9 Flashcards

1
Q

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

A

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

16 and 18 - high risk - cause cervical cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Physiological functions of skin?

A
  • Vitamin D synthesis
  • Temperature regulation
  • Immune defence
  • Protection against UV radiation
  • Sensation and nerve signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the layers of the epidermis?

A
  • Stratum corneum
  • (Stratum lucidum) - only found in thick skin llike palms
  • Stratum granulosum
  • Stratum spinosum
  • Stratum basale
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which cells would you find in the stratum basale?

A
  • Keratinocytes - synthesise keratin
  • Melanocytes - synthesise melanin
  • Merkel cells - touch sensitive cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which cell would you find in the stratum spinosum?

A

Langerhan cells

These are found in other epithelial layers but highest concentration found here

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which cell would you find in the stratum granulosum?

A

Keratinocytes continuing their journey

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which cell would you find in the stratum corneum?

A

Corneocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which 2 parts make up the dermis?

A

Thin papillary layer and thick reticular layer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Necrosis associated with bacterial infections?

A

Liquefactive (aka Colliquativ )

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What causes gout?

A

Xanthine oxidase overactivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where is most likely to suffer haemorrhagic necrosis?

A
  • Testis - testicular torsion
  • Spleen
  • Lung
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where are you most likely to find fat necrosis?

A

Pancreas - pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

An example of gummatous necrosis?

A

Syphilis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

List cytoplasmic changes in necrosis.

A
  • Increased eosinophilia

- Swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are nuclear changes in necrosis?

A

Pyknosis - dark clumps
- irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis

Karyolysis - dissolution of cell nucleus

Karyorrhexis - fragmentation of nucleus whereby its chromatin is. irregularly distributed throughout the cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is an obligate anaerobe?

A

Die in the presence of oxygen - Klebsiella Pneumoniae

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the structure of a gram negative bacteria.

A
  • Thin peptidoglycan layer

- LPS outer membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What can prokaryotes be divided into?

A

Bacteria and archaea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the structure of gram positive bacteria.

A

Thick peptidoglycan layer

No outer membrane

Teichoic acid - PAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Biochemical markers of cell death.

