Pathology Flashcards
State the 5 cardinal signs of inflammation.
Rubor (redness) Tumor (swelling) Calor (increased heat) Dolor (pain) Functio leasa (loss of function)
State what is activated by phagocytosis.
What are the 3 mechanisms by which a phagolysosome causes destruction?
Release of soluble mediators
- Release of toxic radicals and Hydrogen-Oxygen products.
- Lower pH
- Digestive enzymes
Which two molecules promote local inflammation?
State how.
Cytokines
Chemokines
- attracting cells inc. neutrophils
- causing vasodilation, increased permeability (junctions between endothelial cells widens) and increased adhesion molecules on blood vessel endothelium.
What are the 4 possible outcomes of inflammation?
- Resolution- insult removed and the tissue heals completely.
- Fibrosis- insult removed but scar tissue remains
- Chronic inflammation- insult cannot be removed
- Abscess formation- inflammation causes tissue destruction to form a cavity containing lots of neutrophils and dead tissue(appears pink)
Suggest 5 advantages of inflammation.
- AMPLIFIES RESPONSE- small stimulus results in large local and systemic response
- Focuses immune response by flooding area with leucocytes.
- Allows fibrin formation
- Activates next stage of immunity ( T cell response/memory)
- Facilitates transport of drugs
Suggest 3 disadvantage of inflammation.
- Damage healthy tissue by digestion
- May by activated inappropriately
- Activated uncontrollably: septic shock
What is an ulcer?
Effects on a) skin b) gastrointestinal tract?
A macroscopically apparent loss of surface epithelium.
a) crust of dried fibrin, unlikely to lead to severe haemorrhage
b) haemorrhage, perforation, loss of defence as epithelium protect submucosa from acid and enzymes.
Describe the 4 main cells involved in chronic inflammation.
- Histiocytes (macrophages inside tissues)
- Lymphocytes (one nucleus and small cytoplasm. T: inflammation ; B: plasma cells)
- Eosinophils (look like cartoon sun with sunglasses as nuclei take up stain well. Involved in allergic and parasitic conditions.)
- Plasma cells
Describe what a polymorph/neutrophil is.
Involved in phagocytosis and bacterial killing
Has multiple joined nuclei
Which cell types accumulation is mediated by IgE produced by plasma cells?
Eosinophils
How is the number of eosinophil involved in an immune response related to symptoms?
They produce inflammatory mediators.
The more present, the more symptoms the patient suffers.
What is a polyp?
How may a microscopic slide of a polyp appear?
An abnormal growth protruding growth into a cavity
Pale due to excess fluid oedema
What is a monocyte ? Describe its appearance.
Single kidney-shaped nucleus and lots of cytoplasm.
Phagocyte but only inside tissues where its called a macrophage.
State three causes of chronic inflammation.
Describe the distinct pattern of chronic inflammation
Which cytokines are involved in this?
- persistent infection
- inability to heal ( e.g. in a peptic ulcer)
- immune mediated inflammatory disease (Chrohns)
- Prolonged exposure to toxic agents
Granulomatous inflammation - contains granuloma (collection of macrophages surrounded by lymphocytes- in order ones some scarring also)
IL-1- initiation
TNF- maintenance
IL-2- increase in size
What are the 5 R’s involved in bodily response to injury?
Recognition of injurious agent Recruitment of leukocytes Removal of injurious agent Regulation Resolution
Describe the pathophysiology of acute inflammation.
- Vasodilation- this causes stasis of blood and increased hydrostatic pressure. Causes Rubor (redness) and calor (high temperature)
- Increased vascular permeability- Its mediated by histamine and NO. Theres damage to the endothelium by leukocytes and osmotic pressure in tissue increase and more fluid leaves vessels than moves in. Causes tumor (swelling)
- Exudation- (1) involves margination & rolling, (2) adhesion and (3) emigration caused by CD31
Whats the difference between an exudate and a transudate?
Transudate - exiting fluid contains few proteins and cells
Exudate- exiting fluid contains lots of proteins and cells
Describe the events involved in margination and rolling.
- White blood cells peripheral to RBC in capillary
- Transient connections between WBC’s and endothelium
Upregulated by TNF and IL1
State three ways in which growth can occur
- Multiplication by mitosis
- Auxetic - increase in cell size either by cell elongation or organelle number
- Accretionary - increase in extracellular tissue
Define labile cells, stable cells and permanent cells.
