Case 5 pbl
2. Respiratory System
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Divided in upper and lower respiratory system
 Upper respiratory system: nose, nasal cavity, paranasal sinuses, pharynx
 Lower respiratory system: larynx, trachea, bronchi, bronchioles and alveoli of lungs
Thoracic inlet narrower
 Anything that expands here exerts pressure
 Will squash oesophagus and veins
 Superior vena cava syndrome or superior mediastinal
syndrome
Upper respiratory system
Nose, nasal cavity, paranasal sinuses
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Nose primary passageway for air entering the respiratory system
Air enters through nares open into nasal cavity
Nasal vestibule is space within flexible tissue of nose
Nasal septum divides nasal cavity into left and right portion
 Bony portion: fusion of perpendicular plate of ethmoid bone and plate of vomer
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 Anterior portion: hyaline cartilage nasi and apex of nose
Maxillary, nasal, frontal, ethmoid, sphenoid bones form lateral and superior walls of nasal
cavity
Nasal cavity consists of vestibule, respiratory portion and olfacotyr area.
Paranasal sinuses (frontal, sphenoid, ethmoid, paired maxillary and palantine bones) secrete
mucous
 Keep surfaces of nasal cavity moist and clean
Olfactory region is superior portion of nasal cavity
 Areas lined by olfactory epithelium
1. Interior surface of cribiform plate
2. Superior portion of nasal septum
3. Superior nasal conchae
Superior, middle, inferior nasal conchae project toward nasal septum
Air flows between adjacent conchae to pass from vestibule to internal nares
 Through superior, middle, inferior meatuses
 Narrow grooves not open passageways
Air bounces off conchal surface
 Churns
 As it swirls, small particles come into contact with mucous
 Turbulences provides extra time for warming and humidifying
Bony hard palate
 Portions of maxillary and palatine bones
 Forms nasal cavity and separates it from oral cavity
Soft palate
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Fleshy
 Posterior to hard palate, marks boundary between superior nasopharynx and rest of
pharynx
Nasal cavity opens into nasopharynx (connection called internal nares)
Pharynx
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Chamber shared by digestive and respiratory system
Extends between internal nares and entrances to larynx and oesophagus
Superior and posterior walls closely bound to axial skeleton
Lateral walls are flexible and muscular
Pharynx divided into three regions
1. Nasopharynx
 Superior portion
 Connected to posterior portion of nasal cavity through internal nares
 Separated from oral cavity by soft palate
 Lined by pseudostratified ciliated columnar epithelium
 Pharyngeal tonsil located on posterior wall
 Each auditory tube opens into nasopharynx at nasopharyngeal meatus on either side
of tonsil
1. Oropharynx
 Extends between soft palate and base of tongue at level of hyoid bone
 Posterior portion of oral cavity and posterior inferior portion communicates directly
with oropharynx
 Boundary between nasopharynx and oropharynx: epithelium changes from
pseudostratified columnar epithelial to stratified squamous epithelium
1. Laryngopharynx
 Inferior portion of pharynx
 Portion of pharynx between hyoid bone and entrance to pharynx and oesophagus
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Lined with stratified squamous epithelium
Lower respiratory system
Larynx
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Cartilaginous tubes that surrounds and protects glottis
At top of trachea
Prevents foreign material other than air going down
Helps with phonation
Begins at level of C or C
Ends at level of C
Divided into three regions
1. Supraglottis
 Epiglottis
 False vocal cords
 Laryngeal ventricles
1. Glottis
 Consists of true vocal cords
 Anterior and posterior commissues
1. Subglottis
 Region below true vocal cords
 Extending down to lower border of cricoid cartilage
Three, unpaired cartilages form larynx
1. Thyroid cartilage
 Largest laryngeal cartilage
 Hyaline cartilage
 Anterior and lateral walls of larynx
 U shaped (posteriorly incomplete)
 Inferior surface articulates with cricoid cartilage
 Superior surface has ligamentous attachments to hyoid bone and to epiglottis and
smaller laryngeal cartilages
 Superior to cricoid cartilage
1. Cricoid cartilage
 Hyaline cartilage
 Posterior portion greatly expanded provide support in absence of thyroid cartilage
 Protects glottis and entrance to trachea
 Broad surfaces for attachments of laryngeal muscles and ligaments
 Ligaments attach inferior surface to first tracheal cartilage
 Superior surface articulates with arytenoid cartilages
1. Epiglottis
 Projects superior to glottis
 Elastic cartilage
 Ligamentous attachments to anterior and superior borders of thyroid cartilage and
hyoid bone
 During swallowing, larynx elevated epiglottis folds back over glottis prevents
liquids and solids entering respiratory tract
Larynx contains three pairs of small hyaline cartilages
1. Arytenoid cartilages
 Articulates with superior border of enlarged portion of cricoid cartilage
1. Corniculate cartilages
 Articulates with arytenoid cartilages
 Corniculate and arytenoid cartilages function in opening and closing of glottis and
production of sound
1. Cuneiform cartilages
4
6
5
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Elongated, curving
Lie within folds of tissue that extend between lateral surface of each arytenoid
cartilage
Ligaments bind varius laryngeal cartilages
Ligaments attach thyroid cartilage to hyoid bone and cricoid cartilage to trachea
 Cricotrachael ligament
Median cricothyroid ligament attaches thyroid cartilage to cricoid cartilage
Vestibular ligaments and vocal ligaments extend between thyroid cartilage and arytenoid
cartilages
Vestibular and vocal ligaments covered by folds of laryngeal epithelium
 Vestibular ligaments: lie within superior pair of folds (vestibular folds)
 Folds inelastic
 Lie laterally to glottis
 Prevent foreign objects entering open glottis
 Protect vocal folds of glottis
Glottis is made up of vocal folds
 Space between them rima glottides
 Highly elastic
 Involved with production of sound known as vocal cords
Trachea
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Tough, flexible
tube
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2,5cm in diameter, 11cm in length
Begins anterior to C in ligamentous attachment to cricoid cartilage
Ends in mediastinum at level of T branches into right and left pulmonary bronchi
Contains 15-20 tracheal cartilages stiffen tracheal walls and protect airway prevent it
from collapsing or over expanding in respiratory system
Each tracheal cartilage is C-shaped
 Closed portion of C protects anterior and lateral surfaces of trachea
 Open portion of C faces posteriorly toward oesophagus
 Cartilages not continuous posterior tracheal wall can distort when swallowing
 Elastic ligament and trachaelis muscle connect ends of tracheal cartilage
 Tracheal lumen size
 Adult: 12mm (4,5cm )
 1mm decrease in diameter will result in 16% reduction in lumen size
 Neonate: 3mm (0,28cm )
 1mm decrease in diameter will result in 43% reduction in lumen size
 First year of life lumen not >3mm
 In childhood, in mm. responds roughly to age in year
 Implications for infections and trauma to trachea and larynx: children vs adults (eg.
