9 Flashcards
What are the low and high risk strains of human papillomavirus (HPV) virus?
6 and 11 - low risk - cause anogenital warts and CIN
16 and 18 - high risk - cause cervical cancer
Types of necrosis and an example for each
Coagulative - can see structure but lose nuclei e.g. ischaemic kidney
Caseating - granulomatous inflammatory response e.g. TB granuloma
Liquefactive - influx of inflammatory cells producing pus e.g. gangrene or cerebral infarct
Physiological functions of skin?
- Vitamin D synthesis
- Temperature regulation
- Immune defence
- Protection against UV radiation
- Sensation and nerve signalling
What are the layers of the epidermis?
- Stratum corneum
- (Stratum lucidum)
- Stratum granulosum
- Stratum spinosum
- Stratum basale
Note: -Stratum lucidum is only found in thick skin like palms
Which cells would you find in the stratum basale?
- Keratinocytes - synthesise keratin
- Melanocytes - synthesise melanin
- Merkel cells - touch sensitive cells
Which cell would you find in the stratum spinosum?
Langerhan cells - dendritic cells (antigen-presenting immune cells) of the skin, and contain organelles called Birbeck granules.
They are present in all layers of the epidermis and are most prominent in the stratum spinosum.
Which cell would you find in the stratum granulosum?
Keratinocytes continuing their journey
Which cell would you find in the stratum corneum?
Corneocytes
Many layers of keratinised dead, flattented, non-nucleated cells (aka corneocytes)
Which 2 parts make up the dermis?
Thin papillary layer and thick reticular layer
Types of necrosis and where they are most likely to be found summary.
- Liquefactive: brain
- Caseous necrosis: infection with TB
- Fat necrosis: liver, pancreas
- Coagulative necrosis: kidney, liver, heart muscle
- Gangrene: limbs
- Haemorrhagic: testis, spleen, lung
- Gummatous: syphilis
What causes gout?
Xanthine oxidase overactivity
Where is most likely to suffer haemorrhagic necrosis?
- Testis: testicular torsion
- Spleen
- Lung
Where are you most likely to find fat necrosis?
Pancreas: pancreatitis
Liver
An example of gummatous necrosis?
Syphilis
Gummatous necrosis is a form a necrosis that involves the growth of non-cancerous tissues during the late stages of syphilis.
List cytoplasmic changes in necrosis.
- Eosinophilia
- Swelling
What are nuclear changes in necrosis?
Pyknosis - irreversible condensation of chromatin
Karyolysis - dissolution of cell nucleus
Karyorrhexis - fragmentation of nucleus
What is a facultative anaerobe and give an example?
Without oxygen can switch to fermentation and will grow
E. coli
Staphylococcus aureus
What is an obligate anaerobe?
Die in the presence of oxygen
Klebsiella Pneumoniae
Describe the structure of a gram negative bacteria.
- Thin peptidoglycan layer
- LPS outer membrane
What can prokaryotes be divided into?
Bacteria and archaea
Describe the structure of gram positive bacteria.
Thick peptidoglycan layer
No outer membrane
Teichoic acid - PAMP
Biochemical markers of cell death.
ALT - liver enzyme
Troponin - cardiac myocytes
Creatinine kinase - muscle
Which gram bacteria can sometimes cause spores and give an example?
Gr+
Clostridium Difficile
Clostridium Botulinum
Give the features of bacterial cells.
- Cell wall
- No nucleus
- No mitochondria
- Circular chromosome
- Pili
- Flagellum
- No organelles
- Transcription and translation occur at the same time
Pathophysiology of septic shock
- Bacterial LPS activates macrophages and neutrophils
- Systemic release of cytokines (IL-1, TNF-alpha)
- Activation of endothelial cells leading to systemic vasodilation and hypotension
- Vascular leakage and oedema
- Activation of complement
List 4 methods of diversity in bacteria.
Transformation - Small fragments of DNA taken up by the cell.
Transduction - Phage mediated transfer of non-phage DNA between bacteria.
Conjugation - Bacteria having sex, pili join to create a channel.
Transposons - Jumping genes, mobile genetic units integrate into genome.
Phases of bacterial growth?
- Lag
- Exponential - once they have enzyme, it moves quickly
- Stationary - nutrient deficit
- Death - lysing
List 4 stages of lobar pneumonia.
- Congestion - lung is oedematous and red - 1st 24hrs
- Red hepatisation - extravasation of red cells into alveolar spaces and increased number of neutrophils
- Grey hepatisation - red cells disintegrate and neutrophils persist
- Resolution - complete recovery - exudate digested by enzymes and cleared up by macrophages - exudate liquefied and either coughed up in sputum or drained in the lymph
Which microbes would you find on the skin?
- Staphylococcus aureus
- Staphylococcus epidermidis
- Lactobacillus species
Which microbes would you find in the upper respiratory tract?
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococcus pneumoniae
- Haemophilus influenzae
Which areas of the body should be microbe free?
- Blood
- CSF
- Urine
What is an opportunistic pathogen and an example of one?
Normal flora that only cause disease when introduced to unprotected sites.
Pseudomonas aeruginosa
What is a strict pathogen and an example?
Neisseria gonorrhoea only associated with human disease
Give some virulence factors.
Adhesins - pili, fimbriae, outer membrane protein
Flagella - penetrate mucus
Capsule
Toxins
What is an exotoxin?
- Protein released extracellularly
- Protein destroyed by heat
What is a toxoid?
Inactivated toxin useful as vaccine
What is listeriosis?
- Gr+
- Rod
- Facultatively anaerobic
- Does not produce endospores
Systemic infection initiated in GIT
Food borne - pate, soft cheese, unpasteurised milk, deli meats
Listeriosis is usually caught from eating food containing listeria bacteria
List features of viruses.
Obligate intracellular parasites
Cannot make energy or proteins independent of host
Genome either DNA or RNA
Replication by self-assembly
Prions do not contain any genetic information
What is the virion in enveloped virus?
Envelope and nucleocapsid
What is the virion in naked virus?
Nucleocapsid
What does the H and N stand for in influenza virus e.g. H1N1
H = hemagglutinin N = neuraminidase
What are features of enveloped virus?
- Spread through large droplets
- Sensitive to detergents
- Must stay wet to remain infectious
E.g. Ebola, HIV, influenza
What are features of naked virus?
- More stable in environmental stress e.g. acid, temperature, drought
- Spreads more easily
- Survived gut
- Norovirus and rotavirus
Infectious cycle of virus
- Attach
- Penetrate
- Uncoat
- Replicate
- Assemble
- Release
Example of +ssRNA
- Hep C
- Polio
- Dengue
Example of dsRNA
Rotavirus
Example of -ssRNA
- Measles
- Mumps
- Influenza
- Rabies
Process of HIV?
gp120 binds to CD4 cells (CD4 T cells or macrophages) and then binds to a co-receptor CCR5 or CRCX4. gp41 - 6 folded helix.
Then duplicates in each mitotic division.
What happens when you’re too cold?
Detected by thermoreceptors in the skin.
Signals to cerebral cortex - voluntary actions and hypothalamus - activates sympathetic NS causing piloerection and adrenaline release which causes skin vasoconstriction.
Also stimulates hypothalamus to produce TRH, causing pituitary to release TSH and then producing T3 and T4 = all increases BMR
What happens when you’re too hot?
- Opposite of cold
- Also activates cholinergic system - sweating and other brain centres
- RAAS system also contributes to concentration of urine
Effects on thyroid hormones on temperature?
- Increase synthesis of sodium potassium ATPase pumps - increase ATP breakdown which increases heat
- Cholesterol synthesis and lipolysis increase.
- Protein synthesis increase.
- Enhances effects of catecholamines by increasing beta receptor expression.
- Increases BMR by stimulating use of oxygen to make ATP.
List 3 diseases from bites.
Rabies: lyssaviruses
Malaria: mosquitoes
Dengue fever: Aedes type mosquitoes
West Nile Virus: mosquitoes
Japanese encephalitis: mosquitoes, specifically those of the Culex
Zika Virus: Aedes mosquitoes
Chikungunya virus: Aedes albopictus and Aedes aegypti mosquitoes
Yellow fever: Aedes aegypti mosquitoes (mainly)
Tick-borne disease: many different types and pathogens
Give a blood borne disease.
- Malaria: mosquito-borne infectious
- Syphilis: Treponema pallidum
- Brucellosis: unpasteurized milk
- Hepatitis B (HBV)
- Hepatitis C (HCV)
- Human Immunodeficiency Virus (HIV)
What is herpes labialis?
From latent site in trigeminal ganglia and also pharynx
Usually herpes simplex 1
Coldsore
List types of herpes.
HHV-1 (HSV1) - Herpes simplex virus 1
HHV-2 (HSV2) - Herpes simplex virus 2
HHV-3 (VZV) - Varicella zoster virus
HHV-4 (EMV) - Epstein-Barr virus
HHV-5 (CMV) - Cytomegalovirus
HHV-8 (KSHV) - Kaposi’s sarcoma-associated virus
What is Reye’s syndrome?
Reye syndrome is a rapidly progressive encephalopathy.
Symptoms:
- Vomiting
- Personality changes
- Confusion
- Seizures
- Loss of consciousness
Even though liver toxicity typically occurs, jaundice usually does not.
Death occurs in 20–40% of those affected and about a third of those who survive are left with a significant degree of brain damage.
The cause of Reye syndrome is unknown.
- It usually begins shortly after recovery from a viral infection, such as influenza or chickenpox.
- ~90% of cases in children are associated with aspirin (salicylate) use.
- Inborn errors of metabolism are also a risk factor.
Changes on blood tests may include a high blood ammonia level, low blood sugar level, and prolonged prothrombin time.
What is the difference between hyperpyrexia and fever?
Hyperpyrexia is malignant - over 40 degrees
What is the difference between chronic and acute inflammation?
Acute - mainly neutrophils
Chronic - mainly macrophages
What are the microvascular changes in acute inflammation?
Oedema
Generation of inflammatory exudate
May lead to pus
What are the 2 major pathways of arachidonic acid production?
Cyclo-oxygenase - produces prostaglandins
Lipo-oxygenase - produces leukotrienes
What are the cellular mediators of acute inflammation?
Platelets - serotonin
Mast cells - histamine
Inflammatory cells
What are live vaccines?
- You get the infection
- Naturally attenuated
- Not fully virulent
- Single dose
- Cheaper than non-living
- May return to virulence
Plasma mediators of acute inflammation?
- Kinins
- Clotting cascade
- Complement inflammation
What would a langerhan giant cell indicate?
Although traditionally their presence was associated with tuberculosis, they are not specific for tuberculosis or even for mycobacterial disease.
In fact, they are found in nearly every form of granulomatous disease, regardless of aetiology.
What is a giant cell?
