CP Flashcards
Notifiable Diseases
- Acute Meningitis
- Measles
- Mumps
- Rubella
- Acute Polymyelitis
Which Immunoglobulin is produced in acute infection
IgM
Which Immunoglobulin is produced in long term immunity
IgG
Differential diagnoses for a child with a rash
Parvovirus Measles Chickenpox Rubella Non-polio enterovirus infection (bacterial e.g Staphylococcus aureus, N. meningitidis)
Definitive signs of measles (most infective)
Buccal mucosa bluish white spots with red base
Florrid rash macupapular rash they join up as the disease progress
Starts face and neck and spreads to extremities
What virus causes measles
Paramyxovirus
Droplet transmission person to person
Virus in Rubella
Togavirus
Droplet transmission
Treatment of chickenpox/varicella zoster
Oral or IV Acyclovir depending on severity
What virus causes “slapped cheek syndrome”?
Parvovirus B-19
Differential diagnosis for a child with respiratory symptoms
Respiratory Syncytial Virus Parainfluenza Influenza Adenovirus Metapneumovirus Rhinovirus
What does respiratory syncitial virus/pneumovirus cause
Bronchiolitis: SOB, wheezing, fever, in under 1s.
Can be fatal, winter epidemics
Treatment of RSV/pneumovirus
O2, steroids, bronchodilators
IV Ribavarin
(immunoglobulin and monoclonal abs - Palivizumab)
What is metapneumovirus
Paramyxovirus
Causes respiratory illness similar to RSV (same treatment) – ranges from URTI to pneumonia.
What virus causes parainfluenza
Paramyxovirus
Viruses that cause diarrhoea in children
Rotavirus
Norovirus
Rotavirus: virus, symptoms and treatment
Caused by reovirus
Cause diarrhoea and vomiting
Can be fatal in young children
Treatment: rehydration
What is mumps
Caused by paramyxoviridae family
Bilateral gross parotitis (can be unilateral)
What are the two main groups of parasites
Microparasites: protozoa
Macroparasites: helminths
4 main groups of protozoa
Flagellates e.g. giardia
Amoeboids e.g. acanthamoeba
Sporozoans e.g. plasmodium, toxoplasma
Trypanosomes e.g. leishmania
2 main groups of helminths
Nematodes e.g. ascaris, trichuris
Platyhelminths/flatworms e.g. schistosoma
What causes ascariasis
Intestinal nematode: Ascaris lumbricoides
Acquired by ingesting worm eggs
3-8 years old, poor hygiene
1 billion people affected worldwide
What is Loeffler’s syndrome
Migration of ascariasis to lung
dry cough, dyspnea, wheeze, haemoptysis, eosinophilic pneumonitis
Treatment of ascariasis
Albendazole/Benzimidazole
Prevents glucose absorption by worm
Worm starves-detaches-passed PR
(Improve sanitation to control spread)
What is schistosomiasis/bilharzia disease
Caused by a trematode/fluke worm (carried by snails in water)
Causes chronic disease resulting in bladder cancer (S. haematobium) and liver cirrhosis (S. Japonicum)
Treatment of schistosomiasis
Praziquantel
What causes hydatid disease
Caused by a Tapeworm Echinococcus sp
Humans are accidental host- Usual hosts are sheep and dogs
Found all over the world wherever sheep are farmed
What are the symptoms of hydatid disease
Cysts: 70% liver, 20% lungs May remain asymptomatic for years Mass effect Secondary bacterial infection Cyst rupture- hypersensitivity
What are the 4 species of sporozoans that cause malaria
Plasmodium falciparum (most common) P. vivax P. ovale P. Malariae Carried by female anopheles mosquitos
Mechanism of disease and symptoms of malaria
Parasites rupture red cells, block capillaries and cause inflammatory reaction
Fever, rigors, renal failure, hypoglycaemia, headaches, coma, pulmonary oedema, DIC etc
What causes cryptosporidiosis/ diarrhoeal disease
Cryptosporidium parvum and hominis (micro-parasite, sporozoan)
Faecal-oral route
human- human (cattle, sheep, goats)
Treatment of cryptosporidiosis
Rehydration etc. For immunocompromised: Nitazoxanide Paromomycin (to kill parasite) Octreotide (reduce cramps and frequency) HIV patients, HAART should be quickly initiated
Enteroviral infections
Coxsackie, enterovirus, echovirus
Rarer clinical manifestations of mumps
CNS involvement is the most common extrasalivary gland manifestation of mumps
Epididymo-orchitis is the most common extrasalivary gland manifestation in the adult
What are dimorphic fungi
Fungi that can grow as unicellular yeast or multicellular mould e.g. penicillium marneffei or histoplasma
What causes dutch elm disease
plant parasitic fungi
Examples of superficial fungal infections
Thrush, ringworm etc.
