Restrictive lung disease Flashcards
Explain a little about the interstitium of the lung (restrictive lung disease)
the connective tissue space around the airways and vessels and space between the basement membranes of the alveolar walls
In the normal alveolar wall, most of the alveolar epithelium (pneumocyte) and interstitial capillary endothelial cell basement membranes are in direct contact.
what sort of process is largely (but not exclusively) involved in restrictive lung diseases?
inflammatory process
Where is the principal location of restrictive lung diseases?
the interstitium of the lung
what does restrictive lung disease mean with compliance?
reduced compliance - stiff lungs
what does restrictive lung disease mean with Fev1/fev
low fev1 and low fvc but the fev1/fev ratio is normal
what does restrictive lung disease mean with ventilation/perfusion
reduces gas transfer (Tco or Kco)- diffusion abnormality
ventilation/perfusion imbalance
when small airways affected by pathology
due to fibrous and inflammation tissue
fev1/fvc figures in spirometry for restrictive lung disease
fev1 = 1.8Litres
fvc = 2.1 Litres
fev1/fvc 0.85
(normal woulf be fev1 = 4L fvc - 4.9L fev1/fvc = 0.91)
Restrictive lung disease presentation
discover on an abnormal chest xray or ct scan
dyspnoea (short of breath on exertion, short of breath at rest as disease progresses)
respiratory failure type 1
heart failure
in restrictive lung disease - explain the inflammatory process
diffuse interstitial lung disease > parenchymal (interstitial lung injury)
causes acute (which can become chronic) or chronic response.
chronic response:
unusual interstitial pneumonitis (ui); granulomatous response; other pattern
all end fibrosis - end-stage honeycomb lung.
an acute inflammatory process for restrictive lung disease
diffuse alveolar damage (DAD)
diagnosis = acute interstitial pneumonia
what is diffuse interstitial damage (dad) or acute interstitial pneumonia associated with
- major trauma - chemical injury (toxic inhalation) - circulatory shock - drugs - infection including viruses (influenza SARScov1 SARScov2) - auto(immune) disease - radiation - can be idiopathic
Histology of diffuse acute damage syndrome DADS
protein-rich oedema fibrin hyalin membranes denuded basement membranes epithelial proliferation fibroblast proliferation scarring - interstitium and airspaces
sarcoidosis
multisystem granulomatous disorder (unknown aetiology)
involving abnormal collections of inflammatory cells that form lumps (granulomata). The disease usually begins in the lungs, skin, or lymph nodes. Less commonly affected are the eyes, liver, heart, and brain. Any organ, however, can be affected.
Histopathology of sarcoidosis
Epitheloid and giant cell granulomas
NOT necrosis/caseation very unusual
little lymphoid infiltrate
variable associated fibrosis
type 4 hypersensitivity reaction
RARELY PROGRESSES TO SIGNIFICANT FIBROSIS AS not type 3 reaction or chronic inflammatory reaction
Sarcoidosis - incidence
multisystem disorder unknown origin
commonly affects young adults (females more than males)
3-4/1000 in Uk
20/100000 in African Americans in USA
low equatorial regions
a disease of temperature climates
Sarcoidosis - what organs does it commonly involve
lymph nodes almost 100% cases lungs >90%
spleen 75% liver 70% skin, eyes, skeletal muscle 50% bone marrow 20%
saliva glands up to 50%
presentation of sarcoidosis
1 yound adults: acute arthralgia (joint pain) erythema nodosum (tender red nodules on the anterior shins) bilateral hilar lymphadenopathy
2 indidental abnormal chest x-ray or ct scan with no symptoms
3 shortness of breath, cough and abnormal chest x-ray
chest x-ray presentation of sarcoidosis
massive enlargement of hilar lymph nodes
presentation ct for sarcoidosis
diffuse interstitial involvement in the lungs with granular lead to fibrosis = respiratory failure
sarcoidosis - will it go away without treatment?
usually is a time-limiting disease
on the rare occasion it may need corticosteroids/
getting a sarcoidosis diagnosis
often can be given a clinical diagnosis - does not need therapeutic intervention or pathological sample.
