L02: Tissue Structure and Integrity
• Pathology: Study of Diseases and their effects on normal structure and
function. Tissue Pathology studies the changes that occur at the tissue level
in a disease
• Tissue sample preparation
o Biopsy
o Tissue collection
o Tissue fixation
o Tissue is embedded in a cassete
o Tissue is cut in a microtome
o Tissue is placed in a slide
o Tissue is stained
• H&E Tissue Staining
o Haematoxylin: Stains the nucleus of cells
o Eosin: Stains cytoplasmic components and collagen, elastic fibers
(pink)
• Immunohistochemistry
o Indirect immunohistochemistry
▪ a primary antibody specific to the antigen of interest is applied to
the tissue sample, followed by a secondary antibody that is
conjugated to a detectable label, such as a fluorescent molecule
or an enzyme. The secondary antibody recognizes and binds to
the primary antibody, amplifying the signal and allowing the
antigen to be visualized.
o Immunofluorescence
▪ use of primary antibodies specific to the antigen of interest,
followed by secondary antibodies that are conjugated to a
fluorescent dye, such as fluorescein isothiocyanate (FITC),
rhodamine, or Alexa Fluor dyes. When the sample is excited
with light of the appropriate wavelength, the fluorescently-
labeled antibodies emit light, allowing the antigen to be
visualized under a fluorescence microscope.
• H&E studies are employed:
o In blood analysis
o Quantitation of collagen fibers
o Detection of proteins in tissue
o Stains the nucleus and cytosolic components
• Digital Pathology and AI:
o In blood analysis
o Automated analysis and quantification of stained tissues
o Can be employed for light and fluorescence microscopy
, o It is able to predict disease formation and progression from the
beginning of the disease
L03/L04: Lung pathology Commented [MN1]: faq asked about the
lack of focus on restrictive disorders
• There are 2 lungs with the right lung having 3 lobes and the left lung having 2
lobes
• The division between a lobe is called bronchopulmonary segment
• The main function of the lung is the exchange of gas (CO2, and O2)
• Gas exchange occurs in the alveoli- it's a passive exchange through gradient -
higher to lower partial pressures
• Breathing starts with the nose. The nose has very important functions like
filtration, antibacterial and pathogenic mechanisms.
• There are cellular resemblances through the entire respiratory tract
• Pleura- membrane that surrounds the lungs and ensure difference in
pressures allowing the lungs to expand
• The diaphragm helps with inspiration and aspiration
• The bronchus has variety of different cells:
o Progenitor cells (basal cells)- repair and replenish the tissue
o Ciliated cells- present a cilia
o Goblet cells: secrete mucus, mucus has a protective role
o Smooth muscle
o Cartilage
o Submucosal glands
• Alveoli has capillary cells because blood has to flow to allow gas exchange to
occur. There are different types of pneumocytes I and II
• Type II pneumocytes secrete surfactant. Surfactant increases surface tension
and prevent collapsing of alveoli
• Lung mechanics:
o Compliance: measure of lung expandability (ability to stretch and
expand). Important factors: elastic fibres and surfactant (Surface
tension)- stretchability
▪ In diseases where the two factors are dysregulated it results in a
change in compliance hence promoting pathological
consequences
o Recoil: lung’s intrinsic tendency to deflate following inflation
• Compliance in restrictive vs obstructive diseases:
o Restrictive lung diseases- decreased compliance
▪ Loss of elasticity- fibrosis, oedema
▪ Loss of surfactant- ARSD
o Obstructive lung disease- increased compliance
• Obstructive lung disease- Asthma/COPD
• Restrictive lung disease- fibrosis/pneumothorax
• Recoil and compliance are usually inverse
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, • Tidal volume- breathing volume without any extra- the amount of air that
moves in or out of the lungs with each respiratory cycle
• Inspiratory Reserve Volume (IRV)- It is the amount of air that can be forcibly
inhaled after a normal tidal volume. IRV is usually kept in reserve, but is used
during deep breathing
• Residual volume (RV) is not accessed
• In obstructive lung disease like asthma and COPD the residual volume (RV) is
increased.
• In restrictive lung diseases, since compliance is decreased lung volumes are
decreased
Restrictive lung disease Obstructive lung disease
Reduced distensibility Increases resistance to airflow
Lung expansion compromised (decreased Increase in compliance
in lung compliance/ stretchability)
Reduced total lung capacity (TLC) Increase total lung capacity (TLC)
20% of lung diseases as restrictive 80% of lung diseases
Decreased ERV and IRV Increased RV
Normal or slightly increased FEV1/FVC Decreased FEV1/FVC
• FEV1/FVC ratio- forced expiratory volume in one second over the forced vital
capacity of the lungs
• In obstructive diseases the air flow occurs at a slower rate- breathing is slower
• In restrictive disease the amount of air breathed in is reduced but the speed of
breath out is preserved
• There are two main components related to how we breath- structure and
inflammatory
• Part of the innate immune system- granulocytes (neutrophils, basophils and
eosinophils), macrophages, dendritic cells, NK cells, mast cells, complement
• Part of the adaptive immune system- B cell, T cells (CD4, CD8) and
antibodies
• Innate immune system: first line of defence, general, rapid responses
• Adaptive immune system: directed by the innate immune cells, antigen-
specific, memory, late response
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, • Asthma and allergy are different
• Hypersensitivity is a immunologically driven host tissue damaging process or
an immunologically driven tissue irritating process
o Either causes irritation or damage but is driven by the immune system
• Types of hypersensitivity: type I, type II, type III, type IV
• Type I: Immediate hypersensitivity (Allergy, Anaphylaxis and Atopy)
o Non-microbial environmental antigen that are innocuous. Response
within immune. Mediated by IgE mast cells
o Hallmarks: IgE production and activation of Th2 cells
• Type II: Antibody mediated
o IgM, IgG antibodies against surface/extracellular matrix. Complement
mediated
• Type III: immune complex mediated
o Soluble immune complexes antigen – IgM or IgG. Complement
mediated
• Type IV: cell mediated (delayed)
o CD4 and CD8 cell. Cell killing and cytokine mediated inflammation,24h
to 48h
• Type I and type IV are the two types that interact closer to the lung pathology
studied
• Mode of action: Type I hypersensitivity
o Dendritic cell encounters antigen which in turn activates Th2 cells
o Th2 cells secrete IL13, IL4, IL5
o The cytokines cause class switching in B cells, making IgE
o IgE is related to allergy and IgE binds to the surface of mast cells which
have IgE receptors on their surface. The binding between IgE with IgE
receptors is called sensitization
o When two IgEs bind to IgE receptors it causes degranulation of mast
cells
o Mast cells release histamine
o IL-5 causes the activation and proliferation of eosinophils. Eosinophils
have toxic granules that cause tissue damage
o IL13 increases mucus hypersecretion- excessive mucus is not desired
• Sensitization refers to the first interactions with the allergen prior to
developing an allergy
• Mast cells have storage granules that contain histamine and tryptase
• Histamine increases vascular permeability and smooth muscle contraction
• Tryptase causes tissue remodelling and increase mucus secretion
• Mast cells when activated undergo de novo synthesis. De novo synthesis is
associated with factors that are not premade but factor that made new when
mast cells are activated.
o Activation comes from antigen crosslinking of two IgE
• De novo synthesis factors: prostaglandins, leukotrienes and cytokines
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