Examples of subcutaneous fungal infections
sporotrichosis, chromoblastomycosis etc
Examples of systemic fungal infections
Pneumocystis, Aspergillosis, Systemic candidosis, Histoplasmosis
Main classes of anti-fungal agents
Pyrimidine (1) Polyenes (2) Allyamine (1) Azoles (4) Echinocandins (3)
What is the active component of pyrimidine/5-fluorocytosine
Taken up by fungal specific cytosine permease
Deaminated into active component is 5-fluorouracil
2 modes of action of 5-fluorouracil
- fluorodeoxyuridine monophosphate (FdUMP) inhibits thymidylate synthetase inhibiting DNA synthesis
- fluorouridine triphosphate affects RNA incorporation disrupting translation
What is 5-fluorocytosine spectrum of activity
limited spectrum of activity
Active against: Cryptococcus neoformans, Candida species (most)
Inactive against: Candida krusei, Most moulds
Why is 5-fluorocytosine usually used in combination therapy rather than mono therapy
Resistance to 5FC develops quickly in Candida and Cryptococcus spp. when used as monotherapy
Now used mainly as combination therapy with Amphotericin B to treat cryptococcal meningitis
What can high levels of 5-flurocytosine for an extended period cause
bone marrow supression
What is the main side effect of IV Amphotericin B
Nephrotoxicity
Can use liposomal forms of Amphotericin which have reduced side effects
2 examples of polyenes and what they are derived from
natural products of Streptomyces sp.
Nystatin
Amphotericin B
What is the mode of action of polyenes
Increase cell permeability e.g. measured by K+ release
Polyenes bind sterols, particularly ergosterol a fungal membrane sterol
Oxidative damage via auto-oxidation of amphotericin B
Spectrum of activity of Amphotericin B
Broad spectrum
Most yeasts and moulds are sensitive
Some notable exceptions : Aspergillus terreus is resistant
Spectrum of activity of nystatin
Most yeasts are sensitive
e.g. Treatment of oral or vaginal candidosis
Why is Nystatin administered as topical cream
Not absorbed orally and too toxic to give IV
What is terbinafine
Only oral allyamine
Inhibits ergosterol synthesis and disrupts cell membrane synthesis by inhibiting squalene epoxidase
Spectrum of activity of terbinafine
Dermatophyte fungi: cause of ringworm e.g. Trichophyton rubrum
Aspergillus sp.
Many filamentous fungi
Variable activity against most yeasts
Some species of yeast e.g. Candida krusei resistant
How is terbinafine administered and what for
Oral tablet
Official Licensed indication:infections of the skin, hair and nails caused by dermatophytes
Can be fungicidal or fungistatic
2 subclasses of Azoles
Imidazoles – older group 2 nitrogens in azole ring. E.g. clotrimazole
Triazoles – newer group 3 nitrogens in azole ring e.g. Fluconazole
What enzyme do Azoles inhibit
C14alpha- demethylase
Mode of action of Azoles
Accumulation of 14alpha methyl sterols and disruption of structure and function of membrane
Affect on membrane leads to disruption of cell wall biosynthesis and growth
Are Azoles fungistatic or fungicidal
Azoles generally fungistatic
Itraconazole and voriconazole may be fungicidal when fungus is exposed to high concentrations for extended periods
Spectrum of activity of azoles
Fluconazole: Most yeasts, Some yeasts e.g. Candida krusei and most moulds intrinsically resistant
Itraconazole and Voriconazole: Most yeasts including C. krusei and moulds, Zygomycetes resistant
Posaconazole: Most yeasts and moulds, Some activity against zygomycetes
Primary side effects of Azoles
Primary- Rash, raised liver function tests, nausea
Secondary- inhibition of cytochrome P450 enzymes, increasing concentration of drugs metabolised by such enzymes
Examples of echinocandins
Caspofungin
Anidulafungin
Micafungin
Mode of action of echinocandins
Inhibition of cell wall beta1-3 glucan biosynthesis
Echinocandins bind product of Fsk1 gene which is part of a membrane complex producing beta1-3 glucan
beta1-3 glucan is important part of most fungal cell walls
What organisms are echinocandins effective against
Most yeasts
Aspergillus and some moulds
Pneumocystis jirovecii – protozoan-like fungus causing pneumonia – not licensed indication
What organisms are echinocandins ineffective against
Cryptococcus
Zygomycetes
Fusarium and Scedosporium
Clinical uses of Azoles
Fluconazole: Candida and Cryptococcus infections
Itraconazole: Aspergillus infections in immunocompetent patients, some mould infections, Prophylaxis for immunocompromised patients
Voriconazole: Aspergillus infections in any patient, other mould infections
Posaconazole: Prophylaxis for immunocompromised patients, Treatment of serious fungal infections where other approaches fail, Zygomycosis
What route are echinocandins administered as
All IV
Clinical uses of echinocandins
systemic candidosis
For some Treatment of unresponsive aspergillosis
and Empiric treatment of suspected infection
What is the only immunoglobulin that can pass through the placenta
IgG
Examples of inactivated/dead vaccine
Flu, cholera, plague, and hepatitis A. Most vaccines of this type are likely to require booster shots.
Examples of live attenuated vaccines
Yellow fever, measles, rubella, and mumps (MMR), varicella, rotavirus. Responses are more durable and do not generally require booster shots.
