroke
o Cardiac failure
o Ventricular arrhythmias
o Sudden death, especially in some affected families (most common causes of sudden death in athletes)
99
What is the treatment of Hypertrophic Cardiomyopathy?
o Decrease heart rate and contractility - β-adrenergic blockers.
o Reduction of the mass of the septum, which relieves the outflow tract obstruction
100
What is Restrictive Cardiomyopathy?
• Rare
• Primary decrease in ventricular compliance- impaired ventricular filling during diastole
• Idiopathic or secondary (infiltration); fibrosis, amyloidosis, sarcoidosis, metastatic tumors or deposition of metabolites (inborn errors of metabolism)
• Morphology;
o Ventricles normal size / slightly enlarged chambers normal
o Myocardium is firm and noncompliant (normal thickness)
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What is Arrythmogenic R Ventricular Cardiomyopathy ?
Arrythmogenic R Ventricular Cardiomyopathy (arrhythmogenic R.V. dysplasia)
• Genetic disease (A.D.), ~1 in 5000
• RV dilation / myocardial thinning
• Fibrofatty replacement of RV (lots of fat- affect direction of elec conduc= can cause arrhythmias)
• Disorder of cell-cell desmosomes
• Exercise = cells detach and die
• Silent, syncope, chest pain, palpitations
• Sudden cardiac death – young / exercise
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What is Myocarditis?
* Inflammatory cells in cardiac cells
* Inflammatory cells around vessels- that’s how inflamm cells get into myocardium
* Definition: inflammation of myocardium
* Epidemiology: varies, depends on cause
* Aetiology (don’t need to memorise- just shows how many causes- most often viral):
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What is the pathogenesis of Myocarditis ?
o Infection or inflammatory trigger = cytokines, cytotoxic damage, damage myocytes =myocytes +/or endothelium malfunction = electrical problems / mechanical problems / clotting problems
104
What are the clinical features of Myocarditis ?
```
o Broad spectrum of changes
o Asymptomatic
o Chest pain
o CHF
o Arrhythmias
o Sudden death
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What is Bacteraemia?
* Blood cultures- important infection test
* Bacteraemia not a diagnosis- simply means bacteria been detected in blood
* Bacterimaia + symptoms/ signs of infec= bloodstream infec
* E.g. Intravascular catheter-related bloodstream infec
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What are the different types of Bacteraemia?
* Transient (lasts for a short time)
* Intermittenet (n.o. organisms in blood increase & decrease)- pneumonia, pyelonephritis, abcesses, meningitis, CRBSI (catheter related blood stream infec)
* Continuous (n.o. organisms in blood continuous) - endocarditis, mycotic aneurysm, pacing lead infec, infected DVT
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What is the Pathology of Infective Endocarditis?
* Endocardial surface similar to endothelial cells
* IE- infec of endocardium/ devices in heart
* Vegetation- electron micrograph of vegetation shows densely packed bacteria
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What are the types of presentation of infective endocarditis?
• Types of presentation;
1. Non-specific illness- lethargy, malaise, night sweats, anorexia, weight loss
2. Heart failure (valves eroded away- blood regurg)- SOB, orthopnea, PND
3. Results of extra-cardiac foci of infec (back pain from HVO, stroke, abdo pain from splenic infarct)
• Particularly known if heart valve disease, pacemaker, prosthetic valve, congenital HD
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What are the clinical features of infective endocarditis?
* Fevers (96%)
* Splinter haemorrhages (8%)
* Oslers nodes (3%)
* Janeway lesions (palm) (5%)
* Roth spots (retinal haemorrhages) (2%)
* Conjunctival haemorrhages (5%)
* Splenomegaly (11%)
* New murmur (48%)
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What is the aetiology of infective endocarditis?
```
o Staphylococci (34%)
o Streptococci (32%)
o Enterococci (14%)
```
111
What is the diagnosis of infective endocarditis?
• Dukes criteria- 2 major criteria;
o +ve echocardiogram=transthoracic (gel thorax- probe on skin) & transoeophageal (endoscope down oesoph can see back of heart)
o +ve blood culture (3 sets taken at diff times, 2 sets in severe sepsis)= recommend taking blood cultures regularly e.g. every 6 hrs (don’t delay- 2 sets immediately if very sick)
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What is the treatment of infective endocarditis?
