Seminar 3 - IVDU and Complications Flashcards
Describe the histological features of aspiration pneumonia
Desquaminated epithelial cells
Gastric contents
Clumps of bacteria
Alveolar haemorrhage
How do you manage mitral stenosis
Only requires management in severe cases
Can do a percutaneous balloon valvotomy, open valve commissurotomy or valve replacement
Describe the epidemiology of infective endocarditis
Incidence has been increasing
Approx. 12.7 cases per 100000
Proportion due to intracardiac devices rising but cases due to HIV fell
Describe the structure of the AV valves
Valve leaflets attach at the annulus which is a a collagenous, crown-shaped structure that is part of the fibrous skeleton of the heart
The valve has 4 layers of varying compositions of elastic and collagenous tissue – atrialis, lamina spongiosa, lamina fibrosa, ventricularis
The chordae tendinae are branching structures made up of collagen and elastic fibres
Which valve does most endocarditis develop on
Mitral valve
How can drug metabolites affect interpretation of toxicology results
Some drugs produce the exact same metabolites when broken down
e.g. opioids
Patient taking codeine will have both codeine and morphine in urine, must look at levels and determine if they also took morphine
What are the 2 types of valve disease
Stenosis - failure of valve to fully open
Insufficiency/regurgitation - failure of valve to fully close
How does aortic stenosis present
May not have symptoms until disease is severe and prognosis poor
May have signs of CHF, angina and syncope
Describe the effect of M6G
It is pharmacologically active
2x more potent than normal morphine when administered systemically
Describe the risk of contracting HIV at autopsy
Occupational exposure has been documented but is rare and there is no evidence that it is easily acquired at autopsy.
Staff at risk if they receive a cut or needlestick injury when working on an infected corpse
Estimated HIV transmission rate after a single needlestick injury is 0.1-0.36%.
Risk is increased by AIDS, high viral load or a deep injury with visible blood.
IVDU are higher risk.
How can a moving injury occur during autopsy
Incorrect moving and lifting of the body can lead to serious back injury
What is secondary haemostasis
Second stage of haemostasis
Involves the activation of the clotting cascade and the deposition of fibrin
What causes deep vein thrombosis
Trauma Surgery Contraceptive pill Tumours Pregnancy Prolonged travel/immobility Hypercoagulability or stasis usually
Describe how blood is taken for toxicology at autopsy
At least 10ml of peripheral blood taken Ideally from femoral or iliac vessels Identify location in report Sodium fluoride/potassium oxalate should be used as a preservative unless suspect poisoning with fluoride or a fluoride-producing compound exists Always taken
List the pathological features of the skin due to injection of drugs
Track marks with puckered scarring, hyper pigmentation and chronic sinuses
Skin popping scars
At time of injection you have acute bleeding and then progresses to inflammatory reaction after a few hours
Hemosiderin forms at the injection site 2-3 days post injection (shows an older site)
May have granulomatous inflammation present if foreign material also injected
Rarely some people get hypersensitivity uticarial rash post injection
What is the major metabolic pathway for morphine in the body
Conjugation with glucuronic acid (glucuronidation)
Becomes morphine-6-glucuronide (M6G) and M3G
Which valves are most susceptible to non-infectious endocarditis
Affects mitral valve > aortic valve > tricuspid valve > pulmonary valve
What is Libman-sacks endocarditis
Small sterile lesions in the heart in the context of SLE
How does morphine affect the respiratory centers in the brain
Directly affects nucleus accumbens in brainstem
Decreases responsiveness to arterial CO2
Depresses the centers responsible for regulating the rhythm of breathing
What causes superficial vein thrombosis
Varicose veins
6MAM is only detectable once the heroin has been metabolised - true or false
True (mostly)
Some forms of heroin such as black tar may contain some 6MAM but most types only produce it on metabolisation
Give examples of sharps based hazards from the body and explain how you reduce the risk
Scrape injury from the ends of cut bone - cover ends with surgical towel to prevent injury
Needle , bullet or other fragments may be found within the body
High risk corpses may get radiography prior to autopsy
Special equipment and resistant gloves used to remove
Define ‘risk’
The chance of a negative event occurring.
e.g. chance of contracting HIV from a sharp injury
List the microscopic features of subacute endocarditis
Granulation tissue at the base - sign of healing
Fibrosis -> calcification -> development of a chronic inflammatory infiltrate
Describe the risk of contracting Hep B or C at autopsy
Staff at risk if they receive a cut or needlestick injury when working on an infected corpse.
