Histology + Basic Science Flashcards
What is the most common type of cancer in the UK?
Basal cell skin cancers
Are basal cell skin cancers malignant or benign?
Malignant
but rarely metastasise
Are melanomas malignant or benign?
Malignant
Are squamous cell carcinomas malignant or benign?
Melignant
what is the incidence trend of skin cancers?
increasing incidence
what is the incidence trend of atopic dermatitis?
increasing incidence
what is the incidence trend of venous leg ulceration?
staying the same
why are venous leg ulcerations increasing in prevalence despite incidence being the same?
because people with the disease are living longer
what is the definition of prevalence?
the total number of cases within the population at any one time
what is the definition of incidence?
the number of new cases of a disease (as a percentage of the population over time)
what type of cells make up the epidermis?
stratified squamous epithelium
what type of tissue is the dermis?
connective tissue
From what embryonic germ layer is the epidermis formed?
Ectoderm
What is the name of the single layer which is formed from ectoderm cells and goes on to become epidermis?
Periderm
From what embryonic germ layer is the dermis formed?
Mesoderm
What is the name of pigment producing cells that reside in the epidermis?
Melanocytes
Where do melanocytes come from?
Neural crest
What is the name of the embryonic phase (days 7-10) where cellular organisation into germ layers occurs?
Gastrulation
From what embryonic germ layer are endothelial linings formed?
Endoderm
At 4 weeks of foetal development, what are the 3 layers of skin that are present?
Periderm
Basal layer
Dermis (corium)
At 16 weeks of foetal development, what are the 5 layers of skin that are present?
Keratin layer Granular layer Prickle cell layer Basal layer Dermis
What happens to the periderm as the foetus develops?
Gradual increase in layers of cells until keratin layer, granular layer and prickle cell layer are formed. The periderm casts off.
What is the name of the developmental growth pattern of skin?
Blaschko’s lines
What type of marks follow blaschko lines?
birth marks
what is the sub-cutis predominantly made of?
fat
what cells make up 95% of the epidermis?
keratinocytes
what is differentiation of a keratinocyte?
migration from basement membrane to keratin layer to be shed
what are the 4 defined layers of the epidermis?
keratin layer
granular layer
prickle cell layer
basal layer
What layer of the epidermis is noticeably thicker on the soles of feet and palms of hands?
keratin layer
what is epidermal turnover?
the rate of keratinocytes moving from the basement membrane to the keratin layer to be shed
compare epidermal turnover over of normal skin to the skin of a patient with psoriasis?
normal skin epidermal turnover: 28 days
psoriasis epidermal turnover: 45 days
what shape are the cells of the basal layer of the epidermis?
cuboidal
what shape are the cells of the prickle cell layer of the epidermis?
polyhedral
what adheres the cells of the prickle cell layer together?
desmosomes
+ intermediate filaments
what shape are the cells of the granular layer?
flattened cells
what phase in the life cycle of a keratinocyte happens in the granular layer?
keratinocytes start to die- cell nuclei is lost
what secretory organelles are released from keratinocytes in the granular layer?
odland bodies
lamellar bodies
what layer of the epidermis is not present in psoriasis?
granular layer
what are corneocytes?
overlapping non-nucleated cell remnants (dead keratinocytes) which make up the keratin layer
what forms a tight waterproof barrier within the keratin layer of the epidermis?
the insoluble cornified envelope
+
lipids, flaggrin and involucrin proteins from granules secreted from keratinocytes in granular layer
What 3 main components are in the keratohyalin granules?
from the keratinocytes in the granular layer
lipids
flaggrin
involucrin proteins
why does HPV commonly affect children below 6 years of age?
because corneocyte layer hasn’t sealed properly yet so there is no effective barrier
Is oral masticatory mucosa keratinised or non-keratinised?
keratinised
Is oral lining mucosa keratinised or non-keratinised?
non-keratinised
What does a white area on mucosal surfaces (eg buccal mucosa) suggest?