Croup)
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6
5
2
2
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Implications for damage to small diameter airways
Primary bronchi
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Extrapulmonary bronchi
Trachea branches into mediastinum into left and right primary bronchi
Carina separates two bronchi
Have C-shaped rings
 Ends of C overlap
 Right bronchus supplies right lung, left bronchus supplies left lung
 right pulmonary bronchus larger in diameter, descends toward lung at steep angle
 each primary bronchus travels to groove along medial surface of lung
 groove hilum of lung
 provides access for entry to pulmonary vessels, nerves, lymphatics
 entire complex is the root of the lung (anterior to T (right) and T (left))
 root attaches to mediastinum and fixes positions of major nerves, blood vessels and
lymphatic vessels
5
Lungs
 surrounded by pleural
cavities
 each lung is a blunt cone
 its apex points superiorly
 extend above clavicle
 apex on each side extends superior to first rib
 concave inferior rests on superior surface of diaphragm
6
 many impressions on lung
 left: arch of aorta
 right: azygous vein
 hilar contents
 bronchi
 pulmonary arteries
 pulmonary veins
 bronchial arteries
 lymphatics and nodes
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parasympathetic nerves
sympathetic nerves
Lobes and surfaces of lungs
 lungs have lobes separated by deep fissures
 right lung has three lobes separated by horizontal and oblique fissures
 Superior
 Middle
 Inferior
 Left lung has two lobes separated by oblique fissure
 Superior
 Has a lingula
 Inferior
 Right lung broader than left lung
 Left lung is longer than right lung
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Indented by cardiac
notch
Lymphatic
drainage
Bronchi
 As primary bronchi enter lungs, they divide to form smaller passageways
 Intrapulmonary bronchi
 Primary bronchus divides to form secondary bronchi (lobar bronchi)
 One secondary bronchus goes to each lobe
 Right lung has three secondary bronchi
 Left lung has two secondary bronchi
 Secondary bronchi branch to form tertiary bronchi (segmental bronchi)
 Supplies air to single bronchopulmonary segment
 Portion of lung supplied by specific tertiary bronchus and arteries
 Smallest subunit that a surgeon will resect when taking out a bit of lung
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Has own arterial, lymphatics, venous, air
supply
Right lung: 10 bronchopulmonary segments
Left lung: 8 or 9 bronchopulmonary segments
 Walls of 1 , 2 and 3 bronchi contain progressively less cartilage
 2 and 3 , cartilages form plates arranged around lumen
 Serve same structural purpose as rings of cartilage in trachea and primary bronchi
 As amount of cartilage decreases, amount of smooth muscle increases
 With less cartilaginous support, amount of tension in smooth muscle has greater
effect on bronchial diameter and resistance to airflow
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o
o
o
o
o
Bronchioles
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Tertiary bronchus branches within bronchopulmonary segment
 Forms many bronchioles
 Bronchioles branch into finest conduction branches
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Terminal bronchioles
 Bronchioles have no cartilage
 Smooth muscle tissue
Pulmonary lobules
 Connective tissue of root of each lung extend into lung’s parenchyma
 Trabeculae (fibrous partitions) branch repeatedly, dividing lobes into smaller compartments
 Branches of conducting passageways, pulmonary vessels and nerves of lungs follow
these trabeculae
 Finest partitions (interlobular septa) divide lung into pulmonary lobules
 Branches of pulmonary arteries, pulmonary veins, respiratory passageways supply each
lobule
 Connective tissues of septa are continuous with those of visceral pleura
 Terminal bronchiole delivers air to single pulmonary lobule
 Within lobule, terminal bronchiole branches to form several respiratory bronchioles
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Thinnest
Alveolar ducts and alveoli
 Respiratory bronchioles connected to individual alveoli and to multiple alveoli along alveolar
ducts
 Alveolar ducts end at alveolar sacs (common chambers connected to multiple individual
alveoli)
 Alveoli give lungs open, spongy appearance
 Each alveolus associated with extensive network of capillaries
Pleura
 Two layers
 Visceral layer
 Seals lung surface
 Prevents leakage of air into thoracic cavity
 Parietal layer
 Thicker
 Lines inner surface of thoracic c
2.
