Seminar 1 - Pneumonia Flashcards
Describe the pathogenesis of HSV1 encephalitis
Virus enters brain – via trigeminal nerve or reactivation in brain itself
Virus PAMPs recognised by TOL receptors of innate immune cells
Inflammatory response triggered leading to necrosis and apoptosis of viral cells and brain cells
Leads to swelling, oedema and raised ICP
Describe the structure of a foreign body granuloma
Foreign materials found in the center of the granuloma
Sometimes found within giant cells
There will be epithelioid cells & giant cells on the surface of the foreign body
Describe the pathogenesis of a cerebral abscess
Bacteria enter the brain
Recognized by TOL receptors on astrocytes and microglia
Initiate the inflammatory response compromising the BBB and bringing peripheral inflammatory cells to the site causing massive inflammation and abscess formation
Fibroblasts from the vessel walls in the granulation tissue then contribute to the capsule formation
Describe the difference between gram positive and gram negative
Gram positive organisms have a thick peptoglycan layer and single phospholipid bilayer in cell wall
Gram negatives have 2 phospholipid bilayers and a thin peptoglycan layer in their cell wall
Gram positive will stain purple (as thick layer can retain dye) whereas gram negative stains pink (dye is washed out)
How do viruses infect a cell
They bind to receptors on host cells and enters them where they use the cell to replicate their own DNA
Products can trigger cell death
Name the 4 main types of acute inflammation
Serous inflammation
Fibrinous inflammation
Purulent inflammation and abscesses
Ulcers
What is primary TB
When disease occurs in previously unexposed individual
What are club cells
Cells found in cuboidal epithelium in the respiratory system that have roles in immune modulation, surfactant production, and detoxification
They are secretory and non-ciliated
What are the signs of constrictive pericarditis
Muffled heart sounds,
Raised JVP
Oedema (incl. hepato and splenomegaly)
What is the purpose of granuloma formation
It is a cellular attempt to contain an offending agent that is difficult for the body to get rid of
Which type of inflammation is more likely to lead to scarring - acute or chronic
Chronic
How do you diagnose pericarditis
Blood tests (FBC, U&E cardiac enzymes)
Appropriate test for underlying cause
Echo (effusion) or CXR (cardiomegaly)
How does tissue necrosis cause inflammation
Dying cells release molecules which stimulate the inflammatory response
This includes uric acid from DNA breakdown and ATP from the mitochondria
Picked up by receptors on other cells - signal of cell damage
Inflammation will occur regardless of the cause of cell death (trauma, ischaemia etc.)
What structures are considered part of the upper respiratory tract
all of the structures above the vocal folds: nasal cavity, paranasal sinuses and the pharynx (split into naso- oro- and laryngo-)
Sometimes includes the larynx
What cell types are found in the alveoli
Type 1 alveolar cells cover 95% of the surface and are simple squamous epithelium, providing a permeable barrier for gases
Type 2 alveolar cells produce surfactant and are involved in alveolar repair since they can proliferate and give rise to type I alveolar cells
Also find resident alveolar macrophages which digest particles which have been missed by the mucous lining of the airway.
What is the definition of transmissibility
How easily pathogens are spread i.e. the proportion of persons exposed to a pathogen who are infected by it
What are the 2 main types of granuloma
Foreign body granulomas
Immune granuloma
What is the definition of a pathogen
A microorganism (or virus) that causes disease
How do you diagnose streptococcal toxic shock syndrome
No specific test
Diagnosis is made if organ failure and low blood pressure is found in a patient with a group A strep infection
What causes a cerebral abscess
Usually bacterial infection
Common organisms: strep and staph
Describe the epidemiology of cerebral abscesses
More common in developing countries Men Vs Women almost 3:1 Most at risk groups: Men< 30 Children aged 4-7 Neonates PWIDs Immunocompromised
How do infections spread locally
By releasing toxins or enzymes they can move through tissues by causing damage
What are the microscopic features of an empyema
A a high neutrophil count and large numbers of other leukocytes.