thickened epithelial lining
What is lost when scar tissue is formed on epidermis?
appendages
Why are appendages lost in scar tissue?
fyboblasts try to repair skin with collagen tissue
what are the 3 main other cells (apart from keratinocytes) in the epidermis?)
melanocytes
langerhans cells
merkel cells
where are melanocytes located?
basal and suprabasal
what are melanocytes?
pigment producing dendritic cells
what are the organelles within melanocytes which produce melanin?
melanosomes
what is converted by melanosomes into melanin pigment?
tyrosine
what type of melanin is brown or black?
eumelanin
what type of melanin is red or yellow?
phaeomelanin
how are melanosomes (melanin granules) transferred to adjacent keratinocytes?
via dendrites
what does melanin pigment do once inside a keratinocyte?
forms a protective cap from UV light over nucleus
what organelle within the melanocyte is the origin of the melanosome membrane?
golgi apparatus membranes
why is there a loss of colour in vitiligo?
due to loss of melanocytes
what type of disease is vitiligo?
autoimmune
what type of disease is albinism?
genetic
what is the name of the syndrome where there is excess melanin-stimulating hormone produced by the pituitray?
Nelson’s syndrome
what visual sign does Nelson’s syndrome have?
tanned appearance
what is the name of a tumour of the melanocyte cell line?
(malignant) melanoma
where do Langerhans cells originate from?
bone marrow
where do Langerhans cells reside in the epidermis?
pricke cell layer
what type of cells are langerhans cells?
antigen presenting cells
what are the names of the tennis racket shaped organelles found in langerhans cells?
birbeck granules
what are merkel cells?
mechanoreceptors that directly synapse with free nerve endings
where do merkel cells reside in the epidermis?
basal layer
why can diabetes mellitus cause reduced/loss of feeling?
glycation (glucose tagging) of the myelin sheath which affects function of nerve
what are merkel cell cancers caused by?
viral infection
what is a pilosebaceous unit?
a hair follicle with an adjacent sebaceous gland
how does pigmentation of hair occur?
via melanocytes above dermal papilla
what is the beginning of a pilosebaceous unit in embryology?
hair bud
what are the 3 phases of hair growth?
anagen
catagen
telogen
what is the telogen phase also known as?
shedding phase
what happens to the dermal papilla n the catagen phase?
moves away from marix leaving an epithelial column
what is the anagen phase also known as?
growth phase
what is the catagen phase also known as?
resting phase
what does the hair matrix become in the telogen phase?
club hair
why in autoimmune disease such as alopecia, does the hair regrow as white/grey before colour returns?
hair regrows before melanisation occurs
In humans the telogen phase is asynchronus. What does this mean?
hairs all fall out at different times
what can commonly drive synchronisation of telogen phase and therefore cause hair loss?
psychosocial stress
what are the 3 patterns of male hair loss?
ventral
typical
anterior
compare nail growth in summer to winter?
faster nail growth in summer than in winter
where is the region of stem cells that become nails?
the nail matrix
underneath the posterior nail fold
what are the 3 layers of the nail plate?
dorsal
intermediate
ventral
why is the luna white and the rest of the nail plate red?
luna is thicker, in the rest of the nail plate you can see the blood vessels underneath
why can trauma cause poorly shaped/crumbly nails?
permanently damages stem cells causing a differentiation defect
What anchors the epidermis to the dermis?
DE junctions
What are the names of the keratin filaments which stick the basal cells to the papillary dermis at the DE junction?
hemidesmosomes
What is epidermolysis bullosa?
an inherited disease of the DE junction which causes skin fragility
Name 3 acquired conditions caused by auto-antibodies to proteins in the skin?
pemphigus
bullous pemphigoid
dermatitis herpetiformis
what are the main cell types in the dermis?
fibroblasts macrophages mast cells lymphocytes langerhans cells
what are the main 2 fibres found in the dermis?
collagen (higher percentage)
elastin
what is the function of collagen in the skin?
strengthening
what is the function of elastin in the skin?
elastic recoil to skin
what is the function of fibroblasts in the dermis?
secrete collagen
What is the name for physical urticaria?
ie an exaggerated wealing tendency that occurs when skin is touched
dermographism
what cells degranulate to cause an urticarial response?
mast cells
what 2 main substances can increase wrinkling?