A

ALT - liver enzyme

Troponin - cardiac myocytes

Creatinine kinase - muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

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

A

Gr+

Clostridium Difficile + Clostridium Botulinum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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 Transduction Conjugation Transposons
27
Describe transformation.
Small fragments of DNA taken up by the cell.
28
Describe transduction
Phage mediate transfer of non-phage DNA between bacteria
29
Describe transposons.
Jumping genes - mobile genetic units integrate into genome
30
Describe conjugation.
Bacteria having sex - pili join to create a channel
31
What are the phases of growth of a bacteria?
1. Lag 2. Exponential - once they have enzyme moves quickly 3. Stationary - nutrient deficit 4. Death - lysing
32
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
33
Which microbes would you find on the skin?
- Staphylococcus aureus - Staphylococcus epidermidis - Lactobacillus species
34
Which microbes would you find in the upper respiratory tract?
- Staphylococcus aureus - Staphylococcus epidermidis - Streptococcus pneumoniae - Haemophilus influenzae
35
Which areas of the body should be microbe free?
- Blood - CSF - Urine
36
What is an opportunistic pathogen and an example of one?
Normal flora that only cause disease when introduced to unprotected sites. Pseudomonas aeruginosa
37
What is a strict pathogen and an example?
Neisseria gonorrhoea only associated with human disease
38
Give some virulence factors.
Adhesins - pili, fimbriae, outer membrane protein Flagella - penetrate mucus Capsule Toxins
39
What is an exotoxin?
- Protein released extracellularly | - Protein destroyed by heat
40
What is a toxoid?
Inactivated toxin useful as vaccine
41
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
42
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
43
What is the virion in enveloped virus?
Envelope and nucleocapsid
44
What is the virion in naked virus?
Nucleocapsid
45
What does the H and N stand for in influenza virus e.g. H1N1
``` H = hemagglutinin N = neuraminidase ```
46
What are features of enveloped virus?
- Spread through large droplets - Sensitive to detergents - Must stay wet to remain infectious E.g. Ebola, HIV, influenza
47
What are features of naked virus?
- More stable in environmental stress e.g. acid, temperature, drought - Spreads more easily - Survived gut - Norovirus and rotavirus
48
Infectious cycle of virus
- Attach - Penetrate - Uncoat - Replicate - Assemble - Release
49
Example of +ssRNA
- Hep C - Polio - Dengue
50
Example of dsRNA
Rotavirus
51
Example of -ssRNA
- Measles - Mumps - Influenza - Rabies
52
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.
53
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
54
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
55
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.
56
List 3 diseases from bites.
Rabies, malaria, dengue
57
Give a blood borne disease.
Malaria Syphilis Brucellosis But Hepatitis B (HBV), Hepatitis C (HCV), and the Human Immunodeficiency Virus (HIV) are the 3 diseases specifically addressed by the bloodborne pathogens standard
58
Name a mucosal contact disease.
Herpes simplex
59
Name a cutaneous contact disease
Papillomavirus
60
What is herpes labialis?
From latent site in trigeminal ganglia and also pharynx Usually herpes simplex 1 Coldsore
61
List types of herpes.
HHV-1 (HSV1) - Herpes simplex virus 1 HHV-2 (HSV2) - Herpes simplex virus 2 HHV-3 (VZV) - Varicella sorter virus HHV-4 (EMV) - Epstein-Barr virus HHV-5 (CMV) - Cytomegalovirus HHV-6 HHV-7 HHV-8 (KSHV) - Kaposi’s sarcoma-asscoiated virus
62
What is the arachidonic acid pathway?
Phospholipids --> arachidonic acid --> PGH2 --> PGE2 --> PE1, PE2, PE3, PE4
63
Which prostaglandin is responsible for pain?
P3
64
Which prostaglandin responsible for inflammation?
P4
65
What is reye's syndrome?
Can cause fatty liver and severe encephalopathy Reye's syndrome seems to be triggered by using aspirin to treat a viral illness or infection — particularly flu (influenza) and chickenpox — in children and teenagers who have an underlying fatty acid oxidation disorder.
66
What is the difference between hyperpyrexia and fever?
Hyperpyrexia is malignant - over 40 degrees
67
What is the difference between chronic and acute inflammation?
Acute - mainly neutrophils | Chronic - mainly macrophages
68
What are the microvascular changes in acute inflammation?
Oedema Generation of inflammatory exudate May lead to pus
69
Why is pus yellow?
It contains myeloperoxidase which is yellow
70
What are the 2 major pathways of arachidonic acid production?
Cyclo-oxygenase - produces prostaglandins Lipo-oxygenase - produces leukotrienes
71
What are the cellular mediators of acute inflammation?
Platelets - serotonin Mast cells - histamine Inflammatory cells
72
Pros of living vaccines
Living - You get the infection - Naturally attenuated - Not fully virulent - Single dose - Cheaper than non-living - May return to virulence
73
Plasma mediators of acute inflammation?
- Kinins - Clotting cascade - Complement inflammation
74
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.
75
What is a giant cell?
Fusion of macrophages
76
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.
77
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
78
What s a non-living vaccine?
- Not as effective as living vaccine | - Multiple doses may be required
79
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
80
What is a subunit vaccine?
Where you break apart an organism and vaccinate with part that is most likely to induce an immune response
81
Why does a subunit vaccine require adjuvant?
Because it produces a low immune response
82
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
83
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
84
List features of fungi?
- Eukaryote - Chitin cell wall - 80s ribosomes - Reproduction may be sexual or asexual - Has cell bound organelles
85
How does mold grow?
Formation of filaments - these are hyphae Entangled mass of hyphae form mycelium (network of white filaments)
86
How does mold reproduce?
Asexual - production of conidia which can develop within hyphae Sexual reproduction through sexual spores
87
Which mold can cause bronchospasm in humans?
Aspergillus
88
Describe yeasts.
- Single-cell organisms - Round or ovoid - Reproduce by budding
89
Give an example of superficial mycoses?
Tinea (ringworm) Tinea pedis - dermatophyte infection of the soles of the feet and the interdigital spaces.
90
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
91
What can dermatophytes use as a nutrient?
Keratin as they produce keratinase
92
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.
93
What are the 3 stages of malaria?
Exo-Erythrocytic (liver) cycle Erythrocytic cycle Sporogonic cycle
94
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
95
Which stage of malaria life cycle is associated with disease?
Erythrocytic cycle
96
Which disease does South American Trypanosomiasis give rise to?
Chagas disease - megacolon
97
What can amoebiasis cause?
Dysentery
98
4 classes of normal regulatory genes?
Proto-oncogenes - growth promoting Tumour suppressor genes - growth inhibiting Genes that control apoptosis Genes that repair DNA
99
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
100
What is the transmission cycle of roundworm?
Faecal oral | Common in pets such as dogs
101
What does hookworm do?
Penetrates the skin and migrates from the skin into the lungs into the trachea and then swallowed again
102
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
103
What are proto-oncogenes?
They code for oncoprotein which positively regulate cell growth
104
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
105
Where is toxoplasmosis normal life cycle?
Cats
106
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
107
What is an intermediate host of schistosomiasis?
Snails
108
What is elephantiasis due to?
Blocked lymphatics
109
What would you use to treat Giardiasis?
Metronidazole
110
3 major categories of helminth parasites?
- Tapeworms - Flukes - Roundworms
111
What is tumour grading based on?
Level of differentiation
112
What does TNM staging stand for?
T - primary tumour (T0-T4) N - lymph node status (N0-N3) M - metastasis (M0-M1)
113
What staging is used for colorectal cancer?
Duke's staging (A to D)
114
List Dukes A to Dukes D
Dukes A - limited to bowel wall Dukes B - beyond bowel wall Dukes C - nodal metastasis Dukes D - distant metastasis
115