Why is a cocktail of anti viral HIV drug therapy used instead of just one drug
Approx 3 diff drugs as one is not usually enough to suppress viral load as they can mutate and become resistant to one drug
Treatment of Hep C and B
Interferons
Stages of viral replication
Virus attachment to cell (via receptor) Cell Entry Virus Uncoating Early proteins produced – viral enzymes Replication Late transcription/translation – viral structural proteins Virus assembly Virus release
How do viruses leave the cell once they have replicated
Reverse endocytosis or kill the cells
What is AZT (azidothymidine)
Inhibits HIV replication
Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Nh3 group prevents polymerase from working as there is no longer a free 3’ OH group
2 main groups of NRTIs
Pyrimidine analogues: Thymidine analogues: Zidovudine Cytosine analogues: Lamivudine Purine analogues (Adenine and Guanidine) Abacavir and Tenofovir
What viruses use Reverse transcriptase to convert their RNA sequences into DNA sequences in the host
HIV and Hep B Virus/HBV
some NRTIs work on HBV too e.g. Lamividine + Tenofovir
What are NNRTIs
Non-nucleotide reverse transcription inhibitors
e.g. Nevirapine, Efavirenz
What are protease inhibitors
Antiviral drugs used to treat HIV/AIDS and hepatitis C virus. Protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles.
Examples of protease inhibitors
Atazanavir, Darunavir, Fospamprenavir, Lopinavir, Nelfinavir
What is HAART
Highly Active Anti-Retroviral Therapy
2 NRTIs + NNRTI or
2 NRTIs + boosted PI
When is HAART started
when CD4 count falls
Taken lifelong to suppress viral replication
What HIV mutation leads to resistance to Lamivudine
M184V
What are the only sexually transmitted infections which commonly cause epididymitis
chlamydia and gonorrhoea
Which antibiotic carries a high-risk for patients to develop C.difficile infections after use
Cephalosporins
What are bacteristatic antibiotics
Inhibit bacterial growth
Protein synthesis inhibitors
e.g Tetracyclines, Sulfonamides
What are bactericidal antibiotics
Kill bacteria
Cell wall-active agents
Beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems) and vancomycin.
What is the Minimum inhibitory concentration
Minimum concentration of antibiotic at which visible growth is inhibited e.g. testing antifungal activity
What are the 3 main antibiotic interactions
Synergism: Activity of two antimicrobials given together is greater than the sum of their activity if given separately
Antagonism: One agent diminishes the activity of another
Indifference: Activity unaffected by the addition of another agent
An example of synergistic interaction of antibiotics
β-lactam/aminoglycoside combination therapy of streptococcal endocarditis
Targets of antibiotics
Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane
What was the first true antibiotic used in clinical practice
Benzylpenicillin (β-lactam)
What are β-lactams
All contain β-lactam ring: Structural analogue of D-alanyl-D-alanine so taken up into cell wall
They act by interfering with penicillin binding proteins: enzymes (Transpeptidases) involved in the synthesis and maintenance of peptidoglycan.
4 main subclasses of β-lactams
Penicillins
Cephalosporins
Carbapenems
Monobactams
Examples of Penicillins
Benzylpenicillin (PEN), amoxicillin, flucloxacillin
Relatively narrow spectrum
Examples of Cephalosporins
chemically modified Cefuroxime (CXM), ceftazidime pseudomonas originosus etc.
Broad spectrum- prone to C.Diff infection post use
Examples of Carbapenems
Meropenem (MER), imipenem, ertapenem
Extremely broad spectrum
Examples of Monobactams
Aztreonam (AZT)
Gram-negative activity only
Used when patients have allergies to other b-lactam antibiotics
Deficiency of which of the following complement proteins is most likely to result in recurrent Neisserial infection?
C5-C9 (MAC)
A staphylococcus aureus infection that is not methicillin resistant is best treated with what antibiotic?
Flucloxacillin
Staph. aureus is a gram positive, coccus. It produces ß-lactamases which break down the ß-lactam ring in penicillins. Flucloxacillin is resistant to ß-lactamases. Vancomycin would be the next option and also used if the bacteria was methicillin resistant.
What are Negative Acute Phase Proteins
Albumin, transferrin, antithrombin levels, along with several other molecules, are decreased during inflammation
The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing “positive” acute-phase proteins more efficiently.
Examples of Positive Acute Phase Proteins
CRP
Fibrinogen (leads to elevated ESR)
Complement proteins
Why is CRP a more accurate indicator of inflammation that ESR
ESR is dependent on elevation of fibrinogen, an acute phase reactant with a half-life of approx one week. This protein will therefore remain higher for longer despite removal of the inflammatory stimuli.
CRP (with a half-life of 6-8 hours) rises rapidly and can quickly return to within the normal range if treatment is employed.
E.g. in active systemic lupus erythematosus, one may find a raised ESR but normal C-reactive protein.
Which drug is used extensively in organ transplantation?
Cyclosporin
Temperature-dependent pruritis, following a hot bath typically, is a characteristic symptom of what
Polycythaemia vera
What type of acidosis is a recognised complication of uncontrolled diabetes mellitus
Metabolic Acidosis
What is the usual treatment for viral meningitis
Aciclovir
What is the usual treatment for bacterial meningitis
Cefotaxime
What do NRTIs inhibit
Inhibits the viral reverse transcriptase, stopping the viral RNA from being reverse transcripted into DNA.
What do protease inhibitors do
Act upon the aspartyl protease enzyme within HIV.