• Need antimicrobial therapy- ideally directed towards pathogens identified by blood cultures
• In addition surgery may be required to;
o Replace/ repair damaged valves
o Remove infec when antimicrobials don’t work
o Remove infected devices e.g. pacemaker
o Prevent complications e.g. stroke (e.g. had a stroke & embolus in heart valve- remove it)
o Drain purulent collections e.g. in spleen or spine
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What is a Mycotic Aneuryms?
* Aneurysms due to any infec e.g. fungal or bacteria
* Aneurysms from, or secondarily infected by, microorganisms
* Tend to occur at bifurcations- abnormal blood flow lodges bacteria onto endothelial surfaces aneurysm
* Vessels usually rigid
* E.g. can get femoral artery aneurysm
114
What is the presentation of Mycotic Aneuryms?
• Usually systemic symptoms of infection & variable symptoms from aneurysm- depending on location;
o No localising symptoms
o Painless swelling
o Painful swelling
o Symptoms caused by rupture (e.g. intracerebral haemorrhage, collapse)
115
What is the aetiology of Mycotic Aneuryms?
* Salmonella spp. & staphylococcus aureus main ones
| * Streptococcus spp., Pseudomonas aeruginosa, E.coli
116
What is the management of Mycotic Aneuryms?
surgical removal, stenting/ coiling (if bleeding) depending on location with antibiotics
117
What is the pathogenesis of Mycotic Aneuryms?
o Haematogenous seeding (e.g. 2ndry to infective endocarditis)
o Trauma to arterial wall + direct contamination (e.g. IVDU)
o Extension from a contiguous infected focus
o Secondary to septic microemboli (e.g. 2ndry to infective endocarditis
118
What is an Infected Deep Vein Thrombosis?
Infected DVT
• DVTs- can be seeded with bacteria during bacteraemia/ directly infected e.g. IVDU injecting into femoral vein, seeds femoral DVT
Presentation
• Symptoms/ signs of DVT & systemic infection
• &/or resp symptoms (when infected emboli breaks from DVT & travel via venous system to lungs- infected pulmonary emboli)
• If see consolidation on x-ray- think could be infected emboli
Aetiology
• Depends on mechanism but commonly S.aureus, streptococci & anaerobes in IVDU
Diagnosis; multiple (3) blood cultures, DVT confirmation plus exclusion of other causes e.g. infective endocarditis (IE)
Management: antibiotics plus anticoagulation
119
What are the Different Types of Primary Infections of the CNS?
* Meningitis- inflamm of MENINGIES
* Encephalitis- inflamm of brain PARENCHYMA
* Brain abscess
* Subdural empyema
120
How do Infectious Agents Spread to CNS?
* Hematogenous spread most common- usually via arterial route, can be retrograde (veins)
* Direct implantation; often is traumatic, iatrogenic (rare), congenital (meningomyelocele)
* Local extension of infecs (2ndry to established infections)- most often from mastoid, frontal sinuses, infected tooth etc
* Along peripheral nerves- usually viruses; rabies, herpes zoster
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What is Meningitis?
* MEDICAL EMERGENCY- life threatening (1 of top 10 causes of death worldwide)
* Meningitis- inflamm process of leptomeninges & CSF
* (Meningoencephalitis- refers to inflamm to meninges & brain parenchyma)
* Need empiric antibiotics
* Mortality rates up to 30%, survivors- may have lifelong effects
* Mostly in babies & young children <5 but 2ndry peak in teen years & elderly can have it
* All of CNS is sterile- when infec meningeal membs inflamed response
* Incidence 2-5 per 100,000
122
What is the classification of Meningitis?
• Meningitis classified as;
o Acute pyogenic=bacterial meningitis
o Aseptic meningitis-= usually viral meningitis
o Chronic meningitis=inflamm in CST persists for 4 wks or more (milder symptoms to begin with in contrast to acute meningitis), need to do detailed investigation to find cause THEN start treatment (not medical emerg like acute is), causes; Mycobacterium tuberculosis (TBM), spirochetes (neurosyphilis), Cryptococcus
• Chronic meningitis onset measured in wks to mnths, but generally defined when symptoms, signs & CSF remain abnormal for at least 4 wks
123
What is Meningitis?
any meningitis (infectious/ non-infectious) which cause is not apparent after initial evaluation & routine stains & cultures of CSF
124
What clinical features suggest Meningitis?
Clinical features suggesting meningitis;
• Headache
• Irritable
• Neck stiffness
• Photophobia
• Fever
• Vomiting
• Varying levels of consciousness
• Rash
• Kernic sign- flex thigh @ 90 degrees then try to extend knee patient will feel pain
• Groups that may have non-specific presentation; neonates, elderly, immunosuppressed
• Smaller children- may have bulging fontanelle
125
What pathogens affect different ages causing Meningitis?
