Anatomy - Pneumonia Flashcards
(112 cards)
1
Q
What is volume of distribution?
A
Apparent volume in which drug is dissolved in body = amount in body / conc. = dose / conc. at t=0
2
Q
What is clearance?
A
Volume of plasma cleared of drug in unit time (ml/min or L/h) = renal + hepatic clearance (eGFR)
3
Q
What does a first order elimination graph look like?
What is the equation?
A
Rate of elimination = proportional to drug concentration
Ct = C0e-kt
Ct = conc. at t=t
C0 = conc. at t=0
k = rate constant (per minute or per hour)
t = time
4
Q
What does the rate constant (k) stand for?
A
Fraction eliminated per unit time = clearance / Vd
5
Q
How do you work out half-life using equation?
A
t1/2 = loge2 / k
k = loge2 / t1/2
6
Q
What are the properties of IV infusion?
A
Administration of drug at constant rate (0 order)
Steady state = elimination (first order graph plateau) = infusion rate
Input = output = Css
Maintenance dose = amount removed Infusion rate = clearance X Css
7
Q
What is aminophylline and its properties?
A
- Used for severe asthma
- Bronchodilator
- Given intravenously
- Is salt of theophylline (80% of aminophylline is theophylline)
- Infusion rate = (CL X Css) / 0.8
8
Q
What does and oral dosing graph look like and its properties?
A
- Curve = influenced by rate of dissolution and rate of absorption
- Rise to peak = absorption + elimination
- After peak = just elimination
- Functional half-life = prolonged absorption super-imposed on elimination (slow oral)
9
Q
How do you work out bioavailability?
How do you work out dose given?
A
Bioavailability = F = fraction absorbed = AUC oral / AUC iv
Dose given = amount needed / F
10
Q
What are the properties of repeated oral dose?
A
- Each dose is independent of each-other if given far apart enough from each-other
- Aim = to reach stead-state
- Takes 5 half-lives (approx..) to reach steady state
11
Q
What is the dose calculation equation?
What does ‘tau’ stand for?
What does doubling the dose do?
A
tau = dosage interval
Double dose = double concentration
12
Q
What do you need for designing dosage regimens?
A
- Measure therapeutic window
- Loading dose large initial does to rapidly increase plasma conc. to therapeutic window range = target level X V/F
- Elimination half-life
13
Q
What are the properties of gentamicin dosaging?
A
Have period where dose is subtherapeutic and below therapeutic window to reduce damage done to kidneys and ears
Given via IV boluses
+ clearance renally
CL = CLcreatinine
14
Q
What does the Hartford nomogram for gentamicin llok like and how do you find correct dose?
A
Use sampling
15
Q
What is anti-microbial chemotherapy and it’s targets?
A
The use of drugs to selectively kill bacteria (and viruses / fungi) without affecting the host.
Targets:
- Bacterial cell wall
- Bacterial ribosomes
- Bacterial folate metabolism
- Bacterial DNA gyrase
Antibiotics
- Produced by an organism to attack other organisms eg penicillin
Antibacterials
- Man-made chemicals
16
Q
What type of antibiotic are penicillins and what are it’s properties?
A
‘Beta’-lactam antibiotic
- Inject with enzyme penicillin if suspected meningitis
- Beta-lactam ring gives chemistry of drug
- Inhibit bacterial cell wall synthesis à irreversibly bind to a transpeptidase which cross-links peptidoglycans in cell wall
- Only effective against dividing organisms
- Bactericidal, causing bacterial lysis
17
Q
What are the properties of beta-lactamases?
A
- Secreted by resistant bacteria
- Deactivates some penicillins
- Other penicillins are resistant to them
- Inhibited by clavulanic acid + other agents –> Co-amoxiclav
18
Q
What are the properties of a penicillin allergy?
A
- Penicillins are immunogenic
- Allergic reaction develops upon repeat exposure
19
Q
What type of antibiotic are cephalosporins and how do they work?
