Year 1 Case 10 ILOs

what does COPD stand for

Chronic Obstructive Pulmonary Disease

What is COPD

an umbrella term for diseases characterised by airflow obstruction that is not fully reversible

risk factors for COPD

-cigarette smoking
-occupational chemicals and dust
-air pollution
-infection
-heredity
-aging

risk factors for COPD (intrinsic factors)

- antiproteinase (a1-antitrypsin) deficiency
- airways hyper-reactivity

symptoms of COPD

dyspnoea, chronic cough, white or clear sputum production, wheeze

what investigations are used to diagnose COPD

- lung function test
- sputum examination
- blood gases
- a1-antitrypsin levels and genotype

lung function tests results in COPD

spirometry
- evidence of airway limitation
- FEV1: FVC ratio < 70%
-PEFR is low
- FEV1 less than 80%

why might blood gases be used in COPD

check for hypoxaemia and hypercapnia in advanced cases

treatment for COPD

- smoking cessation
- oxygen therapy
-pharmacological therapy (bronchodilators, corticosteroids)
- pulmonary rehab

why is quitting smoking important to COPD

decelerates decline in lung function

when are bronchodilators used in COPD

ü Mild COPD: β-Adrenergic agonists (salbutamol)
ü In severe COPD: long-term β-Adrenergic agonists (salmeterol)
ü Antimuscarinic drugs (ipratropium):
o more prolonged and greater bronchodilation is achieved.
ü Theophyllines

mechanism of action of B2 adrenoreceptors agonists

Beta-2 receptors are G-protein coupled receptors
When the synthetic B2 receptor ligand binds, it changes the shape of the B2 receptor so it has a higher affinity to the G protein
This means the G protein and the adenylate cyclase will be activated
This causes the adenylate cyclase to convert ATP to cAMP
This cAMP activates the protein kinase A which causes relaxation of the muscles

mechanism of action of xanthine drugs

Inhibitor of phosphodiesterase with a resultant an increase in cAMP, causing muscle relaxation
More side effects than B2-adrenoceptor agonists (as affect other cell phosphodiesterase)
Also acts as adenosine receptor antagonist so competes with the adenosine for the receptor on smooth muscles (with cause constriction) and the receptor of immune cells which cause degranulation

muscarinic receptor antagonists mechanism of function

Muscarinic receptors are g-protein couped receptors
In bronchial smooth muscle the muscarinic receptors lead to an increase in calcium ions which usually causes constriction of the muscles
If there is a hyperactive parasympathetic nervous system, then more acetylcholine is released than necessary so more constriction occurs than necessary
Therefore, if the receptor is antagonised then there is fewer receptors activated so less constriction

corticosteroids mechanism of function

Binds to glucocorticoid receptor
Acts as transcription factor and binds to DNA
Produces lipocortin which prevents production of leukotrienes so no bronchoconstriction, airway oedema, mucous secretion or leukocyte recruitment occurs
Inhibit generation of vasodilators PGE2 and PGI2 by inhibiting induction of COX-2
Reduces transcription of proinflammatory protein

why is oxygen therapy used

o Improve survival
o Prevent progression of pulmonary hypertension
o Decrease the incidence of secondary polycythaemia
o Improve neuropsychological health

why isn't 100% oxygen given to patients with COPD

ü . In a COPD patient, there is less new oxygen going in and less old carbon dioxide coming out. Therefore, there is a higher carbon dioxide concentration in the alveoli. Over time the patient becomes sensitised to this hypercapnia and so relies on hypoxaemia to drive their ventilation. Administering oxygen will reduce the hypoxaemia, thus reducing the respiratory drive whilst the levels of CO2 remain high. The patient hypoventilates instead of hyperventilating, thus their respiratory drive ids reduced which is fatal

what levels of oxygen is usually given to the patient with COPD?

