9 Flashcards

1
Q

What are the low and high risk strains of human papillomavirus (HPV) virus?

A

6 and 11 - low risk - cause anogenital warts and CIN

16 and 18 - high risk - cause cervical cancer

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2
Q

Types of necrosis and an example for each

A

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

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3
Q

Physiological functions of skin?

A
  • Vitamin D synthesis
  • Temperature regulation
  • Immune defence
  • Protection against UV radiation
  • Sensation and nerve signalling
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4
Q

What are the layers of the epidermis?

A
  • Stratum corneum
  • (Stratum lucidum)
  • Stratum granulosum
  • Stratum spinosum
  • Stratum basale

Note: -Stratum lucidum is only found in thick skin like palms

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5
Q

Which cells would you find in the stratum basale?

A
  • Keratinocytes - synthesise keratin
  • Melanocytes - synthesise melanin
  • Merkel cells - touch sensitive cells
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6
Q

Which cell would you find in the stratum spinosum?

A

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.

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7
Q

Which cell would you find in the stratum granulosum?

A

Keratinocytes continuing their journey

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8
Q

Which cell would you find in the stratum corneum?

A

Corneocytes

Many layers of keratinised dead, flattented, non-nucleated cells (aka corneocytes)

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9
Q

Which 2 parts make up the dermis?

A

Thin papillary layer and thick reticular layer

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10
Q

Types of necrosis and where they are most likely to be found summary.

A
  • 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
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11
Q

What causes gout?

A

Xanthine oxidase overactivity

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12
Q

Where is most likely to suffer haemorrhagic necrosis?

A
  • Testis: testicular torsion
  • Spleen
  • Lung
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13
Q

Where are you most likely to find fat necrosis?

A

Pancreas: pancreatitis

Liver

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14
Q

An example of gummatous necrosis?

A

Syphilis

Gummatous necrosis is a form a necrosis that involves the growth of non-cancerous tissues during the late stages of syphilis.

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15
Q

List cytoplasmic changes in necrosis.

A
  • Eosinophilia

- Swelling

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16
Q

What are nuclear changes in necrosis?

A

Pyknosis - irreversible condensation of chromatin

Karyolysis - dissolution of cell nucleus

Karyorrhexis - fragmentation of nucleus

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17
Q

What is a facultative anaerobe and give an example?

A

Without oxygen can switch to fermentation and will grow

E. coli

Staphylococcus aureus

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18
Q

What is an obligate anaerobe?

A

Die in the presence of oxygen

Klebsiella Pneumoniae

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19
Q

Describe the structure of a gram negative bacteria.

A
  • Thin peptidoglycan layer

- LPS outer membrane

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20
Q

What can prokaryotes be divided into?

A

Bacteria and archaea

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21
Q

Describe the structure of gram positive bacteria.

A

Thick peptidoglycan layer

No outer membrane

Teichoic acid - PAMP

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22
Q

Biochemical markers of cell death.

A

ALT - liver enzyme

Troponin - cardiac myocytes

Creatinine kinase - muscle

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23
Q

Which gram bacteria can sometimes cause spores and give an example?

A

Gr+

Clostridium Difficile

Clostridium Botulinum

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24
Q

Give the features of bacterial cells.