What are the hormonal effects of neoplasm?
Endocrine insufficiency - destruction of glands Endocrine elaboration - mainly in benign tumours e.g. hypercalcemia in parathyroid adenoma
116
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
117
How does level of differentiation relate to aggressiveness?
Less differentiated tend to be more aggressive neoplasms
118
What is cachexia?
Wasting syndrome - catabolic state resulting in profound loss of body fat and mass, weakness and anorexia
119
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
120
What happens at G1?
- Increase in cell contents | - Some cells arrest at this phase G0
121
What happens at S?
- Replication of DNA | - Centrosome duplicates
122
What is the purpose of the DNA damage checkpoint?
Scans DNA and if there's a problem stops the cell cycle
123
When is the transition point in mitosis?
Between metaphase and anaphase
124
What is the purpose of the DNA replication checkpoint?
Ensures DNA is completely replicated
125
What are gatekeeper genes?
p53 and Rb Their loss leads to excessive proliferation
126
Describe basal cell carcinoma?
Slow growing cancer that rarely metastasises
127
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
128
What are the different types of basal cell carcinoma?
- Nodular - Morphoeic - Superficial
129
Which proteolytic enzymes does apoptosis involve?
Caspases
130
What is p21?
A CDK inhibitor
131
What levels are p53 normally kept at?
Low levels
132
What are caretaker genes?
Maintain genetic stability e.g. gene repair BRCA 1 and 2
133
What can maintain telomere length and where?
Telomerase enzymes in stem cells and germ cells
134
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
135
What is a vesicle?
Small blister less than 5mm
136
What is a bulla?
A large blister greater than 5mm in diameter
137
What is a nodule?
Small, solid elevation of skin but bigger than 5mm (similar to a papule but bigger)
138
What is a papule?
Small, solid elevation of skin (less than 5mm in diameter) (basically a small raised area of skin)
139
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
140
What is a pustule?
Visible collection of free pus in a blister
141
What is a cyst?
Nodule consisting of an epithelial-lined cavity filled with fluid
142
What is a macule?
Flat mark on skin.
143
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)
144
Which cancer is associated with dysfunction in the hedgehog pathway?
Basal cell carcinoma
145
How can basal cell carcinoma metastasise?
If it gets into your brain - can go through the CSF
146
What condition is a macule hypopigmented in?
Vitiligo
147
What is a scale?
Accumulation of thickened stratum corneum in the form of readily detached fragments
148
Which drug would give you a reaction which looks like someone has whipped themselves?
Bleomycin - anticancer drug
149
Which bacteria heavily colonises atopic skin?
Staphylococcus aureus
150
Which bacteria most commonly cause cellulitis?
Staphylococcus aureus Streptococci
151
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
152
List the precancerous lesions in squamous cell carcinoma?
Actinic keratosis Cutaneous horns of keratin Chronic ulcers Bowen's disease
153
What is impetigo?
Bacterial skin infection caused by S. aureus or S. pyogenes
154
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),
155
What does calcium overload lead to?
Irreversible cell damage
156
Why is pathology a dynamic process?
Initial stages are potentially reversible. After necrosis and inflammation, pathology irreversible.
157
What is cellular level necrosis?
Normal, pyknosis, karyolysis, karyorrhexis
158
What is tissue level necrosis?
Coagulative necrosi (can't happen in brain) Liquefactive necrosis (can happen in brain) Caseating necrosis (unusual form)
159
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
160
Which 2 interleukins in particular, can increase the hypothalamic set point?
IL-1 | IL-6
161
If room temperature is greater than that of the skin, how does the body cool down?
Evaporation (sweating)
162
Thermoregulation is controlled by which area of the anterior hypothalamus?
Preoptic
163
During acute infections, where is EBV shed?
Saliva
164
To increase the BMR which hormone does the hypothalamus release?
TRH - thyrotropin releasing hormone
165
To increase the BMR which hormone does the pituitary gland release?
TSH - thyroid stimulating hormone
166
What is the hormone T4 also known as?
Thyroxine
167
What is the hormone T3 also known as?
Triiodothyronine
168
What layer is present in thick skin but not thin skin?
Stratum lucidum
169
Which stages of pathology is irreversible?
After necrosis and inflammation pathology irreversible
170
What are congenital diseases?
Genetic or non-genetic Present from birth
171
Which antibody is involved in a type 2 cytotoxic hypersensitivity reaction?
IgG or IgM
172
Which 2 hypersensitivities are non-autoimmune?
Type 1 | Type 4
173
What type of cells make up the most superficial layers of the epithelium?
Cornified cells in the scontratum corneum
174
Which layer is mainly responsible for the barrier function of skin?
Cornified layer
175
Which features make the stratum cornified a good barrier?
- Lipids - Insoluble proteins (forms hydrophobic layer) - Strong filaments (linked by cell-cell junctions)
176
Which cells are the most abundant in the epidermis?
Keratinocytes
177
What is the function of keratinocytes?
Produce keratin and lamellar granules (waterproof sealant)
178
Which cells are responsible for immune defence against surface pathogens in the epidermis?
Langerhans cells
179
Where are merkel cells found?
In basal layer In associated w/ nerve fibres responsible for fine touch sensation
180
What is scaling?
Imbalance between cell renewal and cell loss in the epidermis
181
What cause skin blisters?
Breakage of cell-cell junctions
182
Which layer is important in wound repair of superficial cuts?
Basal layer Stratum basale
183
At which epidermal layer are cells no longer capable of cell division?
Stratum spinosum
184
Name 4 liquid filled lesion types.
Blister, vesicle, bulla, pustule
185
Name 4 types of solid lesions?
Papule, plaque, nodule, wheal
186
Name 4 types of skin colour?
Macule, patch, naevis, erythema
187
What is an ulcer?
Loss of epidermis and papillary layer of dermis
188
What is a callus?
Hyperplasia of epidermis following pressure or friction
189
What is erosion?
Loss of superficial epidermis
190
List 5 types of oedema.
``` o Increased hydrostatic pressure o Decreased osmotic pressure o Lymphatic obstruction o Sodium retention o Inflammation ```
191
List 3 causes of water extravasation from the vasculature?
⁄ Increase in vascular volume/pressure ⁄ Decreases in plasma protein content ⁄ Changes in endothelial cell function
192
What is thrombosis?
Formation of blood clot inside a blood vessel, obstructing flow of blood through circulatory system.
193
What is .a thrombi detached from vessel wall known as?
Emboli
194
What 3 things cause thrombi?
``` o Endothelial injury o Abnormal blood flow o Hypercoagulability (blood composition) ```
195
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.
196
What reactive hyperaemia?
Local vasodilation in response to ischaemia
197
What is active hyperaemia?
Increased blood flow/vasodilation in response to period of activation (increased blood in skeletal muscle during exercise)
198
What is systemic congestion often associated with?
HF | It can lead to widespread oedema
199
What is local congestion caused by?
COmpression of blood vessels
200
What 3 things does fluid homeostasis require?
¥ Vessel wall integrity ¥ Osmolarity ¥ Maintenance of intravascular pressure
201
What could changes in fluid homeostasis lead to?
Extravasation across the vascular wall or Reduction of blood fluidity
202
What is extravasation?
movement of water (or blood) across the vascular wall
203
Define shock.
Lack of blood flow (systemic hypoperfusion) Leading to reduced nutrient delivery
204
What is uncontrolled systemic reaction to infection called?
Sepsis
205
List 5 types of shock.
``` Cardiogenic shock Hypovolemic shock Septic shock Neurogenic shock Anaphylactic shock ```
206
What does an atheroma contain?
Macrophages, debris (lipids, calcium, fibrous connective tissue)
207
What is purpura?
o Small haemorrhage (3-5mm), usually due to trauma or vasculitis.
208
Where does blood clots form?
Within blood vessel | Tunica intima and media
209
What causes pseudo-aneurysms.
Arterial traumaI. E.I. use of artery for injection
210
What is fastidious bacteria?
Bacteria that have a complex nutritional requirement and will only grow when specific nutrients are available.