Labile cells- Continuously proliferate, short lifespan and rapid turnover time e.g. blood cells and epithelial cells
Stable cells (facilitative dividers)- Good regenerative ability but would normally have low cell turnover.( e.g. quiescent tissues - hepatocytes)
Permanent cells- little/no regenerate ability (cardiac muscle, neurons)
If a cell cannot adapt then it will likely die. Define the 4 reversible changes involved in adaptation.
What is cell injury. Example?
- Metaplasia- conversion of one mature(differentiated) cell type to another
- Hyperplasia- cell number increases
- Atrophy- cell size decrease
- Hypertrophy- cell size increases
Cells become so severely stressed that they can no longer adapt. In renal tubule, hypoxia causes cells to become disordered and then eventually necrotic.
Consider metaplasia. Give a physiological and pathological example.
Physiological:
Simple columnar epithelium changes to stratified squamous epithelium due to acidity of vagina.
Pathological:
Oesophagus- squamous to columnar due to gastric acid
Pseudostratified ciliated columnar epithelium changes to squamous due to smoking
Columnar endocervical mucosa to squamous once infected by HPV.
Consider hyperplasia. Give a physiological and pathological example.
Physiological:
Hormonal- increases functional capacity e.g. in breast feeding
Compensatory- when tissue is lost( partial liver resection_
Pathological:
Excess hormonal stimulation -
Endometrial (causes increased oestrogen)
Prostatic (causes increased androgens)
Consider atrophy. Give a physiological and pathological example.
Physiological:
Post menopausal atrophy of the uterus due to lack of oestrogen stimulation
Pathological: Denervation of muscle Malnutrition Disuse of muscle/bone Pressure atrophy owing to adjacent mass effect (tumour)
Consider hypertrophy. Give a physiological and pathological example.
Physiological:
Uterine lining (muscle increases during pregnancy)
Weight training
Pathological: Cardiac hypertrophy (causes ventricular wall to increase from 1.5cm to 4cm, higher nutrition demand, coronary heart vessels don't increase in size -> MI)
Bladder hypertrophy (caused by prostatic enlargement)
Describe the two forms of cell death.
Apoptosis- programmed cell death. Membrane remains intact, nuclei fragment.
Necrosis- death due to accidental damage. Involves groups of cells. Cellular debris stimulates inflammatory cell response. Membrane becomes impaired and contents leak out.
Describe the mechanism by which necrosis occurs.
ATP depletion Mitochondrial damage Influx of calcium ions Accumulatio of oxygen radicals Increased membrane permeability DNA and protein damage
Describe the three types of necrosis.
Coagulative -shape and architecture preserved
Liquefactive- liquefied, viscous, soft lesion usually in brain as a result on bacterial infection
Caseous- cottage cheese like (mycobacterial)
Briefly describe the mechanism of apoptosis and give a physiological and pathological example.
Activation of caspase 3 leads to degradation of DNA and protein.
Pathological: In embryogenesis( between fingers) High turnover tissues Elimination of autoimmune lymphocytes Death of inflammatory cells after response
Physiological:
DNA damage
Infection
Duct obstruction
What is autophagy?
A survival mechanism by which the cell breaks down its contents to maintain metabolic processes in states of nutrition deprivation.
It can be employed to combat neoplasia.
Describe the three methods by which the body can recover from injury.
- Resolution & Scavenging - the tissue damage is limited and there is fast enough removal of debris
- Regeneration- extracellular matrix is intact, mild superficial injury.
- Repair- extracellular matrix is impaired. Severe injury. Occurs in permanent tissues such as brain and heart muscle.
Which cells are most important in resolution and scavenging? Describe their role.
Macrophages
Monocytes travel to sinusoids in liver, bone marrow and spleen.
They act as filter tissue to remove abnormal cells and clear off stimuli.
Produce growth factors for the proliferation of cells in healing response
Describe the 5 activities involved in resolution and scavenging.
- Chemotaxis (attraction of macrophages to site)
- Hypertrophy ( histiocytes get larger and aggregate)
- Pseudopodia (active movement)
- Pinocytosis (degradation of small molecules and ingest fluid from surroundings)
- Phagocytosis (ingestion of large molecules)
Describe the importance of stem cells in regeneration.