A
  • Cell wall
  • No nucleus
  • No mitochondria
  • Circular chromosome
  • Pili
  • Flagellum
  • No organelles
  • Transcription and translation occur at the same time
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25
Pathophysiology of septic shock
1. Bacterial LPS activates macrophages and neutrophils 2. Systemic release of cytokines (IL-1, TNF-alpha) 3. Activation of endothelial cells leading to systemic vasodilation and hypotension 4. Vascular leakage and oedema 5. Activation of complement
26
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.
27
Phases of bacterial growth?
1. Lag 2. Exponential - once they have enzyme, it moves quickly 3. Stationary - nutrient deficit 4. Death - lysing
28
List 4 stages of lobar pneumonia.
1. Congestion - lung is oedematous and red - 1st 24hrs 2. Red hepatisation - extravasation of red cells into alveolar spaces and increased number of neutrophils 3. Grey hepatisation - red cells disintegrate and neutrophils persist 4. 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
29
Which microbes would you find on the skin?
- Staphylococcus aureus - Staphylococcus epidermidis - Lactobacillus species
30
Which microbes would you find in the upper respiratory tract?
- Staphylococcus aureus - Staphylococcus epidermidis - Streptococcus pneumoniae - Haemophilus influenzae
31
Which areas of the body should be microbe free?
- Blood - CSF - Urine
32
What is an opportunistic pathogen and an example of one?
Normal flora that only cause disease when introduced to unprotected sites. Pseudomonas aeruginosa
33
What is a strict pathogen and an example?
Neisseria gonorrhoea only associated with human disease
34
Give some virulence factors.
Adhesins - pili, fimbriae, outer membrane protein Flagella - penetrate mucus Capsule Toxins
35
What is an exotoxin?
- Protein released extracellularly | - Protein destroyed by heat
36
What is a toxoid?
Inactivated toxin useful as vaccine
37
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
38
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
39
What is the virion in enveloped virus?
Envelope and nucleocapsid
40
What is the virion in naked virus?
Nucleocapsid
41
What does the H and N stand for in influenza virus e.g. H1N1
``` H = hemagglutinin N = neuraminidase ```
42
What are features of enveloped virus?
- Spread through large droplets - Sensitive to detergents - Must stay wet to remain infectious E.g. Ebola, HIV, influenza
43
What are features of naked virus?
- More stable in environmental stress e.g. acid, temperature, drought - Spreads more easily - Survived gut - Norovirus and rotavirus
44
Infectious cycle of virus
- Attach - Penetrate - Uncoat - Replicate - Assemble - Release
45
Example of +ssRNA
- Hep C - Polio - Dengue
46
Example of dsRNA
Rotavirus
47
Example of -ssRNA
- Measles - Mumps - Influenza - Rabies
48
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.
49
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
50
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
51
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.
52
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
53
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)
54
What is herpes labialis?
From latent site in trigeminal ganglia and also pharynx Usually herpes simplex 1 Coldsore
55
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
56
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.
57
What is the difference between hyperpyrexia and fever?
Hyperpyrexia is malignant - over 40 degrees
58
What is the difference between chronic and acute inflammation?
Acute - mainly neutrophils | Chronic - mainly macrophages
59
What are the microvascular changes in acute inflammation?
Oedema Generation of inflammatory exudate May lead to pus
60
What are the 2 major pathways of arachidonic acid production?
Cyclo-oxygenase - produces prostaglandins Lipo-oxygenase - produces leukotrienes
61
What are the cellular mediators of acute inflammation?
Platelets - serotonin Mast cells - histamine Inflammatory cells
62
What are live vaccines?
- You get the infection - Naturally attenuated - Not fully virulent - Single dose - Cheaper than non-living - May return to virulence
63
Plasma mediators of acute inflammation?
- Kinins - Clotting cascade - Complement inflammation
64
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.
65
What is a giant cell?
Fusion of macrophages
66
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.
67
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
68
What is a non-living vaccine?
- Not as effective as living vaccine | - Multiple doses may be required
69
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
70
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
71
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
72
List features of fungi?
- Eukaryote - Chitin cell wall - 80s ribosomes - Reproduction may be sexual or asexual - Has cell bound organelles
73
How does mold grow?
Formation of filaments - these are hyphae Entangled mass of hyphae form mycelium (network of white filaments)
74
How does mold reproduce?
Asexual - production of conidia which can develop within hyphae Sexual reproduction through sexual spores
75
Which mold can cause bronchospasm in humans?
Aspergillus
76
Describe yeasts.
- Single-cell organisms - Round or ovoid - Reproduce by budding
77
Give an example of superficial mycoses?
Tinea (ringworm) Tinea pedis - dermatophyte infection of the soles of the feet and the interdigital spaces.
78
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
79
What can dermatophytes use as a nutrient?
Keratin as they produce keratinase
80
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.
81
What are the 3 stages of malaria?
Exo-Erythrocytic (liver) cycle Erythrocytic cycle Sporogonic cycle
82
What is the life cycle of malaria?
1. Mosquito is infected with malaria - can be found in salivary glands 2. Mosquito bites naive human skin, some parasite gets into the bloodstream - parasite sporozoite at this stage 3. Parasite goes in bloodstream to liver where it infects the hepatocytes 4. Then turns into a replicated structure called a schizont 5. Schizont then ruptures producing merozoites which are able to infect RBCs. 6. Ring stage trophozoites mature into schizonts which can then rupture and produce merozoites 7. Some ring stage trophozoites differentiate into sexual erythrocytic stages (gametocytes) 8. Microgametocyte (male) penetrate the macrogametocyte (female), forming a zygote 9. Zygote becomes motile and elongates - ookinetes 10. Ookinetes invade the midgut wall of the mosquito where they develop into oocytes 11. Oocytes grow and rupture releasing sporozoites, which go into mosquito salivary glands
83
Which stage of malaria life cycle is associated with disease?
Erythrocytic cycle
84
Which disease does South American Trypanosomiasis give rise to?
Chagas disease - megacolon
85
What can amoebiasis cause?
Dysentery
86
4 classes of normal regulatory genes?
Proto-oncogenes - growth promoting Tumour suppressor genes - growth inhibiting Genes that control apoptosis Genes that repair DNA
87
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
88
What is the transmission cycle of roundworm?
Faecal oral | Common in pets such as dogs
89
What does hookworm do?
Penetrates the skin and migrates from the skin into the lungs into the trachea and then swallowed again
90
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
91
What are proto-oncogenes?
They code for oncoprotein which positively regulate cell growth
92
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
93
Where is toxoplasmosis normal life cycle?
Cats
94
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
95
What is an intermediate host of schistosomiasis?
Snails
96
What is elephantiasis due to?
Blocked lymphatics
97
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.
98
3 major categories of helminth parasites?
- Tapeworms - Flukes - Roundworms
99
What is tumour grading based on?
Level of differentiation
100
What does TNM staging stand for?
T - primary tumour (T0-T4) N - lymph node status (N0-N3) M - metastasis (M0-M1)
101
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
102
What are the hormonal effects of neoplasm?
Endocrine insufficiency - destruction of glands Endocrine elaboration - mainly in benign tumours e.g. hypercalcemia in parathyroid adenoma
103
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
104
How does level of differentiation relate to aggressiveness?
Less differentiated tend to be more aggressive neoplasms
105
What is cachexia?