HBV is highly infectious, and transmission can occur following exposure to extremely small volumes of infected blood
HCV is less infectious but still has a transmission rate of 2.7-10% following exposure
IVDUs are at higher risk
In which body fluids can 6MAM be detected and how long for
Oral fluid - for several hours after heroin use
Urine - 12 hour detection window
May be found in vitreous humor and CSF
How can lines of Zahn be used to differentiate between between ante-mortem and postmortem thrombi
Lines of Zahn are only seen when a thrombi is formed in flowing blood
Therefore tell you it was ante-mortem
List the invasive procedures which can lead to endocarditis
Pacemaker insertion Endoscopy Colonoscopy Barium enema Dental extractions Transurethral resection of the prostate Transesophageal echocardiography Lines
Describe the effects of infection induced valvular damage
Leads to valvular insufficiency and a backflow of blood
The heart cannot pump effectively and the tissues don’t get enough O2
Leads to fatigue, muscles tiring quickly, SOB and kidney malfunction
In forensic cases, is a blood sample enough for toxicology
No
Collection of blood should be supplemented with collections of vitreous, urine, bile, gastric contents, and in some instances, CSF.
What causes pulmonary insufficiency
Pulmonary HTN, L-sided heart pathologies Endocarditis Connective tissue abnormalities Commonly occurs following surgical repair of heart eg in Tetralogy of Fallot
What are the infectious disease hazard groups
Organised by the likelihood of acquisition, severity of resulting disease, availability and efficacy of treatment and risk of transmission from staff to general public.
Group 1 - unlikely to cause human disease.
Group 2 - can cause disease and may affect employees, unlikely to spread to community and treatment available.
Group 3 - cause severe human disease and may be serious hazard to employees, may spread to community but effective treatment available.
Group 4 - cause severe human disease and may be serious hazard to employees, likely to spread to community and effective treatment not available.
List the general pathological lung changes that are caused by drug misuse
Agonal or PM movement can lead to gastric content in the lung without the inflammation
Injecting talc/lactose/crushed tablets can cause intravascular granulomatous disease
May develop septic emboli in lungs following infective endocarditis
IVDU of any drug can cause TB, pulmonary talk granulomas, foreign body emboli and pulmonary necrotising angitis
HIV can increase risk of bacterial or pneumocytic pneumonia
Which thrombi are called white thrombi
Arterial thrombi
Made up of lots of platelets and few red cells
What are the semilunar valves
The aortic and pulmonary valves
They close in diastole and open for systole
What causes pulmonary stenosis
Mostly congenital
May occur in carcinoid heart disease
Describe the microscopic features of venous thrombosis
Lots of red cells with few platelets
Lines of Zahn present - alternating layers of red cells and layers of platelets and fibrin
How do you manage tricuspid stenosis
f mild or moderate, fluid restriction, diuretics
Valve replacement, balloon dilation if severe
Which valve disease is the result of of abnormalities of the valve leaflets or aortic root dilation
Aortic regurgitation
What causes aortic stenosis
Calcification of the valve leaflets
How does aortic stenosis progress to heart failure
Valve opening becomes narrower due to calcification
This increases pressure in the left ventricle and leads to hypertrophy with ischaemia
The heart decompensates and you get congestive heart failure
Describe the risk of contracting TB at autopsy
Can get pulmonary or cutaneous infection
Incidence in post-mortem staff is greater than clinical staff.
May actually be a higher risk at autopsy than during life.
Bacilli have been found on surfaces up to 24hrs after autopsy
Intravenous drug users are at higher risk
If ante-mortem blood samples are used in toxicology, what should be considered
The gels used in many serum gel tubes may absorb drugs and affect the blood concentration
Can a person take heroin and still have a negative 6MAM test
Yes
It has a short half life so may only show up if taken recently
After 6MAM has been metabolised the person will only be positive for morphine
What can increase the window of 6MAM detection
Chronic heroin use
List the pathological features of the skin associated with crack cocaine use
Burns due to preparation
Self inflicted excoriations due to psychological delusions - often parasitic
List external signs of drug use seen on the face
Jaundice = liver failure
Necrosis of nasal tip = infective endocarditis
What are the main causative organisms of healthcare-associated or nosocomial infective endocarditis
Related to the underlying bacteremia
Typically gram-positive cocci i.e. S aureus, CoNS, enterococci, non-enterococcal streptococci
When is pre-autopsy testing carried out
If there is suspicion of a HG3 infection (or higher)
Can test for HIV if they had a high risk lifestyle without prior consent from deceased
Pulmonary manifestations of infective endocarditis are common in which patient
Those with tricuspid infections
1/3 have pleuritic chest pain
3/4 have radiograph changes
List the standard PPE for autopsy
Scrub suits, gowns, waterproof sleeves, plastic disposable aprons, caps, N95 particulate masks, eye protection (goggles or face shields), shoe covers or footwear restricted to contaminated areas, and double sets of gloves
Remove rings to prevent gloves punctures
Cut resistant gloves should be available for high risk procedures
What are the pros and cons of bioprosthetic valves
Pros – Do not require anticoagulation, can be inserted via transcatheter procedures
Cons – May only last 10-15 years so further replacement surgery may be required
Which antibiotics are used to treat prosthetic valve endocarditis
Penicillin-sensitive S viridans: penicillin G/ceftriaxone + gentamicin
Vancomycin & gentamicin
MSSA = nafcillin
What are the clinical features of endocarditis
Rapid onset of fever - most consistent symptom
Chills
Weakness and fatigue
Flu-like syndrome
Weight loss
If IE is left sided they probably have a murmur
During autopsy, whos health and safety needs to be considered
The lead pathologist
Any other staff helping in the autopsy room
Visitors such as clinical staff or medical students
Those involved in the handling of the body (relatives, funeral home staff etc.)