Fusion of macrophages
What would a touton giant cell indicate?
Touton giant cells are a type of multinucleated giant cell seen in lesions with high lipid content such as fat necrosis, xanthoma, and xanthogranulomas.
They are also found in dermatofibroma.
What is active immunisation?
Induce a state of immunological readiness so that a first infection with a pathogen is recognised as though it were a second infection by the same pathogen
What is a non-living vaccine?
- Not as effective as living vaccine
- Multiple doses may be required
What is passive immunisation?
Transfer pre-formed immunological mediators into a normal individual e.g. IgG mother -> foetus or IgA in colostrum or snakebite venom
Why is human infection rare with saprophytic fungi?
They are not well adapted to growth at 37 degrees
Their enzymatic pathways function most efficiently at redox potentials found in non-living substrates
Host defence mechanism effective at dealing with ingested/inhaled fungi
Why does a subunit vaccine require adjuvant?
Immunologic adjuvants are agents that enhance specific immune responses to vaccines.
Because it produces a low immune response on its own
Subunit: when you break apart an organism and vaccinate with part that is most likely to induce an immune response
List features of fungi?
- Eukaryote
- Chitin cell wall
- 80s ribosomes
- Reproduction may be sexual or asexual
- Has cell bound organelles
How does mold grow?
Formation of filaments - these are hyphae
Entangled mass of hyphae form mycelium (network of white filaments)
How does mold reproduce?
Asexual - production of conidia which can develop within hyphae
Sexual reproduction through sexual spores
Which mold can cause bronchospasm in humans?
Aspergillus
Describe yeasts.
- Single-cell organisms
- Round or ovoid
- Reproduce by budding
Give an example of superficial mycoses?
Tinea (ringworm)
Tinea pedis - dermatophyte infection of the soles of the feet and the interdigital spaces.
Which yeast causes ringworm?
Malassezia furfur
Malassezia furfur is a species of fungus that is naturally found on the skin surfaces of humans and is associated with seborrhoeic dermatitis
What can dermatophytes use as a nutrient?
Keratin as they produce keratinase
Leishmaniasis features?
It is a tropical and subtropical disease caused by leishmania and transmitted by the bite of sandflies. It affects either the skin or the internal organs.
Can cause splenomegaly
Forms skin sores which erupt weeks to months after the person is bitten by infected sand flies.
What are the 3 stages of malaria?
Exo-Erythrocytic (liver) cycle
Erythrocytic cycle
Sporogonic cycle
What is the life cycle of malaria?
- Mosquito is infected with malaria - can be found in salivary glands
- Mosquito bites naive human skin, some parasite gets into the bloodstream - parasite sporozoite at this stage
- Parasite goes in bloodstream to liver where it infects the hepatocytes
- Then turns into a replicated structure called a schizont
- Schizont then ruptures producing merozoites which are able to infect RBCs.
- Ring stage trophozoites mature into schizonts which can then rupture and produce merozoites
- Some ring stage trophozoites differentiate into sexual erythrocytic stages (gametocytes)
- Microgametocyte (male) penetrate the macrogametocyte (female), forming a zygote
- Zygote becomes motile and elongates - ookinetes
- Ookinetes invade the midgut wall of the mosquito where they develop into oocytes
- Oocytes grow and rupture releasing sporozoites, which go into mosquito salivary glands
Which stage of malaria life cycle is associated with disease?
Erythrocytic cycle
Which disease does South American Trypanosomiasis give rise to?
Chagas disease - megacolon
What can amoebiasis cause?
Dysentery
4 classes of normal regulatory genes?
Proto-oncogenes - growth promoting
Tumour suppressor genes - growth inhibiting
Genes that control apoptosis
Genes that repair DNA
What happens in cervical cancer?
Virus infects cervical epithelial cells where it produces viral proteins E1-E7
E6 and E7 bind to tumour suppressor genes Rb and p53 and causes a reduction in their levels, it promotes DNA synthesis and interrupts p53 mediated growth, arrest and apoptosis of the genetically altered cells
What is the transmission cycle of roundworm?
Faecal oral
Common in pets such as dogs
What does hookworm do?
Penetrates the skin and migrates from the skin into the lungs into the trachea and then swallowed again
List routes of metastasis?
Haematogenous - mainly through veins as they are thinner and once in the venous system follow normal drainage so a lot of malignant cells deposited in liver and lungs
Lymphatic - malignant cells can penetrate lymphatic vessels draining the primary site travelling to regional lymph nodes
Transcoelomic - spread directly across coelomic spaces and surfaces e.g. peritoneal or pleural cavities. Common in ovarian cancers
What are proto-oncogenes?
They code for oncoprotein which positively regulate cell growth
Histological features of malignant neoplasm.
- Variable differentiation from well differentiated to poorly
- Many mitoses - abnormal forms
- High nuclear:cytoplasmic ratio
- Cellular and/or nuclear pleomorphism
Where is toxoplasmosis normal life cycle?
Cats
What does schistosomiasis cause?
Schistosomiasis is a disease caused by parasitic flatworms called schistosomes.
The disease is spread by contact with fresh water contaminated with the parasites
Fluid filled peritoneal cavity due to immune responses in the liver changing our fluid dynamics
The urinary tract or the intestines may be infected.
Symptoms include abdominal pain, diarrhoea, bloody stool, or blood in the urine.
Those who have been infected for a long time may experience liver damage, kidney failure, infertility, or bladder cance
What is an intermediate host of schistosomiasis?
Snails
What is elephantiasis due to?
Blocked lymphatics
What would you use to treat Giardiasis?
Treatment is not always necessary as the infection usually resolves on its own. However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.
3 major categories of helminth parasites?
- Tapeworms
- Flukes
- Roundworms
What is tumour grading based on?
Level of differentiation
What does TNM staging stand for?
T - primary tumour (T0-T4)
N - lymph node status (N0-N3)
M - metastasis (M0-M1)
What staging is used for colorectal cancer?
Duke’s staging
Dukes A - limited to bowel wall
Dukes B - beyond bowel wall
Dukes C - nodal metastasis
Dukes D - distant metastasis
What are the hormonal effects of neoplasm?
Endocrine insufficiency - destruction of glands
Endocrine elaboration - mainly in benign tumours e.g. hypercalcemia in parathyroid adenoma
What are local clinical effects of neoplasm?
Compression - e.g. of SVC in lung cancer
Obstruction
Intussusception - telescopes into itself
Displacement - of trachea in thyroid cancer
Ulceration
How does level of differentiation relate to aggressiveness?
Less differentiated tend to be more aggressive neoplasms
What is cachexia?
Wasting syndrome - catabolic state resulting in profound loss of body fat and mass, weakness and anorexia
What are the 8 hallmarks of cancer?
- Self sufficiency in growth signals
- Insensitivity to antigrowth signals
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Tissue invasion and metastasis
- Reprogramming of energy metabolism
- Evasion of immune destruction
What happens at G1?
- Increase in cell contents
- Some cells arrest at this phase G0
What happens at S?
- Replication of DNA
- Centrosome duplicates
What is the purpose of the DNA damage checkpoint?
Scans DNA and if there’s a problem stops the cell cycle
When is the transition point in mitosis?
Between metaphase and anaphase
What is the purpose of the DNA replication checkpoint?
Ensures DNA is completely replicated
What are gatekeeper genes?
p53 and Rb
Their loss leads to excessive proliferation
Describe basal cell carcinoma?
Slow growing cancer that rarely metastasises
Where does basal cell carcinoma present and how?
Presents in sun exposed areas with pearly papules which ulcerate in the middle as they lose their blood supply
Telangiectatic blood vessel - cardinal sign
What are the different types of basal cell carcinoma?
- Nodular
- Morphoeic
- Superficial
Which proteolytic enzymes does apoptosis involve?
Caspases
What is p21?
Cyclin-dependent kinase (CDK) inhibitor 1
0 Capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2
- p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest.
What are caretaker genes?
Maintain genetic stability e.g. gene repair
BRCA 1 and 2
What can maintain telomere length and where?
Telomerase enzymes in stem cells and germ cells
What do telomerase enzymes do?
Maintain telomere length so that they can continue replicating and acts as a primer which allows gaps to be filled by DNA polymerase
Telomerase is activated in most human cancer cells - this is how they keep on proliferating
What is a vesicle?
Small blister less than 5mm
What is a bulla?
A large blister greater than 5mm in diameter
What is a nodule?
Small, solid elevation of skin but bigger than 5mm (similar to a papule but bigger)
What is a papule?
Small, solid elevation of skin (less than 5mm in diameter) (basically a small raised area of skin)
What are the 2 growth phases of melanoma?
Radical when the melanoma grows horizontally within the epidermis
Vertical - tumour grows downwards into deeper dermal layers
What is a pustule?
Visible collection of free pus in a blister
What is a cyst?
Nodule consisting of an epithelial-lined cavity filled with fluid
What is a macule?
Flat mark on skin.
What is a plaque?
Palpable, plateau like elevation of abnormal skin - a group of papule may from a plaque (basically a big raised area of skin)
Which cancer is associated with dysfunction in the hedgehog pathway?
Basal cell carcinoma
How can basal cell carcinoma metastasise?
If it gets into your brain - can go through the CSF
What condition is a macule hypopigmented in?
Vitiligo
What is a scale?
Accumulation of thickened stratum corneum in the form of readily detached fragments
Which drug would give you a reaction which looks like someone has whipped themselves?
Bleomycin - anticancer drug
Which bacteria heavily colonises atopic skin?
Staphylococcus aureus
Which bacteria most commonly cause cellulitis?
Staphylococcus aureus
Streptococci
Describe malignant melanoma.
Atypical mole with varying colour and scalloped edges
Major criteria - change in size, colour and shape
Minor criteria - inflammation, bleeding, sensory change
List the precancerous lesions in squamous cell carcinoma?
Actinic keratosis
Cutaneous horns of keratin
Chronic ulcers
Bowen’s disease
What is impetigo?
Bacterial skin infection caused by S. aureus or S. pyogenes
What is erysipelas?
A superficial form of cellulitis - involves upper dermis + superficial lymphatics
Caused by Streptococcus pyogenes (also known as beta-hemolytic group A streptococci),
What does calcium overload lead to?
Irreversible cell damage
Why is pathology a dynamic process?
Initial stages are potentially reversible.
After necrosis and inflammation, pathology irreversible.
What is cellular level necrosis?
Normal, pyknosis, karyolysis, karyorrhexis
What is tissue level necrosis?
Coagulative necrosi (can’t happen in brain)
Liquefactive necrosis (can happen in brain)
Caseating necrosis (unusual form)
Give examples of iatrogenic diseases.
o Drugs: allergy, overdose, side effects
o Radiation: inflammation, scarring, neoplasia
o Blood transfusion: hepatitis, HIV
o Complications: surgery, immobility
Which 2 interleukins in particular, can increase the hypothalamic set point?