What is meningitis
Inflammation/ infection of all 3 layers of the meninges surrounding the brain
How can we distinguish between strep throat (bacterial) and viral causes of URTI
The following symptoms suggest a virus is the cause of the illness instead of strep throat: cough, runny nose, hoarseness and conjunctivitis
What is the definition of infection
The invasion and multiplication of pathogens in the body causing damage to tissues/ triggering an immune response
What are the macroscopic features of meningitis
Dense exudate covering the surface of the brain - worse in some areas
Prominent engorged blood vessels protruding from surface
What cancers affect the larynx
Most commonly squamous cell carcinoma
Less commonly adenocarcinoma
Affects the supraglottis most commonly
How much fluid is normally found in the pleural space
Normally there is less than 15ml in the space to lubricate the surfaces
Describe the appearance of lobar pneumonia
Confluent consolidation involving entire lung lobe.
When is complete resolution most likely to occur
When the injury is limited or short lived
When the damaged cells are able to regenerate due to limited tissue destruction
Also depends on that particular tissues capacity for regeneration
e.g. Liver can, heart and brain cannot
What are the symptoms of adherence mediastinopericarditis
Systolic indrawing of diaphragm Pulsus paradoxus (systolic drops by at least 10mmHg on inspiration)
What is chronic inflammation
A response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist in varying combinations
In response to persistent stimuli or those that are hard to destroy
What are the two main subtypes of chronic pericarditos
Adherence mediastinopericarditis and constrictive pericarditis
What is the definition of a virus
A core of nucleic acid surrounded by a protein shell that can only reproduce in a living cell
Not classed as a microorganism
What causes fibrinous/serofibrinous pericarditis
Acute MI, trauma, cardiac surgery, uraemia and cancer.
What causes serous pericarditis
Mainly caused by non-infectious inflammatory disease (rheum fever, SLE, scleroderma)
Infections in nearby tissue (if they cause enough irritation)
Viral infections in other areas of the body (URTI, lung) can sometimes lead onto it
Tumours if they invade the pericardium or nearby lymph nodes
How do you diagnose an empyema
Signs of effusion on CXR
Yellow and turbid fluid on aspiration
Presents as exudate on analysis with high neutrophil count
How does a cerebral abscess cause death
Raises ICP which affects perfusion or causes herniation
This damages the respiratory and cardiac centers in the brainstem
Describe adherence mediastinopericarditis
Fibrotic adhesions attach the heart to surrounding structures in the mediastinum.
The heart works harder as each contraction is pulling against new resistance - can lead to cardiac hypertrophy and dilation
Describe the histology of the pleura
The pleura are a serous membrane formed of simple squamous cells also called the mesothelium
This layer faces into the pleural space
Underneath is a supporting layer of connective and elastic tissues
How long does it take a cerebral abscess to form
Takes about 2 weeks from point of infection
Symptoms may start to arise at any point during abscess formation
Define drug resistant TB
Classed as resistance to rifampicin and isoniazid with or without any other resistance.
Requires a regime of at least 6 anti-TB drugs to which the mycobacterium is likely to be sensitive.
Describe the structure and histology of the bronchioles
<1mm diameter
No cartilage or glands but some goblet cells
Epithelium decreases in height from columnar to cuboidal as it descends the respiratory tree to the smallest bronchiole
What are the symptoms of an empyema
Usually begins as a pneumonia or another infection (and their symptoms)
Then develops a recurring fever
What is the definition of a commensal
An organism that lives in or on, and benefits from, another organism
The host receives no benefit but is not harmed.
May be part of body’s normal flora
What are the common pathogens that enter via the skin
Epidermal injury – Staph aureus, Strep pyogenes
Needles – HIV, Hep C
Bites – malaria, rabies, Lyme’s disease
Superficial infections – dermatophytes (fungi)
Which cell types are involved in an immune granuloma
Activated Th1 cells produce cytokines like interferon gamma which activated macrophages
Some parasitic infections can trigger a Th2 response and eosinophils
How do leukocytes reach the site of injury
They enter the tissues through the gaps in endothelial cells
Mediated by adhesion molecules and chemokines
Margination - move to the outside of lumen due to stasis
They roll along the endothelium and then bind to integrins
Move across the wall and then follow the chemical signals to the site of damage where they become active
They are key to eliminating the inflammatory trigger
What is the definition of a bacteria
A unicellular microorganism that has an organised nucleus and usually a cell wall but lacks organelles
Some have the ability to cause disease
What are the risk factors for streptococcal toxic shock syndrome
Age 65+
These with chronic illness (diabetes, alcohol use)
Breaks in the skin (recent surgery etc.)