- imaging
- serum, calcium +++ and ACE
- biopsy
hypersensitivity pneumonitis
thermophilic actinomycetes (farmers lung)(high-temperature aerobic bacteria which belong to the group actinomycetes) mycropolyspora faeni, thermoactinomycytes vulgaris
bird/animal proteins - faeces, bloom
fungi aspergillus spp
chemicals
others.
A 48-year-old woman of African ethnicity presents to her family doctor complaining of a lump in her neck. She reports that the lump has been there for the past week and has not increased in size significantly. She denies any pain or swallowing difficulty. Her previous medical history is unremarkable, and she has never been admitted to the hospital before, except for a visit to the ophthalmologist last year for red-eye, which necessitated treatment with topical steroid drops. Upon examination, the doctor notices some red tender nodules on the patient’s shin but the patient says that these come and go and do not bother her much. A chest x-ray reveals bilateral hilar lymphadenopathy with no other significant findings. Which one of the following is usually associated with this patient’s condition?
Elevated angiotensin-converting enzyme levels
Hypocalcemia
Poor sleep
Exposure to silica
Pain in the small joints of the hand
This patient presented with the signs and symptoms suggestive of sarcoidosis. The diagnosis is supported by the symptoms of a neck lump, which is most likely to be an enlarged lymph node, as well as examination findings of tender nodules on the shin, which are called erythema nodosum. In addition, there is a history of red-eye necessitating treatment with steroids and sarcoidosis patients often have eye involvement in the form of uveitis. The chest X-ray findings confirm the presence of bilateral lymphadenopathy which is one of the findings in sarcoidosis. Angiotensin-converting enzyme levels are usually elevated in sarcoidosis and would further support a diagnosis of sarcoidosis.
hypersensitivity pneumonitis presentation
acute
Acute presentation - fever; dry cough; myalgia; chills (4-9 hours after allergen exposure) crackles, tachypnoea, wheeze, precipitating antibody
hypersensitivity pneumonitis presentation
Chronic
insidious, malaise, shortness of breath, cough, low-grade illness, crackles and some wheeze.
*Can lead to respiratory failure gas transfer low = history is important*
histology of hypersensitivity pneumonitis
immune complex-mediated combines type 3 and 4 hypersensitivity
soft centriacinar epitheloid grnulomata
interstitial pneumonitis
foamy histiocytes
bronchiolitis oblitirans
upper zone disease.
Respiratory alkalosis
Common causes
anxiety leading to hyperventilation
pulmonary embolism
salicylate poisoning*
CNS disorders: stroke, subarachnoid haemorrhage, encephalitis
altitude
pregnancy
*salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis
A 60-year-old man presents to his GP with a 10-day history of a productive cough and shortness of breath. His GP prescribes antibiotics. 1 week later his symptoms are not improving and he now has a persistent fever and pain on inspiration. The GP sends him for a chest x-ray which is suggestive of an empyema. What is the most likely causative organism?
Mycobacterium tuberculosis Pneumocystis jirovecii Streptococcus pneumoniae Haemophilus influenzae Listeria monocytogenes
An empyema is a collection of pus in the pleural space. It is a potential complication of pneumonia and, in this case, is the cause of the gentleman’s pleurisy.