A
‘Beta’-lactam antibiotics
- Act in similar way to penicillin
- Inhibit transpeptidases which cross-link peptidoglycan chains
- Cross-reactivity - penicillin allergy = cephalosporin allergy in small no. of people
20
Q
How do glycopeptides work and give an example?
A
Vancomycin
- Inhibit bacterial cell wall synthesis by inhibiting peptidoglycan chain growth
- Largely bactericidal
- Used for superbug infections
21
Q
Give and example of a tetracycline and how do they work and properties?
A
Tetracycline
- Inhibit protein synthesis by binding to 30S subunit of bacterial ribosome
- Prevent tRNA binding to acceptor site (A site)
- Actively accumulate in bacterial cells
- Are bacteriostatic
- Decreased use from resistance increase
22
Q
Give an example of a macrolides and how do they work and properties?
A
Erythromycin
- Prevent translocation of 50S subunit of bacterial ribosome along mRNA
- Prevent protein synthesis
- Are bacteriostatic
- Used as penicillin alternative for those with allergies
- Are cytochrome P450 inhibitors and associated with + drug interactions
23
Q
Give an example of an aminoglycoside and how do they work and properties?
A
Neomycin
- Irreversibly bind to 30S subunit of bacterial ribosomes, causing misreading of mRNA
- Interfere with protein synthesis
- Are bactericidal
- Used to manage Gram-negative bacteria
- Complicated use due to toxicity
- Have complex regimens
24
Q
Give an example of a quinolone and how do they work?
A
Ciprofloxacin
- Inhibit bacterial DNA gyrase (topoisomerase ll) and topoisomerase lV
- Gram-negative bacteria = inhibit supercoiling of bacterial DNA, essential for DNA repair and replication à DNA gyrase is target
- Gram-positive bacteria = interfere with separation of DNA strands during replication à Topoisomerase lV is target
25
What is trimethoprim and what are it's properties?
* Structurally related to folate
* Is a folate antagonist
* Inhibits bacterial dihydrofolate reductase which converts folate to tetrahydrofolate
* Less potent against human form of enzyme
* Are bacteriostatic
* Used for UTIs
26
What are the properties of sulphonamides?
* Analogues of p-aminobenzoic acid (PABA)
* Inhibit growth of bacteria by competitively inhibiting dihydropteroate synthase (involved in folate synthesis from PABA)
* Reduction of DNA and RNA precursors
27
What are the properties of metronidazole?
* Pro-drug that’s activated by anaerobic bacteria to cytotoxic products
* Damage DNA helical structure, protein and cell membrane
* Used against anaerobic bacteria and protozoa
* Can’t drink alcohol
28
What are the steps of antibiotic selection?
* Guided by sensitivity of organisms
* Broad spectrum antibiotics
* Resistance
* “Complete the course”
* Allergies
* Pharmacokinetics:
* IV for rapid effects
* Oral route: depends on bioavailability
* Drug interactions
29
What is the most important antibiotic feature?
Selective toxicity
30
What are the differences in gram positive and negative bacteria?
31
What are the properties of an upper respiratory tract infection?
32
Who is community acquired pneumonia more common in?
Men
Elderly
Alcoholics
Chronic disease sufferers
33
What are the main symptoms of pneumonia?
* Sputum
* Coughing
* Coughing up blood
34
What microbes cause community acquired pneumonia?
- Conventional bacteria (60-80%)
- ‘atypical’ bacteria (10-20%) (mycoplasma and legionella)
- Viruses (10-20%)
35
What are the steps for community acquired pneumonia investigation?
* Confirm diagnosis
* Assess disease severity
* Identify aetiological agent
* Identify somplications
36
What tests do you do to confirm diagnosis of CAP?
* Temperature
* Full blood count
* U rea, electrolytes and LFT
* CXR
* Arterial por capillary blood gases
37
What are the microbiological investigations for CAP?
* Sputum culture and sensitivity
* Blood cultures
* Urine for pneumococcal antigen
* Investigation for legionella if suspected
* PCR/immunofluorescence for atypical organisms and viruses
* Pleural fluid for microscopy, culture and antigen detection
38
What are the 3 steps for CAP management?