IL-1
IL-6
If room temperature is greater than that of the skin, how does the body cool down?
Evaporation (sweating)
Thermoregulation is controlled by which area of the anterior hypothalamus?
Preoptic
During acute infections, where is EBV shed?
Saliva
To increase the BMR which hormone does the hypothalamus release?
TRH - thyrotropin releasing hormone
To increase the BMR which hormone does the pituitary gland release?
TSH - thyroid stimulating hormone
What is the hormone T4 also known as?
Thyroxine
What is the hormone T3 also known as?
Triiodothyronine
What layer is present in thick skin but not thin skin?
Stratum lucidum
Which stages of pathology is irreversible?
After necrosis and inflammation pathology irreversible
What are congenital diseases?
Genetic or non-genetic
Present from birth
Which antibody is involved in a type 2 cytotoxic hypersensitivity reaction?
IgG or IgM
Which 2 hypersensitivities are non-autoimmune?
Type 1
Type 4
What type of cells make up the most superficial layers of the epithelium?
Cornified cells in the scontratum corneum
Which layer is mainly responsible for the barrier function of skin?
Cornified layer
Which features make the stratum cornified a good barrier?
- Lipids
- Insoluble proteins (forms hydrophobic layer)
- Strong filaments (linked by cell-cell junctions)
Which cells are the most abundant in the epidermis?
Keratinocytes
What is the function of keratinocytes?
Produce keratin and lamellar granules (waterproof sealant)
Which cells are responsible for immune defence against surface pathogens in the epidermis?
Langerhans cells
Where are merkel cells found?
In basal layer
In associated w/ nerve fibres responsible for fine touch sensation
What is scaling?
Imbalance between cell renewal and cell loss in the epidermis
What cause skin blisters?
Breakage of cell-cell junctions
Which layer is important in wound repair of superficial cuts?
Basal layer
Stratum basale
At which epidermal layer are cells no longer capable of cell division?
Stratum spinosum
Name 4 liquid filled lesion types.
Blister, vesicle, bulla, pustule
Name 4 types of solid lesions?
Papule, plaque, nodule, wheal
Name 4 types of skin colour?
Macule, patch, naevis, erythema
What is an ulcer?
Loss of epidermis and papillary layer of dermis
What is a callus?
Hyperplasia of epidermis following pressure or friction
What is erosion?
Loss of superficial epidermis
List 5 types of oedema.
o Increased hydrostatic pressure o Decreased osmotic pressure o Lymphatic obstruction o Sodium retention o Inflammation
List 3 causes of water extravasation from the vasculature?
⁄ Increase in vascular volume/pressure
⁄ Decreases in plasma protein content
⁄ Changes in endothelial cell function
What is thrombosis?
Formation of blood clot inside a blood vessel, obstructing flow of blood through circulatory system.
What is a thrombi detached from vessel wall known as?
Emboli
What 3 things cause thrombi?
o Endothelial injury o Abnormal blood flow o Hypercoagulability (blood composition)
What is congestion?
Impaired venous return causing local increased blood volume in a tissue; may occur systemically (HF) or locally (isolated venous obstruction); tissue cyanosed as deoxygenated haemoglobin accumulated.
What reactive hyperaemia?
Local vasodilation in response to ischaemia
What is active hyperaemia?
Increased blood flow/vasodilation in response to period of activation (increased blood in skeletal muscle during exercise)
What is systemic congestion often associated with?
HF
It can lead to widespread oedema
What is local congestion caused by?
COmpression of blood vessels
What 3 things does fluid homeostasis require?
¥ Vessel wall integrity
¥ Osmolarity
¥ Maintenance of intravascular pressure
What could changes in fluid homeostasis lead to?
Extravasation across the vascular wall
or
Reduction of blood fluidity
What is extravasation?
movement of water (or blood) across the vascular wall
Define shock.
Lack of blood flow (systemic hypoperfusion)
Leading to reduced nutrient delivery
What is uncontrolled systemic reaction to infection called?
Sepsis
List 5 types of shock.
Cardiogenic shock Hypovolemic shock Septic shock Neurogenic shock Anaphylactic shock
What does an atheroma contain?
Macrophages, debris (lipids, calcium, fibrous connective tissue)
What is purpura?
o Small haemorrhage (3-5mm), usually due to trauma or vasculitis.
Where does blood clots form?
Within blood vessel
Tunica intima and media
What causes pseudo-aneurysms.
Arterial traumaI.
E.I. use of artery for injection
What is fastidious bacteria?
Bacteria that have a complex nutritional requirement and will only grow when specific nutrients are available.
What is bacteria having sex known as?
Conjugation
A conjugative plasmid moves from one bacterium to another; requires cell-to-cell contact
What is bacterial transformation?
Uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids.
What is bacterial transduction?
Transfer of DNA from 1 bacterium into another via bacteriophages (bacterial virus that contains DNA)
Which areas of the body should be microbe free?
- Fluids: blood, CSF, urine
- Tissue/organs: muscles, glands, brain, inner ear…
What is the infection dose?
Quantity of pathogen required to cause an infection or immunological response in a susceptible host.
Which bacteria reside in the upper respiratory tract?
H. influenza
S. epidermidis
S. aureus
S. pneumoniae
Which bacteria reside in the skin?
S. epidermidis
S. aureus
Lactobacillus
What is an enterotoxin?
The group of exotoxins that act on the small intestine
What is an exotoxin?
Proteins that are released extracellularly produced by certain Gr+ and Gr- species
Give examples of enterotoxins
C. difficile toxin A
Cholera toxin
E. coli toxins
What is an endotoxin?
LPS of Gr- bacteria
Are exotoxins or endotoxins heat labile?
Exotoxins (destroyed by heat)
Endotoxins heat stable because they aren’t proteins (they are cell bound)
Is S. pneumoniae gram + or -?
Gram+, cocci
What are type III secreted molecules?
factors which are secreted by bacterium directly into host cell, destroying the cell.
What makes up the innate immune system?
- Phagocytes – Macrophages, polymorphonuclear granulocytes
- Soluble factors – Complement, lysozyme
What are 3 types of pathogen?
- Overt or strict pathogens (e.g. Neisseria gonorrhoeae, cholera)
- Opportunistic pathogen (e.g. Pseudomonas aeruginosa)
- Facultative pathogen (e.g. Bacillus anthracis – soil bacteria)
To establish infection and cause disease what do bacterial virulence factors facilitate?
o Attachment and entry into body o Local or general spread in the body o Multiplication o Evasion of host defences o Shedding from body o Cause damage in host
List 6 virulence factors.
o Adhesions: e.g. fimbriae, pili, outer membrane protein – specific molecules for specific receptors (to attach to host cell).
o Flagella: for motility – to penetrate mucin.
o Factors that help obtain essential nutrients: e.g. siderophores (produced by bacteria and have a high affinity to iron).
o Toxins: these do direct damage to host.
o Capsule: a sugar layer that helps the bacteria to evade the immune system.
o Type III secreted molecules: factors which are secreted by bacterium directly into host cell, destroying the cell.
Are toxin producing pathogens extra- or intra- cellular?
Extracelular
What does selective toxicity exploit?
Difference between prokaryotic and eukaryotic cells
What are anti-metabolites?
Metabolic analogues inhibit synthesis of nucleic acid precursors
E.g. sulfonamides and trimethoprim
What does beta-lactams target?
Peptidoglycan in both gram –ve and +ve bac (penicillin, cephalosporins)
• Inhibit enzymes (PBPs) required for last step: transpeptidation.
Which class of antibacterials target gram+ organism?
Glycopeptides
Because it can’t cross cell wall of gram-ve
What do quinolones inhibit?
inhibit DNA replication
♣ Specifically, enzymes required to untangle DNA: gyrases; topoisomerases
What do rifamycins block?
Blocks mRNA synthesis
♣ E.g. ciprofloxacin
♣ Higher affinity to TMP for the bacterial enzyme than for the human enzyme.
Which ribosomal subunits do prokaryotes posses?
70s (30s + 50s subunits)
What ribosomes do eukaryotes have?
80s (40s + 60s subunits)
Name 2 groups of 30s inhibitors.
Aminoglycosides
Tetracyclines
Give an example of an aminoglycoside.
Gentamycin
List some 50s inhibitors
Oxazolidinones
Lincosamides:
- Clindamycin
- Lincomycin
- Pirlimycin
Macrolide:
- Azithromycin
- Erythromycin
- Clarithromycin
- Spiramycin
- Clindamycin
Name 2 tRNA inhibitors.
Puromycin, Mupirocin
What are polymyxins?
Antimicrobial drugs which act like detergent on membrane.
Mainly topical use due to neurotoxicity and nephrotoxicity in systemic use
Define bactericidal and bacteriostatic.
Bactericidal (=kills)
Bacteriostatic (=inhibits growth)
What happens in coagulative necrosis?
Proteins in the cell breakdown when cellular liquid becomes acidified due to the disrupted blood flow.
The tissue stays firm + cells hold their structure
Ghost-like appearance
What causes coagulative necrosis?
Due to inadequate blood supply.
It’s the most common type of necrosis
Which tissues do coagulative necrosis affect?
Can affect any tissue in the body except the brain.
Commonly occurs in major organs like kidney, heart, liver - when oxygen deprived for certain amount of time.
What happens in liquefactive necrosis?
Dead tissue softens + appears liquid-like + pus develops.
Basically the result is a ‘goo’ of cell material wo/ shape
What causes liquefactive necrosis?
Enzyme imbalance that causes cell to digest itself/
Can be caused by bacterial or fungal infections + can occur in the brain
What happens in caseous necrosis?
Cell’s structure completely destroyed due to degradation by enzymes.
The remaining tissue is white, soft, ‘cheese-like’
What causes caseous necrosis?
Tuberculosis
Histoplasmosis
What is the most likely mode of transmission for dengue fever?
Biting insects
What is dengue fever?
An acute febrile disease w/ greatest in the tropics.
What is papilloma virus?
Infect the skin + mucous membranes of humans.
Some cause warts other can cause cancer.
All HPV are transmitted by skin-to-skin contact + by inorganic objects.
What does rotavirus cause?
Severe diarrhoea in young children
It’s caused by faecal-oral transmission
What viruses is kaposi sarcoma associated with?
Human herpesvirus type 8 (HHV8)
Kaposi sarcoma associated virus (KSHV)
What does HPV present like in women?
Blood-stained vaginal discharge + abnormal cervical mass
What cancer is Helicobacter pylori associated w/?
Stomach cancer
also commonly causes gastric ulcers
What do beta-lactam antibiotics inhibit the formation of?
Peptidoglycan cross-links in the bacterial cell wall –> rapid cellular death
E.g. penicillin, cephalosporins
What antibiotic classes are 30s inhibitors?