They have prolonged self renewal capacity and asymmetric replication.
For example liver tissue, regeneration occurs via stem cells if stromal reticulum scaffolding remains intact
Epithelial cells increase stem cell division and decrease time it takes for cell cycle to occur.
How is regeneration controlled?
- Interactions between macrophages and stromal reticulum scaffolding/ extracellular matrix
- Growth and transcriptional factors which set of signalling pathways.
Describe repair in terms of tissue response to injury.
State the processes which lead to scar formation.
A response by fibroblasts that leads to the formation of fibrotic scar tissue.
Normal tissue Tissue injury Inflammatory response Granulatiom tissue formation Scar tissue
Explain the events involved in scar formation in terms
- Formation of Angiogenesis
- Formation of granulation tissue
- Scar formation
- Scar modelling
- Vasodilation, BM degradation, migration of end cells and endothelium precursor cells from bone marrow, proliferation of end cells, maturation of end cells into tubes and finally development of blood vessel walls.
VASCULAR ENDOTHEIUM GROWTH FACTOR - Angiogenesis and proliferation of fibroblasts, new vessels are leaky which leads to oedema. Granulation tissue contains new blood vessels, fibroblasts and neutrophils.
- Growth factors from macrophages caused migration and proliferation of fibroblasts into gran tissue. This produces extracellular matrix proteins.
FIBROBLAST GROWTH FACTOR & TRANSFORMING GROWTH FACTOR ALPHA - interactions of collagen deposition and degradation by MMPs. Contraction of scar tissue. Type 3 collagen to type 1. Tissue only 80% strength of original tissue.
Describe healing by a)primary intention b)secondary intention c) tertiary intention.
a) No loss of tissue (lacerations, bone fractures)
b) Significant loss of tissue (abscess, infection laceration that has led to necrosis of some tissue)
c) Initially left open to allow drainage and the would heals from bottom up
Consider the local impediments to reparation of tissue.
Infection Haemotoma Denervation Site Necrotic tissue Poor blood supple Mechanical stress
Consider the systemic impediments to reparation of tissue.
Age Diabetes Malignancy Malnutrition Anaemia Obesity Trauma Vitamin C deficiency Infection/sepsis Drugs
Consider the possible complications of would healing.
Give examples in the case of
a) deficient scar formation
b) excessive scar formation
a) dehiscence (wound rupture along a surgical line)
ulceration
b) keloid, abnormal adhesions
Describe the microscopic appearance of granulate tissue that is being replaced by collagen
How does scar tissue differ to adjacent dermis?
How does the overlying epidermis differ from the adjacent epidermis?
Edge of wound = granulate tissue and acute inflammation
Centre= collagen
Less collagen, more cellular due to presence of fibroblasts
Thicker, longer protrusions (hyperplasia).
What are the 8 things you want to know about a disease?
Epidemiology- prevalence, incidence, distribution Aetiology- cause Pathogenesis- mechanism "how" Pathological & clinical features Complications Sequalae- consequences Prognosis Treatment
Describe the 8 steps involved in preparing a histological artefact.
- Receipt
- Data Entry
- Fixation
- Specimen dissection (in numerous planes)
- Processing (removing tissue fluid and replacing it with paraffin and bees wax)
- Embedding in wax block
- Microtome cutting (block cut into micron thickness)
- Staining in order to see specimen - Haematoxylin(purple nucleus) & Eosin (Red cytoplasm)
What is immunohistochemistry ?
Name a protein granular cell tumours are positive for.
Which other cell type is positive for this?
Detection of proteins on cells
s100
Langerhan cells
Which germ layer do epithelium originate from?
What are glands/ducts?
Can originate from all three germ layers (ectoderm, mesoderm, endoderm)
Specialised ingrowths of epithelium.
Describe three types of epithelium.
Squamous epithelium- look like flattened circles
Columnar epithelium- nuclei at basal side
Stratified epithelium- looks cuboidal
What are the two types of glandular epithelium? Give examples.