The commonest cause of empyema is Streptococcus pneumoniae, which is also the commonest cause of pneumonia.
where does hypersensitivity pneumonitis usually begin?
centriacinar region
this condition is associated with inhaled antigens - precipitated centriacinar region - laminar airflows converts to gas diffusion tiny particulate or macromolecular particles
biopsy here.
histology difference sarcoidoma and hyprsensitivity pneumonitis
granulomar in hypersensitivity pneumonitis tend to be softer and more diffuse in character
granulomas - a chronic inflammatory process not seen in sarcoidosis
alveolar walls around respiratory bronchioles subject to chronic inflammatory process
which zone of the lung does hyperinflammatory pneumonitis tend to affect
upper zone due to inhaled antigens - clearance mechanisms in the upper parts of the lung. not as efficient in lower parts.
idiopathic pulmonary fibrosis
connective tissue, drugs, asbestos, viruses
pathological process present in lungs has PIF
what is the fibrosis or end-stage of honeycomb lung circumstance
increased mortality or DADS can die within disease when acute
what are conditions of usual interstitial pneumonitis (UIP)
idiopathic pulmonary fibrosis
it is almost routine patients end up with end-stage honeycomb lung and die of that disease.
pathology process of usual interstitial pneumonitis
maybe seen in connective tissue diseases - esp scleroderma and rheumatoid disease
drug reaction
post-infection
industrial exposureasbestos
others
most are idiopathic - hence idiopathic pulmonary fibrosis (IPF)
cryptogenic fibrosis alveolitis (CFA)
Histopathology of usual interstitial pneumonitis
Patchy interstitial chronic inflammation
- type 2 pneumocyte hyperplasia
- smooth muscle and vascular proliferation
- evidence of old and recent injury; temporal heterogeneity; spatial heterogeneity
- proliferating fibroblastic foci
idiopathic pulmonary fibrosis (usual interstitial pneumonitis) clinical indications
elderly > 50-year-old. males more than females
clinically shows as dyspnoea, cough, basal crackles, clubbing
progressive disease: most die within 5 years
Chest x-ray basal. posterior, diffuse infiltrates, cysts, ground glass
Restrictive PFT (pulmonary function test) and reduced gas transfer
poor prognosis: some fulminant some steroid responsive.
usual interstitial pneumonitis
basal and posterior fibrosis with honeycombing
this case is complicated by peripheral adenocarcinoma.
can lead to cancer (adenocarcinoma)
Normal pulmonary gas exchange processes
airflow in airways - bulk flow or air in large conducting airways +URT - flow = laminar or turbulent
flow driven by the pressure difference (breathing muscles intercostal and diaphragm).
beyond terminal bronchiole: diffusion
the blood-air barrier
HB affinity to 02 means blood leaving capillary bed is 98% saturated for FI02 of only 0.21 (21%)
Abnormal pulmonary gas exchange
Normal paO2
Normal paCO2
- 5-13.5kPa
- 8-6.0kPa
parameters for Respiratory failure
Type 1 - Pao2 <8kpa (paCO2 normal or low)
type 2 (PaCO2 >6.5 kPa (pao2 usually low)
what %% of oxygen in air do we breathe in?
21%
what is the saturation of haemoglobin we can measure in peripheral arterial blood?
98%
what is fIo2
the fraction of inspired air that is oxygen e.g. 21% o2 so 0.21
Four abnormal states associated with hypoxaemia are:
ventilation/perfusion imbalance (VQ)
diffusion impairment
alveolar hypoventilation
shunt
ventilation/perfusion imbalance (VQ mismatch):
normally breathing 5-litres per minute. cardiac is 4L/min so normal VQ is 4/5 or 0.8
low v/q is commonest cause of hypoxaemia encountered clinically.
low v/q in some alveoli rises due to local alveolar hypoventilation due to some focal disease.
hypoxaemia is due to low v/q responds well to even small increased in fio2
WHAT IS SHUNT
blood that passes from the right side of the heart to left without contacting ventilated alveoli (gas exchange occurring)
normally 2-4% shunt
pathological shunt in AV malformation, congenital heart disease and PULMONARY DISEASE
large shunts respond poorly to increase in Fio”
blood leaving normal lung is already 98% saturated
pneumonia: why hypoxaemia?