Laboratory workers handling the samples
Which antibiotics are used to treat native valve endocarditis
Penicillin G & gentamicin
Vancomycin if MRSA
What is the risk from ICDs on autopsy and explain how you reduce it
Risk of electric shock. To reduce, it should be inactivated before autopsy and high quality gloves used on handling.
Must be removed prior to cremation = explosion
How does heroin affect the heart
Injection of heroin can lead to infective endocarditis – does effect both left and right heart (R more common)
Will see inflammatory cells in myocardium but not fibrosis
May have myocarditis and cardiomyopathy due to HIV infection from needle sharing
Which patients are at risk from fungal endocarditis
IV drug users
ICU patients who have received broad spectrum antibiotics
Where are fibroblast samples typically taken from
Skin, fascia, lung, diaphragm and muscle
How does ecstasy affect the liver
2 forms of liver damage
Type 1 - steatosis, sinusoidal dilatation and hepatonecrosis
Causes death through hyperpyrexia
Type 2 - hepatitis and fulminant liver failure
May be due to direct toxic effect
Describe endocarditis in the context of SLE
Significant valvulitis with vegetations formed from fibrin and immune complexes
Mostly asymptomatic but may cause valvular dysfunction in severe cases
How can general drug use affect the kidneys
IV drug use causing suppurative skin infections may cause renal amyloidosis
HIV can cause FSGS
Prosthetic valves in which position are most susceptible to infective endocarditis
Mitral position are more susceptible than the aortic areas
Give examples of aerosol based hazards from the body and explain how you reduce the risk
Examples: bone dust, smoke from searing tissue for sample.
Risk of inhalation
Aerosol generating procedure limited if possible
Can use masks, filters or vacuums
How does morphine affect the respiratory centers in the brain
Directly affects it
Decreases responsiveness to arterial CO2
Depresses the centers responsible for regulatiing the rhythm of breathing
List the key vaccines suggested for autopsy workers
Hep B, TB, tetanus, polio, diphtheria, MMR
All staff should be up to date
How do you diagnose fungal IE
Microscopic examination of large emboli
What is the main difference between pharmaceutical and street heroin
Pharmaceutical heroin is made from pure morphine
Street heroin is made from morphine purified from opium extract and is extract ten contaminated with other alkaloids, e.g. codeine, noscapine
How does mitral stenosis present
Patients may present with symptoms of R-sided heart failure +/- atrial fibrillation, but even severe cases may be asymptomatic
What are the main types of embolism
Pulmonary
Fat - caused by soft tissue injuries, bone breaks or burns
Air - scuba divers rising to fast or air entering circulation
Systemic - most from cardiac mural thrombi
Amniotic - can reach mother’s lungs
Septic - particles from infection reach bloodstream and block
Retinal - small clots can block tiny vessels in the eye
Describe how injection sites are sampled for toxicology at autopsy
Resect a wide skin ellipse of needle puncture mark & surrounding skin (down to subcutaneous tissue).