3.
4.
5.
Mechanics of pulmonary ventilation
Muscles causing lung expansion and contraction
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Lungs expanded and contract in two ways:
1. Downward and upward movement of diaphragm
2. Elevation and depression of ribs
Normal quiet breathing accomplished mostly by first method
 Inspiration: contraction of diaphragm pulls lower surfaces of lungs downward
 Expiration: diaphragm relaxes, elastic recoil of lungs, chest wall and abdominal
structures compress lungs and expels air
Heavy breathing
 Elastic forces not powerful enough to cause necessary rapid expiration
 Extra force achieved by contraction of abdominal muscles
 Pushes abdominal contents upward against bottom of diaphragm
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Compresses lungs
Expanding lungs by raising rib cage
 In natural resting position
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Ribs slant downwards
 Allows sternum to fall backward toward vertebral column
 Rib cage is elevated, ribs project directly forward
 Sternum moves forward
 Away from spine
 Makes anteroposterior thickness of chest 20% greater during maximum
inspiration than during expiration
Muscles that elevate chest cage muscles of inspiration
 External intercostal
 Sternocleidomastoid muscle (lift up sternum)
 Anterior serrati (lift many of ribs)
 Scalene (life first two ribs)
Muscles that depress chest cage muscles of expiration
 Abdominal recti (powerful effect of pulling downward on lower ribs at same that
they and other abdominal muscles compress abdominal contents against
diaphragm)
 Internal
intercostals
Movement of air in and out of lungs and pressure that cause movement
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Lung is elastic structure, collapses
No attachment between lung and walls of chest case
 Only suspended at its hilum from mediastinum
Lung floats in thoracic cavity
 Surrounded by pleural fluid
 Lubricates movement of lungs within cavity
Continual suction of excess fluid into lymphatic channels
 Maintains slight suction between visceral surface of lung pleura and parietal pleural
surface of thoracic cavity
Pleural pressure and its changes during respiration
 Pleural pressure: pressure of fluid in thin space between lung pleura and chest wall pleura
 Slight suction negative pressure
 Normal pleural pressure at beginning of inspiration: -5cm water
 Amount of suction need to hold lungs open to their resting level
 During normal inspiration, expansion of chest cage pulls outward on lungs with greater force
 Creates more negative
pressure
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-7,5cm water
Alveolar pressure
 Pressure of air inside lung alveoli
 Glottis open no air flowing into or out of lungs
 Pressures in all parts of respiratory tree equal to atmospheric pressure (0cm water
pressure)
 To cause inward flow of air into alveoli during inspiration
 Pressure in alveoli must fall to value slightly below atmospheric pressure
 Normally -1cm water
 Enough to pull 0,5l of air into lungs in 2 seconds required for normal quiet
inspiration
 During expiration
 Alveolar pressure rise to +1cm of water
 Forces 0,5l of inspired air out of lungs during 2-3 seconds of expiration
Transpulmonary pressure
 Difference between alveolar pressure and pleural pressure
 Pressure different between that in alveoli and that on outer surface of lungs
 Measure of elastic forces in lungs that tend to collapse the lungs at each instant of
respiration
 Called recoil pressure
Compliance of lungs
 Extend to which lungs will expand for each unit increase in transpulmonary pressure
 Total compliance of both lungs together in normal lung: 2ml of air per cm of water
transpulmonary pressure
Compliance diagram of lungs
 Relates lung volume changes to changes in transpulmonary pressure
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characteristics of compliance diagram determined by elastic forces of
lungs
1. Elastic forces of lung tissue itself
 Determined by elastin and collagen fibres interwoven among lung parenchyma
 In deflated lungs: fibres elastically contracted
 In expanded lungs: fibres stretched, elongate and exert more elastic force
1. Elastic forces caused by surface tension of fluid that lines the inside wall of the alveoli
and other lung air spaces
 Lungs filled with air interface between alveolar fluid and air in alveoli
Transpleural pressures required to expand air-filled lungs are 3x as great as those required
to expand saline solution-filled lungs
 No air-fluid interface
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Surface tension effect no present
Only tissue elastic forces operative in saline-solution filled lungs
Tissue elastic forces tending to cause collapse of air-filled lung represent only 1/3 of total
lung elasticity, fluid-air surface tension forces in alveoli represent 2/3
Fluid-air surface tension elastic forces increase when surfactant not present
6.
Typical versus atypical bacteria:
include S. pneumoniae, Haemophilus influenzae,
Staphylococcus aureus, group A streptococci and gram-negative
bacteria e.g. Klebsiella pneumoniae.
Atypical pneumonia refers to pneumonia caused by Legionella spp,
Mycoplasma pneumoniae, Chlamydophila pneumoniae, and
Chlamydophila psittaci.
Typical organisms
:Influenza viruses ,Parainfluenza viruses, Respiratory syncytial
virus, Coronavirus e.g. SARS-CoV-2.
Viruses
In paediatrics:
-Viruses are the commonest cause – RSV most common, parainfluenza,
influenza, adenovirus, human metapneumovirus.