24-28%
if respiratory rate is above 30 then 40% oxygen used

three mechanisms found to cause limitation of airflow in small airways in COPD

1. Loss of elasticity and alveolar attachments of airways due to emphysema.
2. Inflammation and scarring cause the small airways to narrow.
3. Mucus secretion which blocks the airways.

what features co-exist in COPD

emphysema
chronic bronchitis

what is emphysema

Ø Abnormal, permanent enlargement of the air spaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis.

risk factors of emphysema

-genetic deficiency
-genetic tendency
-cigarette smoking
-pathogenic bactera

types of emphysema

centriacinar and panacinar

what is centriacinar emphysema

-usually lesions affects upper lobes
-usually associated with smoking—smoke usually can't reach distal lung tissue
- walls contain large amounts of black pigment

what is panacinar emphysema

- less common
- distension and destruction appear across the whole of the acinus #, from the levels of the respiratory bronchiole to the terminal alveoli
- α1-antitrypsin deficiency (genetic disorder)
- tends to occur in lower lobes

what type of emphysema is associated with smoking

centriacinar

what type of emphysema is associated with α1-antitrypsin deficiency (genetic disorder)

panacinar

what is chronic bronchitis

inflammation of the bronchi and bronchioles due to chronic exposure to irritants
enlargement of mucus glands in the trachea and bronchi leading to hypersecretion of mucus

mechanism of emphysema

Tobacco products release inflammatory products from white blood cells (mostly neutrophils)
The inflammatory products break down elastic tissue
Circulating alpha-1-antitrypsin (alpha-1-antiprotease) has anti-elastase activity which is inhibited by alpha-1-antitrypsin
Typical elastase activity involves breaking down proteins

what is a1-antitrypsin

An enzyme inhibitor that prevents elastase and collagenase from damaging tissues
typically elastase breaks down elastin proteins

clinical inspections found in COPD

Ø Barrel-chested and dyspneic, with obviously prolonged expiration.
Ø Sits forward in a hunched-over position.
Ø Breathes through pursed lips ("pink puffers").

what causes death in emphysema

Ø Respiratory acidosis
Ø Right-sided heart failure
Ø Massive collapse of the lungs secondary to pneumothorax.

pathogenesis of chronic bronchitis

- inhaled substances cause irritation
- proteases are release by neutrophils to stimulate hypersecretion of mucus in larger airways
- this results in hypertrophy of submucosal glands

what is cor pulmonale

abnormal enlargement of the right side of the heart as a result of disease of the lungs or the pulmonary blood vessels.

acute lung infections

Ø Mainly lower respiratory tract infections.
Ø Acute bronchitis
Ø Pneumonia

chronic lung infections

bronchiectasis

what is pneumonia

Infection of the lung interstitium, alveoli and airways, resulting in inflammation of the lungs; usually caused by bacteria

symptoms of pneumonia

cough, fever, chills, chest pain, rust coloured sputum, pleuritic chest pain

what is acute bronchitis

Recent onset of inflammation in the bronchi
Typically in patients without underlying lung disease
Dry cough can cause pain
As bronchi are larger, breathlessness is reduced

what is infective exacerbation of chronic lung disease

Onset of inflammation
Found in patients with lung disease

how are lung infections classified

source
localisation
mechanism/ pathogen

sources of pneumonia

community, hospital, ventilator

types of localisation pneumonia

Bronchopneumonia
Lobar pneumonia (fills lobe of lung)

types of pathogen pneumonia

Bacterial pneumonia
Viral pneumonia
Aspiration pneumonia
Fungal pneumonia (in patients who are heavily immunosuppressed)

what are general examinations found in lung infections

Tachypnoea
Tachycardia
Fever
Low blood pressure

what auscultation in found in lung infections

Bronchial breathing
Coarse crackles
Pleural rub
Wheeze

how do we identify causative organism

Sputum culture
Blood/ urine rapid pneumococcal/ legionella antigen
Blood culture
Nasopharyngeal swabs serology

treatment for acute bronchitis

only supportive treatment unless prolonged disease

treatment for infective exacerbation of COPD

Treat for presumed bacterial infection
Treat for exacerbation- bronchodilators, steroids, oxygen

why might a patient with a lung infection not respond to treatment

Resistant pathogen
Structural disease
Recurrent insult
Severe/ complicated disease
Non-infective

what is bronchiectasis

Abnormal permanent dilation of the conduction airways
Caused by post-infection, idiopathic
Inflammation damages the muscle and elastin in the bronchi
Dilated bronchi are predisposed to persistent microbial colonisation as mucus traps in the dilated bronchi