What is vertical transmission
From mother to foetus or newborn
Mother infected in pregnancy can pass it on to growing foetus which may cause defects
Babies can pick up infections when passing through the birth canal such as chlamydia
Some pathogens can be passed through breast milk (HIV, Hep B)
What are the terminal bronchioles
The final and smallest bronchioles not involved in gas exchange (end of conducting zone)
Beyond this are the respiratory bronchioles
Describe fibrinous inflammation
Occurs when there is greater vascular permeability (as fibrinogen is a large molecule) or when there is a pro-coagulant stimuli (e.g. cancer)
Commonly seen in inflammation of the linings of body cavities (e.g. pericardium)
Fibrin is formed and deposited in extracellular space and can form mesh-like structures
Then either dissolved by fibrinolysis and cleared by macrophages or it develops into scarring
What causes haemorrhagic pericarditis
The most common cause is metastases to the pericardial space.
Other causes include cardiac surgery, infection, underlying bleeding disorders or TB.
How is the innate immune system activated in sepsis
Infection causes release of pro-inflammatory cytokines and other inflammatory mediators
Activation of the complement system to signpost the infection site and upregulates the immune response
What are the main types of meningitis
Bacterial - most common
Viral
Chronic
Non-infectious
Describe the histology of the oropharynx
Non-keratinized stratified squamous epithelium
It is different from the rest of the URT as it has to transmit both air and swallowed food
Which individuals are at higher risk of HAP
Those with severe underlying disease, immunosuppression, prolonged antibiotic therapy, or invasive access devices, e.g. intravascular catheters.
Mechanical ventilation is particualrly high risk
What is the definition of virulence
The pathogenic ability of a microbe ( their ability to cause disease)
Used a measure of severity
Describe the pathogenesis of TB
M. tuberculosis uses host receptors to enter host macrophages via phagocytosis
The bacteria replicates within alveolar macrophages and prevents itself being killed
Its proliferation within macrophages and air spaces results in a bacteremia and multiple seeding sites Most still asymptomatic at this stage
Around 3 weeks post-infection, a TH1-mediated response is initiated and leads to granulomatous inflammation
What are the 3 main outcomes of inflammation
Complete resolution
Healing by connective tissue replacement/ scarring
Progression to chronic inflammation
What infections usually affect the larynx
Laryngitis is the main disease and can be an isolated infection but is more commonly a feature of generalized URTI
H.influenza can lead to laryngoepiglottitis
Croup - laryngotracheobronchitis
Define a transudate
Fluid is low in protein (pleural:serum ratio < 0.5)
Pleural LDH: serum LDH <0.6
Low specific gravity
No cells present
List the 5 R’s of inflammation
Recognition of the offending agent/stimulus by receptors on inflammatory cells
Recruitment of leukocytes and plasma proteins into the tissues
Removal of the stimulus by phagocytosis
Regulation of the response
Repair (regeneration and/or scarring)
What are zoonotic illnesses
Those which spread from animals to humans via bites or consumption of animal products
How would a CSF sample appear in viral meningitis
Not purulent
Lymphocytes present
Moderate protein elevation
Normal glucose content
What are the risk factors for cerebral abscesses
Immunocompromise
Bacterial endocarditis
Bronchiectasis
What are the microscopic features of meningitis
Subarachnoid space filled with neutrophilic exudate
Also has enlarged blood vessels
Describe caseous pericarditis
This subtype is commonly seen in TB patients.
There will be focal regions of caseation in the pericardium.
Presents very similarly to purulent/suppurative
What are the symptoms and signs of a pleural effusion
May be asymptomatic
Shortness or breath and pleuritic pain
Stony/dull percussion, reduced chest expansion, vocal resonance and air entry on affected side
Trachea may deviate away from affected side if severe
Mycoplasma pneumoniae causes pneumonia in which population groups
Children and young adults
Often get local epidemics (schools etc)
What organisms are common cause of lung abscesses
Staphylococci, streptococci, numerous gram-neg species, and anaerobes are implicated.
Mixed infections are common due to aspiration being a common cause
What are the main causative organisms in aspiration pneumonia
A mixed picture of anaerobic oral flora and aerobic bacteria
Oral: bacteroides, prevotella, fusobacterium, pepto-streptococcus.
Aerobes: Strep. Pneumonia, staph. Aureus, h. influenzae, pseudomonas aeruginosa.