-Streptococcus
agalactiae, Listeria monocytogenes, Escherichia coli, Bordetella pertussis,
Staphylococcus aureus
7. Hypersensitivity The basic pathophysiological reaction of hypersensitivity results from the
interaction between antigen of endogenous or exogenous origin with specific antibody, cells
or complement (immune effectors). These reactions, instead of protecting the individual, are
associated with tissue damage or harm.
Allergy is an immune-mediated reaction associated with tissue damage or harm caused by
exposure to a particular foreign antigen (allergen), usually harmless. The reaction can be
reproduced and is often more severe on repeat exposure
8.
10. a)
i) Beta-2 agonits couse smooth muscle dilation, Bronchodilation, Vasodilation and
Release of insulin.
Types of beta-2 agonists
-
Short-acting beta-2 agonists
Long-acting beta-2 agonists
Ultra-long-acting beta-2 agonists
Short-acting beta-2 agonists is rescue drugs because they are used to treat acute
bronchospasm.
E.G
- Albuterol (Ventolin, Proventil)
- Levalbuteral (Xopenex)
- Metaproterenol (Alupent)
Long-acting beta-2 agonists are maintenance medications because they are used to
control and maintain conditions that cause chronic bronchospasm. Useful for
maintaining patients with asthma and COPD who are not having an acute
exacerbation.
E.G
- Arformoterol ( Brovana)
- Salmeterol (Serevet)
- Form
ii) Inhaled β2-agonists and corticosteroids often used together in control of asthma
-
Corticosteroids increase gene transcription of β2
Corticosteroids protect against down-regulation of β2-receptors after long term
administration
- The airway smooth muscle has few adrenergic nerve fibres but many β2-receptors
stimulation causes bronchodilation
- Activation of β2-adrenoreceptors relaxes smooth muscle by increasing intracellular cAMP
 Activates kinase
- Inhibits muscles contraction by phosphorylating and inhibiting myosin-light-chain kinase
 )
b) Compare the effectiveness and safety of inhaled versus oral corticosteroids. Why are oral
corticosteroids are indicated in the acute treatment of severe asthma exacerbations and
inhaled steroids preferred for chronic maintenance treatment?
- Inhaled steroids are usually effective in 3-7 days hence oral corticosteroids may be indicated
in severe asthma exacerbations
- Oral administration is associated with many serious adverse effects hence not indicated for
long term effects
- Low bioavailability of active drug in inhaled corticosteroids
-
-
-
c)Controllers
act by providing long-acting bronchodilation and/or have anti-inflammatory action
 prevent/diminish inflammatory process and its increase in airway hyper-reactivity
some mediations are primarily directed at underlying inflammatory mechanism of asthma
that leads to chronic symptoms and possible permanent lung damage
corticosteroid asthma medications are probably most effect controller treatments
 block or suppress most aspects of inflammation in all individuals
 inhaled or oral corticosteroids
also mast cell stabilizers
controller medications are used on daily basis for long-term control of chronic asthma
 take even when you have no symptoms
 not effect in treatment of acute symptoms
Importance of adherence
It is very important to adhere to medication and use the controllers and relievers
appropriately
Overuse of relievers (more potent drugs) leads to over medication and possible death
If one uses a controller instead of a reliever there is a chance of death or hospital
admittance because they do not relieve acute symptoms
If one does not adhere to the controller:
 There will be chronic inflammation leas to possible permanent lung damage
 The asthma is poorly controlled and leads to repeated, increasingly severe acute
asthma attacks

14. Definition: large-scale grouping of people who share common economic resources
which strongly influence types of lifestyles they are able to leader
-
-
Ownership of wealth with occupation are bases of class differences
Upper class – wealthy, employers, industrialists, top executives (those who own or directly
control productive resources)
Middle class – white-collar workers and professionals
Working class – blue collar or manual jobs
Peasants – people engaged in traditional types of agricultural production, largest class in
third world countries
Class determines what opportunities one has access too
People in lower class often cannot get opportunities to access health care
 They may not be able to afford
 They may not be able to get time off work to access health care
 Health professionals may not explain things properly because the health professional
believes they are uneducated
3. 4.Prevention
• Bacillus Calmette–Guérin (BCG) vaccine
• Live, attenuated strain of M. bovis
• Given intradermally at birth
• Variable success
• Probably reduces disseminated TB and TB meningitis
• Can cause “BCGitis”
• Antiretrovirals
• Improve patient’s immune status
• Population-level effect of reducing TB incidence
• Undiagnosed TB can be uncovered by the immune reconstitution inflammatory syndrome (TB-IRIS)
• Treated TB can also worsen (“paradoxical” TB-IRIS) Prevention
• INH preventive therapy
• For latent TB
• Prevents progression to active TB
• Indicated for children with close household contacts
• Still under consideration for people living with HIV (PLHIV)
• Usually, INH for 6-9 months
• Improvement of socio-economic conditions / health inequalities
• Poor living conditions
• Overcrowding
• Undernutrition
• HIV
Tuberculin skin test (Mantoux)
• Purified protein derivative (PPD) of MTB is injected intradermally
• Test for latent TB
• Skin surface is monitored for reaction over 3 days
• Reaction represents immune response to PPD,
• The size of the reaction determines positivity
• Used primarily in paediatrics in high burden areas
Epidemiology
• In 2019, an estimated 10 million people fell ill with TB worldwide
• A total of 1.4 million people died from TB in 2019 worldwide
• The estimated prevalence of TB (all ages, all forms) in South Africa in 2018 was 737 per 100,000
population
• It is estimated that about 80% of the population of South Africa is infected with TB bacteria (latent
TB)