What do fusion inhibitors do
Prevent the HIV virus from entering the healthy T-cell
What do Integrase inhibitors do
Inhibit the integration of the proviral DNA into the host DNA, which is the step after reverse transcription of RNA into proviral DNA
What is used as a marker of Glomerular Filtration Rate in the clinical setting
Creatinine clearance
The clinical features of painless jaundice, steatorrhoea, pale stools, loss of weight and appetite are strongly suggestive of what
Pancreatic carcinoma
Raised CA 19-9 marker levels
Which bacterium is the usually commonest cause of community-acquired pneumonia in healthy adults in the UK
Streptococcus Pneumoniae
Which antibiotic should be avoided for use in pregnancy
Ciprofloxacin
A form of quinolone antibiotic and should be avoided in pregnancy as they have been shown to cause arthropathy
Where are Class II antigens (HLA-DR, DQ, DP) PRIMARILY expressed
B lymphocytes
What are glycopeptide antibiotics
Bind directly to terminal D-Alanyl-D-Alanine on NAM pentapeptides- inhibiting peptidogylcan synthesis
Gram-positive activity- Unable to penetrate Gram-negative outer membrane porins
e.g. Vancomycin, teicoplanin etc
Under what circumstances would you use glycopeptide antibiotics (even though they can be toxic)
Patients who are critically ill,
who have a demonstrated hypersensitivity to the β-lactams, or who are infected with β-lactam-resistant species (MRSA)
They exhibit a narrow spectrum of action, and are bactericidal only against the enterococci.
What are amino glycosides
Protein synthesis inhibitor antibiotics
Gentamicin, amikacin
Bind to 30S ribosomal subunit
What are Macrolides, Lincosamides etc
Protein synthesis inhibitor antibiotics Erythromycin, clarithromycin (macrolides) Clindamycin (lincosamide) Bind to 50S ribosomal subunit1 Inhibit protein elongation
What are tetracyclines
Protein synthesis inhibitor antibiotics
e.g. tetracycline, doxytetracycline)
Bind to 30S ribosomal subunit
Inhibit RNA translation/ Interfere with binding of tRNA to rRNA
What are Oxazolidinones
Protein synthesis inhibitor antibiotics e.g. Linezolid Inhibits initiation of protein synthesis Binds to 50S ribosomal subunit Inhibits assembly of initiation complex May also bind to 70S subunit
What protein synthesis inhibitor is used topically to reduce mrsa up nose
Mupirocin
What protein synthesis inhibitor is used topically for skin and systemic infections
Fusidic Acid
What is a precursor of purine synthesis
Folic Acid
Therefore inhibiting folic acid synthesis inhibits DNA synthesis
What do many bacteria make folic acid from
Para-aminobenzoic acid
What enzyme do sulphonamides inhibit
inhibit dihydropteroate synthetase, the enzyme that catalyses the first step in folic acid synthesis
What enzyme does trimethoprim inhibit
Dihydrofolate reductase
Inhibiting folate acid synthesis
Used to treat UTIs
What is co-trimoxazole
Trimethoprim-sulfamethoxazole
Combination of trimethoprim and sulphonamides
Used to treat resistant bacterial infections, Pneumocystis jirovecii, and some protozoal infections
Why are sulphonamides rarely used as a mono therapy
Toxicity problems and high levels of resistance
What are Fluoroquinolones and quinolones
DNA synthesis inhibitors
Inhibit DNA gyrase and topoisomerase IV involved in remodelling of DNA during DNA replication
Supercoiling/strand separation
e.g. Nalidixic acid, ciprofloxacin, levofloxacin etc
An example of an RNA synthesis inhibitor antibiotic
Rifampicin RNA polymerase inhibitor Prevents synthesis of mRNA Antistaphylococcal Treats TB Combined with flucloxacillin etc as resistance is quite high
Example of a plasma membrane agent antibiotic
Daptomycin
Cyclic lipopeptide
Inserts lipophilic tail into cell membrane resulting in depolarisation and ion loss
Effective in Gram-positives only
Adverse effects of amino glycosides
Reversible renal impairment on accumulation
Therapeutic drug monitoring indicated
Irreversible ototoxicity
Main adverse effect of β-lactams
Allergic reaction: generalised rash or rarely anaphylaxis
Main adverse effect of Linezolid
Bone marrow depression reversible on stopping use
What beta-lactams can you use in a patient with non-severe penicillin allergy
Cephalosporins and carbapenems
What drug can be used in patients with any penicillin allergy
Aztreonam (Monobactam)
Aztreonam does not contain a bicyclic nucleus
Key antibiotic/bacteria combinations
Flucloxacillin - Staphylococcus aureus (not MRSA)
Benzylpenicillin – Streptococcus pyogenes
Cephalosporins (avoid in elderly) – Gram-negative bacilli
Metronidazole – anaerobes
Vancomycin – Gram-positives (MRSA)
Meropenem – most clinically-relevant bacteria
How do bacteria become resistant to β-lactams
By synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring.
To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.