* Correction of respiratory failure
* Correction of haemodynamic compromise
* Specific antimicrobial therapy
39
What tests and values determine the severity of CAP?
* Confusion --\> mini-mental test = 8
* Urea --\> \> 7mmol/l
* Respiratory rate \> 30 bpm
* Blood pressure --\> sys \< 90 mmHg dia \< 60 mmHg
* Older than 65
40
What are the 3 basis for antimicrobial chemotherapy?
* Assessment of likely pathogen
* Severity of illness
* Likelihood of drug resistance
41
What is the treatment for low severity CAP (score0-1)?
Amoxicillin 500mgs qds / 5 days OR doxycycline 200mgs loading them 100mg od
Unable to take oral therapy = iv amoxicillin 500mgs tds OR iv cefuroxime 1.5g tds if mild penicillin allergy
Sever penicillin allergy = ciprofloxacin 400mgs bd + vancomycin
42
What is the treatment for moderate severity CAP (score 2)?
Amoxicillin 500mgs – 1g tds 7 days + clarithromycin 500mgs bd for 7 days OR doxycycline 200mgs loading then 100mg od
Unable to take oral therapy = iv amoxicillin or benzylpenicillin (cefuroxime 1.5 g tds if mild penicillin allergy) + iv clarithromycin 500 mgs bd
If severe allergy to penicillin ciprofloxacin 400 mgs bd + vancomycin
43
What is the treatment severe CAP (score \>3)?
Co-amoxiclav 1.2 g tds +clarithromycin 500 mgs bd iv for 10 days
_If severe allergy to penicillins or likely MRSA:_
Levofloxacin 500 mgs bd + vancomycin 1 g bd
Treat for 10 days - extending to 14-21 days for legionella, staphylococcal or Gram neg pneumonia
44
What are the properties of hospital acquired pneumonia?
- HAP is defined as pneumonia that occurs more than 48 hrs after hospital admission or within 10 days of a previous admission
- HAP is the second most common infection acquired in hospital
- Candidate organisms include: E.coli, Klebsiella spp., proteus spp., S. pneumoniae, S. aureus (MSSA or MRSA)
45
What are the treatments for mild and severe HAP?
Mild: co-amoxiclav 625 mgs (as co-amoxiclav 375 mgs plus amoxicillin 250 mgs) po tds
Severe: augmentin 1.25 g iv tds plus gentamicin 5 mgs/kg stat
46
Whats puts people at higher risk of MRSA?
* Previous MRSA infection
* Long-term urinary catheter
* Treated as inpatient within last 6 months
* Resident of nursing home with skin breaks
* Indwelling line
47
What is the treatment for aspiration pneumonia?
Co-amoxiclav 625 mg po tds OR co-amoxiclav 1.2 g tds iv plus gentamicin 5 mgs/kg iv if ?MRSA
If allergic to penicillins levofloxacin 500 mgs po od + metronidazole po 400 mgs tds for 5 – 7 days
48
When does mycoplasma pneumonia usually occur and treatment?
* Young patient
* Long prodrome
* Patchy consolidation on CXR
* Prominent extra-pulmonary disease
* Use tetracyclines for at least two weeks
49
When does legionellosis pneumonia usually occur and treatment?
* Severe CAP? outbreak
* Multi-lobe involvement on CXR
* Hyponatraemia
* Focal neurological disease
* Check legionella antigen and use high dose macrolide (up to 4 g erythromycin per day) with rifampicin 600 mgs bd
50
When does S.aureus pneumonia usually occur and treatment?
* CAP during an influenza outbreak may be caused by S. aureus
* Flucloxacillin at a dose of 2 g iv qds must be added to standard regimens
* PVL S. aureus in young previously healthy cause of necrotising haemorrhagic pneumonia
51
What are the properties of mycobacterium tuberculosis?
* Obligate aerobes - grow in tissues with a high O2 content
* (i.e. the lungs).