Take a similar sample at a distant or contralateral site as a control. If specimen is for histology, add neutral buffered formalin
How do valve leaflets become calcified
Repeated injury to valve encourages calcium deposition
This eventually limits the movement of the valves and they stop opening fully - stenosis
Define early prosthetic valve endocarditis
Occurring within 60 days of the valve implantation
What is thrombosis
When a blood clot blocks the circulation
Disruption of normal haemostasis
List the features of ‘crack’ lung
Alveolar haemorrhage Hemosiderin laden macrophages Pneumonitis Interstitial fibrosis Carbon laden macrophages ( see right) Small artery medial hypertrophy
Additionally you’ll get barotrauma and emphysematous lung disease
Describe the extrinsic pathway of the coagulation cascade
In the presence of tissue factor, factor 7 becomes activated
This then activates factor 10
Factor 10, in the presence of Factor 5 and calcium then generates a molecule called prothrombin activator
This converts prothrombin to thrombin
Thrombin then converts fibrinogen to fibrin
How would you take a foetal tissue sample
Chorionic villus sampling has best chance of growing cell culture
Must be done as soon as intrauterine death confirmed
Fibroblasts can also be used but 1/4 will fail
How do DVTs present
May be asymptomatic
Also have localised pain, heat, oedema
At what point in the autopsy should toxicology samples be taken
Before any disruption of the body has occurred
How does rheumatic fever progress to heart failure
Acute RF leads to fusion of the leaflet commissures and thickened leaflets
This reduces flow which increases pressure in the L atrium and decreases it in the L ventricle
This leads to reduced CO and pulmonary hypertension
Results in RHF
What are the typical causative agents of subacute native valve endocarditis
Alpha-haemolytic strep or enterococci
How do you reduce transmission of transmissible spongiform encephalopathies at autopsy
Should be carried out in a separate/isolated room with limited staff if possible.
To reduce risk use waterproof gown, HEPA filters, disposable equipment where possible, keep reusable equipment wet and have a dedicated set for TSEs.
Care must be taken when removing the brain and fixing it.
Samples must be marked
Certain detergents need to be used as they denature the prions
What is the issue with existing toxicology results ‘ranges/scales’
They were created before redistribution was discovered so this is not taken into consideration
What oesophageal changes may be seen in drug misuse
Mallory Weiss tears if drug use causes a lot of vomiting
Varices may be present if liver disease
What is the most common way to take crack cocaine
To smoke it
What are the effects of carcinoid heart disease
Typically causes R sided pathology (tricuspid insufficiency, pulmonary stenosis) as this side receives blood from the liver first
How is heroin synthesised
In the presence of acetic anhydride, morphine is initially acetylated at position 3 producing 3-acetylmorphine
There is a further acetylation reaction at position 6 to give 3,6-diacetylmorphine which is heroin
Which type of vegetations are associated with more valvular destruction
Those from subacute endocarditis rather than acute endocarditis
What are the acute causes of mitral regurgitation
Infective endocarditis
Ischaemic damage to the papillary muscles
Rupture
Acute rheumatic fever
What is the half life of 6-MAM
0.6 hours
Very quickly metabolised into morphine or excreted from the body
Describe the macroscopic features of venous thrombosis
Thrombi extend in direction of blood flow
Long clot in the shape of the lumen (like a cast)
List some of the complications of infective endocarditis
Glomerulonephritis - due to antigen-antibody complex deposition
Particularly ill patients may develop sepsis, arrhythmias or emboli
Now uncommon ones include :
microthrombi (splinter or subungual haemorrhage)
Janeway lesions and osler nodes
Roth spots - retinal haemorrhages
Untreated IE can be fatal
Describe how gastric content are taken for toxicology at autopsy
Stomach tied off (reduce contamination) and emptied
The total volume is recorded
Only a few labs routinely analyse
Look for undigested pills etc.
How do opiates affect the lungs
Classically causes mushroom plume in overdose
Histologically non specific with amorphous eosinophilic material in alveolar spaces
May have aspiration pneumonitis/pneumonia – suggest opiate overdose over stimulant overdose
List the cure rates for specific IE organisms
S. viridans: 98%
Enterococci & S. aureus: 60-90%
Gram-negative bacilli/fungi: 50%
What is the purpose of vasoconstriction in haemostasis
It is an immediate response to try and stop haemorrhage
Rarely effective alone and requires the other processes
Explain how a pacemaker ‘settles into’ the heart
When implanted a fibrin/platelet thrombus can form on the generator box and leads - this is a sterile vegetation
After around a week connective tissue proliferates which partially embedding the leads in the wall of vein & endocardium
This process may offer partial protection against infection during a bacteremia
Which valve disease is the result of abnormalities to the functional unit of the valve
Mitral regurgitation
How can you reduce transmission of TB at autopsy
Autopsy should be carried out in a separate/isolated room with limited staff
Aerosol generating procedures are high risk so N95 masks or suits with HEPA filters should be worn and bulb syringe used for body fluids rather than hose aspirator.
Staff can get yearly TB tests and should be vaccinated.