What are the 4 main routes of infection into the CNS
Haematogenous - most common
Direct implantation - usually after trauma or surgery, may be due to malformations that allow access
Local extension - sinuses, teeth, skull or vertebrae are the most commo
Along peripheral nerves (for viruses like zoster)
Describe the pathological appearance of a secondary TB infection
Usually affects the lung apices
Florid cavitation occurs - tissue damage more extensive
Initial lesion in secondary infection tends to be small, well-circumscribed, firm, grey-white to yellow in colour and with variable degrees of caseation and fibrosis
Describe an ulcer
A local defect/excavation of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue
Occur only when tissue necrosis & resultant inflammation exist on/near a surface
What are the common symptoms and signs of pericarditis
Sharp, central pleuritic pain, may be better on leaning forward, worse on inspiration or lying flat
Fever
Pericardial rub
Saddle shaped ST elevation on ECG
May have congestive symptoms if there’s an effusion (SOB etc.)
What is the definition of incubation period
The time between exposure to a pathogen and the development of symptoms
How does fibrinous/serofibrinous pericarditis present
Classic pericarditis symptoms
If there is a significant volume of fluid the rub may be diminished
Microscopically the fluid is made up of serous fluid and fibrinous exudate
What are the 2 main complications of chronic inflammation
Abscess
Granuloma
What are the symptoms of peritonsillar or retropharyngeal abscesses
Severe pain
Difficulty swallowing
Breathing difficulty - if it obstructs the airway
What is granulomatous inflammation
A form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes (sometimes associated with necrosis)
Describe the epidemiology of TB
Leading cause of death worldwide from a single infectious agent (above HIV/AIDS)
Highest incidence in South-East Asia
What is the benefit of granulomatous inflammation in TB
In most, this response will halt the infection response to avoid significant tissue destruction
More likely to progress to caseous necrosis in the elderly and immunosuppressed (particularly HIV+)
What are the pathological features of TB
Granulomatous inflammation – accumulation & aggregation of activated macrophages (“epithelioid” cells), some may fuse to form giant cells
Caseating granulomas are characteristic - central necrosis is surrounded by lymphocytes and activated macrophages
The combination of granulomatous lesions in the lung parenchyma + lymph nodes = Ghon complex
Define hospital acquired pneumonia
Defined as pulmonary infections acquired >48hrs after hospital admission
Which pathogens are the most common cause of bacterial meningitis
Strep pneumonia, Neisseria meningitides E.coli Group B strep Listeria monocytogenes
What is the role of macrophages in chronic inflammation
They are the dominant cell type
They secrete cytokines and growth factors to activate other cells such as lymphocytes - stimulate inflammatory response
hey also ingest harmful pathogens and cellular debris and also initiate repair
How does streptococcal toxic shock syndrome present
Begins with fever and chills, muscle aches, nausea and vomiting
24-48 hours later the blood pressure drops and symptoms develop: tachycardia, tachypnea and other signs of organ failure e.g. bleeding/ bruising, jaundice
What are some of the complications of treating a cerebral abscess
Mainly complications of the craniotomy Blood clot needing further surgery Brain swelling CSF leak Movement of the skull cap Infection Seizure Stroke Nerve damage Loss of mental function
What is complete resolution
When the site is returned to normal once the inflammatory reaction is complete
Why are women more susceptible to infections of the urinary tract
They have a much shorter urethra so pathogens don’t have to travel as far
How does post-streptococcal glomerulonephritis occur
Strep products can lead to formation of immune complexes that get deposited in the kidneys
Not a strep infection in the kidneys! It is the immune response and complexes which cause it
Produces a local inflammatory reaction in the kidney which leads to injury
What organisms commonly cause meningitis in the immunocomprimised
Listeria, TB, Klebsiella, cryptococcus neoformans, anerobics
How do neutrophils and macrophages aid the inflammatory response
They can ingest and destroy the pathogens
Macrophages also produce growth factors to aid repair
What is a cerebral abscess
A thin walled, discrete collection of suppurative material within the brain parenchyma often with inflammation surrounding it.
In young people pericarditis often occurs alongside which other condition
Myocarditis
Describe the histology of the nasal cavity
Vestibule (initial part) = keratinised stratified squamous epithelium
As you move deeper into cavity, the keratin is lost and eventually becomes respiratory epithelium
There is specialized olfactory epithelium found in the roof of the nose to allow smell
What are the 3 main types of nasopharyngeal cancer
Keratinising squamous cell carcinoma (worst prognosis)
Non-keratinising carcinoma (undifferentiated) and non-keratinising carcinoma (differentiated)
Basaloid squamous cell carcinoma
What are the systemic features of a secondary TB infection
Low grade fever
Night sweats
Weight loss
Pleuritic pain if it extends into pleura
How do you treat a pleural effusion
Slow and controlled drainage- through appropriate pleural space
Pleurodesis with talc if recurrent - sticks layers together to obliterate space, prevents fluid accumulating
Surgery if there is recurrent collections and thickening of the pleura
Describe constrictive pericarditis
A dense fibrotic scar surrounds the heart.