211
What is bacteria having sex known as?
Conjugation A conjugative plasmid moves from one bacterium to another; requires cell-to-cell contact
212
What is bacterial transformation?
Uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids.
213
What is bacterial transduction?
Transfer of DNA from 1 bacterium into another via bacteriophages (bacterial virus that contains DNA)
214
Which areas of the body should be microbe free?
- Fluids: blood, CSF, urine | - Tissue/organs: muscles, glands, brain, inner ear…
215
What is the infection dose?
Quantity of pathogen required to cause an infection or immunological response in a susceptible host.
216
Which bacteria reside in the upper respiratory tract?
H. influenza S. epidermidis S. aureus S. pneumoniae
217
Which bacteria reside in the skin?
S. epidermidis S. aureus Lactobacillus
218
What is an enterotoxin?
The group of exotoxins that act on the small intestine
219
What is an exotoxin?
Proteins that are released extracellularly produced by certain Gr+ and Gr- species
220
Give examples of enterotoxins
C. difficile toxin A Cholera toxin E. coli toxins
221
What is an endotoxin?
LPS of Gr- bacteria
222
Are exotoxins or endotoxins heat labile?
Exotoxins (destroyed by heat) Endotoxins heat stable because they aren't proteins (they are cell bound)
223
Is S. pneumoniae gram + or -?
Gram+, cocci
224
What are type III secreted molecules?
factors which are secreted by bacterium directly into host cell, destroying the cell.
225
What makes up the innate immune system?
- Phagocytes – Macrophages, polymorphonuclear granulocytes | - Soluble factors – Complement, lysozyme
226
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)
227
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 ```
228
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.
229
Are toxin producing pathogens extra- or intra- cellular?
Extracelular
230
What does selective toxicity exploit?
Difference between prokaryotic and eukaryotic cells
231
What are anti-metabolites?
Metabolic analogues inhibit synthesis of nucleic acid precursors E.g. sulfonamides and trimethoprim
232
What does beta-lactams target?
Peptidoglycan in both gram –ve and +ve bac (penicillin, cephalosporins) • Inhibit enzymes (PBPs) required for last step: transpeptidation.
233
Which class of antibacterials target gram+ organism?
Glycopeptides Because it can't cross cell wall of gram-ve
234
What do quinolones inhibit?
inhibit DNA replication ♣ Specifically, enzymes required to untangle DNA: gyrases; topoisomerases
235
What do rifamycins block?
Blocks mRNA synthesis ♣ E.g. ciprofloxacin ♣ Higher affinity to TMP for the bacterial enzyme than for the human enzyme.
236
Which ribosomal subunits do prokaryotes posses?
70s (30s + 50s subunits)
237
What ribosomes do eukaryotes have?
80s (40s + 60s subunits)
238
Name 2 groups of 30s inhibitors.
Aminoglycosides Tetracyclines
239
Give an example of an aminoglycoside.
Gentamycin
240
List some 50s inhibitors
Oxazolidinones Lincosamides: - Clindamycin - Lincomycin - Pirlimycin Macrolide: - Azithromycin - Erythromycin - Clarithromycin - Spiramycin - Clindamycin
241
Name 2 tRNA inhibitors.
Puromycin, Mupirocin
242
What are polymyxins?
Antimicrobial drugs which act like detergent on membrane. Mainly topical use due to neurotoxicity and nephrotoxicity in systemic use
243
Define bactericidal and bacteriostatic.
Bactericidal (=kills) | Bacteriostatic (=inhibits growth)
244
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
245
What causes coagulative necrosis?
Due to inadequate blood supply. It's the most common type of necrosis
246
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.
247
What happens in liquefactive necrosis?
Dead tissue softens + appears liquid-like + pus develops. Basically the result is a 'goo' of cell material wo/ shape
248
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
249
What happens in caseous necrosis?
Cell's structure completely destroyed due to degradation by enzymes. The remaining tissue is white, soft, 'cheese-like'
250
What causes caseous necrosis?
Tuberculosis | Histoplasmosis
251
What is the most likely mode of transmission for dengue fever?
Biting insects
252
What is dengue fever?
An acute febrile disease w/ greatest in the tropics.
253
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.
254
What does rotavirus cause?
Severe diarrhoea in young children It's caused by faecal-oral transmission
255
What viruses is kaposi sarcoma associated with?
Human herpesvirus type 8 (HHV8) Kaposi sarcoma associated virus (KSHV)
256
What does HPV present like in women?
Blood-stained vaginal discharge + abnormal cervical mass
257
What cancer is Helicobacter pylori associated w/?
Stomach cancer | also commonly causes gastric ulcers
258
What do beta-lactam antibiotics inhibit the formation of?
Peptidoglycan cross-links in the bacterial cell wall --> rapid cellular death E.g. penicillin, cephalosporins
259
What antibiotic classes are 30s inhibitors?
Aminoglycosides e.g. gentamycin, tobramycin Tetracyclines e.g. oxytetracycline
260
What antibiotic classes are 50s inhibitors?
Macrolides
261
What's the difference between bactericidal + bacteriostatic antibiotics?
Bactericidal - Bacterial cell wall inhibition - Kill bacteria Bacteriostatic - Protein synthesis/reproduction - Help host defence take over-
262
Name 2 antibiotics that target bacterial folic acid metabolism.
Trimethoprim Sulfonamides
263
Name antibiotics that target cell wall synthesis.
Cycloserine Vancomycin (glycopeptide - only works on gram +ve) Bacitracin ``` Beta lactams: Penicillins Cephalosporins Monobactams Carbapenems ```
264
What do quinolones target?
DNA gyrase Inhibit enzymes topoisomerase II + IV (which are required for bacterial DNA replication, transcription, repair, stran supercoiling repair + recombination)
265
How do viruses replicate?
By self-assembly of individual components, including nucleic acid + capsid
266
What are some examples of enveloped viruses?
HIV | Influenza virus
267
Give examples of non-enveloped viruses.
Bacteriophage | Plant viruses
268
Which bacteria causes strep throat?
Streptococcus pharyngitis
269
List complications of shingles.
Post herpetic neuralgia Ophthalmic herpes zoster infection can cause blindness
270
Name 4 mediums via HIV can be transmitted.
Blood Semen Vaginal fluid Breast milk
271
What is the treatment for HIV?
HAART | Highly active anti-retroviral therapy
272
Give examples of protease inhibitors used in HAART
Indinavir, Ritonavir, Saquinavir, Lopinavir
273
What ribosomes do fungi have?
80s | They are eukaryotes
274
What in fungal cell walls are targetted w/ antifungals?
Chitin
275
Name 3 major classes of antifungals.
Polyenes Azoles Allylamines
276
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
277
What is MoA of azoles?
Interfere with fungal enzymes, thereby preventing ergosterol production for the cell membrane. E.g. ketoconazole
278
What is MoA of allylamines?
Interferes with other fungal enzymes, preventing ergosterol production e.g. flunarizine
279
Name 2 prophylaxis medications used to prevent malaria.
Doxycycline - cheapest Malarone - most expensive Mefloquine - combination med
280
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)
281
Name 5 types of vaccination.
``` Live attenuated Inactivated Subunit Toxoid Conjugate ```
282
What is live attenuated vaccinations?
Weakened version of living microbe that can't cause disease
283
What is inactived vaccines?
Microbes killed w/ chemicals, heat or radiation
284
What is subunit vaccines?
Include antigens (or epitopes) that best stimulate immune system
285
What is toxoid vaccines?
Formalin inactivated toxins used as vaccine
286
What is conjugated vaccines?
Specialised subunit vaccines where antigens are linked to polysaccharides
287
What are the challenges with live attenuated vaccinations?
Mutation | Storage
288
What are the challenges with inactivated vaccinations?
Weaker immune response | Need boosters
289
What are the challenges with subunit vaccinations?
Identifying specific antigen takes time
290
When are toxoid vaccinations used?
When main cause of illness is a bacterial toxin
291
When are conjugate vaccinations most effective?
Most effective for immature immune system of infants
292
Give examples of live attenuated vaccinations.
Measles, mumps, rubella (MMR combined vaccine) Rotavirus Smallpox Chickenpox Yellow fever
293
What type of vaccination is diphtheria + tetanus?
Toxoid
294
Give examples of conjugate vaccine.
H. influenzae type b | S. Pneumoniae
295
Give examples of inactivated vaccine.
Influenza Hep A Polio Rabies Cholera
296