* Facultative intracellular pathogens - usually infecting mononuclear phagocytes (e.g. macrophages).
* Slow growing (generation time of 12 to 18 hours; 20-30 minutes for Escherichia coli).
* Hydrophobic - high lipid content in the cell wall. Less permeable to usual bacterial stains (e.g. Gram stain).
* Known as "acid-fast bacilli" because, once stained, the cells resist decolourisation.
52
What is the pathophysiology of TB?
* TB is spread by airborne droplet nuclei (1-5 mm).
* Nuclei can remain airborne after coughing for several hours.
* Droplets are inhaled, lodge in alveoli and the organism is taken up by alveolar macrophages.
* Slow replication and spread (via lymphatic system) to hilar lymph nodes.
53
How does TB infection develop once in a human?
* In most individuals – cell-mediated immunity (CMI) develops 2-8 weeks after infection (associated with the development of a positive tuberculin skin test).
* Activated T lymphocytes and macrophages form granulomas that limit further replication and spread.
* Bacterial cells remain (sometimes viable) in centre of necrotic ‘caseating’ granulomas.
* Most individuals are asymptomatic (latent infection) and never develop active disease (unless a subsequent defect in CMI occurs).
54
What are these parts called?
55
What are the clinical features of TB?
* Non-specific --\> fever, weight loss, night sweats
* Respiratory symptoms --\> cough, SOB, haemoptysis, chest pain
* Mainly pulmonary
* Extrapulmonary more common in HIV
* CNS disease --\> TB meningitis, space-occupying lesions (tuberculomas)
56
What are the TB sites of infection in skin / soft tissue?
* Commonest type of non-pulmonary disease
* Cervical lymphadenitis (firm, discrete, painless lymph nodes)
* Diffuse swelling in neck (‘cold’ abscess)
57
Where in bone and joints does TB mainly infect?
Spine
Pott's disease
58
What are the effects of TB infection in genitourinary tract?
* Prostatitis, orchitis, or renal lesions
* May cause infertility in women
* Sterile pyuria (WBC in urine but no growth)
59
What is disseminated disease in TB and its properties?
Many organs involved simultaneously – ‘miliary’ pattern MAY be seen on CXR
May result from primary progressive disease or reactivation of latent infection
60
What is the arrow pointing at?
Cerebral tuberculoma
61
What type of TB is this?
Miliary TB
62
What samples are required for TB diagnosis?
* Sputum (requires decontamination)
* Bronchoalveolar lavage
* Pus / tissue
* Urine --\> 3 X 24 hour collection
* Cerebrospinal fluid
63
What stain is used for TB diagnosis and why?
Zeihl-Neelsen stain
Rapid, cheap, simple, robust, moderate specificity and sensitivity
64
What are the properties of TB cultures?
* Slow --\>2-8 weeks
* Requires specialised media (Lowenstein-Jensen slope in shatter-proof glass)
* Performed in category 3 facility
65
What are the properties of rapid TB cultures?
* 1-2 weeks
* Liquid media (Kirchner’s liquid medium)
* Automated system (MGIT)
66
What is the treatment for pulmonary TB?
* Initial phase: 2 months of 4 drugs (rifampicin, isoniazid, pyrazinamide, ethambutol)
* Continuation phase: 4 months of rifampicin and isoniazid
* If resistance is suspected, 5 drugs may be used initially. For confirmed resistant strains, longer courses are required with second line agents
67
What are the properties of URTIs and examples of some?
Very common; often viral in aetiology.
Secondary bacterial (or fungal) infections are common.
* Rhinitis
* Otitis media
* Sinusitis
* Pharyngitis
* Laryngitis
* Epiglottitis.
68
What are examples of coryza (common cold) viruses?
* Rhinoviruses (\>100 serotypes)
* Parainfluenza viruses 1-4
* Coronaviruses
* RSV
* Adenoviruses
* Enteroviruses (coxsackie, echo)
* May predispose to 2o bacterial infection
* sinusitis, otitis, bronchitis, pneumonia
69
What is pharyngitis and what can cause it?