Aminoglycosides e.g. gentamycin, tobramycin
Tetracyclines e.g. oxytetracycline
What antibiotic classes are 50s inhibitors?
Macrolides
What’s the difference between bactericidal + bacteriostatic antibiotics?
Bactericidal
- Bacterial cell wall inhibition
- Kill bacteria
Bacteriostatic
- Protein synthesis/reproduction
- Help host defence take over-
Name 2 antibiotics that target bacterial folic acid metabolism.
Trimethoprim
Sulfonamides
Name antibiotics that target cell wall synthesis.
Cycloserine
Vancomycin (glycopeptide - only works on gram +ve)
Bacitracin
Beta lactams: Penicillins Cephalosporins Monobactams Carbapenems
What do quinolones target?
DNA gyrase
Inhibit enzymes topoisomerase II + IV (which are required for bacterial DNA replication, transcription, repair, stran supercoiling repair + recombination)
How do viruses replicate?
By self-assembly of individual components, including nucleic acid + capsid
What are some examples of enveloped viruses?
HIV
Influenza virus
Give examples of non-enveloped viruses.
Bacteriophage
Plant viruses
Which bacteria causes strep throat?
Streptococcus pharyngitis
List complications of shingles.
Post herpetic neuralgia
Ophthalmic herpes zoster infection can cause blindness
Name 4 mediums via HIV can be transmitted.
Blood
Semen
Vaginal fluid
Breast milk
What is the treatment for HIV?
HAART
Highly active anti-retroviral therapy
Give examples of protease inhibitors used in HAART
Indinavir, Ritonavir, Saquinavir, Lopinavir
What ribosomes do fungi have?
80s
They are eukaryotes
What in fungal cell walls are targetted w/ antifungals?
Chitin
Name 3 major classes of antifungals.
Polyenes
Azoles
Allylamines
What is MoA of polyenes?
Interacts with ergosterol, punching holes in the cell membrane, causing cells to lose ions and small molecules.
E.g. amphotericin B
What is MoA of azoles?
Interfere with fungal enzymes, thereby preventing ergosterol production for the cell membrane.
E.g. ketoconazole
What is MoA of allylamines?
Interferes with other fungal enzymes, preventing ergosterol production
e.g. flunarizine
Name 2 prophylaxis medications used to prevent malaria.
Doxycycline - cheapest
Malarone - most expensive
Mefloquine - combination med
What is Mefloquine (anti-malaria) contraindicated in those w/ a history of epilepsy or psychiatric disorders?
Due to neuropsychiatric side-effects e.g. anxiety + hallucinations)
Name 5 types of vaccination.
Live attenuated Inactivated Subunit Toxoid Conjugate
What is live attenuated vaccinations?
Weakened version of living microbe that can’t cause disease
What is inactived vaccines?
Microbes killed w/ chemicals, heat or radiation
What is subunit vaccines?
Include antigens (or epitopes) that best stimulate immune system
What is toxoid vaccines?
Formalin inactivated toxins used as vaccine
What is conjugated vaccines?
Specialised subunit vaccines where antigens are linked to polysaccharides
What are the challenges with live attenuated vaccinations?
Mutation
Storage
What are the challenges with inactivated vaccinations?
Weaker immune response
Need boosters
What are the challenges with subunit vaccinations?
Identifying specific antigen takes time
When are toxoid vaccinations used?
When main cause of illness is a bacterial toxin
When are conjugate vaccinations most effective?
Most effective for immature immune system of infants
Give examples of live attenuated vaccinations.
Measles, mumps, rubella (MMR combined vaccine)
Rotavirus
Smallpox
Chickenpox
Yellow fever
What type of vaccination is diphtheria + tetanus?
Toxoid
Give examples of conjugate vaccine.
H. influenzae type b
S. Pneumoniae
Give examples of inactivated vaccine.
Influenza
Hep A
Polio
Rabies
Cholera
What is neck stiffness, high fever, photophobia, headache, vomiting symptoms of?
Meningococcal meningitis (Neisseria meningitidis)
Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis. It carries a high mortality rate if untreated but is a vaccine-preventable disease.
What is pneumocystis jiroveci?
Yeast-like fungus of the genus Pneumocystis.
The causative organism of Pneumocystis pneumonia, it is an important human pathogen, particularly among immunocompromised hosts.
What is Legionnaire’s (Legionellosis)?
Caused by Legionella Pneumophila, a bacterium usually found in streams, rivers and lakes.
You can get them from hot tubs or air con
Cause respiratory infection
Projectile diarrhoea and vomiting after reheating rice is commonly associated with what?
Bacillus cereus
Gram-positive, rod-shaped, aerobic, facultatively anaerobic, motile, beta hemolytic bacterium commonly found in soil and food.
What is antibiotic associated diarrhoea caused by?
Clostridium difficile
Due to use of: cephalosporin, ciprofloxacin, co-amoxilclav, clindamycin
Klebsiella oxytoca, Clostridium perfringens, Staphylococcus aureus, and Candida species might also contribute to AAD.
Most cells spend the majority of time in what phase of the cell cycle? Give an exception.
Interphase part, except cancer cells
What is the G1 checkpoint?
Place where cell cycle is regulated.
Apoptosis can occur if DNA is damaged
What doesn’t occur at the G2 checkpoint if DNA is damaged?
Mitosis will not occur is DNA is damaged or not replicated
What is the M checkpoint?
Mitosis stops if chromosomes aren’t properly aligned
Why do cyclins need to be present for cell dividion to occur?
So they can then bind to specific Cyclin dependent kinases and inhibit proteins that normally inhibit cell division
What are cyclins?
Proteins made at specific times:
When active a phosphate group is added to a protein e.g. Rb
Rb inhibits cell division but this phosphate group inactives it therefore cell division carries on
What are cyclin dependent kinases?
Always present but the majority of the time are inactive.
Activated by specific cyclins
What do tumour suppressor gene mutations need 2 hits to stop functioning?
Because the tumour suppressor gene mutations tend to be recessive – both alleles need to be mutated in order to lead to the cancerous phenotype (first proposed when looking at cases of retinoblastoma)
How do tumour suppressor genes work?
Halt cell cycle and/or cause apoptosis
Give examples of tumour suppressors + how they work.
DNA repair proteins - recognise DNA damage + repair it or cause apoptosis
Cell cycle repressors - inhibit proteins essential for the cell cycle
What are oncogenes?
Genes that code for proteins that promote cell growth.
They start as proto-oncogenes.
Give examples of oncogenes.
Src Ras Myc VEGR + EGFR BCR-Abl1
What does Src code for?
A specific cytoplasmic tyrosine kinase and over activates it. Involved in sarcomas
What does Ras code for?
GTPase which in turn turns on other genes which cause cell division. Involved in colorectal cancer
What does Myc code for?
Transcription factor and is involved in Burkitt’s lymphoma
What are VEGF and EGFR?
Receptor tyrosine kinases.
Bind to tyrosine kinase receptors and switches them permanently on so cell is constantly dividing.
What is the philadelphia chromosome a.k.a.?
BCR-Abl1
It’s a cytoplasmic tyrosine kinase.
The coded protein is unregulated and signals for cell division.
Involved in CML.
What was the first oncogene to be discovered in 1970?
Src
List hallmarks of cancer.
- Self-sufficiency in growth signals (oncogenes)
- Insensitivity to antigrowth signals (tumour suppressors)
- Evasion of apoptosis
- Replicative immortality (telomerase)
- Sustained angiogenesis
- Tissue invasion + metastasis
- Reprogramming of energy metabolism
- Evasion of immune destruction
- Underlain by genome instability and inflammation
What is telomerase?
The enzyme in a eukaryote that repairs the telomeres of the chromosomes so that they do not become progressively shorter during successive rounds of chromosome replication
What is dysplasia?
The enlargement of an organ or tissue by the proliferation of cells of an abnormal type, as a developmental disorder or an early stage in the development of cancer.
Cells have not invaded the basement membrane
Define neoplasia.
New or abnormal growth of tissue which is irreversible
What are carcinomas?
Tumours of the epithelial tissue
What are sarcomas?
Tumuors of connective tissues
What are teratomas?
A tumour composed of tissues not normally present at the site (the site being typically in the gonads).
What are the 5 most common cancers in men?
Prostrate Lung Bowel Bladder Non-Hodgkin lymphoma
What are the 5 most common cancers in women?
Breast Lung Bowel Uterus Ovary
What are the 5 cancers in men with the highest mortality?
Lung Prostrate Bowel Oesophagus Pancreas
What are the 5 cancers in women with the highest mortality?
Lung Breast Bowel Pancreas Ovary
What are the 5 most common cancers in children?
Leukaemia Brain and other central nervous system tumours Neuroblastoma Wilms tumour Lymphoma
What is Wilms tumour?
Also called Wilms’ tumor or nephroblastoma)
Is a type of cancer that starts in the kidneys.
It is the most common type of kidney cancer in children.
What is lymphoma?
Cancer of the lymphatic system.
There are 2 main types :
- Hodgkin lymphoma
- Non-Hodgkin lymphoma.
How do lymphoma present?
Lumps in lymph nodes, spleen, lower abdomen (MALT)
What are the differences between Hodgkin and non-Hodgkin lymphomas?
Difference between the 2 groups is due to the histology.
Presence of Reed-Sternberg cells in Hodgkin
No Reed-Sternberg cells in non-Hodgkin
What is the difference between low + high grade lymphomas?
Low grade = mature cell malignancy
High grade = immature cell malignancy
What is leukaemia?
Abnormal blood cells in peripheral blood
What are the 4 types of laekaemia?
Acute lymphoid leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic myeloid leukaemia (CML) - BCR-APL1
Chronic lymphoid leukaemia (CLL)
Which type of leukaemia has the best prognosis?
CLL
What is the difference between acute and chronic leukaemia?
Acute = malignancy of immature cells (have less function so symptoms come on quicker)
Acute more common in. children
Chronic more common in adults
Chronic = malignancy of mature cells (have more normal function so symptoms come on slower)
What does myeloid mean?
Everything other that B, T + NK cells.
monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes or platelets
What are symptoms of leukaemia?
Related to decreased function of bone marrow so anemia (fatigue, SOB), increased infection, bruising and nosebleeds
What is myeloma?
Myeloma is not a malignancy of a myeloid cell, it is a malignancy of B cells which is a lymphocyte cell
Clonal proliferation of mature plasma cells that secrete immunoglobulins
How does myeloma present?
Bone pain
Hypercalcaemia
Night sweats
Weight loss
Extreme fatigue
Renal impairment
Why does myeloma present with bone pain?
The cancer cells bind to stromal cells which activates osteoclast activity and therefore cause lytic lesions in bone, pathological fractures and hypercalcaemia (stones, moans, thrones, groans).