This restricts the heart’s movement and therefore function
Hypertrophy is not possible as the heart is encased
Cardiac output may be reduced but also cant increase in response to normal systemic needs
What organisms commonly cause meningitis in the elderly
Strep pneumo > listeria
Describe how vasodilation occurs in the inflammatory process
Mediators of inflammation such as histamine act on the smooth muscle to induce dilation
How do Miliary TB and TB meningitis occur
Haematogenous spread of a primary TB infection
Rare occurrence
What are the potential outcomes of an empyema
Can resolve but more commonly organisation occurs and it leaves a dense fibrous adhesion
This will affect lung expansion
What is the purpose of inflammation
It is a protective mechanism
It rids the body of the initial cause of cell injury (microbes, toxins etc.)
It also rids the host of the consequences of such injury like necrotic cells and tissues
What are the common pathogens that infect the upper respiratory tract
Rhinovirus
Adenoviruses
Influenza viruses
How do you determine whether fluid is a exudate or transudate
Aspiration and analysis of the sample
Further cytology and cellular counts can indicate underlying cause - e.g. Find malignant cells
What are the major complication of a strep throat infection
Peritonsillar or retropharyngeal abscesses
Rheumatic fever
Glomerulonephritis
Toxic shock syndrome.
How does meningitis cause death
Viral tends not to be fatal
Bacterial can cause raised ICP and herniation
Can also cause sepsis and subsequent septic shock
What happens when group A strep infects the URT
It causes acute pharyngitis and tonsillitis otherwise known as “strep throat”
Infections can range from minor, self-limiting illnesses to severely debilitating, deadly diseases
What happens when the endothelium becomes activated due to sepsis
Loosened endothelial junctions mean that proteins can pass through
Vessels become ‘leaky’ leading to widespread interstitial oedema
What are the clinical features of HSV1 encephalitis
Fever Malaise Headache Nausea Altered mental state- confusion, memory problems Seizures Focal neurological deficits Personality changes Reduced consciousness, coma and stupor
Which part of the brain is most commonly affected by HSV1 encephalitis
Temporal lobe
What are the 4 main causes of inflammation
Infections
Tissue necrosis
Foreign bodies
Immune reactions
How does breaching the epithelial surface allow infection
Breaks in the physical epithelial barrier can allow pathogens to enter the body
Any form of injury (needles, bites, cuts) can allow pathogens in
What are the most common sites for ulcer formation
Mucosa of mouth, stomach, intestines or genitourinary tract
Skin & subcutaneous tissue of the lower extremities in those with vascular insufficiency (diabetes)
When does streptococcal toxic shock syndrome occur
Occur when the strep get into the bloodstream (across mucus membranes)
Name the recesses formed by the pleura
Costodiaphragmatic and costomediastinal recesses
These are clinically relevant as this is where fluid will collect
What is the definition of colonization
The presence of bacteria on a body surface which is not causing disease in the host
How do foreign bodies cause inflammation
Presence alone may cause inflammation - identified as non-self antigens
The trauma caused by them entering the body can be the cause or this can introduce microbes
Some substances produced by the body itself can lead to inflammation if the are deposited in large amounts in tissue (e.g. Urate crystals in gout)
What is the definition of a saprophyte
An organism that grows and feeds on dead or decaying organic material.
A lot of fungi come under this group too
Describe the pathological appearance of a lung abscess
May be single or multiple and vary in size
Will have a suppurative central destruction of lung tissue within the central area of cavitation
Central cavity may be filled with pus or air
If chronic they will be surrounded by a reactive fibrotic wall
How do infections cause inflammation
Different pathogens will elicit the immune response through different means such as toxins, host response etc
Reaction can be mild to severe
How does purulent/suppurative pericarditis present
Classic symptoms + symptoms of systemic infection
Macroscopic findings include: reddened and granular serous surfaces with exudate covering it and the exudate which ranges from cloudy serosal fluid to frank pus.