UV light
smoking
what happens to the collagen during aging?
it becomes depleted
what happens to the DE junctions during aging?
DE junctions become flatter
compare the supply of the skin blood vessels to the metabolic demand?
supply is greater than demand
what is the name of a localised overgrowth of blood vessels?
angioma
what is the cause of a port wine stain?
an angioma of the face
overgrowth of blood vessel population
what is the function of pacinian corpuscles?
pressure sensory free nerve endings
what is the function of meissner corpuscles?
vibration (light touch) sensory free nerve endings
what is the name of the inherited condition which causes an overgrowth of cutaneous nerve endings?
neurofibromatosis
what is the name of the benign tumour of cutaneous nerve endings?
neurofibromas
what are the 3 types of skin glands?
eccrine glands
sebaceous glands
apocrine glands
which skin glands sweat to cool you down?
eccrine glands
which skin glands secrete a feromone odour?
apocrine glands
when do apocrine glands start secreting?
puberty
what are the 2 main sites of apocrine glands?
axilla and groin
what is the of the structure formed by a sebaceous gland and a hair follicle?
pilosebaceous unit
where are the largest sebaceous glands found?
face and chest
when do sebaceous glands start secreting?
puberty
what are the 2 main functions of sebaceous glands?
- control moisture loss
2. protection from bacterial and fungal infection
why do sebaceous glands protect the body from bacterial and fungal infection?
the sebum secreted creates a slight acidic environment
what hormone are the apocrine sweat glands dependent on?
androgens
which skin glands are the most involved in thermoregulation?
eccrine glands
what nervous system controls the secretions of eccrine glands?
sympathetic autonomic nervous system
where do sebaceous glands open onto?
hair follicles
where do eccrine glands open onto?
skin surface
what is the main cause of toxic epidermal necrolysis (acute skin failure)?
drugs
why does scale cause direct protein loss?
scale is made of keratin
what is a compound fracture?
a break in the bone AND bone exposed (direct break in skin)
where does vitamin D metabolism occur?
keratinocytes in the skin
what is the equation for vitamin D synthesis?
cholecalciferol –> vit D3
using UV
what thyroid hormone is produced in the skin? (and from what hormone?)
T3
T4 –> T3
what is crusted scabies?
scabies but with a much higher number of mites on the body than usual scabies
what failure is usually present in individuals who get crusted scabies?
immune system failure
what is tuberculoid leprosy?
a type of leprosy where you have few parasites but a huge immune response
what is the name of disseminated herpes simplex virus infection?
(widespread infection instead of localised cold sores)
eczema herpeticum
what type of tendency can cause eczema herpeticum to occur?
atopic tendency
Are langerhans cells innate or adaptive immunity?
innate immunity
What is the keratin layer made of?
corneocytes
what makes corneocytes?
terminal differentiation of keratinocytes
what 3 important structural proteins are found in the epidermis?
filaggrin
involucrin
keratin
What do keratinocytes produce that can directly kill pathogens?
anti-microbial peptides
what granules characterises langerhans cells?
birbeck granule
what T cells are mainly found in the epidermis?
CD8+ T cells4
cytotoxic
what peptide produced by keratinocytes is found in a high level in psoriasis lesions?
anti-microbial pepitides
what type of helper T cells are associated with psoriasis?
Th1
Th17
what type of helper T cells are associated with atopic dermatitis?
Th2
Th17
where are T cells produced?
bone marrow
where are T cells sensitised?
thymus
what MHC class is found on the surface of almost all cells?
MHC-I
what type of T cells do MHC-I present antigens to?
cytotoxic T cells
what MHC class is found on professional antigen presenting cells?
