Week 1 lectures

What does risk factor mean?

An increased risk of developing disease.

What does predisposition mean?

An increased susceptibility to develop disease.

What does pathogenesis mean?

Pathological mechanisms resulting in clinical disease.

What does premalignant mean?

A lesion or process that will probably transform to be invasive malignancy.

What does aetiology mean?

The cause of disease.

What is the definition of disease?

The consequences of the failure of homeostasis with the potential to impair function.

What are acidic and basic dyes in staining?

Acidic dyes are responsible for reacting with the cationic/basic structures of the cell and the basic dyes are responsible for staining the anionic/acidic structures of the cell.

What are the 2 stains of H&E staining?

Hematoxylin and eosin.

Eosin - acidic dye and stains basic structures a pink/red colour.

Hematoxylin - basic dye that stains acid structures a purple/blue colour.

What are 4 key targets of cell damage?

Mitochondria, plasma membrane, ionic channels in the membranes and cytoskeleton.

What is the potential final cue to irreversible cell damage?

Calcium overload.

What are examples of sublethal changes?

Pale cytoplasm, increased vacuolation and intracellular lipid accumulation.

What are examples of chromosomal abnormalities?

Ploidy and structure.

What changes in DNA can result in mutation?

Breakage of a single or double strand(s). Point mutation. Cross-linkage.

What is metaplasia?

It is where there is the replacement of one type of differentiated cell type with another mature differentiated cell type that is not usually present. Generally adaptive, benign and reversible. However, can be a precursor of dysplasia and therefore could progress to carcinoma so it is important to monitor.

What is dysplasia?

Irreversible condition where cells have abnormal cellular architecture - nuclear atypia, nuclear hyperchromasia and the loss of cell polarity.

What is neoplasia?

It is new, uncontrolled growth that is not under physiological control.

What are the consequences of mast-cell activation and granule release in the GI tract, airways and blood vessels?

GI tract - increased fluid secretion and peristalsis.

Airways - decreased diameter and increased mucus secretion.

Blood vessels - increased blood flow and increased permeability.

What is meant by iatrogenic disease?

It is as a result of treatment or intervention. Overdose, allergy, side effects, inflammation, scarring, neoplasia, hepatitis, AIDS, surgery and immobility are examples of after effects of drugs, radiation, blood transfusion and complications.

What does the skin act as a physical barrier against?

Mechanical damage, water, chemicals, particles and infectious agents.

What are the physiological functions of the skin?

Temperature regulation, sensation/nerve signalling, vitamin D synthesis, immune defence and protection against UV radiation.

What are the 3 main layers of the skin?

The epidermis, dermis and hypodermis.

Which skin type is more abundant?

Thin skin is more abundant than thick skin as it lines most of the body.

What is the difference in the stratum corneum between the thin and the thick skin?

Thick skin has a more defined stratum corneum compared to thin skin that has a less prominent stratum corneum,.

Where are the hair and glands found?

In the thin skin.

What is the 5th layer that is found in thick skin?

The stratum lucidum. It is between the stratum granulosum and the stratum corneum.

What are the layers of the epidermis?

The stratum corneum, the stratum granulosum, stratum spinosum and the stratum basale.

How many layers thick is the basal layer of the epidermis?

It is a single layer of cells thick.

What cell type is found in the basal layer of the epidermis?

Stem cells that are capable of mitosis.

What happens to the daughter cells that are formed from the stem cells of the basal layer of the epidermis?

They either become new stem cells that remain in the basal layer of the epidermis or they differentiate to form the cells that are found in the upper epidermis layers.

What is formed in the spinous layer and what links these structures?

Prominent intracellular keratin filaments are formed and desmosomes link them to adjacent cells.

How is further differentiation continued into the stratum granulosum layer?

The production of keratohyalin granules and lamellar bodies.

What is the role of keratohyalin granules?

They contain proteins that are responsible for binding and aggregating keratin filaments.

What is the role of lamellar bodies?

They contain a lipid that is important for the hydrophobic barrier to water.

What happens to cells in the stratum corneum?

They undergo apoptosis and lose their nuclei and other organelles. This forms the tough surface layer of skin.

What is the most abundant cell type in the epidermis?

Keratinocytes.

What are other cell types that are found in the epidermis?