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.
297
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.
298
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
299
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.
300
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.
301
Most cells spend the majority of time in what phase of the cell cycle? Give an exception.
Interphase part, except cancer cells
302
What is the G1 checkpoint?
Place where cell cycle is regulated. Apoptosis can occur if DNA is damaged
303
What doesn't occur at the G2 checkpoint if DNA is damaged?
Mitosis will not occur is DNA is damaged or not replicated
304
What is the M checkpoint?
Mitosis stops if chromosomes aren't properly aligned
305
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
306
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
307
What are cyclin dependent kinases?
Always present but the majority of the time are inactive. Activated by specific cyclins
308
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)
309
How do tumour suppressor genes work?
Halt cell cycle and/or cause apoptosis
310
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
311
What are oncogenes?
Genes that code for proteins that promote cell growth. They start as proto-oncogenes.
312
Give examples of oncogenes.
``` Src Ras Myc VEGR + EGFR BCR-Abl1 ```
313
What does Src code for?
A specific cytoplasmic tyrosine kinase and over activates it. Involved in sarcomas
314
What does Ras code for?
GTPase which in turn turns on other genes which cause cell division. Involved in colorectal cancer
315
What does Myc code for?
Transcription factor and is involved in Burkitt’s lymphoma
316
What are VEGF and EGFR?
Receptor tyrosine kinases. Bind to tyrosine kinase receptors and switches them permanently on so cell is constantly dividing.
317
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.
318
What was the first oncogene to be discovered in 1970?
Src
319
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
320
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
321
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
322
Define neoplasia.
New or abnormal growth of tissue which is irreversible
323
What are carcinomas?
Tumours of the epithelial tissue
324
What are sarcomas?
Tumuors of connective tissues
325
What are teratomas?
A tumour composed of tissues not normally present at the site (the site being typically in the gonads).
326
What are the 5 most common cancers in men?
``` Prostrate Lung Bowel Bladder Non-Hodgkin lymphoma ```
327
What are the 5 most common cancers in women?
``` Breast Lung Bowel Uterus Ovary ```
328
What are the 5 cancers in men with the highest mortality?
``` Lung Prostrate Bowel Oesophagus Pancreas ```
329
What are the 5 cancers in women with the highest mortality?
``` Lung Breast Bowel Pancreas Ovary ```
330
What are the 5 most common cancers in children?
``` Leukaemia Brain and other central nervous system tumours Neuroblastoma Wilms tumour Lymphoma ```
331
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.
332
What is lymphoma?
Cancer of the lymphatic system. There are 2 main types : - Hodgkin lymphoma - Non-Hodgkin lymphoma.
333
How do lymphoma present?
Lumps in lymph nodes, spleen, lower abdomen (MALT)
334
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
335
What is the difference between low + high grade lymphomas?
Low grade = mature cell malignancy High grade = immature cell malignancy
336
What is leukaemia?
Abnormal blood cells in peripheral blood
337
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)
338
Which type of leukaemia has the best prognosis?
CLL
339
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)
340
What does lymphoid mean?
B + T cells (and NK cells)
341
What does myeloid mean?
Everything other that B, T + NK cells. monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes or platelets
342
What are symptoms of leukaemia?
Related to decreased function of bone marrow so anemia (fatigue, SOB), increased infection, bruising and nosebleeds
343
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
344
How does myeloma present?
``` Bone pain Hypercalcaemia Night sweats Weight loss Extreme fatigue Renal impairment ```
345
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).
346
Why does myeloma present with renal impairment?
Because immunoglobulins (called paraproteins deposit in the kidneys).
347
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
348
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
349
What are risk factors for BCC?
Repeated UV exposure X-ray irradiation Chronic scarring Genetic Predisposition
350
What is hedgehog protein?
An oncogene which when mutated is overactivated + constantly stimulates cellular division. Happens in BCC
351
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
352
How is BCC managed?
Surgical excision | Radiotherapy
353
What is squamous cell carcinoma?
Malignant tumour of epidermal keratinocytes Compared to BC:C which is malignant tumour arising from basal keratinocytes of epidermis
354
What are risk factors for SCC?
- Excessive UV exposure - Pre-malignant skin condition - Chronic inflammation - Immunosuppression
355
How does SCC present?
Keratotic (scaly and crusty), ill-defined nodule which can ulcerate
356
How is SCC managed?
Surgical excision | Radiotherapy
357
Define malignant melanoma.
Invasive malignant tumour of epidermal melanocytes, has potential to metastasise
358
List 4 types of. malignant melanoma.
Superficial spreading Lentigo Acral lentiginous Nodular
359
What is lentigo malignant melanoma?
Nodular lesion arising in pre-existing lentigo maligna typically occurring in sun-damaged skin of face in elderly
360
What is nodular malignant melanoma?
Pigmented nodule that may grow rapidly + ulcerate - typically on trunks of males
361
What is acral lentiginous malignant melanoma?
Resembles lentigo but affects palms soles + nail beds
362
What is superficial spreading malignant melanoma?
Flat tumour w/ variable pigmentation and irregular edges. Most common in lower leg
363
How is malignant melanoma managed?
Surgical excision Radiotherapy Chemotherapy
364
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…..
365
What is cancer grading?
Based on what the cells look like under a microscope.
366
What is cancer staging?
Based on cancer spread.
367
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.
368
What is FAP?
Familial adenomatous polyposis
369
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
370
What is HNPPCC?
Hereditary non-polyposis colorectal cancer
371
Describe HNPPCC.
- Autosomal dominant - Early onset colorectal cancer (mid-forties) - Mainly right side colon cancer
372
HNPPCC increases itsk of other cancers such as?
Small bowel + gastric
373
Define polyp.
Small growth, usually benign and with a stalk, protruding from a mucous membrane
374
What is colorectal cancer?
An adenocarcinoma - arises from glandular cells in the mucosal lining of colon
375
What is radiation?
high energy photons, electrons, protons, neutrons or alpha particles
376
How does radiation work?
High energy damages DNA in cancer cells so the cells can no longer replicate indefinitely
377
Side effects of radiotherapy?
Tiredness, oedema, redness and mild burning. Chronic = infertility, increased risk of cancers in later life
378
What is the aim of chemotherapy?
Deplete tumour cells! Breaks between cycles give normal stem cells time to recover
379
What are alkylating agents?
Chemotherapy drug
380
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
381
Why are alkylating agents aggressive + toxic?
alkylating agents target all phases
382
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)
383
What do topoisomerase enzymes prevent?
DNA strands from becoming tangled
384
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
385
What is tubulin?
Main constituent of the microtubules of living cells.
386
Name 2 classes of tubulin binders.
Vinca alkaloids Taxenes
387
How do vinca alkaloids work?
Bind to tubulin and prevents the assembly of microfilaments so prevent cell division
388
Give examples of vinca alkaloids.
E.g. Vincristine, Vinblastine
389
GIve examples of topoisomerase I and Topoisomerase II inhibitors
Topoisomerase I inhibitors = Topotecan, Irinotecan Topoisomerase II inhibitors = Etoperside, Teniposide
390
How do taxenes work?
Binds to tubulin and prevents disassembly of it which also prevents cell division
391
Give examples of taxenes.
E.g. Paclitaxal, Docetaxal, Eribulin (doesn’t cause hair loss)
392
What phase of the cell cycle do antimetabolites effect?
S phase
393