MHC-II
what type of T cells do MHC-II present antigens to?
helper T cells
what mutation is associated with severe/early onset of atopic eczema?
mutation in fillagrin gene
what is the function of fillagrin?
bind to water molecules- water retention
natural moisturiser
in vitiligo, what cells are being attacked by autoantibodies?
melanocytes
what antibodies mediate type 1 hypersensitivities?
IgE
what antibodies mediate Type 2 hypersensitivities?
IgM and IgG
what cell type mediates Type 4 hypersensitivities?
Th1 cells
what are the 2 types of fascia?
superficial fascia (subcutaneous tissue) deep fascia
compare the connective tissue in superficial fasca to deep fascia?
superficial fascia:
loose connective tissue mixed with fat
deep fascia:
dense connective tissue
what is the name of the deep fascia that separates muscle compartments?
intermuscular septa
in which fascia do the cutaneous nerves and veins run?
superficial fascia
which artery of the forearm forms the deep palmar arch?
radial artery
which artery of the forearm forms the superficial palmar arch?
ulnar artery
what is the name of the network of veins seen on the dorsal aspect of the palms?
dorsal venous network
what vein drains blood from the lateral aspect of the forearm?
cephalic vein
what vein drains blood from the medial aspect of the forearm?
basilic vein
what are the names of any 2 veins which accompany an artery and eventually join?
venae comitantes
what connects the cephalic vein to the basilic vein?
median cubital vein
what artery runs into the anterior comparment oft he leg?
anterior tibial artery
what artery runs into the posterior compartment of the leg?
posterior tibial artery
what artery does the fibular artery bifurcate off of?
posterior tibial artery
what artery supplies the dorsal foot?
dorsal artery
what arteries supplies the plantar foot?
lateral plantar artery
medial plantar artery
which plantar artery forms the plantar arch?
lateral plantar
what are deep veins of the leg?
popliteal vein
femoral vein
what superficial vein drains directly into the femoral vein?
great saphenous vein
what superficial vein drains into the popliteal vein?
small saphenous vein
where does the great saphenous vein arise from?
dorsal venous arch
where does the small saphenous vein arise from?
dorsal venous arch
does the great saphenous vein run in front or behind the medial malleolus?
in front of
does the small saphenous vein run in front or behind the lateral malleolus?
behind
what aspect of the lower limb does the great saphenous vein run?
medial aspect of the lower limb
what aspect of the lower limb does the small saphenous vein run?
posterior midline of the lower limb
what is the name of the most common site of venous ulceration?
gaiter area
where is the gaiter area?
medial aspect of the distal lef
what is the route of the lymphatics in the upper limb?
cubital nodes
lateral axillary nodes
apical axillary nodes
in the limbs, what blood vessels do the lymphatics tend to follow?
veins
in the abdomen, what blood vessels do the lymphatics tend to follow?
arteries
where do the popliteal lymph nodes drain to?
superficial and deep inguinal nodes
What type of immunological reaction is pemphigus or pemphigoid?
type 2 (direct cell killing)
what type of immunological reaction is urticaria usually?
type 1 (IgE mediated)
what type of immunological reaction is erythema/rash usually?
type 4 (delayed type)
what type of immunological reaction is purpura usually?
type 3 (immune-complex mediated)
what is purpura?
red/purple spots that do not blanche
what is the cause of purpura?
bleeding under the skin
what happens to an allergic reaction when the dose of drug is decreased?
nothing
not dose-dependent
what happens to a non-immunologial drug reaction when the dose of drug is decreased?
reaction is usually less
dose-dependent
What is a morbiliform rash?
a rash which looks like measels
What is a pustular rash?
a rash with papules containin pus
What is a papulosquamous rash?
a rash with hyperkeratosis
is a high molecular weight drug or a low molecular weight drug more likely to be involved in drug eruptions?
high molecular weight
what is the most common type of cutaneous drug eruption?
exanthematous
or maculopapular
what type of hypersensitivity is an exanthematous (maculopapular) rash?
type IV (delayed type)
what is the usual onset of an exanthematous drug reaction?
