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