Wasting syndrome - catabolic state resulting in profound loss of body fat and mass, weakness and anorexia
106
What are the 8 hallmarks of cancer?
1. Self sufficiency in growth signals 2. Insensitivity to antigrowth signals 3. Evasion of apoptosis 4. Limitless replicative potential 5. Sustained angiogenesis 6. Tissue invasion and metastasis 7. Reprogramming of energy metabolism 8. Evasion of immune destruction
107
What happens at G1?
- Increase in cell contents | - Some cells arrest at this phase G0
108
What happens at S?
- Replication of DNA | - Centrosome duplicates
109
What is the purpose of the DNA damage checkpoint?
Scans DNA and if there's a problem stops the cell cycle
110
When is the transition point in mitosis?
Between metaphase and anaphase
111
What is the purpose of the DNA replication checkpoint?
Ensures DNA is completely replicated
112
What are gatekeeper genes?
p53 and Rb Their loss leads to excessive proliferation
113
Describe basal cell carcinoma?
Slow growing cancer that rarely metastasises
114
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
115
What are the different types of basal cell carcinoma?
- Nodular - Morphoeic - Superficial
116
Which proteolytic enzymes does apoptosis involve?
Caspases
117
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.
118
What are caretaker genes?
Maintain genetic stability e.g. gene repair BRCA 1 and 2
119
What can maintain telomere length and where?
Telomerase enzymes in stem cells and germ cells
120
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
121
What is a vesicle?
Small blister less than 5mm
122
What is a bulla?
A large blister greater than 5mm in diameter
123
What is a nodule?
Small, solid elevation of skin but bigger than 5mm (similar to a papule but bigger)
124
What is a papule?
Small, solid elevation of skin (less than 5mm in diameter) (basically a small raised area of skin)
125
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
126
What is a pustule?
Visible collection of free pus in a blister
127
What is a cyst?
Nodule consisting of an epithelial-lined cavity filled with fluid
128
What is a macule?
Flat mark on skin.
129
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)
130
Which cancer is associated with dysfunction in the hedgehog pathway?
Basal cell carcinoma
131
How can basal cell carcinoma metastasise?
If it gets into your brain - can go through the CSF
132
What condition is a macule hypopigmented in?
Vitiligo
133
What is a scale?
Accumulation of thickened stratum corneum in the form of readily detached fragments
134
Which drug would give you a reaction which looks like someone has whipped themselves?
Bleomycin - anticancer drug
135
Which bacteria heavily colonises atopic skin?
Staphylococcus aureus
136
Which bacteria most commonly cause cellulitis?
Staphylococcus aureus Streptococci
137
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
138
List the precancerous lesions in squamous cell carcinoma?
Actinic keratosis Cutaneous horns of keratin Chronic ulcers Bowen's disease
139
What is impetigo?
Bacterial skin infection caused by S. aureus or S. pyogenes
140
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),
141
What does calcium overload lead to?
Irreversible cell damage
142
Why is pathology a dynamic process?
Initial stages are potentially reversible. After necrosis and inflammation, pathology irreversible.
143
What is cellular level necrosis?
Normal, pyknosis, karyolysis, karyorrhexis
144
What is tissue level necrosis?
Coagulative necrosi (can't happen in brain) Liquefactive necrosis (can happen in brain) Caseating necrosis (unusual form)
145
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
146
Which 2 interleukins in particular, can increase the hypothalamic set point?
IL-1 | IL-6
147
If room temperature is greater than that of the skin, how does the body cool down?
Evaporation (sweating)
148
Thermoregulation is controlled by which area of the anterior hypothalamus?
Preoptic
149
During acute infections, where is EBV shed?
Saliva
150
To increase the BMR which hormone does the hypothalamus release?
TRH - thyrotropin releasing hormone
151
To increase the BMR which hormone does the pituitary gland release?
TSH - thyroid stimulating hormone
152
What is the hormone T4 also known as?
Thyroxine
153
What is the hormone T3 also known as?
Triiodothyronine
154
What layer is present in thick skin but not thin skin?
Stratum lucidum
155
Which stages of pathology is irreversible?
After necrosis and inflammation pathology irreversible
156
What are congenital diseases?
Genetic or non-genetic Present from birth
157
Which antibody is involved in a type 2 cytotoxic hypersensitivity reaction?
IgG or IgM
158
Which 2 hypersensitivities are non-autoimmune?
Type 1 | Type 4
159
What type of cells make up the most superficial layers of the epithelium?
Cornified cells in the scontratum corneum
160
Which layer is mainly responsible for the barrier function of skin?
Cornified layer
161
Which features make the stratum cornified a good barrier?
- Lipids - Insoluble proteins (forms hydrophobic layer) - Strong filaments (linked by cell-cell junctions)
162
Which cells are the most abundant in the epidermis?
Keratinocytes
163
What is the function of keratinocytes?
Produce keratin and lamellar granules (waterproof sealant)
164
Which cells are responsible for immune defence against surface pathogens in the epidermis?
Langerhans cells
165
Where are merkel cells found?
In basal layer In associated w/ nerve fibres responsible for fine touch sensation
166
What is scaling?
Imbalance between cell renewal and cell loss in the epidermis
167
What cause skin blisters?
Breakage of cell-cell junctions
168
Which layer is important in wound repair of superficial cuts?
Basal layer Stratum basale
169
At which epidermal layer are cells no longer capable of cell division?
Stratum spinosum
170
Name 4 liquid filled lesion types.
Blister, vesicle, bulla, pustule
171
Name 4 types of solid lesions?
Papule, plaque, nodule, wheal
172
Name 4 types of skin colour?
Macule, patch, naevis, erythema
173
What is an ulcer?
Loss of epidermis and papillary layer of dermis
174
What is a callus?
Hyperplasia of epidermis following pressure or friction
175
What is erosion?
Loss of superficial epidermis
176
List 5 types of oedema.
``` o Increased hydrostatic pressure o Decreased osmotic pressure o Lymphatic obstruction o Sodium retention o Inflammation ```
177
List 3 causes of water extravasation from the vasculature?
⁄ Increase in vascular volume/pressure ⁄ Decreases in plasma protein content ⁄ Changes in endothelial cell function
178
What is thrombosis?
Formation of blood clot inside a blood vessel, obstructing flow of blood through circulatory system.
179
What is a thrombi detached from vessel wall known as?
Emboli
180
What 3 things cause thrombi?
``` o Endothelial injury o Abnormal blood flow o Hypercoagulability (blood composition) ```
181
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.
182
What reactive hyperaemia?
Local vasodilation in response to ischaemia
183
What is active hyperaemia?
Increased blood flow/vasodilation in response to period of activation (increased blood in skeletal muscle during exercise)
184
What is systemic congestion often associated with?
HF | It can lead to widespread oedema
185
What is local congestion caused by?
COmpression of blood vessels
186
What 3 things does fluid homeostasis require?
¥ Vessel wall integrity ¥ Osmolarity ¥ Maintenance of intravascular pressure
187
What could changes in fluid homeostasis lead to?
Extravasation across the vascular wall or Reduction of blood fluidity
188
What is extravasation?
movement of water (or blood) across the vascular wall
189
Define shock.
Lack of blood flow (systemic hypoperfusion) Leading to reduced nutrient delivery
190
What is uncontrolled systemic reaction to infection called?
Sepsis
191
List 5 types of shock.
``` Cardiogenic shock Hypovolemic shock Septic shock Neurogenic shock Anaphylactic shock ```
192
What does an atheroma contain?
Macrophages, debris (lipids, calcium, fibrous connective tissue)
193
What is purpura?
o Small haemorrhage (3-5mm), usually due to trauma or vasculitis.
194
Where does blood clots form?
Within blood vessel | Tunica intima and media
195
What causes pseudo-aneurysms.
Arterial traumaI. E.I. use of artery for injection
196
What is fastidious bacteria?
Bacteria that have a complex nutritional requirement and will only grow when specific nutrients are available.
197
What is bacteria having sex known as?