vq mismatch bronchitis/bronchopneumonia (some ventilation of abnormal alveoli) - not enough)
overall measurement of o2 in blood falls
shunt - severe bronchopneumonia - lobar pattern with large areas of consolidation
explain ventilation in:
bronchopneumonia
shunt (e.g. lobar pneumonia)
bronchopneumonia = some ventilation, just not enough and you see 02 in the blood drop
shunt = zero ventilation (lobar pneumonia) looks solid zero vent
how is po02 by hypoventilation corrected by
raising fio2
arterial co2 will rise. the fall in o2 by hypoventilation corrected inspired air concentration of o2 fio2
why may someone have alveolar hypoventilation
global phenomenon affecting all tissue
upper airway or tracheal obstruction
a mechanical problem with breathing (chest wall damage)
functional problems with breathing mechanisms (muscle paralysis, diaphragm damage)
neurological problems with breathing (peripheral nerve damage or loss of function) CNS malfunction - opiate poisoning,
copd why hypoxaemia
v/q mismatch: airway obstruction +/- bronchopneumonia#
diffusion impairment: loss of alveolar surface area in emphysema
alveolar hypoventilation: reduces respiratory drive
shunt: only during acute exacerbation if pneumonia is extensive enough.
histology of normal alveolar wall and one thickened by interstitial infiltrate
the normal alveolar wall is virtually no alveolar membrane because made of a relative basement membrane of epithelial cell - gas can move through or between the cell and through the membrane.
damaged alveolar tissue is much thicker making it harder for gas exchange (slower)
inflammatory cells, fibrosis, fibroblasts
in a normal human, what is the speed of 02 equilibrium and the average time a red blood cell spans the alveolar-capillary
0.25 for 02 to reach equilibrium and 0.75 seconds on average for reb blood cell spans alveolar capillary network
in disease how long may it take for 02 to reach equilibration?
closer to the 0.75 seconds which is the entire time it takes for a red blood cell to transit the capillary network
0.75 IS CIRCULATION AT REST the red cell time falls in exercise = hypoxaemia during exercise.
restrictive disease what is the physiological definition
forced vital capacity < 80%
what are the causes of restrictive disease
lung - interstitial lung disease (idiopathic pulmonary fibrosis) (sarcoidosis)(hypersensitivity pneumonitis)
pleura - (pleural effusion)(pneumothorax) (pleural thickening)
nerve or mucle - (amuotrophic lateral sclerosis)
bone - kyphoscoliosis (alkylosis spondylitis) (thoracoplasty)(rib fractures)
subdiaphragmatic causes obesity, pregnancy
key causes/conditions of restrictive lung disease
Pulmonary fibrosis
Asbestosis
Sarcoidosis
Acute respiratory distress syndrome
Infant respiratory distress syndrome
Kyphoscoliosis e.g. ankylosing spondylitis
Neuromuscular disorders
Severe obesity
restrictive lung disease spirometry features
FEV1 - reduced
FVC - significantly reduced
FEV1% (FEV1/FVC) - normal or increased
spirometry features of obstructive disease
FEV1 - significantly reduced
FVC - reduced or normal
FEV1% (FEV1/FVC) - reduced
obstructive lung diseases
Asthma
COPD
Bronchiectasis
Bronchiolitis obliterans
where is the interstitium?
the space between the epithelium side of the alveolus and the endothelium of the capilarry
in picture you see normal alveolus and thin membrane - the right is very thickened breathless patient
what are interstitial lung diseases and what can this result in?
over 200 diseases causing thickening of interstitium can result in pulmonary fibrosis
Sarcoidosis what is a histological hallmark?