Name the leaflets of the aortic valve
Left coronary, right coronary, non-coronary leaflets
What is primary haemostasis
First stage of haemostasis
Involves arteriolar vasoconstriction and formation of the platelet plug
What are the 3 active metabolites of heroin
6-MAM
Morphine
3-MAM - much less active than 6
Which patients are most prone to recurrent IE
Those who abuse IV drugs
Or those with pretreatment symptoms of IE of more than 3 months’ duration
Which patients are most likely to develop healthcare-associated or nosocomial infective endocarditis
Those with significant comorbidities More advanced age Predominant infection with S aureus High mortality May be associated with new intravascular devices
What are the general indications for surgery in endocarditis
Paraventricular abscess & intracardiac fistula
Treatment of metastatic infections
Patients with multi-resistant organisms
Persistent hypermobile vegetations - history of emboli
Which patients are susceptible to non-infective endocarditis
Those in hypercoagulable states (malignancy, sepsis)
Or those with endocardial trauma
What can contaminate blood from the general body cavity
Highly likely to be grossly contaminated by intestinal contents, effusions, urine, faeces etc.
Blood should not be taken from here.
List external signs of drug use seen on the hands
Palmar erythema and Dupuytren’s contractures = liver disease
Splinter haemorrhages = infective endocarditis
Clubbing
How does a pacemaker lead to endocarditis
A bacteremia cab infect the sterile fibrin/platelet clots or vegetations on the pacemaker
Microorganisms establish themselves on the surface of the vegetation
The process of platelet aggregation & fibrin deposition accelerate at the site
The bacteria multiply
and are covered by ever-thickening layers of platelets and thrombin
This protect them from neutrophils & other host defenses
What thrombi are called ‘red thrombi’
Venous thrombi
lots of red cells
Which antibiotics are used to treat IVDU endocarditis
Should be aimed at s.aureus
Vancomycin or amox/nafcillin
What are some of the complications of left sided IVDU endocarditis
Can be associated with systemic manifestations from embolic events
Must be special attention to renal, splenic and central nervous system involvement
Why might the bladder be distended on a drug death autopsy
MDMA, amphetamine and other psycho-actives may cause urinary retention
List common opioids/opiates
heroin, morphine, pethidine, fentanyl, methadone, oxycodone, dihydrocodeine
Describe the aetiology of native valve endocarditis
Rheumatic valvular disease - primarily of mitral (most common)
Congenital heart disease (PDA, VSD, ToF)
Mitral valve prolapse with associated murmur
Degenerative heart disease such as calcified aortic stenosis, Marfan’s or syphillis
Infections - most commonly strep or staph
Does IVDU endocarditis occur due to underlying valve abnormalities
No
the valves are typically normal
Why are arterial thromboses more dangerous
Can occlude critical vessels resulting in infarction
May lead to MI or stroke
What causes carcinoid heart disease
Carcinoid syndrome - around 50% of patients will develop the heart effects
Neuroendocrine tumours in the gut secrete compounds such as serotonin
If there is significant liver pathology, these cannot be broken down and are carried to the heart where they cause damage
What is the preferred sample for death by carbon monoxide poisoning
Blood sample
List most common causes of IVDA infective endocarditis
Staph aureus is the most common organism
Also Group A, C, G streptococci and enterococci
Gram-negative organisms e.g P aeruginosa and the HACEK family
List the basic precautions taken during autopsy
Prevention of puncture wounds, cuts, and abrasions by safe handling of needles and sharp instruments.
Protection of existing wounds, skin lesions, conjunctiva, and mucous membranes with appropriate barriers.
Prevention of contamination of workers’ skin and clothing with appropriate barriers and hand washing.
Control of work surface contamination by containment and decontamination.
Safe disposal of contaminated waste.
Minimise aerosol production.
Limit the number of staff in the room at one time.
Where are lung samples taken from
Take approximately 2cm3 of tissue
Heroin has a higher affinity for the m-opioid receptor than its metabolites - true or false
False
It has a lower affinity
Therefore called a pro-drug as action comes mainly from metabolites
Give examples of radioactive based hazards from the body and explain how you reduce the risk
Some corpses will be slightly radioactive if just undergone therapeutic or diagnostic radiology procedures
Should be left until level has fallen (most used in diagnostic have short half lives). In these cases the risk of exposure is very low.
If the source cannot be removed a radiology specialist should be involved and levels should be measured
Which valve is most effected by endocarditis in SLE
Mitral valve
What are the major complications of endocarditis treatment
Post-treatment bacteraemia Relapse Valvular dysfunction Myocardial or septal abscesses Congestive heart failure Metastatic infection Embolic phenomenon Organ dysfunction resulting from immunological processes