Why does myeloma present with renal impairment?
Because immunoglobulins (called paraproteins deposit in the kidneys).
What are 3 different skin cancers?
Basal cell carcinoma – can have for 10 + years without it causing too much damage
Squamous cell carcinoma
Malignant melanoma
Define basal cell carcinoma.
Malignant tumour arising from basal keratinocytes of epidermis
Most common form of skin cancer (typically on face of elderly)
Slow-growing, locally invasive, rarely metastasises
What are risk factors for BCC?
Repeated UV exposure
X-ray irradiation
Chronic scarring
Genetic Predisposition
What is hedgehog protein?
An oncogene which when mutated is overactivated + constantly stimulates cellular division.
Happens in BCC
List 3 types of BCC.
1) Nodular: most common, skin coloured nodule, pearly edge – often central ulceration with adherent crust
2) Superficial (multifocal): flat, red plaque with irregular rim-like edge and light pigmentation – often many and most commonly on trunk
3) Morpheic: flat, thickened, whitish-yellow waxy plaque with indistinct edges, may have focal areas of ulceration
How is BCC managed?
Surgical excision
Radiotherapy
What is squamous cell carcinoma?
Malignant tumour of epidermal keratinocytes
Compared to BC:C which is malignant tumour arising from basal keratinocytes of epidermis
What are risk factors for SCC?
- Excessive UV exposure
- Pre-malignant skin condition
- Chronic inflammation
- Immunosuppression
How does SCC present?
Keratotic (scaly and crusty), ill-defined nodule which can ulcerate
How is SCC managed?
Surgical excision
Radiotherapy
Define malignant melanoma.
Invasive malignant tumour of epidermal melanocytes, has potential to metastasise
List 4 types of. malignant melanoma.
Superficial spreading
Lentigo
Acral lentiginous
Nodular
What is lentigo malignant melanoma?
Nodular lesion arising in pre-existing lentigo maligna typically occurring in sun-damaged skin of face in elderly
What is nodular malignant melanoma?
Pigmented nodule that may grow rapidly + ulcerate - typically on trunks of males
What is acral lentiginous malignant melanoma?
Resembles lentigo but affects palms soles + nail beds
What is superficial spreading malignant melanoma?
Flat tumour w/ variable pigmentation and irregular edges.
Most common in lower leg
How is malignant melanoma managed?
Surgical excision
Radiotherapy
Chemotherapy
How does breast cancer present?
Asymmetry, lump, skin changes (peau d’orange), inversion of nipple, discharge. Mets in bone, lung, liver, brain, hypercalcemia, enlarged lymph nodes…..
What is cancer grading?
Based on what the cells look like under a microscope.
What is cancer staging?
Based on cancer spread.
What type of mutations are BRCA1 and BRCA2?
Autosomal dominant
- Both are tumour suppressor genes responsible for production of proteins that repair DNA damage during cell reproduction.
What is FAP?
Familial adenomatous polyposis
Describe FAP.
- Autosomal dominant
- Inherit a ‘bad copy’ of the APC gene
- Have one remaining ‘good copy’ of the gene, which is still liable for mutation, and when it does polyposis results
- 90% of these people will develop colorectal cancer
- Mainly left side colorectal cancer
What is HNPPCC?
Hereditary non-polyposis colorectal cancer
Describe HNPPCC.
- Autosomal dominant
- Early onset colorectal cancer (mid-forties)
- Mainly right side colon cancer
HNPPCC increases itsk of other cancers such as?
Small bowel + gastric
Define polyp.
Small growth, usually benign and with a stalk, protruding from a mucous membrane
What is colorectal cancer?
An adenocarcinoma - arises from glandular cells in the mucosal lining of colon
What is radiation?
high energy photons, electrons, protons, neutrons or alpha particles
How does radiation work?
High energy damages DNA in cancer cells so the cells can no longer replicate indefinitely
Side effects of radiotherapy?
Tiredness, oedema, redness and mild burning.
Chronic = infertility, increased risk of cancers in later life
What is the aim of chemotherapy?
Deplete tumour cells! Breaks between cycles give normal stem cells time to recover
What are alkylating agents?
Chemotherapy drug
How do alkylating agents work?
Transfer an alkyl to the purine bases on cancer DNA and inhibit it
Monofunctional = affect one base
e.g. Dacarbazine
Bifunctional = affect more than one base
e.g. Nitrogen mustard, cyclophophamide
Why are alkylating agents aggressive + toxic?
alkylating agents target all phases
What are intercalating agents?
Platinum compounds
- Interrupt DNA double helix
- E.g. Cisplatin
Anthracyclines
- Intercalate in DNA between base pairs and blocks DNA replication
- E.g. Doxarubacin (cardiomyopathy so limited amount allowed in lifetime)
What do topoisomerase enzymes prevent?
DNA strands from becoming tangled
How does Topoisomerase I and Topoisomerase II inhibitors work?
These agents stop the topoisomerase enzyme from working therefore DNA becomes tangled and the cells can no longer replicate
What is tubulin?
Main constituent of the microtubules of living cells.
Name 2 classes of tubulin binders.
Vinca alkaloids
Taxenes
How do vinca alkaloids work?
Bind to tubulin and prevents the assembly of microfilaments so prevent cell division
Give examples of vinca alkaloids.
E.g. Vincristine, Vinblastine
GIve examples of topoisomerase I and Topoisomerase II inhibitors
Topoisomerase I inhibitors = Topotecan, Irinotecan
Topoisomerase II inhibitors = Etoperside, Teniposide
How do taxenes work?
Binds to tubulin and prevents disassembly of it which also prevents cell division
Give examples of taxenes.
E.g. Paclitaxal, Docetaxal, Eribulin (doesn’t cause hair loss)
What phase of the cell cycle do antimetabolites effect?
S phase
Give examples of antimetabolites.
Anticancer drugs
Antifolates
- E.g. Methotrexate
Pyramidine analogues
- E.g. 5-Fluorouracil, Gemcitabine
Purine analogues
- E.g. 6-mercaptopurine, 6-thioguanine
How do antibodies in cancer treatment work?
Bind to specific cell surface proteins expressed in the target tissue. This inhibits the normal activity of the receptor.
Stops intracellular signals that drives processes like cell division and angiogenesis.
GIve examples of antibodies used for cancer treatment.
Bevacizumab (VEGF) = colorectal cancer
Trastuzamab = breast cancer… only if the cells express the HER2 protein
Rituximab = Hodgkin lymphoma (CD20)
How do kinase inhibitors work?
Bind to intracellular domains of a specific cell surface receptor and prevents activation of the intracellular signals that drive cell processes
GIve examples of kinase inhibitor.
Imatinib = CML
Erlotinib = non-small cell lung cancer
Lapatinib = advanced breast cancer
What do the suffix of kinase inhibitors mean?
‘ab’ = monoclonal antibodies ‘ib’ = tyrosine kinase receptors
What do. alkylating agents covalently bind to?
They bind to (alkylate) the nucleic acid bases of DNA and produce cellular death unless the damage is repaired
What are monofunctional alkylating agents?
React with only one strand of DNA
What are bifunctional alkylating agents?
React with an atom on both strands of DNA, producing a cross-link that covalently links the two strands of the DNA double helix.
What do DNA topoisomerases regulate?
They are enzymes that regulate DNA topology
What are DNA topoisomerases essential for?
They are essential for the integrity of the genetic material during transcription, replication, recombination processes.
What is the premotor area of the cerebral cortex involved in? Where is it found?
Found in frontal lobe
Involved in planning + programming og skilled movements
What are TK inhibitors?
A tyrosine kinase inhibitor (TKI) inhibits tyrosine kinases.
The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit.
TKIs = anticancer drugs.
E.g. used in CML
What is procarbazine?
Used in Hodgkin’s disease.
It’s an alkylating agent.
An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin’s disease.
What is the following a definition of ‘increase in cell size’?
Hypertrophy
What is the following a definition of ‘increase in cell number’?
Hyperplasia
What is the following a definition of ‘decrease in cell number and size’?
Atrophy
What is the following a definition of ‘abnormal cytological appearance + tissue architecture’?
Dysplasia
What is the following a definition of ‘conversion of one type of differentiated tissue into another’?
Metaplasia
What is the following a definition of ‘uncontrolled focal proliferation of well differentiated cells’?
Benign
Name the 4 key targets of cell damage.
Mitochondria
Plasma membrane
Ionic channels in cell membranes
Cytoskeleton
What are the differences between cellular level and tissue level necrosis?
o Cellular level necrosis: normal, pyknosis, karyolysis, karyorrhexis
o Tissue level necrosis: coagulative necrosis, colliquative necrosis, caseating necrosis (unusual form)
Define karyolysis
Dissolution of cell nucleus
Especially during mitosis
Define pyknosis
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
Dfeine karyorrhexis
Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm.
It is usually preceded by pyknosis and can occur as a result of either programmed cell death, senescence, or necrosis.
What type of hypersensitivity reaction as the following examples of?
Contact hypersensitivity,
Insect venom, MS
Type IV
Cell-mediated
Non-Autoimmune
What type of hypersensitivity reaction as the following examples of?
Systemic lupus Erythematosus, Rheumatoid arthritis
Type III
Immune-complex
Autoimmune
What type of hypersensitivity reaction as the following examples of?
Asthma, Anaphylaxis,
Eczema, Urticaria,
Atopic dermatitis
Type I
Anaphylactic
Non-Autoimmune
What type of hypersensitivity reaction as the following examples of?
Rheumatic fever, Myasthenia gravis, Thyroiditis
Type II
Cytotoxic
Autoimmune
Which types of hypersensitivity reactions are autoimmune?
Type 2. and 3
Cytotoxic and immune-complex
Which is cell-mediated hypersensitivity also known as?
Type 4
Which hypersensitivity reaction does this mechanism describe?
- First exposure causes sensitisation to allergen
- IgE Ab produced
- IgE binds to FceRI receptors of mast cells and basophils
- Mast cells and basophils degrandulate and release histamine, prostaglandins, leukotrines
- This leads to bronchodilation, vascular permeability, mucus secretoin
Type 1
Anaphylactic
Non-autoimmune
Which hypersensitivity reaction does this mechanism describe?
- Antibody attacks self-cell-surface receptors
- Damaging own cells via lysis
- Damaged cells removed by phagocytosis
Type II
Cytotoxic
Autoimmune
Which hypersensitivity reaction does this mechanism describe?
- Fist constact with antigen sensitises the body
- Subsequent contact elicists reaction
- TH1 relsease cytokines
Type IV
Cell-mediated
Non-Autoimmune
Which hypersensitivity reaction does this mechanism describe?
- Antibody-antigen immune complexes deposite in orgnams
- Complement activation leads to inflammatory damage
It involves activation of PCs (dendritic cell) and priming of T helper cells
Type III
Immune-complex
Autoimmune
What genus bacteria cause leprosy?