Melanocytes, immune cells and merkel cells.

What do keratinocytes produce?

Keratin.

What are melanocytes responsible for?

They are responsible for skin pigmentation and protection against UV damage.

What do melanocytes produce and what happens to it?

They produce melanin which are packaged into melanosomes which are transferred to neighbouring keratinocytes.

Where do melanocytes arise from in development?

The neural crest.

What are Langerhans cells?

They are antigen presenting cells of the epidermis. They are dendritic in shape and develop in the bone marrow before being transferred to the blood.

What are merkel cells?

They are specialised cells that are found in the basal layer of the epidermis. They are in association with the nerve fibres responsible for touch sensation.

What is the type of epithelium of the epidermis?

Stratified squamous epithelium.

What are some pathological changes in the epidermis?

Imbalance between the renewal and loss of cells, breaking of the cell-to-cell junctions, trauma and wound repair, failure of the barrier functions, infection and inflammation and the development of tumours.

What are the downward and upward projections of the epidermal-dermal junction?

The downward projections are the rete ridges and the upward projections are the dermal papillae.

What is the blood flow like within the skin?

There is a papillary plexus just below the epidermis and in the upper papillary region of the dermis.

There is a cutaneous plexus that is found in the lower part of the dermis and the upper part of the subcutis/hypodermis.

What is the papillary dermis?

It is the thin layer of the dermis that is found below the epidermis. It is made up of loose connective tissue - fine collagen fibres and elastin fibres. Blood vessels, lymphatics and nerve endings.

What is the reticular dermis?

It is the thicker portion of the dermis that is made up of dense connective tissue containing prominent bundles of collagen fibres. There are fibroblasts as well as other immune cells that are present. Also the location of skin appendages.

What are the cells that are present in the dermis?

Fibroblasts, adipocytes and a range of immune cells - mast cells, macrophages and lymphocytes.

What do fibroblasts produce?

Collagen and elastin which provides strength and flexibility to the skin.

What skin appendages are located in the dermis?

Nerves, glands and vasculature of the skin.

What physiological roles does the dermis play?

Sensation, protection and thermoregulation.

What is the hypodermis composed of?

Mature adipose tissue separated by fibrous septa.

What are the functions of the subcutis/hypodermis?

Insulator, protector and energy store.

What types of glands can be found in the skin?

Sebaceous glands, eccrine sweat glands and apocrine glands.

What is the nail plate?

It is a hard, keratinised plate at the end of each digit. It rests on a stratified squamous epithelium structure (epidermis). Cells at the nail root proliferate to form the nail matrix.

Where is the hair follicle formed from?

The basal layer of the epidermis - it is a tubular structure.

Describe the structure of a hair follicle.

It is a tubular structure that is formed from the basal layer of the epidermis. At the base there is a bulbous expansion that contains the hair papilla. epithelial cells that are found in the papilla divide and form structured layers.

What are the layers of the hair?

Cuticle, cortex and medulla.

What do sebaceous glands secrete?

Sebum which is a lipid containing substance that ensures that hair is waterproof.

What is the structure of the sebaceous glands?

Branched acinar structure.

What is holocrine secretion?

It is where the acinar cells of the sebaceous glands distend and die which results in the release of their lipid containing contents.

Where are eccrine sweat glands located?

They are located in the reticular dermis. They have a coiled tubular structure.

Where are apocrine glands located?

Axillae, mammary and groin regions.

What do apocrine glands release?

A viscous, cloudy secretion that can contain pheromones and can cause body odour upon reaction with skin bacteria.

How is the skin involved in thermoregulation?

Changes in blood flow in the vessels located in the papillary dermis to control the temperature of the surface of the skin. Sweating causes heat loss from evaporation.

How is the skin involved in sensation?

Because there are specialised sensory receptors that are located in the skin.

How is the skin involved in vitamin D synthesis?

It is carried out by keratinocytes in the presence of UV light. Further activation occurs in the liver and the kidneys.

How is the skin involved in immunity?

Langerhans cells are present in the epidermis. Mast cells, macrophages and lymphocytes are present in the dermis.

How is the skin involved in protection against UV radiation?

Melanin absorbs UV.

What is healing like in superficial wounds?

The epidermis can regenerate from the basal layer.

What are the phases of deep wound healing that extend into the dermis?