Tonsillitis
Adenoviruses
Strep pyogenes
70
What is infectious mononucleosis and its symptoms?
Syndrome
* Pharyngitis, lymphadenopathy (cervical, generalised), fever, malaise
* Atypical mononuclear cells in peripheral blood
* Epstein-Barr virus, cytomegalovirus, toxoplasmosis, HIV seroconversion
71
What are the properties of epiglottitis?
* Bacterial
* Potentially life-threatening
* Haemophilus influenza type b
72
What are the proeprties of croup?
* Young children
* Inspiritory stridor from narrowed airways
* Viruses (paraflu, RSV)
73
What are examples of lower respiratory tract infections?
* Influenza viruses
* Respiratory syncytial virus
* Rare:
* Varicella zoster virus (adults)
* Measles virus (giant cell pneumonia)
* Cytomegalovirus (immunocompromised)
* MERS (and SARS) coronaviruses
74
What are the genetic properties of influenza?
* Segmented -ve ssRNA genome
* 8 segments encode 11 proteins
* TYPES – A, B, or C
* On basis of internal proteins NP, matrix
* SUBTYPES – A only
* On basis of surface proteins, HA, NA
* 16 HA, 9NA known – each differs by \>20% sequence
* Respiratory tract symptoms (rhinitis) and systemic symptoms (fever)
75
What are these parts called?
76
What is the pathogenesis of influenza?
* Pneumotropic virus --\> infects cells lining RT down to alveoli
* Infection = lytic --\> strips off respiratory epithelium
* Removes 2 innate defence mechanisms --\> mucus secreting cells and cilia
* Interferon production --\> circulates in blood (virus doesn’t)
77
Why do these same cell types appear different?
First = exfoliated respiratory epithelial cells
Second = flu infected respiratory epithelial cells
78
What are the complications of influenza?
* Pneumonia
* Primary viral pneumonia: mononuclear cell infiltrate
* Secondary bacterial pneumonia: PMNL infiltrate
* Cardiovascular complications (myocarditis)
* CNS complications (encephalitis)
79
Whos is at risk of influenza?
* Risk groups identified incl. patients with pre-existing
* Lung disease
* Cardiac disease
* Renal disease
* Endocrine disease
* Immunodeficiency
* Liver disease
* Anyone \>65 years
* Pregnant women
* Children
80
What is the epidemiology of influenza?
* Annual seasonal (winter) epidemics
* Unpredictable worldwide epidemics with high mortality
* Pandemics and inter-pandemic epidemics
* Caused by antigenic drift and antigenic shift
81
What are the properties of antigenic drift?
* Occurs in both influenza A and B viruses
* Random spontaneous mutation in viral genes encoding HA and NA --\> 1% aa sequence change
* Mutations clustered within key epitopes in HA and NA ie true Darwinian evolution Accounts for interpandemic epidemics ie year-on-year recurrence of infection
82
Where are influenza A reservoirs?
* Wild aquatic shore birds
* Humans and animals
* Pigs
83
What are the properties of antigenic shift?
* Occurs only in influenza A viruses
* Genetic reassortment between human and non-human viruses leading to new subtypes
* \>20% aa differences, hence emergence of new pandemic strains against which the population has no pre-existing immunity
84
What is respiratory syncytial virus?
* Enveloped paramyxovirus
* – ve ssRNA encodes 9 polypeptides incl. 2 surface proteins F,G
* Highly seasonal infection (winter)
* Extremely common - global infection by age 2
85
What are the properties of RSV?
* Causes LRTI in infants – bronchiolitis, pneumonia
* High hospitalisation rates
* Low mortality (\<0.5%) unless
* congenital heart disease
* congenital lung disease (incl prematurity)
* immunodeficiency (congenital or acquired)
* Requires rapid diagnosis and appropriate infection control measures
* Re-infection occurs throughout life - antigenic drift
86
What is the tunica intima?
_Innermost layer consisting of:_
- A simple squamous epithelium
lining the lumen
- An adjacent layer of connective tissue
87
What is the tunica media?