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
394
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.
395
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)
396
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
397
GIve examples of kinase inhibitor.
Imatinib = CML Erlotinib = non-small cell lung cancer Lapatinib = advanced breast cancer
398
What do the suffix of kinase inhibitors mean?
``` ‘ab’ = monoclonal antibodies ‘ib’ = tyrosine kinase receptors ```
399
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
400
What are monofunctional alkylating agents?
React with only one strand of DNA
401
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.
402
What do DNA topoisomerases regulate?
They are enzymes that regulate DNA topology
403
What are DNA topoisomerases essential for?
They are essential for the integrity of the genetic material during transcription, replication, recombination processes.
404
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
405
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
406
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.
407
Describe the epithelium of the epidermis
Stratified squamous epithelium w/ outer layer of cornified cells in stratum corneum layer
408
Describe the cornified layer of epidermis
Is mainly responsible for the barrier function of skin " It is rich in lipids + insoluble proteins which form a hydrophobic layer, strong filaments linked by cell-cell junctions are also involved " Cornified layer not living but forms a tough barrier, it is continually shed + needs constant replacement " Dividing cells in basal layer, daughter cells form the layer above + differentiate as they are pushed upward, eventually cornifying
409
What is the following a definition of 'increase in cell size'?
Hypertrophy
410
What is the following a definition of 'increase in cell number'?
Hyperplasia
411
What is the following a definition of 'decrease in cell number and size'?
Atrophy
412
What is the following a definition of 'abnormal cytological appearance + tissue architecture'?
Dysplasia
413
What is the following a definition of 'conversion of one type of differentiated tissue into another'?
Metaplasia
414
What is the following a definition of 'uncontrolled focal proliferation of well differentiated cells'?
Benign
415
Name the 4 key targets of cell damage.
Mitochondria Plasma membrane Ionic channels in cell membranes Cytoskeleton
416
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)
417
Define karyolysis
Dissolution of cell nucleus Especially during mitosis
418
Define pyknosis
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
419
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.
420
What type of hypersensitivity reaction as the following examples of? Contact hypersensitivity, Insect venom, MS
Type IV Cell-mediated Non-Autoimmune
421
What type of hypersensitivity reaction as the following examples of? Systemic lupus Erythematosus, Rheumatoid arthritis
Type III Immune-complex Autoimmune
422
What type of hypersensitivity reaction as the following examples of? Asthma, Anaphylaxis, Eczema, Urticaria, Atopic dermatitis
Type I Anaphylactic Non-Autoimmune
423
What type of hypersensitivity reaction as the following examples of? Rheumatic fever, Myasthenia gravis, Thyroiditis
Type II Cytotoxic Autoimmune
424
Which types of hypersensitivity reactions are autoimmune?
Type 2. and 3 Cytotoxic and immune-complex
425
Which is cell-mediated hypersensitivity also known as?
Type 4
426
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
427
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
428
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
429
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
430
What genus bacteria cause leprosy?
Mycobacterium | M. leprae
431
What genus and species of bacteria causes whopping cough?
Bordetella B pertussis
432
List 5 genii of gram positive bacteria
``` Bacillus Clostridium Corynebacterium Mycobacterium Staphylococcus Streptococcus ```
433
Which genus and species is the Diphtheria causes bacterium ?
Corynebacterium | C. diphtheriae
434
Which diseases can H. influenzae bcaateria cause?
Acute respiratory tract infections, UTIs
435
What are epidermal ridges used for?
Fingerprints and footpirints
436
What is hyperplasia of the epidermis following pressure or friction known as?
A callus
437
List 4 causes of oedema
- Increased hydrostatic pressure - Decreased osmotic pressure - Lymphatic obstruction - Sodium retention
438
Name given to small haemorrhage (3-5mm), usually due to trauma or vasculitis
Purpura
439
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
440
What is a subcutaneous haematoma called?
Bruises / Ecchymosis
441
Describe the colour change of a bruise due to metabolism of haemoglobin to bilirubin + hemosiderin.
Red blue/green Yelow/brown
442
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
443
What are nearly all emboli?
Dislodged thrombi (thromboemobolism)
444
What is hyperaemia?
Excess blood in vessels
445
Is congesion and hyperaemia and active or passive process?
Congestion is passive Hyperaemia is active
446
List common sites of atheromas
- Aorta (especially abdominal) - Coronary arteries - Carotid - Cerebral - Leg arteries
447
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.
448
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)
449
What colour do gram positive organisms stain?
Gr+ stain blue/purple, thick peptidoglycan layer, teichoic acid present, cytoplasmic membrane
450
What colour do gram negative organisms stain?
Gr- stain pink/red, thin peptidoglycan layer (periplasm), LPS present, outer + cytoplasmic membrane
451
What are fastidious bacteria?
Bacteria that have a complex nutritional requirement + will only grow when specific nutrients are available
452
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
453
What does this describe ' uptake of short DNA fragments by naturally transformable bacteria; most relevant for plasmids'?
Transformation - A horizontal gene transer method
454
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
455
What do the following bacteria have in common? Clostridium botulinum, Clostridium tetani, Vibrio cholera, Escherichia coli O157:H7
They are toxin producing pathogens, extracellular
456
What class are sulfonamides and trimethoprim?
Anti-metabolites that inhibit synthesis of nucleis acid precurors needed
457
What do beta-lactams target?
Peptidoglycan in both gram negative and positivebacteria
458
What do glycopeptides target?
Target gram +ve organisms because it can’t cross cell wall of gram-ve
459
How do polymyxins act on bacteria?
Act like detergent on membrane Cytotoxic effects
460
How are polymyxins used?
 Mainly topical usage; upon systemic administration poor distribution in tissues, neurotoxicity + nephrotoxicity
461
What do quinolones and rifamycins inhibit?
DNA replication (quinolones) mRNA synthesis (rifamycins)
462
Where to aminoglycosides and tetracyclines act?
Bacterial 30s ribosome inhibitors Protein synthesis inhibitors
463
List protein synthesis inhibitors of the 30s subunit.
- Tetracyclines - Aminoglycosides - Nitrofurans - Spectinomycin - Streptomycin - Gentamicin
464
List some protein synthesis inhibitors of the 50s subunit.
- Macrolides (erythromycin) - Chloramphenicol - Clindamycin - Lincomycin
465
List DNA gyrase inhibitors
Quinolones (nalidixic acid, ciprofloxacin) Novobiocin
466
Where do cephalosporins act
Bacterial cell wall synthesis
467
Which drugs disrupt folic acid metabolism in bacteria?
Trimethroprim and sulfonamides
468
List 3 methods of heat loss
o Conduction/convection - 60% o Radiation - 25% o Evaporation - 15%
469
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
470
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
471
Are the following an example of enveloped or naked viruses? HIV, ebola, influenza Rotavirus, norovirus
HIV, ebola, influenza (enveloped) Rotavirus, norovirus (naked)
472
All negative single stranded RNA are envolved. GIve examples of hese.
Influenza, mumps, measles, rabies, “Ebola”
473
Give examples of positive single strand RNA viruses
Poliovirus, dengue, hepatitis C
474
Which viruses spread via an enteric route (ingestion)?
Norovirus, rotavirus, hepatitis A + E
475
List viruses able to be spread from mother to child.
o Congenital infection: Cytomegalovirus, rubella, parvovirus, B19 o Perinatal: HIV, hepatitis B, herpes simplex
476
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
477
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
478
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
479