• Haemostasis - the formation of a fibrin clot to stop bleeding.

• Inflammation - removal of bacteria and damaged tissue.

• Fibroplasia - new collagen and angiogenesis.

• epithelialisation - migration and mitosis of keratinocytes from edges.

• Remodelling - initial new tissue is replaced through turnover to create a stronger structure.

What does haemodynamics mean?

It refers to the flow of blood through the circulatory system.

What are factors that affect haemodynamics? What can changes in these factors lead to?

Vessel wall integrity, osmolarity (solutes in the plasma) and maintenance of the intravascular pressure.

Changes can lead to extravasion across the vascular wall and reduction of blood fluidity (cause a blockage).

Where does fluid move between in the body?

Blood capillaries, interstitial space and the lymphatic vessels.

How is fluid balance maintained?

Hydrostatic pressure and oncotic pressure.

What is hydrostatic pressure?

It is pressure exerted on a fluid as a result of gravity. It is equal to blood pressure. Drives fluid from the vessels into the tissues. Higher at the arterial end as compared to the venous end.

What is oncotic pressure?

Pressure exerted as a result of protein concentration. It draws fluid to where there is the higher solute concentration.

What does hydrostatic pressure increase as a result of?

Fluid retention causes the hydrostatic pressure to increase therefore meaning that more fluid is pushed out of the microvessels into the interstitial space.

What happens to the oncotic pressure as a result of higher blood protein concentrations?

It increases and more water is pulled back into the vessels.

What is hyperaemia and congestion? What is the difference?

Local increase in tissue blood volume. Focused on the microvasculature.

Hyperaemia is where there is an increased blood flow in whereas congestion is where there is reduced blood flow out.

What kind of process is hyperaemia? What are the 2 types?

It is an adaptive process.

Reactive hyperaemia - increased blood flow to an area because it has less - vasodilation.

Active hyperaemia - increased blood flow to an area because it is needed.

What kind of process is congestion? What causes it?

It is a passive process.

Caused by failure of the heart to pump blood away from the affected area. Or because there is a physical obstruction of the veins.

What is local and systemic congestion?

Local is due to blood vessel compression (isolated venous obstruction).

Systemic is as a result of heart failure and can cause widespread oedema.

What usually causes centrilobular hepatic congestion?

Heart failure.

What does an increase in venous pressure in centrilobular hepatic congestion cause?

It means that blood cannot leave the hepatic capillaries causing a mottled ‘nutmeg’ appearance.

What is chronic pulmonary congestion linked to?

Heart failure. Decreased cardiac output which means that there will be a backup of blood and increased pressure on alveolar capillaries. Erythrocytes will leak out which are engulfed by alveolar macrophages and are then engorged with brownish hemosiderin.

What is oedema?

The abnormal increase in fluid in the interstitial space.

What are 3 causes of oedema?

• Increase in vascular volume/pressure (hydrostatic pressure increases),

• Decrease in plasma protein content (decreases oncotic pressure meaning that less fluid is brought back into the blood vessels and is therefore left in the interstitial space).

• Changes in the endothelial cell function of the vessel wall.

What is a hydrothorax?

Oedema in the thoracic cavity.

What is hydropericardium?

Oedema in the pericardial cavity.

What is pulmonary oedema?

Oedema in the lungs.

What is cerebral oedema?

Oedema in the brain.

What is generalised oedema called?

Anasarca.

What can cause decreased plasma protein concentration?

The reduction in the generation of plasma proteins or as a result of the loss of plasma proteins.

Reduction in production can be because of malnutrition or liver cirrhosis.

Loss can be as a result of burns or because of loss from urine/faeces.

How does lymphatic obstruction cause oedema?

Because the lymph is unable to drain meaning that there is a collection of fluid that is unable to be drained in the interstitial space.

How can sodium retention cause oedema?

It increases the hydrostatic pressure - caused by excessive salt intake in renal insufficiency or increased RAAS system.

How does inflammation cause oedema?

The blood vessels dilate in order to accommodate and increased blood flow to the damaged tissue which leads to increased vessel permeability which means that fluid can leak out of the vessels.

What are the 3 stages of haemostasis?

Haemorrhage (bleeding) , thrombosis (clotting) and fibrinolysis (dissolution of the clot).