Adverse effects of gentamicin
Nephrotoxicity and ototoxicity, vestibulotoxicity
4 methods of sterilising equipment
Heat: Moist (Autoclave), dry (oven)
Chemical: Gas, liquid
Filtration
Ionising radiation: Used for single use disposable equipment
How are mycobacterium different to other bacteria
Unusual waxy cell wall:High lipid content
Slow growing: Different media requirements
Poor take up of standard Gram’s stains: (Gram positive: Ghost cells)
Retain certain stains without decolourisation by acid / alcohol: “acid fast bacilli” (AFBs), Ziehl Neelsen stain (ZN)
What organism causes tuberculosis
Mycobacterium tuberculosis and bovis
What organism causes leprosy
Mycobacterum leprae
What condition are atypical Mycobacterium associated with e.g. M. Marinarum
HIV (opportunistic infections)
What is the disease process of TB
Usually affects lung- apices esp. (highest oxygen tension)
Often latent infection (asymptomatic) that can become active later in life
What is the body’s response to TB
Forms tubercles/Granuloma
Cell - mediated immune response
Central area of epithelioid cells, giant cells, Surrounding lymphocytic cell infiltration.
Central area caseous necrosis.
Fibrosis / calcification of lesions
Bacilli slowly die / may remain viable 20 years
What causes a latent TB infection to be reactivated
Lowered immunity
Western countries : over 50 year old, men
Malnutrition
Alcoholism
HIV infection.
Silicosis, chronic renal failure, gastrectomy..
Anti TNFα blockade (e.g. infliximab)
Symptoms of active TB
Chronic productive cough: Haemoptysis
Weight loss, fever, night sweats.
What is disseminated/miliary TB
Extra-pulmonary TB
Very young / old; immunocompromised
Primary disease
Secondary erosion of necrotic tubercle into blood vessel
Widespread infection, including meningitis.
What causes an IgE mediated allergic reaction
IgE Ab mediated mast cell and basophil degranulation- release of inflammatory mediators
Features of IgE mediated allergic reaction
Fast onset (15-30 min)
Weal and flare
Late phase response: Leukotrienes, Prostaglandins, Eosinophils
Central role for Th2 T cell
What causes Type4 delayed-type hypersensitivity (chronic inflammation and cytokine release).
Th1 overactivation against autoantigens
What are the main effector cells for Th2 cells
Eosinophils, basophils, and mast cells as well as B cells
Allergic rhinitis, atopic dermatitis, and asthma belong to which category of autoimmunity
Th2 autoimmunity
What are the main effector cells of Th1 immunity
Macrophages, CD8 T cells, IgG B cells, and IFN-γ CD4 T cells
80% of what type of food allergies resolve by the age of 16
Milk and eggs
What is the atopic triad
Excema, Rhinitis, Asthma
What causes cytotoxic/Type 2 hypersensitivity reactions
IgG/IgM Ab response against combined self/foreign antigen at the cell surface- complement activation/phagocytosis/ADCC
Clinical features and common antigens of type 2 hypersensitivity reactions
Onset minutes to hours
Cell lysis and necrosis
Penicillin!!
Conditions associated with Type 2 hypersensitivity reactions
Erythroblastosis fetalis,
Goodpasture’s nephritis
What causes immune complex/type 3 hypersensitivity reactions
IgG/IgM Ab against soluble antigen- immune complex deposition
e.g. SLE
Clinical features of Type 3 hypersensitivity reactions
Onset 3-8h
Vasculitis
What causes delayed/Type 4 hypersensitivity reactions
Antigen specific T-cell mediated cytotoxicity (Th1)
e.g. contact dermatitis
Clinical features of Type 4 hypersensitivity reactions
Delayed onset 48-72h
Erythema induration
Common antigens causing type 4 hypersensitivity
Metals-e.g nickel
tuberculin reaction
Organ specific autoimmune diseases
Type 1 diabetes
Graves Disease
Multiple Sclerosis
Systemic autoimmune diseases
SLE
Rheumatoid arthritis
What is the most common causative organism in cases of osteomyelitis
Staphylococcus Aureus
Actinic keratoses are most commonly precursors to which skin condition
Squamous cell carcinoma
During a Mantoux or Heaf test in order to determine immunity to tubercle bacilli a positive reaction is indicative of what type of hypersensitivity reaction?
Type 4
Which antifungal class contains an agent which can cause unwanted inhibitory effects on CYP450
Azoles- bind to cytochrome P450 enzyme and inhibit it from normal metabolic functions. Drugs which are usually metabolised by CYP450 will be in higher concentration as a result of azole-induced inhibition
Which of the 4 pathological classifications of Hodgkin’s lymphoma (HL) is NOT a classification of Classical Hodgkin’s lymphoma?
Nodular lymphocyte-predominant HL
HL is caused by the malignancy of Reed-Stenberg cells in lymph nodes or (rarely) extra-nodal tissue. Reed-Stenberg cells are derived from germinal centre B cells or (rarely) peripheral T cells. To be classified as Classical HL, CD30 and CD15 antigens are usually expressed. However, nodular lymphocyte-predominant HL does not express CD30 and CD15, and alternatively expresses CD20.