• In 2019 a total of 58,000 people died of TB in South Africa
Molecular diagnosis • GeneXpert (Xpert MTB/RIF Ultra) • Widely implemented in South Africa • First
line testing for all pulmonary samples • Decentralised testing through National Health Laboratory
Service (NHLS) • Has replaced sputum microscopy • Also WHO-recommended for certain
extrapulmonary samples • Line probe assay • Highly technical PCR assay to detect resistance to
rifampicin, INH and fluoroquinolones • There are other molecular tests available or in development
Molecular diagnosis • GeneXpert platform • Xpert MTB/RIF Ultra • Cartridge based real-time PCR •
Detects MTB and rifampicin-resistance (rpoB mutations) • Advantage • More sensitive than acid-fast
stain microscopy • Rapid turnaround time (
Lymph Node Gartner: Textbook of Histology Lymph Node functions
• Filtration of lymph (non-specific) Removal of particulate matter and microorganisms
• Interaction T-Lymphocytes with antigen Involves uptake of antigen by APC
• Aggregation and proliferation of lymphocytes Both B- and T-lymphocytes
• Activation of lymphocytes Antibody secretion (B-cells) and T-cell-mediated response Histological
Structure of the Lymph Node Histologically, a lymph node is divided into three regions: Cortex,
Paracortex, and Medulla. Subcapsular sinus Para trabecular sinus Cortex Paracortex Medulla
Medullary cords (consist mainly of lymphocytes, macrophages, and plasma cells Medullary sinuses T
cell rich Macrophages Dendritic cells High endothelial venules B cell rich B-cell rich follicles
Macrophages Dendritic cells Follicular dendritic cells Macrophages Dendritic cells (Stevens and
Lowe: Human histology) Lymphoid Follicle Germinal centre (Pale zone) Mantle /Corona (facing the
cortex) • Primary follicles (lacks a mantle and germinal centre -non-active)
• Secondary follicles (active, with mantle and germinal centre) Dark zone (EL ad Merwe) (Kerr:
Functional Histology) Secondary Follicle structure: Histophysiology Mantle Zone (B cells not specific
for antigen) Germinal centre contains:
•Follicular Dendritic Cells
•Macrophages (phagocytose apoptotic B cells) Mitotic and developing B cells Dark Zone: Antigen
activation of B cells – differentiate & clonal expansion Parafollicular helper T cells (CD4+) activate B
cells to proliferate Mature B cells with high affinity surface IgG determined by FDCs migrate to
medulla & become plasma cells – secrete IgG & IgM into lymph. Lymph Circulation through Lymph
Node (Wheatear’s: Functional Histology)  Afferent lymphatic vessels pierce the capsule and open
into the subcapsular sinus  Para trabecular sinus arise from the subcapsular sinus and penetrate the
cortex and continue into the medulla as branching medullary sinuses surrounded by medullary cords
Palatine tonsils  Separated from underlying tissue by a fibrous hemi capsule  The luminal surface
lined by a stratified squamous epithelium  Parenchyma contains lymphoid follicles with germinal
centres
The Thymus Gland
• Maturation of immunocompetent T-Lymphocytes Immature T-Lymphocytes derived from
bone marrow
• Proliferation of mature T-Lymphocytes Supplies the circulating lymphocyte pool
• Development of immunological self-tolerance Elimination of self-reactive lymphocytes •
Hormone secretion Thymulin, thymopoietin, thymosin: regulate T-cell maturation and
lymphoid tissue development
• During fetal development: haematopoiesis Kierszenbaum & Tres: Histology and Cell
Biology Structure of the Thymus Gland 2 lobes, several “incomplete” lobules Structure of the
Thymus Gland
• T lymphocytes (thymocytes)
• Macrophages
• Dendritic cells
• Subscapular Thymic epithelial cells
• Cortical Thymic epithelial cells
• Blood vessels
• HEV’s
• Blood–thymus barrier Cortex (several distinct lobules) Medulla (shared)
• Immunocompetent T cells
• Macrophages
• Dendritic cells
• Small population of B cells
• Medullary Thymic epithelial cells
• Hassall’s corpuscle Kierszenbaum & Tres: Histology and Cell Biology Cortex: The BloodThymus Barrier Kierszenbaum & Tres: Histology and Cell Biology
• Consists of the cTEC, dual-basal lamina and endothelial cells = Blood–thymus barrier
• Function: Prevent cTEC from interacting with foreign macromolecules - shield developing
thymocytes from exposure to antigens.
• Auto-immune reaction T cell maturation 1 2 3 Proliferation double negative T cells
Maturing double positive T cells (CD4+ & CD8+) become responsive to MHC class I & II MHC
II needed for CD4 MHC I needed for CD8 Cells that recognise self MHC (not self antigens)
allowed to mature to single positive cells (CD4+ OR CD8+) – Positive selection 4
Kierszenbaum & Tres: Histology and Cell Biology Cells recognising self MHC & self antigens –
apoptosis – Negative selection Hassal’s corpuscles - Whorls of thymic epithelial cells Thymic
medulla Kierszenbaum & Tres: Histology and Cell Biology  Capillaries that enter the medulla
from the cortex at the corticomedullary junction drain into postcapillary venules  The
venules are more permeable than are capillaries in the cortex, and the medulla has no
blood-thymus barrier.  Lymphocytes that proliferate in the cortex enter by passing through
walls of these vessels.  Central hyaline core that is eosinophilic and may show signs of
keratinization.  Their function is not well understood, but they express the cytokine thymic
stromal thymopoietin, which instructs dendritic cells in the human thymus to induce CD4 +
regulatory T cell development.  They may also play a role in removing apoptotic
thymocytes. 1) Lymphocytes enter the thymus from blood vessels in the stroma. 2)
Thymocytes enter the cortex. 3) Thymocytes interact with cortical thymic epithelial cells
(cTECs) (positive selection for functional MHC binding). 4) Thymocytes that are positively
selected pass to the medulla where they interact with medullary epithelial cells (mTECs) and
dendritic cells which negatively select cells that bind to self-antigens. 5) T cells leave the
medulla to enter blood vessels in the stroma. 6) T cells of different types now migrate to
secondary lymphoid organs. Lymphocyte Development in the Thymus Nurse cells
Stevens&Lowe: Human Histology The Spleen (Ross et al.)