_Middle layer consisting of:_
- Smooth (or cardiac) muscle, mainly circular
- Varying amounts of elastin, mainly in sheets in the interspersed connective tissue
88
What is the tunica adventitia?
_Outermost layer consisting of:_
- Connective tissue with varying amounts of interspersed elastin fibres
and smooth muscle cells, mainly longitudinal
89
What are these 3 layers?
Red = endocardium - tunica intima
Orange = myocardium = tunica media
Black = epicardium = tunica adventitia
90
What are the properties of the tunica media?
Much thicker than intima
Thick with spirally arranged smooth muscle cells (dark brown) and elastic lamellae, sheets of elastin (black wavy lines)
91
What are the properties of the tunica adventitia?
Mostly loose connective tissue with vasa vasorum (=blood vessels of the blood vessels)
No elastic lamellae, just a few smooth muscle cells.
Bordered by a simple squamous epithelium
92
What are the properties of elastic arteries?
Close to the heart
Experience plulsating blood flow which is met by the lamellae of elastin woven into the media
93
What are the properties of muscular arteries?
Help distribute the bulk of blood to the site of need, for example to the leg muscles when cycling and to the intestinal system during resting periods such as sleep
94
What are the properties of tunica intima of muscular artery?
Simple squamous epithelium (endothelium) bordering the lumen
Internal elastic membrane forming border to media
Loose connective tissue in between
All in folds because the smooth muscle of the media has contracted during tissue processing
95
What are the properties of tunica media in muscular artery?
A thick layer of circumferentially arranged smooth muscle cells with interspersed collagen and very few elastic lamellae
Bordered by the sheet-like external elastic membrane which starts to disappear more distally
In sections from routinely processed samples, the muscle cells are fully contracted, which generates nicely round cross sections
96
What are the properties of tunica adventitia in artery?
More longitudinal strings of elastin, fading out in the periphery
Mostly connective tissue, often loose
Border into adjacent connective tissue structures not defined
Recogniseable vasa vasorum.
97
How do you spot an artery or arteriole from a cross section?
Perpendicular pattern
98
What is the main site of blood pressure regulation?
Arterioles
99
What are the properties of arterioles?
* Site with + resistence
* No internal elastic membrane
* Don't require vasa vasorum as can rely on diffusion
100
What is this pointing at?
Capillaries
101
What are these parts called?
102
What is the difference between continuous and fenestrated capillaries?
Continuous = lumen lined by continuous, uninterrupted layer of single endothelial cells, linked by cell-cell contact of tight and adherens junctions
Fenestrated = numerous pores in endothelial cells and barrier to interstitium is basement membrane
103
What are sinusoids?
* Found in liver and spleen
* Beds of wide capillaries with diameters of several erythrocytes
* Holes in endothelial cells and basement membranes, allowing plasma to reach cells fast
104
What is the function of venules and small veins and their properties?
Collect blood from capillary beds
* 10-100 um diameter
* Large lumen
* No muscle cells
* Tunica intima often pericytes
* No media or barely any adventitia
105
What is the muscle pump?
'Second heart'
rhythmic muscle contraction pushing venous blood toward heart, due to valves
106
What are vein-artery-vein triplets?
Muscular arteries have vein on either side so artery compression slightly compresses veins, driving blood to heart
107
What is a portal system?
Connects two capillary beds (i.e. portal vein)
108
What is an anastomosis?
Direct link between an artery or vein, without capillary bed inbetween
Arterial-arterial (arteries around knee)
Arterial-venous (skin circulation)
Venous-venous (superficial hand veins)
109
What is the funciton of the lymphatic system?
Brings fluid from leaky capillaries back into blood circulation
Have no erythrocytes
110
Which antibiotic types inhibit cell wall synthesis?
Beta lactams
Glycopeptides
111
Which antibiotics inhibit protein synthesis?
Macrolides
Aminoglycosides
Tetracylines
112
Which antibiotics interfere with DNA synthesis and replication?
Sulphonamides
Quinolones
Diaminopyridamines