Common antibiotics used for respiratory tract infection

Tetracycline
Amoxicillin (penicillin)

when is penicillin prescribed for lung infection

This is prescribed in community and hospital-acquired pneumonia

what type of antibiotic is penicillin and amoxicillin

Beta-lactam

mechanism of action of amoxicillin (simple)

They bind to enzymes called penicillin binding proteins responsible for bacterial cell wall synthesis

mechanism of amoxicillin (detailed)

1. This will attack the cell wall.
2. Attaches via its β-lactam ring (which opens up) to the target in the cell wall (Penicillin Binding Protein (PBP)).
3. This changes the functional group of the protein on the cell wall and causes inhibition of the transpeptidation enzyme that cross-links the peptide chains attached to the backbone of the peptidoglycan.
4. As the cell wall grows in coordination with bacterial growth, the cell wall is weakened and crumbles. Extracellular fluid enters the bacteria, leading to the death of the bacteria.
5. The bacteria can responds by producing the enzyme β-lactamase but cefuroxime is β-lactamase resistant.

side effects of penicillin and amoxicillin

Gastrointestinal-related
Hypersensitivity causing skin rashes
Anaphylactic reaction

when is tetracycline prescribed for lung infections

atypical pneumonia (mycoplasma)

what type of antibiotic is tetracycline

protein synthesis inhibitor

mechanism of action of tetracycline (detailed)

Ø The A remains occupied and, thus, the addition of an incoming tRNA and its attached amino acid to the polypeptide chain is inhibited.
Ø This interferes with the production of functionally useful proteins.
Ø Macrolide antibiotics bind reversibly to the P site on the subunit 50S of the bacterial ribosome. This action is considered to be bacteriostatic but may be bactericidal at high concentrations.

mechanism of action of tetracycline (simple)

Inhibits protein synthesis by blocking the attachment of charged tRNA at the P site peptide chain
Tetracycline binds to the 30s and 50s subunit of microbial ribosomes
This blocks the translation of mRNA into bacterial protein

side effects of tetracycline

Gastrointestinal disturbances
Tooth discolouration
Enamel hypoplasia

causes of instantaneous dyspnoea

pneumothorax, pulmonary embolism, asthma

causes of acute dyspnoea

pulmonary embolism, pneumonia, Left ventricular failure

causes of gradual dyspnoea

pleural effusion, lobar collapse, Superior vena cava obstruction

causes of chronic dyspnoea

pleural effusion, lobar collapse, Superior vena cava obstruction
Chronic- COPD, Bronchiectasis, pulmonary fibrosis

what is bullous emphysema

- large sub pleural blebs or bullae (spaces > 1 cm diameter)
- occur near apex/near old TB scarring
- rupture bullae can cause pneumothorax

other than antibiotics, what else is given to patients with lung infections

oxygen, IV fluids, nutrition

features of community-acquired pneumonia (cap)