multi granulomatous disease unknown cause - non-ceasating granuloma (looks like ceasating cheese)
who often gets sarcoidosis
<40 adults
women more than men
you can catch it world-wide
how to investigate for dsarcoidosis
take history
chest x-ray (chest x-ray swelling of glands hilum)
how to investigate for sarcoidosis
pulmonary function test
bloods/urinalysis/ ecg/ tb skin test/ eye exam
further assess bronchoscopy transbronchial biopsy
other ways to get a biopsy for sarcoidosis
less commonly done now, usually diagnosed through glands
may need mediastinoscopy
video-assisted thoracoscopic lung biopsy (VATS).
do chest extrays affect prognosis for those with sarcoidosis?
can stage 1 to 4
how to treat mild sarcoidosis
mild - no vital organ involvement, normal lung function, few symptoms
no treatment needed
in sarcoidosis if you present with sore joints and lumpy red legs
treatment
with erythema nodosum/arthralgia - treat with NSAIDs
in sarcoidosis if you have skin leisions, anterior uveitis or cough
treatment
topical steroids
in sarcoidosis, if you present with cardiac, neurological, eye disease not responding to topical treatment or hypercalcaemia
treatment
systemic steroids
idiopathic pulmonary fibrosis histological difference
fibroblastic focus (small area)
typical presentation idiopathic pulmonary fibrosis
chronic breathlessness and cough
typically in 60-70-year-olds
more common in men
failed treatment for left ventricular failure or infection
clubbed fingers and crackles
xray presentation in idiopathic pulmonary fibrosis
non-specific shadowing at the base.
a hint of sternotomy wired could indicate cardiac surgery so past of? LVF indicator for IPF developing
treatment options for idiopathic pulmonary fibrosis
median survival 3 years
refer to IDL clinic medical option OAF (oral antifibrotic) pirfenidone, nintedanib, palliative care.
surgical option - transplant
hypersensitive pneumonitis - what can cause
exposure to antigen hypersensitivity 4
farmer lung, whisky buildings yeast,
birds
in sleep apnea where is the obstruction mainly?
between base tongue soft palet and posterior pharyngeal wall
sleep apnea is associates with what other comorbidities?
hypertension, increased risk of stroke and likely increase risk of heart disease
prevelance
affects more men than women
diagnosing sleep apnea
history
questionnaire
overnight sleep study
pulse oximetry limit sleep study and full polysonogrophy
sleep apnea OSA severity
desaturation rate (AHI)
0-5 normal
5-15 mild
15-30 moderate
>30 severe
treatment for sleep apnoea
weight reduction
avoid alcohol
diagnose and treat endocrine disorders (hypothyroidism, acromegaly)
- continuous positive airway pressure (CPAP)
mandibular repositioning splint
treatment for narcolepsy
modafinil
dexamphetamine
venlafaxine (for cataplexy)
sodium oxybate (xyrem)
Chronic ventilarotu failure is defined by ABG -
elevated pco2 (>6.0kPa_
pos <8kPa
normal blood Ph
elevated bicarbonate
aesthenia gravis is associated with thyroid tumours.
Select one:
True
False
False – myasthenia gravis is associated with thymus tumours. Anybody with a new diagnosis of MG will undergo investigation for thymus tumour, and many of these people will end up having surgery.
Patients with cystic fibrosis can undergo single or double-lung transplant.
Select one:
True
False
False – if patients with CF receive a lung transplant, it must be a double lung transplant. This is because it is a condition that carries a high risk of recurrent infection, to which the transplanted lung would also be susceptible if a native lung were left in situ.
Steroids are given to mothers going into preterm labour to speed up foetal lung development.
Select one:
True
False
True – steroids stimulate surfactant production, so mothers who go into labour prematurely are given steroids to reduce the risk of the baby having respiratory distress syndrome.
Hypersensitivity pneumonitis predominantly affects the apices.
Select one:
True
False
True – most (but not all) lung diseases caused by inhaled antigens will predominantly affect the upper regions of the lungs.
The embryonic lung buds are derived from the foregut.
Select one:
True
False
True – the lungs begin as an outpouching of the foregut, hence the close proximity of the trachea to the oesophagus.