Conjugation A conjugative plasmid moves from one bacterium to another; requires cell-to-cell contact
198
What is bacterial transformation?
Uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids.
199
What is bacterial transduction?
Transfer of DNA from 1 bacterium into another via bacteriophages (bacterial virus that contains DNA)
200
Which areas of the body should be microbe free?
- Fluids: blood, CSF, urine | - Tissue/organs: muscles, glands, brain, inner ear…
201
What is the infection dose?
Quantity of pathogen required to cause an infection or immunological response in a susceptible host.
202
Which bacteria reside in the upper respiratory tract?
H. influenza S. epidermidis S. aureus S. pneumoniae
203
Which bacteria reside in the skin?
S. epidermidis S. aureus Lactobacillus
204
What is an enterotoxin?
The group of exotoxins that act on the small intestine
205
What is an exotoxin?
Proteins that are released extracellularly produced by certain Gr+ and Gr- species
206
Give examples of enterotoxins
C. difficile toxin A Cholera toxin E. coli toxins
207
What is an endotoxin?
LPS of Gr- bacteria
208
Are exotoxins or endotoxins heat labile?
Exotoxins (destroyed by heat) Endotoxins heat stable because they aren't proteins (they are cell bound)
209
Is S. pneumoniae gram + or -?
Gram+, cocci
210
What are type III secreted molecules?
factors which are secreted by bacterium directly into host cell, destroying the cell.
211
What makes up the innate immune system?
- Phagocytes – Macrophages, polymorphonuclear granulocytes | - Soluble factors – Complement, lysozyme
212
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)
213
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 ```
214
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.
215
Are toxin producing pathogens extra- or intra- cellular?
Extracelular
216
What does selective toxicity exploit?
Difference between prokaryotic and eukaryotic cells
217
What are anti-metabolites?
Metabolic analogues inhibit synthesis of nucleic acid precursors E.g. sulfonamides and trimethoprim
218
What does beta-lactams target?
Peptidoglycan in both gram –ve and +ve bac (penicillin, cephalosporins) • Inhibit enzymes (PBPs) required for last step: transpeptidation.
219
Which class of antibacterials target gram+ organism?
Glycopeptides Because it can't cross cell wall of gram-ve
220
What do quinolones inhibit?
inhibit DNA replication ♣ Specifically, enzymes required to untangle DNA: gyrases; topoisomerases
221
What do rifamycins block?
Blocks mRNA synthesis ♣ E.g. ciprofloxacin ♣ Higher affinity to TMP for the bacterial enzyme than for the human enzyme.
222
Which ribosomal subunits do prokaryotes posses?
70s (30s + 50s subunits)
223
What ribosomes do eukaryotes have?
80s (40s + 60s subunits)
224
Name 2 groups of 30s inhibitors.
Aminoglycosides Tetracyclines
225
Give an example of an aminoglycoside.
Gentamycin
226
List some 50s inhibitors
Oxazolidinones Lincosamides: - Clindamycin - Lincomycin - Pirlimycin Macrolide: - Azithromycin - Erythromycin - Clarithromycin - Spiramycin - Clindamycin
227
Name 2 tRNA inhibitors.
Puromycin, Mupirocin
228
What are polymyxins?
Antimicrobial drugs which act like detergent on membrane. Mainly topical use due to neurotoxicity and nephrotoxicity in systemic use
229
Define bactericidal and bacteriostatic.
Bactericidal (=kills) | Bacteriostatic (=inhibits growth)
230
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
231
What causes coagulative necrosis?
Due to inadequate blood supply. It's the most common type of necrosis
232
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.
233
What happens in liquefactive necrosis?
Dead tissue softens + appears liquid-like + pus develops. Basically the result is a 'goo' of cell material wo/ shape
234
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
235
What happens in caseous necrosis?
Cell's structure completely destroyed due to degradation by enzymes. The remaining tissue is white, soft, 'cheese-like'
236
What causes caseous necrosis?
Tuberculosis | Histoplasmosis
237
What is the most likely mode of transmission for dengue fever?
Biting insects
238
What is dengue fever?
An acute febrile disease w/ greatest in the tropics.
239
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.
240
What does rotavirus cause?
Severe diarrhoea in young children It's caused by faecal-oral transmission
241
What viruses is kaposi sarcoma associated with?
Human herpesvirus type 8 (HHV8) Kaposi sarcoma associated virus (KSHV)
242
What does HPV present like in women?
Blood-stained vaginal discharge + abnormal cervical mass
243
What cancer is Helicobacter pylori associated w/?
Stomach cancer | also commonly causes gastric ulcers
244
What do beta-lactam antibiotics inhibit the formation of?
Peptidoglycan cross-links in the bacterial cell wall --> rapid cellular death E.g. penicillin, cephalosporins
245
What antibiotic classes are 30s inhibitors?
Aminoglycosides e.g. gentamycin, tobramycin Tetracyclines e.g. oxytetracycline
246
What antibiotic classes are 50s inhibitors?
Macrolides
247
What's the difference between bactericidal + bacteriostatic antibiotics?
Bactericidal - Bacterial cell wall inhibition - Kill bacteria Bacteriostatic - Protein synthesis/reproduction - Help host defence take over-
248
Name 2 antibiotics that target bacterial folic acid metabolism.
Trimethoprim Sulfonamides
249
Name antibiotics that target cell wall synthesis.
Cycloserine Vancomycin (glycopeptide - only works on gram +ve) Bacitracin ``` Beta lactams: Penicillins Cephalosporins Monobactams Carbapenems ```
250
What do quinolones target?
DNA gyrase Inhibit enzymes topoisomerase II + IV (which are required for bacterial DNA replication, transcription, repair, stran supercoiling repair + recombination)
251
How do viruses replicate?
By self-assembly of individual components, including nucleic acid + capsid
252
What are some examples of enveloped viruses?
HIV | Influenza virus
253
Give examples of non-enveloped viruses.
Bacteriophage | Plant viruses
254
Which bacteria causes strep throat?
Streptococcus pharyngitis
255
List complications of shingles.
Post herpetic neuralgia Ophthalmic herpes zoster infection can cause blindness
256
Name 4 mediums via HIV can be transmitted.
Blood Semen Vaginal fluid Breast milk
257
What is the treatment for HIV?
HAART | Highly active anti-retroviral therapy
258
Give examples of protease inhibitors used in HAART
Indinavir, Ritonavir, Saquinavir, Lopinavir
259
What ribosomes do fungi have?
80s | They are eukaryotes
260
What in fungal cell walls are targetted w/ antifungals?
Chitin
261
Name 3 major classes of antifungals.
Polyenes Azoles Allylamines
262
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
263
What is MoA of azoles?
Interfere with fungal enzymes, thereby preventing ergosterol production for the cell membrane. E.g. ketoconazole
264
What is MoA of allylamines?
Interferes with other fungal enzymes, preventing ergosterol production e.g. flunarizine
265
Name 2 prophylaxis medications used to prevent malaria.
Doxycycline - cheapest Malarone - most expensive Mefloquine - combination med
266
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)
267
Name 5 types of vaccination.
``` Live attenuated Inactivated Subunit Toxoid Conjugate ```
268
What is live attenuated vaccinations?
Weakened version of living microbe that can't cause disease
269
What is inactived vaccines?
Microbes killed w/ chemicals, heat or radiation
270
What is subunit vaccines?
Include antigens (or epitopes) that best stimulate immune system
271
What is toxoid vaccines?
Formalin inactivated toxins used as vaccine
272
What is conjugated vaccines?
Specialised subunit vaccines where antigens are linked to polysaccharides
273
What are the challenges with live attenuated vaccinations?
Mutation | Storage
274
What are the challenges with inactivated vaccinations?
Weaker immune response | Need boosters
275
What are the challenges with subunit vaccinations?
Identifying specific antigen takes time
276
When are toxoid vaccinations used?
When main cause of illness is a bacterial toxin
277
When are conjugate vaccinations most effective?
Most effective for immature immune system of infants
278
Give examples of live attenuated vaccinations.
Measles, mumps, rubella (MMR combined vaccine) Rotavirus Smallpox Chickenpox Yellow fever
279
What type of vaccination is diphtheria + tetanus?
Toxoid
280
Give examples of conjugate vaccine.
H. influenzae type b | S. Pneumoniae
281
Give examples of inactivated vaccine.
Influenza Hep A Polio Rabies Cholera
282
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.