0-4 wk: strep agalacitiae, E.coli, Strep B (EXAM Q!!!!!!), Listeria monocytogens (usually in neonate, elderly or immunosuppressed), Kelbsiella pneumonia, Enterococcus spp., Salmonella spp
4-12 wk S.agalicitae, E.coli, L.monocytogens, H. influenza, Sterptococcu pneumoniae, Nesseria meningitides
3mnths- 18yrs H.influenzae, N. meningitides, S.pneumoniae
18yr-50yr S.pneumoniae, N.meningitidis
>50yrs S.pneumoniae, N.meningitidis, L.monocytogenes, aerobic gram –ve bacilli
126
What is the pathogenesis of meningitis?
• Nasopharyngeal colonisation= infec seeds into blood & meninges
• We may have these bacteria but not all of us get meningitis, but some have risk factors;
o Extremes of age
o On immunosupressent therapy/ have HIV
o Chronic organ dysfunction e.g. chronic kidney disease
o Cochlear implants
o Sickle cell disease
• More in winter season- more spread of coughs cold etc
127
What is the Lab diagnosis of Meningitis?
* Blood cultures
* Lumbar puncture: macroscopic exam, CSF for microscopy, gram stain then culture & biochemistry (check CSF for glucose)
* EDTA blood for PCR (as may not be able to grow bacteria, PCR may help detect)
128
What are the CSF Abnormalities in Meningitis?
CSF Anormalities in Meningitis
• Gram +ve= strep pneumoniae
• Gram –ve= nisseria meningitis
• Low glucose= bacterial meningitis
Normal: clear colourless
Bacterial: cloudy, turgid, high protein low glucose
Viral(Aseptic): Clear, slightly cloudy, normal protein and glucose
TB: Clear, slightly cloudy high protein low glucose
Cryptococcal: Clear
129
What is Viral Meningitis?
* Usually affect children & young adults
* Milder signs & symptoms
* May start as resp or intestinal infec then viraemia
* CSF abnormalities- shows raised lymphocyte count (50-200/cu mm); protein & glucose normal (compared to acute bacterial meningitis)
* Full recovery expected
130
What are the causes of Viral Meningitis?
o Enteroviruses (Echo, coxsackie A, B, polio)
o Paramyxovirus (mumps)
o Herpes simples (HSV1=cold sores & encephalitis, HSV2=genital herpes & meningitis), VZV
o Adenovirus
o Other: Arboviruses, lymphocytic choriomeningitis, HIV
131
What is Tuberculosis Meningitis?
* Chronic presentation so insidious onset
* Breathe in TB bacteria=form a primary complex in lungs= can spread to meninges/ brain parenchyma & form granulomas there
* Higher incidence in immigrant pops who come from countries with a higher TB incidence
* High freq of complications (as often delay in diagnosis), cranial nerve palsies
* Delayed diagnosis makes complications more likely
* CSF shows predominantly lymphocytic response but polymorphs also present
* High protein, low/absent sugar
* Remember increasing MDR TB (multi-drug-resistant TB)
132
What is Encephalitis?
* Acute inflammatory process affecting brain parenchyma
* Viral infec most common & important cause with over 100 viruses implicated worldwide
* Altered levels of consciousness more likely in encephalitis, neck stiffness more likely in meningitis
133
What are the symptoms of Encephalitis?
```
• Altered levels of consciousness more likely in encephalitis, neck stiffness more likely in meningitis
• Symptoms;
o Fever
o Headache
o Behavioural changes
o Altered level of consciousness
o Focal neurologic deficits
o Seizures
o Incidence of 3.5-7.4 per 100,000 persons per year
```
134
What are the causes of Encephalitis?
o Herpes viruses- HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, Human Herpes virus 6
o Adenoviruses
o Influenza A
o Enetroviruses, Poliovirus
o Measles, mumps & rubella viruses
o Rabies
o Arboviruses: Japanese encephalitis; StLouis encephalitis virus; West Nile encephalitis virus
135
What is Herpes Encephalitis?