Mycobacterium
M. leprae
What genus and species of bacteria causes whopping cough?
Bordetella
B pertussis
List 5 genii of gram positive bacteria
Bacillus Clostridium Corynebacterium Mycobacterium Staphylococcus Streptococcus
Which genus and species is the Diphtheria causes bacterium ?
Corynebacterium
C. diphtheriae
Which diseases can H. influenzae bcaateria cause?
Acute respiratory tract infections, UTIs
What are epidermal ridges used for?
Fingerprints and footpirints
What is hyperplasia of the epidermis following pressure or friction known as?
A callus
List 4 causes of oedema
- Increased hydrostatic pressure
- Decreased osmotic pressure
- Lymphatic obstruction
- Sodium retention
Name given to small haemorrhage (3-5mm), usually due to trauma or vasculitis
Purpura
What is a minute haemorrhage (1-2mm) occuring due to thrombocytopneia, clotting factor deficiency or increased pressure in capillaries known as?
Petechiae which is rash like in appearance
What is a subcutaneous haematoma called?
Bruises / Ecchymosis
Describe the colour change of a bruise due to metabolism of haemoglobin to bilirubin + hemosiderin.
Red
blue/green
Yelow/brown
What does the following describe ‘Solid, liquid, or gaseous mass (detached thrombi) carried in the blood to a site distant from the point of origin’?
Embolism
What are nearly all emboli?
Dislodged thrombi (thromboemobolism)
What is hyperaemia?
Excess blood in vessels
Is congesion and hyperaemia and active or passive process?
Congestion is passive
Hyperaemia is active
List common sites of atheromas
- Aorta (especially abdominal)
- Coronary arteries
- Carotid
- Cerebral
- Leg arteries
What is an acid-fast stain used to identify?
Acid-fast organisms (mainly mycobacterium); e.g. mycobacterium tuberculosis.
Acid-fastnes is a physical property of certain bacteria. They are resistant to decoloursation by acids during staning procedures due to large amounts of lipid substances within their cell walls called mycolic acids.
Describe the gram stain process
Stain w/ crystal violet (CV); CV stain is retained upon washing w/ alcohol in Gr+ due to cell wall biochemistry.
CV washed out; Counterstain Gr- w/ fuchsin (pink)
What colour do gram positive organisms stain?
Gr+ stain blue/purple, thick peptidoglycan layer, teichoic acid present, cytoplasmic membrane
What colour do gram negative organisms stain?
Gr- stain pink/red, thin peptidoglycan layer (periplasm), LPS present, outer + cytoplasmic membrane
What are fastidious bacteria?
Bacteria that have a complex nutritional requirement + will only grow when specific nutrients are available
What does this describe ‘ transfer of DNA from 1 bacterium into another via bacteriophages (bacterial virus that contains DNA’?
Transduction
A horizontal gene transfer method
What does this describe ‘ uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids’?
Transformation
- A horizontal gene transer method
What is binary fission?
o A cell just needs to grow to twice its starting size + then split in 2
o But, to remain viable + competitive, a bacterium must divide at the right time, in the right place, + must provide each offspring w/ a complete copy of its essential genetic material
o Doubling time depends on growth conditions (nutrients available) + vary w/ species
o Growth limited by nutrients they need to growth
What do the following bacteria have in common?
Clostridium botulinum,
Clostridium tetani,
Vibrio cholera,
Escherichia coli O157:H7
They are toxin producing pathogens, extracellular
What class are sulfonamides and trimethoprim?
Anti-metabolites that inhibit synthesis of nucleis acid precurors needed
What do beta-lactams target?
Peptidoglycan in both gram negative and positivebacteria
What do glycopeptides target?
Target gram +ve organisms because it can’t cross cell wall of gram-ve
How do polymyxins act on bacteria?
Act like detergent on membrane
Cytotoxic effects
How are polymyxins used?
Mainly topical usage; upon systemic administration poor distribution in tissues, neurotoxicity + nephrotoxicity
What do quinolones and rifamycins inhibit?
DNA replication (quinolones)
mRNA synthesis (rifamycins)
Where to aminoglycosides and tetracyclines act?
Bacterial 30s ribosome inhibitors
Protein synthesis inhibitors
List protein synthesis inhibitors of the 30s subunit.
- Tetracyclines
- Aminoglycosides
- Nitrofurans
- Spectinomycin
- Streptomycin
- Gentamicin
List some protein synthesis inhibitors of the 50s subunit.
- Macrolides (erythromycin)
- Chloramphenicol
- Clindamycin
- Lincomycin
List DNA gyrase inhibitors
Quinolones (nalidixic acid, ciprofloxacin)
Novobiocin
Where do cephalosporins act
Bacterial cell wall synthesis
Which drugs disrupt folic acid metabolism in bacteria?
Trimethroprim and Sulfonamides
List 3 methods of heat loss
Conduction/convection - 60%
Radiation - 25%
Evaporation - 15%
Describe the consequences of being a naked virus
More stable in the face of environmental stress (acid, temperature, drought)
Spreads more easily
Survives gut, poor water treatment (dehydration)
E.g. rotavirus, norovirus
Describe the consequences of being an enveloped virus
Envelop is derived from host membrane (budding)
Must stay wet to remain infectious
Very sensitive to detergents (membrane!)
Spreads through large droplets
Does not need to kill cell to spread (buds)
E.g. HIV, Ebola, influenza virus
Are the following an example of enveloped or naked viruses?
HIV, ebola, influenza
Rotavirus, norovirus
HIV, ebola, influenza (enveloped)
Rotavirus, norovirus (naked)
All negative single stranded RNA are envolved. GIve examples of hese.
Influenza, mumps, measles, rabies, “Ebola”
Give examples of positive single strand RNA viruses
Poliovirus, dengue, hepatitis C
Which viruses spread via an enteric route (ingestion)?
Norovirus, rotavirus, hepatitis A + E
List viruses able to be spread from mother to child.
o Congenital infection: Cytomegalovirus, rubella, parvovirus, B19
o Perinatal: HIV, hepatitis B, herpes simplex
List the 4 components that make up HIV combination therapy
o Nucleotide reverse transcription inhibitors
o Non-nucleotide reverse transcription inhibitors
o Protease inhibitors
o Integrase inhibitors
What is karposi’s sarcome
o KS is a mesenchymal tumour caused by a viral infection of: human herpesvirus 8 (HHV-8)
Causes red or purpose patches of abnormal tissue (made of cancer cells, blood vessels, blood) to grow
What is CNS toxoplasmosis
o A parasitic disease caused by Toxoplasma gondii
o In healthy people causes: systemic illness, w/ lymphadenopathy + fever
o Immunocompromising people causes CNS infection, abscess, seizure, altered consciousness
Function of alkylating agents.
Covalently bind to (alkylate) the nucleic acid bases of DNA and produce cellular death unless the damage is repaired
What is the difference between monofunctional and bifunctional alkylating agents?
Monofunctional agents react with only one strand of DNA
Bifunctional react with an atom on both strands of DNA, producing across-link that covalently links the 2 strands of the DNA double helix
What class is procarbazine (used in Hodgkin’s disease)
Monofunctional alkylating agent
What class are anthracyclines such as epirubicin?
Topoisomerase inhibitors
What class is nitrogen mustard cyclophosphamide (widely used in solid tumours + leukaemias)?
Bifunctional alkylating agents
What is Schistosoma?
A flatworm, most commonly hostested in a fresh water snail making bathing dangerous in natural lakes.
What does Leishmania parasite cause and what is it mainly spread by?
What does Leishmania parasite cause and what is it mainly spread by?
What does Plasmodium parasite cause?
What does Leishmania parasite cause and what is it mainly spread by?
Which parasite causes severe intrauterine infections in humans but the main host is cats?
Toxoplasma
What is the trichomoniasis?
Trichomoniasis is a sexually transmitted infection (STI) caused by a tiny parasite called Trichomonas vaginalis (TV).
It’s a protozoan
What is cryptosporidiosis?
Which parasite causes it?
Cryptosporidiosis is a diarrheal disease caused by microscopic parasites, Cryptosporidium.
It can live in the intestine of humans and animals and is passed in the stool of an infected person or animal.
What type of disease is filariasis?
Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type.
These are spread by blood-feeding black flies and mosquitoes.
This disease belongs to the group of diseases called helminthiases.
How are filaria spread?
These are spread by blood-feeding black flies and mosquitoes.
This disease belongs to the group of diseases called helminthiases.
What is Entamoeba histolytica?
An anaerobic parasitic amoebozoa, part of the genus Entamoeba.
What parasite causes amoebiasis?
Entamoeba histolytica, a protozoan parasite
What disease can African trypanosomiasis cause?
African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals.
It is caused by protozoa of the species Trypanosoma brucei.
What is American trypanosomiasis?
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by the protist Trypanosoma cruzi.
What is metaplasia?
Change of one cell type to another
What is the following an example of?
The change in the lining of the oesophagus from squamous to columnar epithelium as a result of acid reflux
Metaplasia
The changes in the prostate fland in bengin enlarment is known as what?
Hyperplasia
Individual cells growing in size
What is hypertrophy?
The enlargement of an organ or tissue from the increase in size of its cells.
Where is the main action of anti-diuretic hormone?
The collecting tubules
What is the action of anti-diurectic hormone on the collecting ducts of kidney nephrons?
Controls aquaporins in the reabsorption of. water via V2 receptors.
What is the difference between hyperplasia +hypertrophy?
Hyperplasia involves cell division, hypertrophy does not.
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.
How does progressive emphysema affect the alveolar walls?
Leads to alveolar wall destruction
What is bronchiectasis associated with?
Bronchial dilation
What does the following describe ‘ 30 year old patient with daily production of sputum dating back to childhood’
Bronchiectasis
In pneumonia how is the alveoli affected?
Alveolar filling due to consolidatoin
What type of pathogen can grow and survive in the environment as well as in host?
Facultative pathogen (.e.g Bacillus anthracis - soil bacteria)
Are toxin producing pathogens extra or intracellular?
Extracellular
Give examples of toxin producing pathogens.
C. botulinum
C. tetani
V. cholera
E. coli O157:H7
Give examples of intracellular pathogens
Salmonella serovar
Typhimurium
Listeria monocytogenes
List the 3 types of toxins produced by pathogens.
Endotoxin - LPS of gram negative bacteria
Exotoxins - proteins that are released extracellularly produced by certain Gr+ + Gr- species
Enterotoxin - group of exotoxins that act on the small intestine
EXTRA* Toxoid - inactivated toxin used as a vaccine
What class are sulphonamides and trimethoprim?
Anti-metabolites
Name the antibacterial drugs which are structural analogues of folic acid.