Function of alkylating agents.
Covalently bind to (alkylate) the nucleic acid bases of DNA and produce cellular death unless the damage is repaired
480
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
481
What class is procarbazine (used in Hodgkin's disease)
Monofunctional alkylating agent
482
What class are anthracyclines such as epirubicin?
Topoisomerase inhibitors
483
What class is nitrogen mustard cyclophosphamide (widely used in solid tumours + leukaemias)?
Bifunctional alkylating agents
484
What is Schistosoma?
A flatworm, most commonly hostested in a fresh water snail making bathing dangerous in natural lakes.
485
What does Leishmania parasite cause and what is it mainly spread by?
What does Leishmania parasite cause and what is it mainly spread by?
486
What does Plasmodium parasite cause?
What does Leishmania parasite cause and what is it mainly spread by?
487
Which parasite causes severe intrauterine infections in humans but the main host is cats?
Toxoplasma
488
What is the trichomoniasis?
Trichomoniasis is a sexually transmitted infection (STI) caused by a tiny parasite called Trichomonas vaginalis (TV). It's a protozoan
489
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.
490
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.
491
How are filaria spread?
These are spread by blood-feeding black flies and mosquitoes. This disease belongs to the group of diseases called helminthiases.
492
What is Entamoeba histolytica?
An anaerobic parasitic amoebozoa, part of the genus Entamoeba.
493
What parasite causes amoebiasis?
Entamoeba histolytica, a protozoan parasite
494
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.
495
What is American trypanosomiasis?
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by the protist Trypanosoma cruzi.
496
What is metaplasia?
Change of one cell type to another
497
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
498
The changes in the prostate fland in bengin enlarment is known as what?
Hyperplasia Individual cells growing in size
499
What is hypertrophy?
The enlargement of an organ or tissue from the increase in size of its cells.
500
Where is the main action of anti-diuretic hormone?
The collecting tubules
501
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.
502
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.
503
How does progressive emphysema affect the alveolar walls?
Leads to alveolar wall destruction
504
What is bronchiectasis associated with?
Bronchial dilation
505
What does the following describe ' 30 year old patient with daily production of sputum dating back to childhood'
Bronchiectasis
506
In pneumonia how is the alveoli affected?
Alveolar filling due to consolidatoin
507
What type of pathogen can grow and survive in the environment as well as in host?
Facultative pathogen (.e.g Bacillus anthracis - soil bacteria)
508
Are toxin producing pathogens extra or intracellular?
Extracellular
509
Give examples of toxin producing pathogens.
C. botulinum C. tetani V. cholera E. coli O157:H7
510
Give examples of intracellular pathogens
Salmonella serovar Typhimurium Listeria monocytogenes
511
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
512
What class are sulphonamides and trimethoprim?
Anti-metabolites
513
Name the antibacterial drugs which are structural analogues of folic acid. Work by inhibiting enzyme DHR to THFA
Trimethoprim
514
Beta-lactams and glycopeptides target what?
Peptidoglycan synthesis needed for bacteria cell walls (of gram positive and negative organisms)
515
Why do glycopeptides only target gram positive organisms?
Because they can't cross the cell wall of gram negative organisms
516
Which class of antibacterials act like detergent on membrane?
Polymyxins
517
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.
518
Which 2 classes of antibacterials target nucleic acid synthesis?
Quinolones and rigamycins
519
Which class of antibiotics inhibit DNA replication and which blocks mRNA synthesis?
DNA replication inhibition (quinolones) mRNA synthesis blocker (rifamycins)
520
Eukaryotes have which ribosomal subunits?
80s (40s and 60s subunits)
521
Bacteria have what ribosomal subunits?
70s (30s and 50s subunits)
522
What class of antibacterial do tetracyclines and aminoglycosides belong to?
30s inhibitors
523
Name 50s inhibitors
Chloramphenicol Erythromycin (macrolide) Clindamycin Oxazolidinones
524
Name 2 (bacterial) tRNA inhibitors
Puromycin | Mupirocin
525
What does antibiotic resistance refer to?
- Resistance relates to sensitivity to antibacterial agent at a certain concentration
526
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
527
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
528
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
529
What is core body temperature?
Temp of internal environment of body, inc. organs and blood
530
What is the difference between fever and hyperthermia?
Pyrogens must be present for fever Other than that both are around 38-40 degrees
531
Difference between hyperthermia and hyperpyrexia?
Hyperpyrexia is 40+ degrees and is life threatening Hyperthermia is 38-40 and not as life threatening
532
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
533
Causes of pyrexia
``` Infection Blood transfusion/iatrogenic pyrogens Inflammation Malignancy Hypothalamic insults ```
534
What is pyrexia usually due to?
Altered set point
535
When is core body temp normally the lowest?
6am when metabolism is slowest It has a circadian rhythm
536
Sweat is produced from which glands?
Eccrine sweat glands
537
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
538
What does viruses code for?
Few specific proteins (enzymes + capsid)
539
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
540
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
541
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)
542
What does transcription make?
+strand mRNA
543
What can be used to make mRNA?
-mRNA strand (complementary sequence) or DNA
544
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
545
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 ```
546
What are the 3 types or DNA viruses?
Negative single strand RNA Positive single strand RNA Double stranded RNA
547
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).
548
List 3 types of antivirals.
Nucleoside analogues Protease inhibtors Fusion inhibitors
549
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
550
Herpes viruses and EBV are examples of what type of virus?
DNA virus
551
Example of a double stranded RNA virus
Rotaviruses (gastroenteritis)
552
Example of a positive single stranded RNA virus
Poliovirus Dengue Hapatitis C
553
Example of a negative single stranded RNA virus
They are all enveloped | E.g. influenza. mumps, measles, radies, ebola
554
How are the following viruses transmitted? Rashes - measles, rubella, varicella Respiratory viruses - influenza, RSV, rhinovirus, coronavirusm parainfluenza
Aerosol (droplet)
555
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV) | Epstein–Barr virus (EBV)
556
Give examples of viruses spread via saliva contact.
Cytomegalovirus (CMV) | Epstein–Barr virus (EBV)
557
Give examples of viruses spread via cutaeneous contact.
Human papillomavirus (HPV)
558
What is human herpesvirus 4 (HHV-4) also called?
Epstein–Barr virus (EBV)
559
Name diseases associated with HHV-5 (human herpes virus 5).
Glandular fever | Pneumonia
560
What is herpesvirus-5 (HHV-5) also known as?
(human) cytomegalovirus
561
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
562
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
563
How is norovirus, rotavirus and hepatitis A and E spread?
Enterically - ingestion
564
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
565
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
566
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.
567
What is human herpesvirus 3 (HHV-3) also called?
Varicella zoster virus - can cause chickenpox and shingles
568
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)
569
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
570
Name 3 blood borne percutaneous viruses
HIV, hepatitis B and C
571
Mode of transmission of arboviruses?
Percutaneous
572
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)
573
What are interferons?
Type of cytokine (protein)
574
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
575
In inflammation bradykinin and histamine stimulate nerve endings causing what?
Pain
576
What is pus?
Purulent exudate with dying cells and bacteria and antimicrobial products released by phagocytic cells
577