* Most common cause of sporadic encephalitis in previously healthy
* May be evidence of herpes infec of skin, mucosae
* Causes severe haemorrhagic encephalitis affecting temporal lobes so focal signs & epilepsy features
* 2-4 cases/million people/yr
* Acute infec or more commonly reactivation of latent infec (trigeminal nerve ganglion)
* Need to treat with clinical suspicion BEFORE get lab results
* 30% mortality with treatment
* 70% mortality without treatment
* High mortality so treatment urgently needed with ACICLOVIR
136
What is the treatment for Herpes Encephalitis?
ACICLOVIR
137
What is Recurrent Meningitis?
* >2 episodes
* Symptoms free intervals (how can differentiate from chronic & recurrent meningitis)
* Normal CSF between episodes
* Must be differentiated from chronic meningitis
* (Herpes simplex virus type 1 (HSV1) may cause recurrent meningitis)
138
What is Rabies?
• Acute, progressive viral encephalitis
• Highest case fatality of any infectious disease
• Once clinical symptoms set in = death so need to see risk factors
• Model zoonosis e.g. dogs
• Usually children <15 yrs of age bitten by dog/ scratched by rabied animal
• Prevention- can have exposure prohylaxis e.g. if bitten by a dog
Fatal once symptoms set in
Treatment: wash wound with soap, vaccinations, medical advice immediately after bitten
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What is the pathogenesis of Rabies?
1. Virus enters through bite
2. Grows @ trauma site & multiplies then enters nerve endings
3. Advances to ganglia, spinal cord & brain
4. Infec cycle completed when virus replicates in salivary glands
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What are the stages of rabies?
o Prodromal phase- fever, nausea, vomiting, headache, fatigue, some experience pain, burning, tingling sensations at site of wound
o Furious phase- agitation, disorientation, seizures, twitching, hydrophobia (irrational fear of water)
o Dumb phase- paralyzed, disorientated, stuporous
o Progress to coma phase resulting in death
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What is a Brain Abscess?
• Brain abscess- focal suppurative process in brain parenchyma (pus in substance of brain)
• Direct spread from contiguous suppurative focus (e.g. from ear 40%, sinuses, teeth)
• Haematogenous spread from distant focus e.g. endocarditis, bronchiectasis (often multiple abscesses)
• Trauma (e.g. open cranial fracture, post-neurosurgery)
• Cryptogenic (no focus is recognised- 15-20% of cases)
• Bacteria responsible depend on pathogenic mechanism involved;
o Streptococci (60-70%) e.g. streptococcus ‘milleri’
o Staphylococcus aureus (10-15%)- most common pathogen in abcesses after trauma/ surgery
o Anaerobes e.g. Bacteroides spp.
o Gram –ve enteric bacteria (E.coli, Pseudomonas spp.)
o Others e.g. fingi, Mycobacterium TB, Toxoplasma gondii
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What are the symptoms of a Brain Abscess?
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• Clinical presentation;
o Headache (most)
o Focal neurological deficit (30-50%)
o Fever (<50%)
o Nausea, vomiting
o Seizures
o Neck stiffness
o (Papilloedema)
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What is the treatment of a Brain Abscess?
• Management;
o Drainage is treatment of choices (small abscesses can be treated with antibiotics alone)
o To urgently reduce intracranial pressure
o To confirm diagnosis
o To obtain pus for microbiological investigation
o To enhance efficacy of antibiotics
o To avoid spread of infec into ventricles
• Principles in antibiotic treatment of CNS infecs;
o Need to use antibiotics that can penetrate blood brain barrier to achieve therapeutic concentrations in blood
o Distinct physiological properties of blood brain barrier & blood CSF-barrier
o Penetration of drugs into CSF & brain tissue differ
o Ampicillin, penicillin, cefotaxime, ceftazidime & metronidazole achieve therapeutic concentrations in intracranial pus
• Steroids- dexamethasone- 10mg IV 15 mins BEFORE antibiotics, shown to decrease morbidity & mortality in S. pneumoniae but NOT in N.meningitidis
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What is Neurosyphilis?
* CNS invasion in syphilis
* Occurs early in infec in 30-40% of patients
* Asymptomatic neurosyphilis can occur at any stage of syphilis
* Patients can remain asymptomatic- develop symptoms in chronic phase
* Early symptomatic forms (months to a few years)
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What are the symptoms of Neurosyphilis?
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• Symptoms:
o Acute meningitis
o Meningovascular (stuttering stroke)
o Late symptomatic forms (>2 yrs)
o General paresis
o Tabes dorsalis (loss of coordination of movement)
o Diagnosis by blood & CSF serology
MAKE SURE ask about risk factors in history to make link with clinical findings
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