Work by inhibiting enzyme DHR to THFA
Trimethoprim
Beta-lactams and glycopeptides target what?
Peptidoglycan synthesis needed for bacteria cell walls (of gram positive and negative organisms)
Why do glycopeptides only target gram positive organisms?
Because they can’t cross the cell wall of gram negative organisms
Which class of antibacterials act like detergent on membrane?
Polymyxins
Why are polymyxins mainly used topically?
Mainly topical useage because upon systemic administration they poorly distribute in tissues and leads to neuro- and nephro- toxicity.
Which 2 classes of antibacterials target nucleic acid synthesis?
Quinolones and rigamycins
Which class of antibiotics inhibit DNA replication and which blocks mRNA synthesis?
DNA replication inhibition (quinolones)
mRNA synthesis blocker (rifamycins)
Eukaryotes have which ribosomal subunits?
80s (40s and 60s subunits)
Bacteria have what ribosomal subunits?
70s (30s and 50s subunits)
What class of antibacterial do tetracyclines and aminoglycosides belong to?
30s inhibitors
Name 50s inhibitors
Chloramphenicol
Erythromycin (macrolide)
Clindamycin
Oxazolidinones
Name 2 (bacterial) tRNA inhibitors
Puromycin
Mupirocin
What does antibiotic resistance refer to?
- Resistance relates to sensitivity to antibacterial agent at a certain concentration
What are the 3 classes of antibiotic resistance?
Resistant
Intermediate
Sensitive
- Based on MIC (minimum inhibitory concentration of antibacterial agent which bacterial growth is not inhibited
What does the E-test measure?
How?
Minimum inhibitory concentration
Using strip with a gradient of concentration of drug soaked in it
The lowest conc. of the drug where bacteria don’t grow is the MIC
What is MRSA?
Methicillin resistant S. aureus
Methicillin is a beta-lactam
We use vancomycin to target S. aureus now but there is some vancomycin resistant S. aureus emerging
What is core body temperature?
Temp of internal environment of body, inc. organs and blood
What is the difference between fever and hyperthermia?
Pyrogens must be present for fever
Other than that both are around 38-40 degrees
Difference between hyperthermia and hyperpyrexia?
Hyperpyrexia is 40+ degrees and is life threatening
Hyperthermia is 38-40 and not as life threatening
Mechanism of pyrexia
o Fevers are caused by pyrogens flowing in the bloodstream
o Pyrogens hypothalamus + bind to certain receptors in the hypothalamus
o PGE2 is released + the set point is altered
o PGE2 alters autonomic mechanisms of heat loss + retention to match the new set point
o IL-1 (common pyrogen) – produced by macrophages when they come in contact w/ bacteria + viruses
IL-1 signals helper T cells into action
Causes of pyrexia
Infection Blood transfusion/iatrogenic pyrogens Inflammation Malignancy Hypothalamic insults
What is pyrexia usually due to?
Altered set point
When is core body temp normally the lowest?
6am when metabolism is slowest
It has a circadian rhythm
Sweat is produced from which glands?
Eccrine sweat glands
How does arteriolar vasodilation allow heat loss?
Arteriolar vasodilation – allows increased blood flow through the artery, this redirects blood into the superficial capillaries in the skin increasing heat loss by convection + conduction
What does viruses code for?
Few specific proteins (enzymes + capsid)
What are the consequences of being a non-enveloped (naked) virus?
More stable in the face of environmental stress (acid, temperature, drought)
Spreads more easily
Survives gut, poor water treatment (dehydration)
E.g. rotavirus, norovirus
What are the consequences of being an enveloped virus?
Envelop is derived from host membrane (budding)
Must stay wet to remain infectious
Very sensitive to detergents (membrane!)
Spreads through large droplets
Does not need to kill cell to spread (buds)
E.g. HIV, Ebola, influenza virus
Define viron for enveloped and naked viruses
The infective viral particle
o For non-enveloped viruses (nucleocapsid = the virus particle = virion)
o For enveloped viruses (virion = nucleocapsid plus envelope)
What does transcription make?
+strand mRNA
What can be used to make mRNA?
-mRNA strand (complementary sequence) or DNA
Where are the 5 drug targets for retroviruses?
o Attachment = attachment inhibitors
o Co-receptor binding = co-receptor inhibitors
o Fusion = fusion inhibitors
o Viral RNA transcribed to DNA (by RT) = reverse transcriptase inhibitors
o Must be cleaned by viral protease enzyme = protease inhibitors
List the stages of the infectious cycle.
Attachment - to host cell Penetration - of host cell Uncoating - capsid falls apart Replication - copying genome and making new viral protein particles Assembly Release
What are the 3 types or DNA viruses?
Negative single strand RNA
Positive single strand RNA
Double stranded RNA
What are hepadnaviruses?
How do they replicate?
Hepadnaviruses have very small genomes of partially double-stranded, partially single stranded circular DNA.
Hepadnaviruses replicate through an RNA intermediate (which they transcribe back into cDNA using reverse transcriptase).
List 3 types of antivirals.
Nucleoside analogues
Protease inhibtors
Fusion inhibitors
How do fusion inhibitors (antiviral) work?
Synthetic analogues to block viral receptors (stops them from docking on host cells)
Anti-HIV drugs called entry (fusion) inhibitors
Herpes viruses and EBV are examples of what type of virus?
DNA virus
Example of a double stranded RNA virus
Rotaviruses (gastroenteritis)
Example of a positive single stranded RNA virus
Poliovirus
Dengue
Hapatitis C
Example of a negative single stranded RNA virus
They are all enveloped
E.g. influenza. mumps, measles, radies, ebola
How are the following viruses transmitted?
Rashes - measles, rubella, varicella
Respiratory viruses - influenza, RSV, rhinovirus, coronavirusm parainfluenza
Aerosol (droplet)
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV)
Epstein–Barr virus (EBV)
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV)
Epstein–Barr virus (EBV)
Give examples of viruses spread via cutaeneous contact.
Human papillomavirus (HPV)
What is human herpesvirus 4 (HHV-4) also called?
Epstein–Barr virus (EBV)
Name diseases associated with HHV-5 (human herpes virus 5).
Glandular fever
Pneumonia
What is herpesvirus-5 (HHV-5) also known as?
(human) cytomegalovirus
How does CMV affect healthy and immunocomprimised people?
HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants
How does CMV affect healthy and immunocomprimised people?
HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants
How is norovirus, rotavirus and hepatitis A and E spread?
Enterically - ingestion
What does norovirus cause and how common is it?
Norovirus, causes diarrhoea and vomiting, is one of the most common stomach bugs in the UK
What viruses is the most common cause of infectious gastroenteritis in infants and young children?
Rotavirus - the most common cause of serious diarrhoea and vomiting in young children
What type of virus is hepatitis E (HEV)?
How is it transmitted?
HEV is a positive-sense, single-stranded, non enveloped, RNA icosahedral virus.
HEV has a fecal-oral transmission route.
What is human herpesvirus 3 (HHV-3) also called?
Varicella zoster virus - can cause chickenpox and shingles
Differences between HHV-1 and HHV-2
Herpes simplex virus 1 = HHV-1
- Predominantly orofacial herpes
Herpes simplex virus-2 = HHV=2
- Predominantly genital herpes
Both stay latent in neurons
Both are spread via close contact (oral or sexually transmitted)
What is HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, and HHV-8 also known as?
HHV-1 = Herpes simplex virus-1
HHV-2 = Herpes simplex virus-1
HHV-3 = Varicella zoster virus
HHV-4 = Epstein-Bar virus
HHV-5 = Cytimegalovirus
HHV-8 = Kaposi’s sarcoma-associated herpes-virus
Name 3 blood borne percutaneous viruses
HIV, hepatitis B and C
Mode of transmission of arboviruses?
Percutaneous
What are arboviruses?
It is an informal name used to refer to any viruses that are transmitted by arthropod vectors
The word arbovirus is an acronym (ARthropod-BOrne virus)
What are interferons?
Type of cytokine (protein)
What are type 1 interferons (IFN-alpha and IFN-beta) mainly associated with?
Viral infections
- they are produced by stimulation of fibroblasts and leukocytes by microbial products
In inflammation bradykinin and histamine stimulate nerve endings causing what?
Pain
What is pus?
Purulent exudate with dying cells and bacteria and antimicrobial products released by phagocytic cells
Functions of platelet aggregation factor (PAF) produced by platelets, endothelial cells and leukocytes.
- Platelet aggregation + release
- Bronchoconstriction + vasoconstriction [high]
- Vasodilation + vascular permeability [low]
- Increases leukocyte adhesion + chemotaxis
- Increases leukocyte degradation / oxidative burst
What is red hepatisation also known as?
Consolidation
- Neutrophils and red cells enter alveolus
- Fluid and cells srpread to adjacent alveoli leading to solidification
What type of vaccine is the smallpox and cowpox vaccines?
Live vaccines (naturally attenuated)
What vaccinations are live and artificially attenuated?
Oral polio, measles, mumps, rubella, yellow fever
Give 2 examples of non-living vaccines which are killed whle organisms
Rabies
Influenza
What type of vaccines are non-living, antigenic components of the organisms?
DTP -diphtheria, pertussis (whooping cough), tetanus.
Experimental (malaria, HIV)
How much do living and non-living vaccinations cost in general?
Living are cheaper than non-living which can be expensive
What type of a virus is HIV-1?
A retrovirus – single stranded RNA genome but reverse transcribed into DNA –> which is integrated into hosts genome
Difference between HIV-1 and HIV-2?
- HIV-1 shows typical behaviour of an RNA virus in having high mutation rate, single infections exhibiting the phenomenon of quasispecies (group of viruses related by a similar mutation)
- HIV-2 = different HIV strain; it’s less prevalent + less pathogenic, found in West Africa
What is kaposi’s sarcoma (KS)?
o KS is a mesenchymal tumour caused by a viral infection of: human herpesvirus 8 (HHV-8)
o Causes red or purpose patches of abnormal tissue (made of cancer cells, blood vessels, blood) to grow: Under skin In lining of mouth, nose, and throat In lymph nodes In other organs
List 4 diseases associated with HIV and AIDs.
Kaposi’s sarcoma (HHV-8)
CNS toxoplasmosis
CMV retinitis
Pneumocystis jirovecii pneumonia
Disease course of Pneumocystis jirovecii pneumonia (PCP)
Attacks interstitial, fibrous tissue of lung, marked thickening of alveolar septa + alveoli –> significant hypoxia –> fatal
Lactate dehydrogenase (coverts lactate to pyruvic acid + back) levels increase + gas exchange is compromised
Oxygen is less able to diffuse into the blood –> hypoxia
Hypoxia + high arterial CO2 levels, stimulates hyper-ventilatory effort, thereby causing dyspnea (breathlessness)
What causes Pneumocystis jirovecii pneumonia (PCP)?