Orphan Annie eye nuclei and psammoma bodies are characteristic of what thyroid condition
Papillary carcinoma of the thyroid
Most common thyroid cancer
Excellent prognosis
Of which autoimmune disease are anti-neutrophil cytoplasmic antibodies (ANCAs) most characteristic
Wegener’s granulomatosis
What syndrome syndrome consists of a triad of protenuria, hypoalbuminaemia and oedema, often accompanied by hyperlipidaemia and lipiduria
Nephrotic Syndrome
How many types of IgG are there
4
IgG1 is the most common circulating IgG
The main difference in structure between the subtypes is the structure of the hinge region
The nephritic syndrome is composed of what symptoms
proteinuria, haematuria and hypertension
Causes hypertension
post-streptococcal glomerulonephritis
crescentic glomerulonephritis
Difference between nephritic syndrome and nephrotic syndrome
thin glomerular basement membrane and small pores in the podocytes of the glomerulus, large enough to permit proteins (proteinuria) and red blood cells (hematuria) to pass into the urine. By contrast, nephrotic syndrome is characterized by only proteins (proteinuria) moving into the urine.
Pathophysiology of Autoreactive B cells and autoantibodies
Directly cytotoxic
Activation of complement
Interfere with normal physiological function
Pathophysiology of auto reactive T Cells
Directly cytotoxic
Inflammatory cytokine production
What is Hashimoto’s thyroiditis
Destruction of thyroid follicles by autoimmune process
Associated with autoantibodies to thyroglobulin and to thyroid peroxidase
Leads to hypothyrodism
What is Grave’s disease
Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
Leads to hyperthyrodism
What is myasthenia gravis
Muscle weakness caused by antibodies that block nicotinic acetylcholine receptors at the postsynaptic neuromuscular junction.
Muscles become progressively weaker during periods of activity, and improve after periods of rest.
Muscles that control eye and eyelid movement, facial expressions, chewing, talking, and swallowing are especially susceptible
What causes SLE
Anti-nuclear antibodies causing inflammation and apoptosis
Type 3 hypersensitivity
What is Rheumatoid Factor
Antibody (IgM, IgG or IgA) directed against the Fc portion of IgG
Commonly found in rheumatoid arthritis but not diagnostic of the disease
What antibody is most specific for Rheumatoid arthritis
Anti-CCP (ACPA) more specific (95%) for RA than RF
Citrullination happens when the cells are dying-
The citrulline is detected by the anti-ccp
What are Anti-neutrophilic cytoplasmic antibodies (ANCA)
An autoantibody mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes.
specific for Wegeners granulomatosis/ granulamatosis with polyangitis
What are the targets of the 2 different types of ANCAs
2 types
perinuclear targets MPO protein (found in Churg Strauss) cytoplasmic targets PR3 (found in Wegeners)
What autoimmune condition is Anti-mitochondrial Ab specific for
Primary biliary sclerosis
What antibodies are found in autoimmune hepatitis
Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs
What are immunomodulators
Medicinal products produced using molecular biology techniques including recombinant DNA technology
e.g. monoclonal antibodies
Which organism is the most common cause of urinary tract infections (UTIs)
E.Coli
What are the most common type of skin cancers.
Basal cell carcinomas
Very invasive and locally destructive but they rarely metastasise
Good Prognosis
What is the name of the bacterium that causes syphilis
Treponema pallidum
What condition is Hydroxychloroquine used to treat
Lupus
Interferes with production of cytokine
Used for joint and skin complaints in CTD
Caution: may cause haemolytic anemia in G6PD def
What condition is Sulphasalazine used to treat
Used in inflammatory bowel disease and RA
Caution: regular FBC monitoring required
What conditions is colchicine used to treat
Used in Familial Mediterranean fever (FMF) and Behcet’s, gout
Interferes with microtubule assembly/neutrophil chemotaxis
Caution: causes GI problems
What conditions is Dapsone used to treat
Dermatitis herpetiformis
Inhibits neutrophil adherence to endothelium
Caution: haemolysis in G6PD def
What conditions is thalidomide used to treat
Several effects on immune system: anti-TNF, decreases expression
of adhesion molecules, favors Th2 T cell responses
Used in Rx of Behcets’s disease and myeloma
Caution: birth defects, peripheral neuropathy
Actions of corticosteroid use
Decreased neutrophil margination
Reduced production of inflammatory cytokines
Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
Lymphopenia
Decreased T cells proliferation
Reduced immunoglobulins production
Side effects of corticosteroid use
Carbohydrate and lipid metabolism: Diabetes, Hyperlipidaemia
Reduced protein synthesis: Poor wound healing
Osteoporosis
Glaucoma and cataracts
Psychiatric complications
Which combination of antibiotics is used in the treatment of intra-abdominal infections caused by an intestinal source in patients less than 65 years of age
Metronidazole and Cefuroxime
They target aerobic enteric bacteria, therefore providing a clinically effective treatment.
These drugs are used in patients under 65 due to an increased risk of developing Clostridium Difficile infection in individuals over 65.
The malignant blood disorder which can result in extramedullary hematopoiesis of the liver and the spleen is
Myelofibrosis
bone morrow is replaced by scar/fibrous tissue. This results in a decrease in the numbers of blood cells being produced and a pancytopaenia. Extramedullary hematopoiesis (creation of new blood cells from stem cells OUTSIDE the bone marrow) in one mechanism which attempts to compensate for this.