283
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.
284
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
285
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.
286
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.
287
Most cells spend the majority of time in what phase of the cell cycle? Give an exception.
Interphase part, except cancer cells
288
What is the G1 checkpoint?
Place where cell cycle is regulated. Apoptosis can occur if DNA is damaged
289
What doesn't occur at the G2 checkpoint if DNA is damaged?
Mitosis will not occur is DNA is damaged or not replicated
290
What is the M checkpoint?
Mitosis stops if chromosomes aren't properly aligned
291
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
292
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
293
What are cyclin dependent kinases?
Always present but the majority of the time are inactive. Activated by specific cyclins
294
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)
295
How do tumour suppressor genes work?
Halt cell cycle and/or cause apoptosis
296
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
297
What are oncogenes?
Genes that code for proteins that promote cell growth. They start as proto-oncogenes.
298
Give examples of oncogenes.
``` Src Ras Myc VEGR + EGFR BCR-Abl1 ```
299
What does Src code for?
A specific cytoplasmic tyrosine kinase and over activates it. Involved in sarcomas
300
What does Ras code for?
GTPase which in turn turns on other genes which cause cell division. Involved in colorectal cancer
301
What does Myc code for?
Transcription factor and is involved in Burkitt’s lymphoma
302
What are VEGF and EGFR?
Receptor tyrosine kinases. Bind to tyrosine kinase receptors and switches them permanently on so cell is constantly dividing.
303
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.
304
What was the first oncogene to be discovered in 1970?
Src
305
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
306
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
307
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
308
Define neoplasia.
New or abnormal growth of tissue which is irreversible
309
What are carcinomas?
Tumours of the epithelial tissue
310
What are sarcomas?
Tumuors of connective tissues
311
What are teratomas?
A tumour composed of tissues not normally present at the site (the site being typically in the gonads).
312
What are the 5 most common cancers in men?
``` Prostrate Lung Bowel Bladder Non-Hodgkin lymphoma ```
313
What are the 5 most common cancers in women?
``` Breast Lung Bowel Uterus Ovary ```
314
What are the 5 cancers in men with the highest mortality?
``` Lung Prostrate Bowel Oesophagus Pancreas ```
315
What are the 5 cancers in women with the highest mortality?
``` Lung Breast Bowel Pancreas Ovary ```
316
What are the 5 most common cancers in children?
``` Leukaemia Brain and other central nervous system tumours Neuroblastoma Wilms tumour Lymphoma ```
317
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.
318
What is lymphoma?
Cancer of the lymphatic system. There are 2 main types : - Hodgkin lymphoma - Non-Hodgkin lymphoma.
319
How do lymphoma present?
Lumps in lymph nodes, spleen, lower abdomen (MALT)
320
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
321
What is the difference between low + high grade lymphomas?
Low grade = mature cell malignancy High grade = immature cell malignancy
322
What is leukaemia?
Abnormal blood cells in peripheral blood
323
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)
324
Which type of leukaemia has the best prognosis?
CLL
325
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)
326
What does myeloid mean?
Everything other that B, T + NK cells. monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes or platelets
327
What are symptoms of leukaemia?
Related to decreased function of bone marrow so anemia (fatigue, SOB), increased infection, bruising and nosebleeds
328
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
329
How does myeloma present?
Bone pain Hypercalcaemia Night sweats Weight loss Extreme fatigue Renal impairment
330
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).
331
Why does myeloma present with renal impairment?
Because immunoglobulins (called paraproteins deposit in the kidneys).
332
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
333
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
334
What are risk factors for BCC?
Repeated UV exposure X-ray irradiation Chronic scarring Genetic Predisposition
335
What is hedgehog protein?
An oncogene which when mutated is overactivated + constantly stimulates cellular division. Happens in BCC
336
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
337
How is BCC managed?
Surgical excision | Radiotherapy
338
What is squamous cell carcinoma?
Malignant tumour of epidermal keratinocytes Compared to BC:C which is malignant tumour arising from basal keratinocytes of epidermis
339
What are risk factors for SCC?
- Excessive UV exposure - Pre-malignant skin condition - Chronic inflammation - Immunosuppression
340
How does SCC present?
Keratotic (scaly and crusty), ill-defined nodule which can ulcerate
341
How is SCC managed?
Surgical excision | Radiotherapy
342
Define malignant melanoma.
Invasive malignant tumour of epidermal melanocytes, has potential to metastasise
343
List 4 types of. malignant melanoma.
Superficial spreading Lentigo Acral lentiginous Nodular
344
What is lentigo malignant melanoma?
Nodular lesion arising in pre-existing lentigo maligna typically occurring in sun-damaged skin of face in elderly
345
What is nodular malignant melanoma?
Pigmented nodule that may grow rapidly + ulcerate - typically on trunks of males
346
What is acral lentiginous malignant melanoma?
Resembles lentigo but affects palms soles + nail beds
347
What is superficial spreading malignant melanoma?
Flat tumour w/ variable pigmentation and irregular edges. Most common in lower leg
348
How is malignant melanoma managed?
Surgical excision Radiotherapy Chemotherapy
349
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…..
350
What is cancer grading?
Based on what the cells look like under a microscope.
351
What is cancer staging?
Based on cancer spread.
352
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.
353
What is FAP?
Familial adenomatous polyposis
354
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
355
What is HNPPCC?
Hereditary non-polyposis colorectal cancer
356
Describe HNPPCC.
- Autosomal dominant - Early onset colorectal cancer (mid-forties) - Mainly right side colon cancer
357
HNPPCC increases itsk of other cancers such as?
Small bowel + gastric
358
Define polyp.
Small growth, usually benign and with a stalk, protruding from a mucous membrane
359
What is colorectal cancer?
An adenocarcinoma - arises from glandular cells in the mucosal lining of colon
360
What is radiation?
high energy photons, electrons, protons, neutrons or alpha particles
361
How does radiation work?
High energy damages DNA in cancer cells so the cells can no longer replicate indefinitely
362
Side effects of radiotherapy?
Tiredness, oedema, redness and mild burning. Chronic = infertility, increased risk of cancers in later life
363
What is the aim of chemotherapy?
Deplete tumour cells! Breaks between cycles give normal stem cells time to recover
364
What are alkylating agents?
Chemotherapy drug
365
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
366
Why are alkylating agents aggressive + toxic?
alkylating agents target all phases
367
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)
368
What do topoisomerase enzymes prevent?
DNA strands from becoming tangled
369
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
370
What is tubulin?
Main constituent of the microtubules of living cells.
371
Name 2 classes of tubulin binders.
Vinca alkaloids Taxenes
372
How do vinca alkaloids work?
Bind to tubulin and prevents the assembly of microfilaments so prevent cell division
373
Give examples of vinca alkaloids.
E.g. Vincristine, Vinblastine
374
GIve examples of topoisomerase I and Topoisomerase II inhibitors
Topoisomerase I inhibitors = Topotecan, Irinotecan Topoisomerase II inhibitors = Etoperside, Teniposide
375
How do taxenes work?
Binds to tubulin and prevents disassembly of it which also prevents cell division
376
Give examples of taxenes.
E.g. Paclitaxal, Docetaxal, Eribulin (doesn’t cause hair loss)
377
What phase of the cell cycle do antimetabolites effect?
S phase
378
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
379