Functions of platelet aggregation factor (PAF) produced by platelets, endothelial cells and leukocytes.
o Platelet aggregation + release o Bronchoconstriction + vasoconstriction [high] o Vasodilation + vascular permeability [low] o Increases leukocyte adhesion + chemotaxis o Increases leukocyte degradation / oxidative burst
578
What is red hepatisation also known as?
Consolidation - Neutrophils and red cells enter alveolus - Fluid and cells srpread to adjacent alveoli leading to solidification
579
What type of vaccine is the smallpox and cowpox vaccines?
Live vaccines (naturally attenuated)
580
What vaccinations are live and artificially attenuated?
Oral polio, measles, mumps, rubella, yellow fever
581
Give 2 examples of non-living vaccines which are killed whle organisms
Rabies | Influenza
582
What type of vaccines are non-living, antigenic components of the organisms?
DTP -diphtheria, pertussis (whooping cough), tetanus. | Experimental (malaria, HIV)
583
How much do living and non-living vaccinations cost in general?
Living are cheaper than non-living which can be expensive
584
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
585
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
586
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
587
List 4 diseases associated with HIV and AIDs.
Kaposi's sarcoma (HHV-8) CNS toxoplasmosis CMV retinitis Pneumocystis jirovecii pneumonia
588
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)
589
What causes Pneumocystis jirovecii pneumonia (PCP)?
Yeast-like pneumocystic iroveii
590
What does pneumocystis jirovecii cause?
Lung infection in people with a weak immune system Seehn especially in HIV/ADIS and cancer patients undergoing chemotherapy
591
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
592
What does the cell wall of fungi contain that antifungas target?
Chitin
593
Give 3 classes of antifungals
Polyenes Azoles Echinocandins
594
MoA of polyenes
Binds to sterols (fatty part) in fungal cell membranes
595
Examples of polyenes
Nystatin (topical use only) | Amphotericin B - systemic use, very broad spectrum, significant toxicity (renal damage + chills)
596
MoA of azoles and echinocandins
Azoles - inhibit lanosterol demetylase which interrupts ergosterol biosynthesis Echinocandins - inhibit glucan synthase which inhibits cell wall synthesis
597
Examples of azoles
Older drugs belong to imidazole group - clotrimazole Newer drugs to triazole group = fluconazole
598
Name the 4 species of malaria that can infect humans
P. falciparum (most virulent), P. vivax, P. ovale, P. malariae.
599
List classes of anti-parasite drugs used for P. falciparum
Quinolones Antifolates Artemisinin compounds
600
During a blood meal, a malaria-infected female Anopheles mosquito inoculates what into the human host?
Sporozoites
601
Quinine, choloroquine, amodiaquine, primaquine are examples of what class of anti-parasite drugs?
Quinolones
602
Sulphonamides, pyrimethamines, proguanil, chlorproguanil are examples of what class of anti-parasite drugs?
Anti-folates
603
Artesunate, artemether, dihydroartemisinin are examples of what class of anti-parasite drugs?
Artemisinin compounds (new antimalarials)
604
What is sleeping sickness also known as?
African trypanomiasis
605
African trypanomiasis is caused by protozoa of the species Trypanosoma brucei. Which 2 types infect humans?
T. b. rhodesiense | T. b. gambiense
606
Which parasite transmits African trypanomiasis?
Tsetse fly
607
What are these drugs used for - pentamidine, suraminem melaroprol?
African trypanomiasis
608
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
609
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"
610
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)
611
Which parasite carries and spreads leishmaniasis?
Sandfly
612
Which parasite carries and spreads toxoplasmosis?
Cats (faeces) or we can eat cysts in undercooked meat
613
Treatment for toxoplasmosis
Pyrimethamine
614
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
615
What does Entamoeba histolytica cause?
Amoebiasis which is often asymptomatic but can cause dysentery and invasive extra-intestinal disease
616
List 3 heliminthic parasite examples which infect by larvae or eggs.
Tapeworms: cestodes Flukes: trematodes Round worms: nematodes
617
Which drugs are used against roundworms?
Mebendazole
618
Which drugs are used against tapeworms?
Albendazole
619
What is the word tumour used synonymously with?
Neoplasm
620
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)
621
What regulates the cell cycle?
Cyclin-dependent kinases + their inhibitors
622
List 4 classes of genes important in cancer.
Proto-oncogenes Tumour suppressor genes Genes that control programmed apoptosis DNA repair genes
623
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)
624
What is the proportion of sporadic to inherited cacner mutations?
Most cancers are sporadic, a minority 2-3% are inherited
625
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
626
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
627
Give examples of radiation that cause cancer
 UV rays – SCC, BCC, melanoma |  Ionising radiation (electromagnetic + particulate) – Leukaemia, Solid organ malignancies (thyroid)
628
List microbial organisms which can cause cancer.
HPV EBV HepB H. pylori
629
List types of cancer EBV can cause
Burkitt lymphoma B-cell lymphoma (IC people) Nasopharyngeal carcinoma Hodgkin lymphoma
630
What is HPV and how can it cause cancer?
Oncogenic DNA virus that interacts with cell cycle proteins pRb and p53 (tumour suppressor genes)
631
What can cause Hepatocellular carcinoma (HCC)?
Hepatitis B
632
Which cancers is H. pylori responsible for?
Gastric lymphoma, Gastric carcinoma
633
What is metaplasia?
Reversible transformation of one type of mature fully differentiated cell into a different fully differentiated cell type
634
2 common types of metaplasia
Squamous metaplasia | Glandular metaplasia
635
Where does squamous metaplasia happen?
Happens in ducts (salivary, pancreas – presence of stones) that are chronically inflamed
636
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
637
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)
638
Metaplasia can lead to dysplasia which can lead to what?
Neoplasia
639
What is a teratoma and where does it common arise?
Tumour containing elements of all 3 embryological germ cell layers Gonads
640
Which types of cancer typically have only circulating cells?
Leukaemias
641
Which diseases typically present with tumour masses?
Lymphoma
642
What is atopic eczema?
Chronic inflammatory itchy skin condition which has a genetic component
643
What condition does this describe - chronic inflammatory skin disease due to hyperproliferation of keratinocytes + inflammatory cell infiltration?
Psoriasis
644
what are melanocytes found?
Basal epidermis
645
Function of melanocytes
Deposit melanin from melanosomes over nuclei of basal cells The melanin forms a barrier over basal cell nuclei
646
What is the absence of melanin in skin due to an autoimmune condition attacking melanocytes called?
Vitiligo
647
Name given to macrophases in dermis.
Langerhans cells
648
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
649
Skin conditions caused by S. aureus
Impetigo, Boils, Cellulitis, Folliculitis
650
Where can Group A beta-haemolytic streptococcus bacteria cause skin infections?
Throat + skin
651
Skin cancer is divided into non-melanoma and melanoma. List the 2 non-melanomas.
Basal cell carcinoma - best to have Squamous cell carcinoma
652
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)
653
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)
654
Shedding or cornfield layer? ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
A. Scaling
655
Loss of superficial epidermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
C. Erosion
656
Leakage of blood into dermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
E. Bruising
657
Loss of epidermis and papillary layer of dermis ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
Ulcer
658
Hyperplasia of epidermis following pressure or friction ``` A. Scaling B. Callus C. Erosion D. Ulcer E. Bruising ```
Callus
659
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.
660
Mnemonic to remember +ssRNA and -ssRNA viruses
``` -ssRNA : My Mum Is Right Measles Mumps Influenza Rubella ``` +ssRNA: He Parked Diagonally Hep C Polio Dengue
661
Which gram bacteria have endotoxins?
Gram negative Endotoxin = the glycoproteins on the LPS Gram positive doesn't a have LPS
662
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?)
663
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