Which chromosomal translocations causes the formation of the “Philadelphia chromosome” in Acute Lymphoblastic Leukaemia
t(9;22)
forms BCR-abl fusion gene
4 classes of drugs targeting lymphocytes
M-TOR inhibitors: Sirolimus
IL-2 receptor mABs: Basiliximab, Daclizumab
Antimetabolites: Azathioprine (AZA), Mycophenolate mofetil (MMF)
Calcineurin inhibitors: Ciclosporin A (CyA), Tacrolimus (FK506)
Mode of action of calcineurin inhibitors and effect on T cells
Prevents activation of NFAT nuclear factor activated t cell
Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription
Reversible inhibition of T-cell activation, proliferation and clonal expansion
Mode of action of Sirolimus (M-TOR inhibitor) and effect on T cells
Macrolide antibiotic
Also binds to FKBP12 but different effects
Inhibits mammalian target of rapamycin (mTOR)
Inhibits response to IL-2
T Cell cycle arrest at G1-S phase
Side effects of calcineurin/M-TOR inhibitors
Hypertension Hirsutism Nephrotoxicity Hepatotoxicity Lymphomas Opportunistic infections Neurotoxicity Multiple drug interactions (induce P450)
What are calcineurin/M-TOR inhibitors used to treat
Transplantation (allograft rejection)
Autoimmune disease
What is the most common cause of croup in children
Parainfluenza viruses
Distinctive Barking cough
What antibiotic does Legionella not respond to
Beta Lactams e.g. penicillin
Similar symptoms to pneumonia
What is the most common organism to cause opportunistic pneumonia (especially in AIDS)
Pneumocystic jiroveci
What are the symptoms of Herpes Simplex
Herpes Simplex is a peri-oral, weeping, vesicular rash preceded by tingling and precipitated by fever and stress.
In what condition is M. Avium Complex likely to cause an opportunistic infection
HIV
MAC causes disseminated disease in up to 40% of patients (HIV)
Fever, sweats, weight loss, and anemia
Is Leprosy culturable in vitro?
No
2 different types of leprotic presentations
Tuberculoid: Th1 mediated
Lepromatous(more severe): Th2 mediated
What is the action of calcineurin inhibitors
CyA- Binds to intracellular protein cyclophilin
Tacrolimus (FK506)- Binds to intracellular protein FKBP-12
Mode of action:
Prevents activation of NFAT nuclear factor activated t cell
Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription
T cell effects:
Reversible inhibition of T-cell activation, proliferation and clonal expansion
Why are children and elderly are much more sensitive to infection
Immaturity or senescence of the immune system
What are primary immunodeficiencies
Genetic defects in individual components of the immune system.
In what ways are an infants immune system immature
Maternal Antibodies Ab production from 5 - 6 months No response to bacterial polysaccharides Lower complement levels Poor cell-mediated immunity Poor macrophage function Poor neutrophil function
Immunodeficiency conditions in lymphocytes
T & B CELL: SCID subtypes Omenn’s Wiskott-Aldrich X-linked Hyper IgM
B cell:
XL & AR hypogammaglobulinaemia
CVID
CSR defects
What are the two inheritance patterns of SCID
Mainly autosomal recessive but can be Xlinked
Presentation of chickenpox in SCID
Fulminant disease
Haemorrhagic lesions
What is Wiskott-Aldrich syndrome
X-linked immunodeficiency
Mainly affects T cells
Eczema, Thrombocytopenia, Immunodeficiency
Antibody deficiency first, then cellular
Complications – Autoimmunity, haematological malignancy
Low Mean Platelet Volume
Infection patterns in immunodeficiency
T Cell: Opportunistic infections
Virus
Intracellular bacteria
Protozoa
Antibody: Respiratory problems
Encapsulated bacteria
Neutropenia: bacterial sepsis
IgA deficiency: upper respiratory tract infections
Asplenia: encapsulated bacteria
SIGNALS POINTING TO POSSIBLE IMMUNODEFICIENCY
Infectious signals:
>4 (proven) bacterial infections per year
SPUR checklist: Severe infections Persistent infections Unusual causative organism Recurrent infections
Where are Class 1 and 2 HLA proteins expressed
Class I antigens (HLA-A, B, Cw) found on all nucleated cells
Class II antigens (HLA-DR, DQ, DP) primarily expressed on B lymphocytes but expression can be induced on T lymphocytes and other cells
Symptoms of Pneumonia
Cough, fever Dyspnoea Pleuritic pain Production of purulent sputum Tachypnoea New focal chest sign
Normal viral causes of pneumonia in adults and children
Adults: Influenza A and B, adenovirus
Children: RSV, parainfluenza
Differences in presentation of typical and atypical pneumonia
Typical: Alveolar inflammation, Peripheral/pleuritic chest pain, copious purulent sputum, Elevated WBC
Atypical: Tracheobronchial-interstitial inflammation, central substernal pain, scanty non-purulent sputum, normal WBC
Bacterial and viral causes of atypical pneumonia
Bacterial: Legionella sp. Chlamydia pneumoniae Chlamydia psittaci Mycoplasma pneumoniae
Viral: Measles, HSV, CMV
Predisposing conditions for pneumococcal pneumonia
Sickle cell disease Asplenia/ splenic dysfunction IgG disorders: agammaglobulinemia, myeloma, chronic lymphocytic leukemia Nephrotic syndrome Cirrhosis Alcoholism
What is legionella pneumophila
Water borne infection (aerosolisation)
Failure to respond to beta-lactam antimicrobials
Severe pneumonia, often associated with non-pulmonary symptoms such as mental confusion, diarrhoea and renal failure
Rapid urinary antigen testing should be available in at least one laboratory per region.