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.
380
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)
381
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
382
GIve examples of kinase inhibitor.
Imatinib = CML Erlotinib = non-small cell lung cancer Lapatinib = advanced breast cancer
383
What do the suffix of kinase inhibitors mean?
``` ‘ab’ = monoclonal antibodies ‘ib’ = tyrosine kinase receptors ```
384
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
385
What are monofunctional alkylating agents?
React with only one strand of DNA
386
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.
387
What do DNA topoisomerases regulate?
They are enzymes that regulate DNA topology
388
What are DNA topoisomerases essential for?
They are essential for the integrity of the genetic material during transcription, replication, recombination processes.
389
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
390
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
391
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.
392
What is the following a definition of 'increase in cell size'?
Hypertrophy
393
What is the following a definition of 'increase in cell number'?
Hyperplasia
394
What is the following a definition of 'decrease in cell number and size'?
Atrophy
395
What is the following a definition of 'abnormal cytological appearance + tissue architecture'?
Dysplasia
396
What is the following a definition of 'conversion of one type of differentiated tissue into another'?
Metaplasia
397
What is the following a definition of 'uncontrolled focal proliferation of well differentiated cells'?
Benign
398
Name the 4 key targets of cell damage.
Mitochondria Plasma membrane Ionic channels in cell membranes Cytoskeleton
399
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)
400
Define karyolysis
Dissolution of cell nucleus Especially during mitosis
401
Define pyknosis
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
402
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.
403
What type of hypersensitivity reaction as the following examples of? Contact hypersensitivity, Insect venom, MS
Type IV Cell-mediated Non-Autoimmune
404
What type of hypersensitivity reaction as the following examples of? Systemic lupus Erythematosus, Rheumatoid arthritis
Type III Immune-complex Autoimmune
405
What type of hypersensitivity reaction as the following examples of? Asthma, Anaphylaxis, Eczema, Urticaria, Atopic dermatitis
Type I Anaphylactic Non-Autoimmune
406
What type of hypersensitivity reaction as the following examples of? Rheumatic fever, Myasthenia gravis, Thyroiditis
Type II Cytotoxic Autoimmune
407
Which types of hypersensitivity reactions are autoimmune?
Type 2. and 3 Cytotoxic and immune-complex
408
Which is cell-mediated hypersensitivity also known as?
Type 4
409
Which hypersensitivity reaction does this mechanism describe? 1. First exposure causes sensitisation to allergen 2. IgE Ab produced 3. IgE binds to FceRI receptors of mast cells and basophils 4. Mast cells and basophils degrandulate and release histamine, prostaglandins, leukotrines 5. This leads to bronchodilation, vascular permeability, mucus secretoin
Type 1 Anaphylactic Non-autoimmune
410
Which hypersensitivity reaction does this mechanism describe? 1. Antibody attacks self-cell-surface receptors 2. Damaging own cells via lysis 3. Damaged cells removed by phagocytosis
Type II Cytotoxic Autoimmune
411
Which hypersensitivity reaction does this mechanism describe? 1. Fist constact with antigen sensitises the body 2. Subsequent contact elicists reaction 3. TH1 relsease cytokines
Type IV Cell-mediated Non-Autoimmune
412
Which hypersensitivity reaction does this mechanism describe? 1. Antibody-antigen immune complexes deposite in orgnams 2. Complement activation leads to inflammatory damage It involves activation of PCs (dendritic cell) and priming of T helper cells
Type III Immune-complex Autoimmune
413
What genus bacteria cause leprosy?
Mycobacterium | M. leprae
414
What genus and species of bacteria causes whopping cough?
Bordetella B pertussis
415
List 5 genii of gram positive bacteria
``` Bacillus Clostridium Corynebacterium Mycobacterium Staphylococcus Streptococcus ```
416
Which genus and species is the Diphtheria causes bacterium ?
Corynebacterium | C. diphtheriae
417
Which diseases can H. influenzae bcaateria cause?
Acute respiratory tract infections, UTIs
418
What are epidermal ridges used for?
Fingerprints and footpirints
419
What is hyperplasia of the epidermis following pressure or friction known as?
A callus
420
List 4 causes of oedema
- Increased hydrostatic pressure - Decreased osmotic pressure - Lymphatic obstruction - Sodium retention
421
Name given to small haemorrhage (3-5mm), usually due to trauma or vasculitis
Purpura
422
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
423
What is a subcutaneous haematoma called?
Bruises / Ecchymosis
424
Describe the colour change of a bruise due to metabolism of haemoglobin to bilirubin + hemosiderin.
Red blue/green Yelow/brown
425
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
426
What are nearly all emboli?
Dislodged thrombi (thromboemobolism)
427
What is hyperaemia?
Excess blood in vessels
428
Is congesion and hyperaemia and active or passive process?
Congestion is passive Hyperaemia is active
429
List common sites of atheromas
- Aorta (especially abdominal) - Coronary arteries - Carotid - Cerebral - Leg arteries
430
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.
431
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)
432
What colour do gram positive organisms stain?
Gr+ stain blue/purple, thick peptidoglycan layer, teichoic acid present, cytoplasmic membrane
433
What colour do gram negative organisms stain?
Gr- stain pink/red, thin peptidoglycan layer (periplasm), LPS present, outer + cytoplasmic membrane
434
What are fastidious bacteria?
Bacteria that have a complex nutritional requirement + will only grow when specific nutrients are available
435
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
436
What does this describe ' uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids'?
Transformation - A horizontal gene transer method
437
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
438
What do the following bacteria have in common? Clostridium botulinum, Clostridium tetani, Vibrio cholera, Escherichia coli O157:H7
They are toxin producing pathogens, extracellular
439
What class are sulfonamides and trimethoprim?
Anti-metabolites that inhibit synthesis of nucleis acid precurors needed
440
What do beta-lactams target?
Peptidoglycan in both gram negative and positivebacteria
441
What do glycopeptides target?
Target gram +ve organisms because it can’t cross cell wall of gram-ve
442
How do polymyxins act on bacteria?
Act like detergent on membrane Cytotoxic effects
443
How are polymyxins used?
 Mainly topical usage; upon systemic administration poor distribution in tissues, neurotoxicity + nephrotoxicity
444
What do quinolones and rifamycins inhibit?
DNA replication (quinolones) mRNA synthesis (rifamycins)
445
Where to aminoglycosides and tetracyclines act?
Bacterial 30s ribosome inhibitors Protein synthesis inhibitors
446
List protein synthesis inhibitors of the 30s subunit.
- Tetracyclines - Aminoglycosides - Nitrofurans - Spectinomycin - Streptomycin - Gentamicin
447
List some protein synthesis inhibitors of the 50s subunit.
- Macrolides (erythromycin) - Chloramphenicol - Clindamycin - Lincomycin
448
List DNA gyrase inhibitors
Quinolones (nalidixic acid, ciprofloxacin) Novobiocin
449
Where do cephalosporins act
Bacterial cell wall synthesis
450
Which drugs disrupt folic acid metabolism in bacteria?
Trimethroprim and Sulfonamides
451
List 3 methods of heat loss
Conduction/convection - 60% Radiation - 25% Evaporation - 15%
452
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
453
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
454
Are the following an example of enveloped or naked viruses? HIV, ebola, influenza Rotavirus, norovirus
HIV, ebola, influenza (enveloped) Rotavirus, norovirus (naked)
455
All negative single stranded RNA are envolved. GIve examples of hese.
Influenza, mumps, measles, rabies, “Ebola”
456
Give examples of positive single strand RNA viruses
Poliovirus, dengue, hepatitis C
457
Which viruses spread via an enteric route (ingestion)?
Norovirus, rotavirus, hepatitis A + E
458
List viruses able to be spread from mother to child.
o Congenital infection: Cytomegalovirus, rubella, parvovirus, B19 o Perinatal: HIV, hepatitis B, herpes simplex