Duct- produce and secrete substances onto an epithelial surface by way of a duct. E.g. sweat, saliva, lacrimal
Ductless- endocrine glands that secrete substance directly into vascular system to distant tissues. E.g. thyroid, islets of Langerhans, adrenal glands.
Describe 5 features of the structure of epithelium.
- Adhere to each other
- Tight junctions to seal borders
- Desmosomes for strength
- Gap junctions- allow transfer of molecules
- Cytokeratin intermediate filaments within cytoplasm to provide internal structure.
Describe the layers of a neurovascular bundle vessel.
Tunica Intima- endothelium on connective tissue
Elastic intima
Tunica Media- circumferential smooth muscle
Elastic externa
Tunica Adventitia- collagen and vascular supply to wall. Outer connective tissue
State the 10 properties/functions of skin.
- immune function
- secretory function
- vitamin d metabolism
- sensory function
- protection from infection (barrier)
- sexual/social significance
- control of body temperature
- waterproofing
- protection from injury
- maintenance of integrity
Describe the three structures that make up skin.
Epidermis- collagen type 4, connected to BM. Stratified squamous epithelium.
Dermis- connective tissue of mesenchymal origin
Subcutaneous fat
What are the steps of terminal differentiation of keratinous epithelium?
Stratum cornum (Horny cell layer)- cornified Stratum lucidium - only in thick skin, separates SC and SG Stratum granulosum (Granular cell layer) Stratum spinosium (Spinous cell layer)- contains desmosomes Stratum basalis (Basal cell layer)
Describe three other cells that occur in the epidermis.
- Melanocytes- originate from neural crest and stuck to BM. 1 melanocyte provides melanin to 36 keratinocytes. Keratinocytes phagocytosise melanin from melanocyte dendrites.
- Langerhan cells- originate from bone marrow, dendritic and antigen presenting cells.
- Merkel cells- originate from neural crest. Mediate tactile sensations(pressure in skin), associated with sensory neurone endings.
How do sebaceous glands in the face cause acne?
What do they look like at low magnification?
They secrete lipid rich liquids. Controlled by sex hormones.
Bunch of grapes.
What happens in eczema?
Irritated skin causes increase in thicknesss of keratinous layer, cornified layer and spinous layer (acanthiosis).
What are the two types of sweat glands? Explain.
What type of epithelium line these glands?
Eccrine All over the body Inner secretory epithelium Outer myoepithelium Responsible for temperature control
Apocrine
Axillary, nipple and groin
Responsible for body odour (bacterial fermentation)
Large irregular shaped lumen
SIMPLE CUBOIDAL
Describe the three commonest skin cancers.
- Basal cell carcinoma- infiltrates locally, mutiple and reoccurring
- Squamous cell carcinoma - described as being well to poorly differentiated based on keratin level. spreads to lymph nodes, lungs, liver and brain commonly
- Malignant melanoma- spreads to lymph nodes, lungs, liver and brain commonly. Pagetoid patterns
State three diseases involving melanocytes.
- Melanoma
- Albinism - defect in tyrosinase which controls of melanin production.
- Congenital naevus - birth mark, hyper pigmentation
Name 5 surfaces covered in non-keratinised squamous epithelium
Where is the body has a thick layer of keratinised epithelium?
- Mouth
- Oesophagus
- Anal canal
- Cervix
- Vagina
Hands and foot bottom
State 4 characteristics/functions of the keratinised layer.
- Protects against infection
- prevents dehydration
- consists of dead cells
- increased thickness when irritated
Where do coronary arteries originate?
Describe the branching of coronary artery
Aortic root
Right coronary artery
Left circumflex coronary artery
Left anterior descending coronary artery
What happens in atherosclerosis?
Intima gets thicker duet liquid deposit of plaque(oxidised fatty acids) causing narrowing artery.
Overtime the plaque becomes calcified.
All atheroma have a thin fibrous cap that can rupture resulting in a prothrombotic cascade of events resulting in a thrombus.
Whats the difference between a thrombus and embolus?
A blood clot forming within a vessel = thrombus
A blood clot loving within a vessel = embolus
What are consequences of vascular occlusion?
Thrombus stops blood flow resulting in ischaemia(lack of blood flow)
This leads to: Hypoxia (lack of oxygen) Accumulation of toxic metabolites Reversible cell injury Irreversible cell injury Cell death