Legionella cultures should be performed on all invasive respiratory samples (bronchoscopy)
Treatment of pneumonia
Usually amoxillin (+clarithromycin) If severe then Co-amoxiclav Alternatively use doxyclycline or if severe benzylpenicillin and a flueorquinolone
What are charcot-leyden crystals indicative of
Eosinophilic inflamtiion e.g. after an asthma attack
Changes in airways during an asthma attack
Increased mucus production and increased goblet cells
Smooth muscle hypertrophy
Thickened Basement membrane
Lots of inflammatory cells e.g. macrophages and neutrophils in lamina propria
What are Curschmann spirals
Stringy condensed mucin found in asthma attacks
What 2 components make up COPD
Chronic bronchitis
Emphysema
Clinical definition of chronic bronchitis
Cough with sputum for three months in 2 consecutive years
Pathological findings in COPD
Hyperinflated lungs with air trapping and bullae
Dilated airspaces, both macro and microscopically
Enlarged right ventricle due to cor pulmonale
Atheromatous coronary arteries
Types of pneumothorax
Primary spontaneous pneumothorax (idiopathic)
- Male
- Tall and thin
- Age 20-40s
Secondary spontaneous pneumothorax
- Emphysema, cystic fibrosis, asthma
- High altitude, scuba diving
Traumatic pneumothorax, including as a complication of a medical procedure
- Insertion of a central venous catheter
- Thoracoscopy
- Mechanical ventilation
Tension pneumothorax
- Due to trauma, chronic lung disease, medical complication
How is rheumatic fever contracted
A disease that affects the joints, kidneys, and heart valves, is a consequence of untreated strep A (S.Pyogenes) infection caused not by the bacterium itself. Rheumatic fever is caused by the antibodies created by the immune system to fight off the infection cross-reacting with other proteins in the body. This “cross-reaction” causes the body to essentially attack itself and leads to the damage above.
What is pharyngitis and a grey pseudmembrane indicative of
Diptheria
V rare- treat with erythromycin
How to treat Strep A throat
Penicillin
What is quinsy
Peritonsilar abscess
Mostly caused by Strep esp Viridans and anaerobes
Requires drainage and antibiotics
What is the main cause of infectious mononucleosis/ glandular fever
EBV
sometimes CMV
What is epiglottitis
MEDICAL EMERGENCY
Cellulitis of epiglottis (“cherry red”) – airway obstruction
Child (2-4 yrs), fever, irritable, difficulty speaking (“hot potato”) and swallowing. Leans forward, drools. Stridor, hoarse.
What is otitis media
Middle ear inflammation. Fluid present in the middle ear.
V common in children
Fever, pain, impaired hearing. Red bulging tympanic membrane.
Usually viral
H influenzae, S. pneumoniae, M. catarrhalis
Antibiotics: amoxicillin or clarithromycin
Complications= Mastoiditis
Risk factors for Gastro oesophageal reflux
Defective lower oesophageal sphincter
Hiatus hernia
Increased intra-abdominal pressure
Increased gastric fluid volume due to gastric outflow stenosis
Types of columnar mucosa in Barrett’s oesophagus
Gastric cardia type
Gastric body type
Intestinal type = “specialised Barrett’s mucosa” more common containing goblet cells with mucin in it.. Diagnostic
Complications of Barretts’ oesophagus
Premalignant condition with an increased risk of developing adenocarcinoma (as they contain glandular structures)
Regular endoscopic surveillance is recommended for early detection of neoplasia
Risk factors for peptic ulcer disease
Hyperacidity H. pylori infection Duodeno-gastric reflux Drugs (NSAIDs) Smoking
Major sites of Peptic ulcer disease
First part of duodenum
GOJ
Junction of antrum and body mucosa
What mutation causes Hereditary diffuse type gastric cancer (HDGC)
Germline CDH1/E-cadherin mutation
Epithelial cells lose adhesions and migrate
Signet ring cell
Pathogenesis of coeliac disease
GLIADIN- Alcohol soluble component of gluten
Contains most of the disease-producing components
Induces epithelial cells to express IL-15
CD8+ Intraepithelial lymphocytes (IELs)
IL15 produced by the epithelium = activation / proliferation of CD8+ IELs
These are cytotoxic and kill enterocytes
CD8+ IELs do not recognise gliadin directly
Coeliac disease and cancer
Enteropathy-associated T-cell lymphoma
Small intestinal adenocarcinoma
Where do diverticular occur most frequently
Mainly sigmoid colon
Weak points occur at sites where blood vessels (vasa recta) penetrate the circular layer of the bowel wall
These points occur in between strips of smooth muscle called TAENIA COLI
These weak points are where diverticula occur due to increased intra-lumenal pressure
What is the pathology go diverticulosis
Thickening of the muscular wall (muscularis propria)
Elastosis / thickening of the teniae coli
Muscosal redundancy
Infolding of mucosa
Sacculation / diverticula formation
What are the symptoms of diverticulosis
Usually asymptomatic Typically elderly (>60) Abdominal pain Left lower quadrant Constant Nausea & vomiting
What are the consequences of diverticulitis
OBSTRUCTION PERFORATION ABCESS FORMATION PERITONITIS FISTULA FORMATION