459
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
460
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
461
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
462
Function of alkylating agents.
Covalently bind to (alkylate) the nucleic acid bases of DNA and produce cellular death unless the damage is repaired
463
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
464
What class is procarbazine (used in Hodgkin's disease)
Monofunctional alkylating agent
465
What class are anthracyclines such as epirubicin?
Topoisomerase inhibitors
466
What class is nitrogen mustard cyclophosphamide (widely used in solid tumours + leukaemias)?
Bifunctional alkylating agents
467
What is Schistosoma?
A flatworm, most commonly hostested in a fresh water snail making bathing dangerous in natural lakes.
468
What does Leishmania parasite cause and what is it mainly spread by?
What does Leishmania parasite cause and what is it mainly spread by?
469
What does Plasmodium parasite cause?
What does Leishmania parasite cause and what is it mainly spread by?
470
Which parasite causes severe intrauterine infections in humans but the main host is cats?
Toxoplasma
471
What is the trichomoniasis?
Trichomoniasis is a sexually transmitted infection (STI) caused by a tiny parasite called Trichomonas vaginalis (TV). It's a protozoan
472
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.
473
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.
474
How are filaria spread?
These are spread by blood-feeding black flies and mosquitoes. This disease belongs to the group of diseases called helminthiases.
475
What is Entamoeba histolytica?
An anaerobic parasitic amoebozoa, part of the genus Entamoeba.
476
What parasite causes amoebiasis?
Entamoeba histolytica, a protozoan parasite
477
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.
478
What is American trypanosomiasis?
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by the protist Trypanosoma cruzi.
479
What is metaplasia?
Change of one cell type to another
480
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
481
The changes in the prostate fland in bengin enlarment is known as what?
Hyperplasia Individual cells growing in size
482
What is hypertrophy?
The enlargement of an organ or tissue from the increase in size of its cells.
483
Where is the main action of anti-diuretic hormone?
The collecting tubules
484
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.
485
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.
486
How does progressive emphysema affect the alveolar walls?
Leads to alveolar wall destruction
487
What is bronchiectasis associated with?
Bronchial dilation
488
What does the following describe ' 30 year old patient with daily production of sputum dating back to childhood'
Bronchiectasis
489
In pneumonia how is the alveoli affected?
Alveolar filling due to consolidatoin
490
What type of pathogen can grow and survive in the environment as well as in host?
Facultative pathogen (.e.g Bacillus anthracis - soil bacteria)
491
Are toxin producing pathogens extra or intracellular?
Extracellular
492
Give examples of toxin producing pathogens.
C. botulinum C. tetani V. cholera E. coli O157:H7
493
Give examples of intracellular pathogens
Salmonella serovar Typhimurium Listeria monocytogenes
494
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
495
What class are sulphonamides and trimethoprim?
Anti-metabolites
496
Name the antibacterial drugs which are structural analogues of folic acid. Work by inhibiting enzyme DHR to THFA
Trimethoprim
497
Beta-lactams and glycopeptides target what?
Peptidoglycan synthesis needed for bacteria cell walls (of gram positive and negative organisms)
498
Why do glycopeptides only target gram positive organisms?
Because they can't cross the cell wall of gram negative organisms
499
Which class of antibacterials act like detergent on membrane?
Polymyxins
500
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.
501
Which 2 classes of antibacterials target nucleic acid synthesis?
Quinolones and rigamycins
502
Which class of antibiotics inhibit DNA replication and which blocks mRNA synthesis?
DNA replication inhibition (quinolones) mRNA synthesis blocker (rifamycins)
503
Eukaryotes have which ribosomal subunits?
80s (40s and 60s subunits)
504
Bacteria have what ribosomal subunits?
70s (30s and 50s subunits)
505
What class of antibacterial do tetracyclines and aminoglycosides belong to?
30s inhibitors
506
Name 50s inhibitors
Chloramphenicol Erythromycin (macrolide) Clindamycin Oxazolidinones
507
Name 2 (bacterial) tRNA inhibitors
Puromycin | Mupirocin
508
What does antibiotic resistance refer to?
- Resistance relates to sensitivity to antibacterial agent at a certain concentration
509
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
510
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
511
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
512
What is core body temperature?
Temp of internal environment of body, inc. organs and blood
513
What is the difference between fever and hyperthermia?
Pyrogens must be present for fever Other than that both are around 38-40 degrees
514
Difference between hyperthermia and hyperpyrexia?
Hyperpyrexia is 40+ degrees and is life threatening Hyperthermia is 38-40 and not as life threatening
515
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
516
Causes of pyrexia
``` Infection Blood transfusion/iatrogenic pyrogens Inflammation Malignancy Hypothalamic insults ```
517
What is pyrexia usually due to?
Altered set point
518
When is core body temp normally the lowest?
6am when metabolism is slowest It has a circadian rhythm
519
Sweat is produced from which glands?
Eccrine sweat glands
520
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
521
What does viruses code for?
Few specific proteins (enzymes + capsid)
522
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
523
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
524
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)
525
What does transcription make?
+strand mRNA
526
What can be used to make mRNA?
-mRNA strand (complementary sequence) or DNA
527
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
528
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 ```
529
What are the 3 types or DNA viruses?
Negative single strand RNA Positive single strand RNA Double stranded RNA
530
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).
531
List 3 types of antivirals.
Nucleoside analogues Protease inhibtors Fusion inhibitors
532
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
533
Herpes viruses and EBV are examples of what type of virus?
DNA virus
534
Example of a double stranded RNA virus
Rotaviruses (gastroenteritis)
535
Example of a positive single stranded RNA virus
Poliovirus Dengue Hapatitis C
536
Example of a negative single stranded RNA virus
They are all enveloped | E.g. influenza. mumps, measles, radies, ebola
537
How are the following viruses transmitted? Rashes - measles, rubella, varicella Respiratory viruses - influenza, RSV, rhinovirus, coronavirusm parainfluenza
Aerosol (droplet)
538
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV) | Epstein–Barr virus (EBV)
539
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV) | Epstein–Barr virus (EBV)
540
Give examples of viruses spread via cutaeneous contact.
Human papillomavirus (HPV)
541
What is human herpesvirus 4 (HHV-4) also called?
Epstein–Barr virus (EBV)
542
Name diseases associated with HHV-5 (human herpes virus 5).
Glandular fever | Pneumonia
543
What is herpesvirus-5 (HHV-5) also known as?
(human) cytomegalovirus
544
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
545
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
546
How is norovirus, rotavirus and hepatitis A and E spread?
Enterically - ingestion
547
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
548
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
549
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.
550
What is human herpesvirus 3 (HHV-3) also called?
Varicella zoster virus - can cause chickenpox and shingles
551
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)
552
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
553
Name 3 blood borne percutaneous viruses
HIV, hepatitis B and C
554
Mode of transmission of arboviruses?
Percutaneous
555
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)
556
What are interferons?
Type of cytokine (protein)
557
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
558