• Mounts immune response to bloodborne antigens • Filters particles and old/defective
blood cells from circulation
• Fetal development: haemopoiesis Structure of the Spleen Support tissue: - Contains
collagen, elastic fibers and smooth muscle cells - Derived from capsule - Contain trabecula
arteries and veins https://www.amboss.com/us/knowledge/Spleen Kierszenbaum & Tres:
Histology and Cell Biology Cellular components within capsule make up pulp  Red pulp
contains many red blood cells (no.6 in the image)  White pulp resembles lymphoid nodules
(no.5 in the image) Structure of the Spleen Kierszenbaum & Tres: Histology and Cell Biology
https://www.amboss.com/us/knowledge/Spleen White Pulp Each central arteriole is
surrounded by lymphatic tissue calledy PALS (25%) White Pulp: Splenic nodules T cells, B
cells, antigen presenting cells & plasma cells “Central Arteriole” Periarteriolar lymphoid
sheath (PALS) T cells B cell Corona Germinal centre (EL vd Merwe) Arborizing arteries,
surrounded by aggregates of lymphoid tissue (lymphoid sheaths, c. 20% of total spleen
mass) Red Pulp https://www.amboss.com/us/knowledge/Spleen  70% of the red pulp is
composed of parenchyma and 30% is venous sinuses/sinusoids  Sinusoids are surrounded
by reticular fibers  Sinusoids drain into the splenic vein Red Pulp
• Blood filled venous splenic sinusoids – lined by rod-shaped endothelial cells; surrounded
by macrophages, plasma cells and reticular fibers
• Splenic cords (Cords of Billroth) - separate splenic sinusoids; contain plasma cells,
macrophages and blood cells - all supported by a stroma of reticular cells and fibers.
• Macrophage-sheathed capillaries – Function: remove aged cells and particulates from
blood Function: Blood filtration Kierszenbaum & Tres: Histology and Cell Biology Red Pulp 
The macrophage-sheathed capillaries drain into the splenic sinusoids (closed circulation;
non-human) or into the stroma of the red pulp (open circulation; human)  Splenic sinusoids
are drained by collecting veins, to trabecular veins, to splenic veins. Kierszenbaum & Tres:
Histology and Cell Biology (1) Antigens enter the spleen from blood. Blood flows into spleen
through splenic artery and enters central arteriole and marginal channel (2) Antigenpresenting cells detect bloodborne antigens or pathogens present in the red pulp and are
sampled by PALS-derived T cells (3) T cells interact with B cells and from this interaction B
cells proliferate and differentiate into Plasma cells (4) Plasma cells release immunoglobins
into the red pulp and blood circulation to trap specific antigens in the blood (5)
Lymphocytes, macrophages and dendritic cells repopulate the white pulp through the
marginal channel White Pulp Kierszenbaum & Tres: Histology and Cell Biology Red Pulp:
Blood filtering (4) Blood from central arteriole is transported into penicillar arteriole which
ends in macrophage-sheathed capillaries (5) Macrophage-sheathed capillaries drain into
splenic sinusoids or stroma of the red pulp Kierszenbaum & Tres: Histology and Cell Biology
Splenic Circulation
• Blood filtration (red pulp) Blood flows through central arteriole, penicillary arteries and
sheathed capillaries; extravasate, percolation through splenic cords, enter splenic
sinuses/veins. Phagocytic cells remove debris
• Interaction with antigen (white pulp) Blood passes through central and radial arterioles
into marginal channel; extensive contact with APC, antigen presentation to lymphoid cells
A 14-year-old young girl named Cindy Parker lives with her mother, father, sister, and
grandmother. It is a low social class family. Their residential property has carpets and
curtains which can accommodate a lot of house dust mites. They also own a cat which is a
fur pet. Cindy is currently doing grade 9 but nearly did not make it out of grade 8 due to
asthma attacking her respiratory system. She passes out sometimes and cannot participate
in some of the activities done by other school kids. There is a boy that charms her in class
and often misses spending with him. She got a ‘cold’ and started coughing out yellow
sputum. Her grandmother believes the cold weather causes chest symptoms to her
granddaughter. Her mother believes if they were wealthy, her daughter would not have
been so ill. Cindy’s cousin has both eczema and asthma. The doctor did many tests and
examination on Cindy including chest x-ray, then told her family a proper way of using
inhalers together with space device. The doctor also told the family how to stay away or
minimize triggers that may cause exacerbations.