4-21 days after first taking drug
what are the 6 indicators of a potential severe exanthematous drug eruption?
- involvement of mucous membranes and face
- facial oedema and erythema
- widespread confluent erythema
- fever (>38.5)
- blisters, purpura, necrosis
- SOB, wheeze
what happens in a non-immunological type 1 drug reaction? (eg urticaria)
direct release of inflammatory mediators from mast cells due to direct effect of drug
(not IgE mediated)
What do you see clinically on a patient with acute generalised exanthematous pustulosis? (AGEP)
extensive sheets of pustules
what is the usual cause of acute generalised exanthematous pustulosis? (AGEP)
drug eruption
What are the 4 main severe cutaneous adverse drug reactions?
- Stevens-Johnson syndrome (SJS)
- Toxic epidermal necrosis (TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acute generalised exanthematous pustulosis (AGEP)
What is a positive nikolsky sign?
gentle touching of the skin causes it to fall off
what is the nikolsky sign for pemphigus?
positive
what is the nikolsky sign for pemphigoid?
negative
what is the nikolsky sign for toxic epidermal nectosis?
positive
is phototoxicity an immunological or non-immunological drug reaction?
non-immunological
what are the 3 acute features of phototoxic drug reactions?
- skin toxicity
- systemic toxicity
- photodegradation
what are the 3 chronic features of phototoxic drug reactions?
- pigmentation
- photoageing
- photocarcinogenesis
What 2 requirements are needed for a phototoxic cutaneous drug reaction?
- sufficient photo-reactive drug
2. appropriate wavelength of light
What is the mild form of polymorphic light eruption (PLE) commonly known as?
prickly heat
compare photo allergy and photoxicity in terms of immune sensitisation?
photo allergy requires immune sensitisation
phototoxicity does not
compare photodermatose to photoaggravated dermatose?
photodermatose: condition caused by light
photoaggravated dermatose: condition not cuased by light but can be made worse by it
What are porphyrias?
a group of conditions where there is a build up of porphyrin chemicals
What is the most common skin porphyria in Scotland?
porphyria cutanea tarda
PCT
what is a porphyrin?
normal metabolites which are part of the haem metabolic pathway
what enzyme is defective in porphyria cutanea tarda?
uroporphyrinogen decarboxylase
what porphyrin builds up in porphyria cutanea tarda?
uroporphyrinogen III
where is the enzyme uroporphyrinogen decarboxylase made?
the liver
what is the typical presentation of porphyria cutanea tarda?
blistering and fragility
also possible hyperpigmentation, hypertrichosis, solar urticaria, morphoea
what is hirtuism?
increased hair growth in male pattern
what is hypertrichosis?
increased hair growth generally
what is morphoea?
scarring process in the dermis
How do you investigate a possible porphyria cutanea tarda?
woods lamp using patients urine
what are the 4 main causes of porphyria cutanea tarda?
alcohol
viral hepatitis
oestrogens
haemochromatosis
all cause decreased uroporphyrinogen decarboxylase production in the liver
what porphyrin builds up in erythropoietic protoporphyria?
protoporphyrin IX
what enzyme is deficient in erythropoietic protoporphyria?
ferrochelatase
what vitamin do patients with porphyrias usually become deficient in?
vit D due to sun avoidance
compare signs and symptoms of erythropoietic protoporphyria?
no signs only symptoms (Severe prickly burning which lasts a few days)
although eventually scars appear
what is usually seen in a patient with a porphyria’s full blood count?
reduced Hb (due to lack of haem) --> anaemic
what is the management of porphyria cutanea tarda?
treatment of underlying condition
what is the management of erythropoietic protoporphyria?
visible light protection measures
what porphyrin builds up in acute intermittent porphyria?
porphobillinogen (PBG)
what enzyme is deficient in acute intermittent porphyria?