In inflammation bradykinin and histamine stimulate nerve endings causing what?
Pain
559
What is pus?
Purulent exudate with dying cells and bacteria and antimicrobial products released by phagocytic cells
560
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
561
What is red hepatisation also known as?
Consolidation - Neutrophils and red cells enter alveolus - Fluid and cells srpread to adjacent alveoli leading to solidification
562
What type of vaccine is the smallpox and cowpox vaccines?
Live vaccines (naturally attenuated)
563
What vaccinations are live and artificially attenuated?
Oral polio, measles, mumps, rubella, yellow fever
564
Give 2 examples of non-living vaccines which are killed whle organisms
Rabies | Influenza
565
What type of vaccines are non-living, antigenic components of the organisms?
DTP -diphtheria, pertussis (whooping cough), tetanus. | Experimental (malaria, HIV)
566
How much do living and non-living vaccinations cost in general?
Living are cheaper than non-living which can be expensive
567
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
568
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
569
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 ```
570
List 4 diseases associated with HIV and AIDs.
Kaposi's sarcoma (HHV-8) CNS toxoplasmosis CMV retinitis Pneumocystis jirovecii pneumonia
571
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)
572
What causes Pneumocystis jirovecii pneumonia (PCP)?
Yeast-like pneumocystic iroveii
573
What does pneumocystis jirovecii cause?
Lung infection in people with a weak immune system Seehn especially in HIV/ADIS and cancer patients undergoing chemotherapy
574
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
575
What does the cell wall of fungi contain that antifungas target?
Chitin
576
Give 3 classes of antifungals
Polyenes Azoles Echinocandins
577
MoA of polyenes
Binds to sterols (fatty part) in fungal cell membranes
578
Examples of polyenes
Nystatin (topical use only) | Amphotericin B - systemic use, very broad spectrum, significant toxicity (renal damage + chills)
579
MoA of azoles and echinocandins
Azoles - inhibit lanosterol demetylase which interrupts ergosterol biosynthesis Echinocandins - inhibit glucan synthase which inhibits cell wall synthesis
580
Examples of azoles
Older drugs belong to imidazole group - clotrimazole Newer drugs to triazole group = fluconazole
581
Name the 4 species of malaria that can infect humans
P. falciparum (most virulent), P. vivax, P. ovale, P. malariae.
582
List classes of anti-parasite drugs used for P. falciparum
Quinolones Antifolates Artemisinin compounds
583
During a blood meal, a malaria-infected female Anopheles mosquito inoculates what into the human host?
Sporozoites
584
Quinine, choloroquine, amodiaquine, primaquine are examples of what class of anti-parasite drugs?
Quinolones
585
Sulphonamides, pyrimethamines, proguanil, chlorproguanil are examples of what class of anti-parasite drugs?
Anti-folates
586
Artesunate, artemether, dihydroartemisinin are examples of what class of anti-parasite drugs?
Artemisinin compounds (new antimalarials)
587
What is sleeping sickness also known as?
African trypanomiasis
588
African trypanomiasis is caused by protozoa of the species Trypanosoma brucei. Which 2 types infect humans?
T. b. rhodesiense | T. b. gambiense
589
Which parasite transmits African trypanomiasis?
Tsetse fly
590
What are these drugs used for - pentamidine, suraminem melaroprol?
African trypanomiasis
591
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
592
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"
593
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)
594
Which parasite carries and spreads leishmaniasis?
Sandfly
595
Which parasite carries and spreads toxoplasmosis?
Cats (faeces) or we can eat cysts in undercooked meat
596
Treatment for toxoplasmosis
Pyrimethamine
597
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
598
What does Entamoeba histolytica cause?
Amoebiasis which is often asymptomatic but can cause dysentery and invasive extra-intestinal disease
599
List 3 heliminthic parasite examples which infect by larvae or eggs.
Tapeworms: cestodes Flukes: trematodes Round worms: nematodes
600
Which drugs are used against roundworms?
Mebendazole
601
Which drugs are used against tapeworms?
Albendazole
602
What is the word tumour used synonymously with?
Neoplasm
603
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)
604
What regulates the cell cycle?
Cyclin-dependent kinases + their inhibitors
605
List 4 classes of genes important in cancer.
Proto-oncogenes Tumour suppressor genes Genes that control programmed apoptosis DNA repair genes
606
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)
607
What is the proportion of sporadic to inherited cacner mutations?
Most cancers are sporadic, a minority 2-3% are inherited
608
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
609
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
610
Give examples of radiation that cause cancer
 UV rays – SCC, BCC, melanoma |  Ionising radiation (electromagnetic + particulate) – Leukaemia, Solid organ malignancies (thyroid)
611
List microbial organisms which can cause cancer.
HPV EBV HepB H. pylori
612
List types of cancer EBV can cause
Burkitt lymphoma B-cell lymphoma (IC people) Nasopharyngeal carcinoma Hodgkin lymphoma
613
What is HPV and how can it cause cancer?
Oncogenic DNA virus that interacts with cell cycle proteins pRb and p53 (tumour suppressor genes)
614
What can cause Hepatocellular carcinoma (HCC)?
Hepatitis B
615
Which cancers is H. pylori responsible for?
Gastric lymphoma, Gastric carcinoma
616
What is metaplasia?
Reversible transformation of one type of mature fully differentiated cell into a different fully differentiated cell type
617
2 common types of metaplasia
Squamous metaplasia | Glandular metaplasia
618
Where does squamous metaplasia happen?
Happens in ducts (salivary, pancreas – presence of stones) that are chronically inflamed
619
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
620
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)
621
Metaplasia can lead to dysplasia which can lead to what?
Neoplasia
622
What is a teratoma and where does it common arise?
Tumour containing elements of all 3 embryological germ cell layers Gonads
623
Which types of cancer typically have only circulating cells?
Leukaemias
624
Which diseases typically present with tumour masses?
Lymphoma
625
What is atopic eczema?
Chronic inflammatory itchy skin condition which has a genetic component
626
What condition does this describe - chronic inflammatory skin disease due to hyperproliferation of keratinocytes + inflammatory cell infiltration?
Psoriasis
627
what are melanocytes found?
Basal epidermis
628
Function of melanocytes
Deposit melanin from melanosomes over nuclei of basal cells The melanin forms a barrier over basal cell nuclei
629
What is the absence of melanin in skin due to an autoimmune condition attacking melanocytes called?
Vitiligo
630
Name given to macrophages in dermis.
Langerhans cells
631
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
632
Skin conditions caused by S. aureus
Impetigo, Boils, Cellulitis, Folliculitis
633
Where can Group A beta-haemolytic streptococcus bacteria cause skin infections?
Throat + skin
634
Skin cancer is divided into non-melanoma and melanoma. List the 2 non-melanomas.
Basal cell carcinoma - best to have Squamous cell carcinoma
635
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)
636
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)
637
Shedding or cornfield layer? ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
A. Scaling
638
Loss of superficial epidermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
C. Erosion
639
Leakage of blood into dermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
E. Bruising
640
Loss of epidermis and papillary layer of dermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
Ulcer
641
Hyperplasia of epidermis following pressure or friction ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
Callus
642
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.
643
Mnemonic to remember -ssRNA and +ssRNA viruses
``` -ssRNA : My Mum Is Right Measles Mumps Influenza Rubella ``` +ssRNA: He Parked Diagonally Hep C Polio Dengue
644
Which gram bacteria have endotoxins?
Gram negative Endotoxin = the glycoproteins on the LPS Gram positive doesn't a have LPS
645
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?)
646
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