Yeast-like pneumocystic iroveii
What does pneumocystis jirovecii cause?
Lung infection in people with a weak immune system
Seehn especially in HIV/ADIS and cancer patients undergoing chemotherapy
What is CMV (cytomegalovirus) retinitis
o Common virus, asymptomatic usually
o Becomes latent in retinal epithelium in immune compromised people and leads to necrosis + bleeding which leads to acute onset of blindness
What does the cell wall of fungi contain that antifungas target?
Chitin
Give 3 classes of antifungals
Polyenes
Azoles
Echinocandins
MoA of polyenes
Binds to sterols (fatty part) in fungal cell membranes
Examples of polyenes
Nystatin (topical use only)
Amphotericin B - systemic use, very broad spectrum, significant toxicity (renal damage + chills)
MoA of azoles and echinocandins
Azoles - inhibit lanosterol demetylase which interrupts ergosterol biosynthesis
Echinocandins - inhibit glucan synthase which inhibits cell wall synthesis
Examples of azoles
Older drugs belong to imidazole group - clotrimazole
Newer drugs to triazole group = fluconazole
Name the 4 species of malaria that can infect humans
P. falciparum (most virulent), P. vivax, P. ovale, P. malariae.
List classes of anti-parasite drugs used for P. falciparum
Quinolones
Antifolates
Artemisinin compounds
During a blood meal, a malaria-infected female Anopheles mosquito inoculates what into the human host?
Sporozoites
Quinine, choloroquine, amodiaquine, primaquine are examples of what class of anti-parasite drugs?
Quinolones
Sulphonamides, pyrimethamines, proguanil, chlorproguanil are examples of what class of anti-parasite drugs?
Anti-folates
Artesunate, artemether, dihydroartemisinin are examples of what class of anti-parasite drugs?
Artemisinin compounds (new antimalarials)
What is sleeping sickness also known as?
African trypanomiasis
African trypanomiasis is caused by protozoa of the species Trypanosoma brucei. Which 2 types infect humans?
T. b. rhodesiense
T. b. gambiense
Which parasite transmits African trypanomiasis?
Tsetse fly
What are these drugs used for - pentamidine, suraminem melaroprol?
African trypanomiasis
What is the different between south american and African trypanomiasis?
South american = transmitted by a bug (triatomine - a.k.a kissing bug)
African - tsetse fly
What causes Chagas disease (megacolon, amastigote nests in heart)?
American trypanosomiasis, is a tropical parasitic disease caused by the protist Trypanosoma cruzi.
It is spread mostly by insects known as Triatominae, or “kissing bugs”
How does the triatomine bug infect humans with Chagas disease?
Triatomine excretes the parasite in faeces, faeces enter human blood stream via: wound or conjunctiva (eye rubbed)
Which parasite carries and spreads leishmaniasis?
Sandfly
Which parasite carries and spreads toxoplasmosis?
Cats (faeces) or we can eat cysts in undercooked meat
Treatment for toxoplasmosis
Pyrimethamine
What does toxoplasmosis cause in pregnant, healthy and immunocompromised adults?
Pregnant - causes congential toxxoplasmosis leading to abortion, hydrocephalus
Mild lymphadenopathy in healthy adults
Serious HIV-associated opportunistic infection
What does Entamoeba histolytica cause?
Amoebiasis which is often asymptomatic but can cause dysentery and invasive extra-intestinal disease
List 3 heliminthic parasite examples which infect by larvae or eggs.
Tapeworms: cestodes
Flukes: trematodes
Round worms: nematodes
Which drugs are used against roundworms?
Mebendazole
Which drugs are used against tapeworms?
Albendazole
What is the word tumour used synonymously with?
Neoplasm
What is malignancy neoplasm also known as?
Cancer - a disorder of cell cycle (enhancement of activity in any molecule promotes growth or a loss of one that inhibits it)
What regulates the cell cycle?
Cyclin-dependent kinases + their inhibitors
List 4 classes of genes important in cancer.
Proto-oncogenes
Tumour suppressor genes
Genes that control programmed apoptosis
DNA repair genes
Give examples of proto-oncogenes and tumour suppressor genes
Proto-oncogenes (RAS, BRAG, KIT)
- when they mutate that become oncogenes (e.g. EGFR)
Tumour-suppressor genes (p53)
What is the proportion of sporadic to inherited cacner mutations?
Most cancers are sporadic, a minority 2-3% are inherited
List examples of highly penetrate mutations.
o Breast cancer - BRCA1/2
o Familial adenomatous polyposis - APC gene
o Hereditary non-polyposis colorectal cancer (HNPCC) – mismatch repair genes
List chemical carcinogenes that cause genetic damage and induce neoplastic transformation
Asbestos – lung cancer mesothelioma
Nitrosamines + amides (preservatives) – gastric cancer
Naturally occurring (Aflatoxin B1) – liver cancer
Aromatic amines + azo dyes – liver + bladder cancer
Give examples of radiation that cause cancer
UV rays – SCC, BCC, melanoma
Ionising radiation (electromagnetic + particulate) – Leukaemia, Solid organ malignancies (thyroid)
List microbial organisms which can cause cancer.
HPV
EBV
HepB
H. pylori
List types of cancer EBV can cause
Burkitt lymphoma
B-cell lymphoma (IC people)
Nasopharyngeal carcinoma
Hodgkin lymphoma
What is HPV and how can it cause cancer?
Oncogenic DNA virus that interacts with cell cycle proteins pRb and p53 (tumour suppressor genes)
What can cause Hepatocellular carcinoma (HCC)?
Hepatitis B
Which cancers is H. pylori responsible for?
Gastric lymphoma, Gastric carcinoma
What is metaplasia?
Reversible transformation of one type of mature fully differentiated cell into a different fully differentiated cell type
2 common types of metaplasia
Squamous metaplasia
Glandular metaplasia
Where does squamous metaplasia happen?
Happens in ducts (salivary, pancreas – presence of stones) that are chronically inflamed
Where does squamous metaplasia happen?
In oesophagus, squamous-lined to columnar-lined w/ goblet cells (Barrett’s oesophagus)
Patients go through biopsies to catch early signs of cancer
What is observed in dysplasia?
o Disordered growth
o Cells undergo morphological transformation
o Loss of architectural relationship between cells
o Increased cell division
o Incomplete maturation (or loss of differentiation)
Metaplasia can lead to dysplasia which can lead to what?
Neoplasia
What is a teratoma and where does it common arise?
Tumour containing elements of all 3 embryological germ cell layers
Gonads
Which types of cancer typically have only circulating cells?
Leukaemias
Which diseases typically present with tumour masses?
Lymphoma
What is atopic eczema?
Chronic inflammatory itchy skin condition which has a genetic component
What condition does this describe - chronic inflammatory skin disease due to hyperproliferation of keratinocytes + inflammatory cell infiltration?
Psoriasis
what are melanocytes found?
Basal epidermis
Function of melanocytes
Deposit melanin from melanosomes over nuclei of basal cells
The melanin forms a barrier over basal cell nuclei
What is the absence of melanin in skin due to an autoimmune condition attacking melanocytes called?
Vitiligo
Name given to macrophages in dermis.
Langerhans cells
Where are merkel cells found and what is their function?
Found in basal epidermis
Store serotonin which they release from associated nerve endings in response to pressure
Skin conditions caused by S. aureus
Impetigo,
Boils,
Cellulitis,
Folliculitis
Where can Group A beta-haemolytic streptococcus bacteria cause skin infections?
Throat + skin
Skin cancer is divided into non-melanoma and melanoma. List the 2 non-melanomas.
Basal cell carcinoma - best to have
Squamous cell carcinoma
What is the ABCDE symptoms of malignant melanoma presentation?
- Asymmetrical shape*
- Border irregularity
- Colour irregularity*
- Diameter >6mm
- Evolution* (e.g. change in size/shape)
- Symptoms (e.g. bleeding, itchy)
List causes of exogenous p53 mutations
UV sunlight – skin cancer (CC to TT pyrimidine dimers)
Aflatoxin B1 in diet – liver cancer (codon 249 AGG to AGT)
Benzo(a)pyrene in tobacco smoke – lung cancer (hotspot codons 157, 248, 273)
Shedding or cornfield layer?
A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising
A. Scaling
Loss of superficial epidermis
A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising
C. Erosion
Leakage of blood into dermis
A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising
E. Bruising
Loss of epidermis and papillary layer of dermis
A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising
Ulcer
Hyperplasia of epidermis following pressure or friction
A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising
Callus
Summary of aerobic and anaerobic bacteria.
They can be identified by growing them in test tubes of thioglycollate broth.
1: Obligate aerobes need oxygen because they cannot ferment or respire anaerobically.
2: Obligate anaerobes are poisoned by oxygen.
3: Facultative anaerobes can grow with or without oxygen because they can metabolise energy aerobically or anaerobically. Aerobic respiration generates more ATP than either fermentation or anaerobic respiration.
4: Microaerophiles need oxygen because they cannot ferment or respire anaerobically. However, they are poisoned by high concentrations of oxygen.
5: Aerotolerant organisms do not require oxygen as they metabolise energy anaerobically. Unlike obligate anaerobes however, they are not poisoned by oxygen.
Mnemonic to remember -ssRNA and +ssRNA viruses
-ssRNA : My Mum Is Right Measles Mumps Influenza Rubella
+ssRNA: He Parked Diagonally
Hep C
Polio
Dengue
Which gram bacteria have endotoxins?
Gram negative
Endotoxin = the glycoproteins on the LPS
Gram positive doesn’t a have LPS
Difference between grading and staging?
Staging is a way of describing or classifying a cancer based on the extent of cancer in the body. The stage is often based on the size of the tumour, whether the cancer has spread (metastasized) from where it started to other parts of the body and where it has spread. Stages are based on specific factors for each type of cancer. (TNM staging system – T = Tumor; N = node involvement and M = metastastic spread)
Grading is a way of classifying cancer cells. The pathologist gives the cancer a grade based on how different they look from normal cells (differentiation), how quickly they are growing and dividing, and how likely they are to spread. (How aggressive is the cancer?)
List examples of subunit, recombinant, polysaccharide, and conjugate vaccines.
These use specific pieces of the germ — like its protein, sugar, or capsid (a casing around the germ).
Because these vaccines use only specific pieces of the germ, they give a very strong immune response that’s targeted to key parts of the germ. They can also be used on almost everyone who needs them, including people with weakened immune systems and long-term health problems.
One limitation of these vaccines is that you may need booster shots to get ongoing protection against diseases.
Hib (Haemophilus influenzae type b) disease
Hepatitis B
HPV (Human papillomavirus)
Whooping cough (part of the DTaP)
Pneumococcal disease
Meningococcal disease
Shingles