There is prove that changes of the world’s climate affect the health of people, with the poor
being mostly affected than the rich (2022). The reason being that the rich have adequate
shelter when there are world disasters such as earthquakes, tsunamis, cyclones, or extreme
cold and hot temperatures. The poor are helpless, even a small disaster can leave them
homeless and take a lot of time to recover. Lower class individuals live in shanty houses
which can be very hot in hot weathers and very cold in cold weathers. Geography also says
the numbers of suicides peaks in extreme high temperature seasons. A combination of
stress developed from frustration and drastic temperatures can be deadly due to
dehydration and respiratory complications (2022). Cindy and her family live in a breaking
new ground built by the government, it is better than a shark but does not provide enough
shelter to harsh weather conditions. In cold weather it is much colder which is a trigger for
asthma attack, hence Cindy experiences chest symptoms.
Environmental pollution is fatal to people especially young children as it can cause
irreversible respiratory injuries (2022). Air pollution can cause contractive pulmonary
diseases such as empyema and chronic bronchitis. Pregnant women who are exposed to
harmful substances can increase chances of congenital diseases to the new-born babies
(2022), some toxic substances can limit blood flow/oxygen supply to the foetus leading to a
lot of health problems. Harmful substances can also be found in the food we consume and
water drink (2022) such as lead and fluoride. Second hand tobacco smoke is also believed to
increase the prevalence of asthma and COPD, thus women who are expecting and children
must be protected from it (2022). The government should provide clean fuel for heating and
cooking, remove pests and dangerous building materials including lead paint. Promote good
health and public hygiene, free from noise and pollution. Provide safe water and sanitation
(2022). The home of Cyndy has a cat which produces urine and saliva that has proteins that
can cause allergic reactions to human
Cindy is struggling to spend time with loved one. She is concerned about the effect
of asthma medication to contraceptives and the other way around. She wants to be
involved in sexual activities, but her condition serves as a barrier. Everyone has the
right to equality and non-discrimination rights The right to be free of torture and
other brutal, humiliating, or degrading treatment or punishment. A person's right to
privacy. The right to the best possible health (including sexual health), as well as
social security. The right to marry, start a family, and enter into marriage with the
free and complete agreement of the intended spouses, as well as equality in and
after divorce. The right to choose how many children to have and how far apart they
should be (2022). Sexual health is not only the lack of sickness, malfunction, or
infirmity regarding sexuality; it is a condition of physical, emotional, mental, and
social well-being. Sexual health necessitates a positive and respectful attitude
toward sexuality and sexual relationships, as well as the ability to have joyful and
safe sexual encounters devoid of compulsion, prejudice, and violence. To achieve
and sustain sexual health, all people's sexual rights must be acknowledged,
safeguarded, and satisfied (2022). Sex, gender identities and roles, sexual
preference, sexiness, pleasure, intimacy, and reproduction are all important aspects
of being human throughout life. Thoughts, fantasies, wants, beliefs, attitudes,
values, behaviours, practices, roles, and relationships are all ways in which sexuality
is experienced and expressed. While all of these qualities may be found in sexuality,
not all of them are always experienced or expressed. The combination of biological,
psychological, social, economic, political, cultural, legal, historical, religious, and
spiritual variables has an impact on sexuality.
Peter Viljoen is a 22-year-old boy whom studies MBChB at the University of Cape Town. He
is takes good care of himself and well fit for his age. Peter does pay the price of being a
medical student through effort and dedication to his academics. He stays at a UCT
residence. Being a senior student, he shares a room with no one except himself. He shares
the bathrooms and toilets with other students in the resident. He repeatedly washes his
face with liquid that prevent growth of microbes. He recently developed a pimple on his
face which made decided to visit Student Wellness Centre to get help. He developed a lot of
stress as his final examination was about to begin. The pimple became larger and more
painful, which made him start to think people are avoiding him adding to the fact that
another student made unkind remark about sharing ablution facilities with him. On
examination his vital signs were normal, and the lesion was assessed to be a boil. Further
investigations and tests where done, treatment options were given to him by a doctor. I am
going to relate Peter Viljoen case with intersectionality and race. Looking influence of skin
colour on lives of people. I am going to also to talk about how much harm discrimination can
cause in victim’s lives, especially Black women.
The other student making unkind remark about Peter skin did not make him feel good.
Anyone can get a pimple anytime and should not be punished for that as the person did not
request it. People judged because of the skin anytime which is something beyond their
control. Skin colour plays a big role in terms of skin discrimination. Some people are
classified as black and some as white. Black is defined as anyone with black ancestry of four
generations (DJ,2022). In south Africa, apartheid which is an Afrikaans term for apartness
made a huge impact from 1948 to 1994. One can be argued that it still exists even today.
People were put into racial categories whites, coloureds, Indians and lastly Bantu which
means Black Africans (DJ,2022). There was a lot of inequalities among the groups including
health inequalities. This resulted in poor education, poor sanitation, lack of nutritious food,
and poverty (DJ,2022). Many countries still require citizens to declare their race official
documents, while others such as Netherlands do not entertain that (DJ,2022). There is a
single human race, which means all of us are the same regardless of skin colour. According
to genetics 99,9% of DNA (Deoxyribonucleic acid) matches in all humans matches (DJ,2022),
which means we only differ by 0.1%. It is hard to believe as we all look different and have
different sex. Africa has more genetic mutations than any other continent. It is also believed
that the first women lived in South Africa according to genetic studies. People with different
skins experiences life in different ways, some do not need to worry about their skin while
some are constantly wishing they had a different skin. Peter also starts to have a different
experience at the University of Cape Town. His skin has caused him discrimination. This is
apparent with black woman who get to be discriminated about both their sex and race,
while white women get to be discriminated of sex (2022).