PBG deaminase
What is virulence?
the capacity of a microbe to cause damage to the host
What is adhesin?
a virulence factor which enables binding of the organism to host tissue
what is invasin?
a virulence factor which enables the organism to invade a host cell/tissue
what is impedin?
a virulence factor which enables the organism to avoid host defense mechanisms
what is aggressin?
a virulence factor which causes damage to the host directly
what is modulin?
a virulence factor which causes damage to the host indirectly
where is S. aureus usually carried by carriers?
anterior nares (in the nose) perineum
what is haemolysin?
a virulence factor which breaks down clots
what adhesin increases the chance of a specific S. aureus strain being able to infect a joint?
collagen binding protein
what impedin, found in some strains of S. aureus is associated with severe skin infections?
Panton Valentine Leukocidin
compare PVL toxin percentage of hospital acquired MRSA strands to community acquired strands?
higher percentage of community acquired MRSA contain PVL than hospital acquired strands
what is refractory hypoxaemia?
oxygen is reduced but because the tissue is dead this cannot be improved by using an oxygen mask
What are superantigens?
antigens which causes immune system to respond with an inappropriate immune response that causes host damage
Why do superantigens cause a massive release of cytokines and an inappropriate immune response? (which leads to huge scale inflammation)
because they don’t go through the normal reaction between receptor and presenting antigen
What superantigen found in S. aureus is associated with Toxic Shock Syndrome?
TSST-1
toxic shock syndrome toxin 1
what are the 3 main skin infections caused by Strep pyogenes? (GAS)
impetigo
cellultis (erysipelas)
necrotising fasciitis
what is the lancefield system?
a system which serotypes the cell wall carbohydrate of a bacteria
what Strep infection has a lancefield classification of A?
Strep pyogenes
GAS
what is celulitis?
skin infection of the dermis
no necrosis
Why is there no bacteremia in S. aureus Toxic Shock Syndrome?
because the superantigen goes through the blood stream causing host destruction, the infection itself is localised
What acts as the brick and mortar in the brick and mortar model of the stratum corneum?
bricks- corneocytes
mortar- intercellular lipids
what are the corneocytes held together by?
corneodesmosomes
what are the 2 entry routes of drug through the skin?
intercellular route (through intercellular lipids) transcellular route (through corneocytes)
why is the intercellular route of drug entry through the skin highly tortuous?
it has to weave between the corneocytes
what is Fick’s law?
J = Kp x Cv J = Rate of Absorption (flux) Kp = permeability coefficient Cv = concenration of drug in vehicle
what is the best combination of drug and base to allow a good partition across the stratum corneum?
lipophilic drug in hydrophilic base
why does a lipophilic drug in a lipophilic base not allow a good partition across the stratum corneum?
lipophilic vehicle will retain the drug
what are excipents?
molecules which are included in the drug vehicle to increase solubility and enhance absorption
what are 2 ways to improve partitioning of the drug across the stratum corneum?
- hydration of the skin by occlusion
2. addition of excipients
what receptors do glucocorticoids signal via?
nuclear receptors
how do glucocorticoids enter cells?
by diffusion across the plasma membrane
when glucorticoids are within the cytoplasm what do they combine with?
GRalpha molecules
what has to dissociate from the GRalpha molecules in order to let glucocorticoids combine?
inhibitory heat shock proteins
what allows the activated GRalpha receptor to translocate to the nucleus once it has binded with a glucocorticoid?
importins
what must form before the GRalphas can bind to glucorticoid response elements in the nucleus?
GRalpha monomers must become homodimers
where are glucocorticoid response elements found in genes?
in the promoter regions
what is the main disadvantage of subcutaneous administration?
injection volume limited
what is iontophoresis?
application of low voltage electrical pulses to the skin via a surface electrode in order to drive low molecular weight molecules of the same charge through the skin
what is electroporation?
very brief high voltage pulses which lead to pore formation in order to deliver hydrophilic and charged molecules into the skin
what is sonophoresis?
use of ultrasound to increase skin permeability