-bacterial or viral
- bacterial infection usually follows an upper respiratory tract viral infection
- usually causes by streptococcus pneumonia

pathogenesis of community acquired pneumonia

1. Attachment of bacteria to the upper respiratory tract epithelium.
2. Necrosis of the cells.
3. Inflammatory response.
4. This extends to the alveoli.
ü Interstitial inflammation .
Inhibition of mucociliary clearance

is streptococcus pneumonia gram-positive or gram-negative

gram-positive

features of hospital-acquired pneumonia

- usually infection by staphylococcus aureus or gram-negative rods (enterobacterium)
- new episode of pneumonia within 2 days after admission to hospital
leading cause of HAI deaths

features of aspiration pneumonia

- occurs in markedly debilitated patients and patients that aspirate gastric contents
- anaerobic bacteria dominate
- partly chemical from the irritating effects of gastric acid

complications of pneumonia

Lung Abscess
Empyema

what is a lung abscess

localized collection of pus w/in parenchyma (necrosis of pulmonary parenchyma)

what is empyema

pus in the pleural space
it arises by bacteria spread of rupture of lung abscess
it becomes infected with anaerobic organisms

what does yellow / green sputum mean?

bacterial or viral infection such as pneumonia (due to the presence of sputum neutrophils)

will antibiotics be effective in the case of yellow sputum

yes

What is haemoptysis?

coughing up blood

what does haemoptysis mean

neoplasm or pulmonary infarct

what does serous/frothy/pink sputum mean

blood is present

what does foamy white sputum mean

obstruction or oedema

will antibiotics be effective in the case of foamy white sputum

no

what does rusty coloured sputum mean

pneumococcal bacteria

what does clear/white/ grey sputum mean

healthy lungs, allergy or viral infection

what does brown sputum mean

old blood, smoker or black lung disease

what is the role of mucus in the lungs

Trap inhaled particles and pathogens
Facilitates their extrusion through the mucociliary clearance and the couch reflex
Mucin acts as a nutritional zone for glycan structures
Mucin contributes to microbial co-existence by providing a trigger for down-regulation of virulence genes involved in toxin secretion and regulation of biofilm

how is mucus produced

The surface of intrapulmonary airways id dominated by ciliated and secretory cell types. The latter produce mucus of differing composition and are subtyped based on microscopic appearance including serous, neuroendocrine, mucin-goblet cells and club cells.

what is lung fibrosis

excessive deposition of collagen and other extracellular matrix components of lungs
scarring of the lung

symptoms of lung fibrosis

shortness of breath

pathogenesis of lung fibrosis

Ø As a result of chronic injury.
Ø Chronic injury leads to chronic inflammation, which is associated with:
ü The proliferation and activation of macrophages and lymphocytes.
ü The production of inflammatory and fibrogenetic growth factors.
ü The production of cytokines.

what is varenicline

-nicotinic receptor partial agonist
-used for: smoking cessation
- does not release great amount of dopamine

how is varenicline taken

oral medication

side effects of varenicline

nausea, insomnia, abnormal dreams, headache

how to stop smoking

- smoking cessation clinics
- hypnotherapy, acupuncture, progressive filters
- literature
- nicotine replacements
- bupropion
- varenicline
- counseling with drugs

what is lung cancer

Caused by radiation, asbestos, smoking etc
Secondary lung cancers commonly rise from breast, kidney and GIT
Clinical features include weight loss, cough, finger clubbing, voice change, haemoptysis
Squamous cell carcinoma is the most common type of lung cancer, followed by small cell carcinoma, adenocarcinoma and large cell undifferentiated carcinoma

clinical features of lung cancer

weight loss, cough, finger clubbing, voice change, haemoptysis

composition of alveoli air

Alveolar air has more CO2 and less O2 than inhaled air
During exhalation, this alveolar air mixes with air in the dead space of the lungs producing exhaled air

layers of the respiratory membrane

A layer of fluid lining the alveolus (surfactant)
The alveolar epithelium composed of simple squamous cells
An epithelial basement membrane
A thin interstitial space between alveolar epithelial and the capillary membrane
A capillary basement membrane that fuses with the alveolar basement membrane
The capillary endothelial membrane

factors affecting gas diffusion

▪Partial pressure gradient
▪Fluid accumulation in alveoli or interstitial space
▪Total surface area available
▪Thickness of alveolar membrane
▪Ventilation-perfusion ratio