Race discrimination has affected Black woman their social support from other people,
loneliness, marriage status, social disruption, environment at work, social status, and social
intersectionality (2020). Black women suffer a lot to get a job which leads to them doing sex
work to feed their families. There are more black sex workers than any other race. They
have unprotected sex with many men every day. This increases the number of HIV infections
among the Black woman community. Many do not have access to proper health care which
in higher HIV mortality among Black women community. Some have access to healthcare
but are afraid of being discriminated against and end up passing away. Blacker women
commit suicide more than any other race. Poverty sets in, as the bread winners pass away.
The Black woman who are in positions of power are mocked and discriminated on every
action they take. They are judged on things that if it was a man doing it, there would not be
any problem. They must always be ready for an attack from any angle. They are abused by
their partners, or even worse murdered. They are taken advantage of by everyone who
wishes to. Peter is also ready for being mocked by the students he shares bathrooms with, it
is something that skips his mind every time. There is no intersectionality between him and
other students. He is seen in a different eye and treated differently, even though he did
nothing wrong. It is possible for him to not want to share the bathrooms anymore, which
means he will suffer when he wants to go to the bathrooms. It is possible he no longer
enjoys bathing as he does not feel welcome to do so. I believe it would have been even
worse if he was a female. He would probably suffer a more severe stress. The other
students should understand that it is beyond his control and live with him like the used to.
This is a difficult thing for them as they also do not want to be like him and only trying to
defend themselves from what infected Peter’s skin.
People are treated differently according to their appearance. It is started long time ago and
it still occurs today. People are not only discriminated about their colour but also lesions
that may occur on their skin. The discrimination can come from something you are born
with or something you develop as you get old. There are fortunate ones that get less
discrimination as compared to others. It is very important for everyone to understand
intersectionality to reduce or completely wipe off discrimination. There are people who
discriminate others to protect themselves and there are others who discriminate out of
being judgemental. In the case of Peter, students discriminated him to avoid being like him.
Discrimination can cause more harm to people than we can think. It can lead to increase in
mortality, spread of diseases such as HIV, generational poverty…etc.
Granuloma
• A localised collection of epithelioid macrophages
TB granulomas
• Collection of epithelioid macrophages
• Often shows central caseous necrosis
• Langhans type giant cells • Rim of surrounding lymphocytes
• Rim of surrounding fibroblasts
PRIMARY PULMONARY TB
• Usually in childhood
• Primary Gohn Complex
• A pulmonary Gohn focus
• 1-2cm area of casesous necrosis
• Subpleural at upper part of lower lobe or lower part of upper lobe
• Regional lymphadenopathy
• Necrotising granulomas in hilar and paratracheal lymph nodes
POST-PRIMARY / SECONDARY TUBERCULOSIS
• Follows reactivation of dormant / walled off bacilli from previous infection • Bacilli dormant in
areas of high oxygen tension
• Apex of the lung • OR • Reinfection of a person who has had a previous infection
• Second or multiple episodes of TB
• ↓ immunity or overwhelming infection
• Extensive caseation and cavity formation
• Usually apex of upper lobes (one or both lungs)
• Less regional lymph nodes involvement compared to primary TB
Isoniazid (INH)
M.O.A: Inhibit mycolic acid synthesis
Toxicity: Peripheral neuropathy
Hepatitis
Pharmacokinetics: Penetrates tissues well
Acetylation
Rifampicin
M.O.A: Inhibits RNA Polymerase
Toxicity: Hepatitis
Hypersensitivity
Pharmacokinetics: Variable bioavailability
Induces metabolism
Pyrazinamide
M.O.A: Non-specific
Toxicity: Hepatitis
Gout
Hypersensitivity
Pharmacokinetics: Penetrates tissues well
Active at low pH
Ethambutol
M.O.A: Inhibits arabinogalactan
Toxicity: Retrobulbar neuritis
Pharmacokinetics: Poor CNS penetration
Renal elimination 80%
Pathophysiology of Pneumonia
A. Description: Acute infection of the lung varying in severity and causing fluid accumulation.
B. Aetiology: causative organisms include bacteria, viruses, fungi, and protozoan.
C. Pathophysiologic process and manifestations.
1. Organisms may enter the respiratory tract through inspiration or aspiration of oral
secretions; staphylococcus and Gram-negative bacilli may reach the lungs through
circulation in the bloodstream.
2. Normal pulmonary defence mechanisms (cough reflex, mucocilliary transport, and
pulmonary macrophages) usually protect against infection. However, in susceptible hosts,
these defences are either suppressed or overwhelmed by the invading organism.
3. The invading organism multiplies and releases damaging toxins, causing inflammation
and oedema of the lung parenchyma; this results in accumulation of cellular debris and
exudates.
4. Lung tissue fills with exudates and fluid, changing from an airless state to consolidated
state.
5. In viral pneumonia, the ciliated epithelial cells become damaged.
6. Severity of symptoms depends on the extent of pneumonia present (e.g., partial lobe,
full lobe [lobar pneumonia], or diffuse [broncho pneumonia]).
7. Symptoms include: I. Fever ii. Chills iii. Malaise iv. Cough v. Pleuritic pain vi. Increased
tactile fremitus on palpitation vii. Rales and ronchi on auscultation viii. Dyspnoea