Week 9 Flashcards
Causes for abnormalities:
- Increased translucency (too black)
- Opacification (too white)
- Solid white
Increase translucency: Air, loss of tissue density
Opacification: Fluid, increased tissue e.g. lymphadenopathy
Solid white: Hardware e.g. Pacemaker, Endotracheal tube (ETT), NG tube, chest drain
What is consolidation?
Replacement of normal air space gas with fluid or solid material
Causes of consolidation?
Pus due to infection Blood due to pulmonary haemorrhage Fluid due to pulmonary oedema Cells due to lung cancer Protein due to alveolar proteinosis
What is atelectasis?
Aka: Collapse, pneumothorax
Definition: Reduction in inflation of all or part of the lung
Suspect atelectasis if on x-ray you see… (6)
- Volume loss
- Displacement of trachea
- Displacement of diaphragm
- Displacement of lung fissures
- Compensatory over inflation of non-collapsed lung
- Crowding of vessels and bronvhi
Causes of deviated trachea?
- Pneumonectomy/ lobectomy
- Lobar collapse
- Tension pneumothorax
- Pleural effusion
Pulmonary oedema signs found on XCR
A: Alveolar oedema (Bat's wing) B: Kerley B lines C: Cardiomegaly D: Upper lobe diversion E: Pleural effusions
For a pleural effusion:
- Describe the abnormality shown in the chest xray?
- What clinical signs might you find on examination?
- How would you manage the acute problem?
- Suggest 2 further investigations you might request?
CXR abnormality: Area of whiteness expanding over mid and lower zones
Clinical signs: Increased RR, low sats, dull to percussion, decreased vocal resonance
Acute management: O2 delivery, drain fluid
Further 2 investigations: CT scan send fluid to lab for investigation to identify fluid
What lobes and fissures are present in the right lung?
Fissures: Horizontal and oblique
Lobes: Superior, middle and inferior
What lobes and fissures are present in the left lung?
Fissures: Oblique
Lobes: Upper and lower
Stucture in left lung that is the equivalent to the right middle lobe?
The lingula
Course of the:
- Oblique fissure?
- Horizontal fissure?
Oblique: From 3rd thoracic vertebrae to 6th costochondral junction
Horizontal: From 4th right CC to meet the oblique fissure as it follows course of 6th rib
Structures and arrangement of the right and left lung hilum?
o Bronchus (most posterior, identified by the small plates of hyaline cartilage)
o Pulmonary artery (Anterosuperior to bronchus)
o Pulmonary veins (superior vein is most anterior structure in hilum, inferior vein is most inferior structure)
o Lymph nodes
o Branches of bronchial arteries and pulmonary nerve plexus
What is pKa?
Defined as the pH at which 50% is ionised and 50% is unionised in the reaction
What direction of reaction is favoured if the normal pH is higher than the pKa?
Favoured to the high so there would be more products vs reactants
The _____ levels of bicarbonate can be changed by breathing
Absolute
What components of the following respiratory equation contribute to respiratory and metabolic acid-base disturbances?
Respiratory: CO2, H20
Metabolic: HCO3-, H+
i.e.
Rise in PCO2 -> Respiratory acidosis
Rise in HCO3- -> Metabolic alkalosis
What are the 4 causes for acid-base disturbances?
- Increase CO2
- Decrease CO2
- Increase non-volatile acid / decrease base
- Increased base / decreased non-volatile acid
What 2 organs offer compensation for acid-base disturbances?
Lungs via alters ventilation (quick)
Kidneys via altered excretion of bicarbonate (2-3 days)
Respiratory acidosis: How does it arise? Acid-base disturbance? Compensation? Cause?
How does it arise:
-Results from an increase in PCO2 in hypoventilation (so less CO2 being blown away)
Acid-base disturbance:
- Increase in PCO2
- Increase in H+, lowering of pH
- plasma HCO3- levels increase to compensate for H+ concentration
Compensation: Renal. Increase HCO3- reabsorption and production to raise pH
Causes:
- COPD
- Blocked airway
- Lung collapse
- Injury to chest wall
- Drugs reducing respiratory drive e.g. morphine
Respiratory alkalosis: How does it arise? Acid-base disturbance? Compensation? Cause?
How does it arise:
Results from a decrease in PCO2 generally caused by alveolar hyperventilation (more CO2 being blown away).
Acid-base disturbance:
Causes a decrease in H+ thus a rise in pH
Compensation: Renal. Reduced reabsorption and production of HCO3-. Lowers pH back to normal as H+ increases
Causes:
- Increase ventilation from hypoxic drive in pneumonia, diffuse interstitial lung diseases, high altitude, mechanical ventilation
- Hyperventilation in brainstem damage, infection driving fever
Metabolic acidosis:
Acid-base disturbance?
Compensation?
Cause?
Acid-base disturbance:
- Result of excess of H+ in the body, reducing equation to left so reduces HCO3 levels
- PCO2 normal as respiration normal
Compensation: Respiratory
- Low pH detected by peripheral chemoreceptors
- Increases ventilation which lowers PCO2
- Shifts bicarbonate equation further to left, lowering H+ further
- pH increases to normal
- Cannot fully correct the pH so excess H+ needs to be removed or HCO3- restored
Causes:
- Loss of HCO3
- Exogenous acid overloading, endogenous acid production
- Failure to secrete H+ e.g. renal failure
Effect of high ventilation on PCO2
Increased ventilation –> lowers PCO2 as CO2 is being blown off
Metabolic alkalosis:
Acid-base disturbance?
Compensation?
Cause?
Acid-base disturbance:
- Increase in HCO3- concentration or fall in H+
- Removing H+ increased HCO3- levels are equation driven to the right
- Raises pH
Compensation: Respiratory
- Increase in pH detected by peripheral chemoreceptors
- Decreases ventilation which raises PCO2
- Equation driven further to right
- pH lowers to normal
- Ventilation cannot reduce enough to correct imbalance. Hence renal response is to secrete less H+
Causes:
- Vomiting (loss of HCl from stomach)
- Ingestion of alkali substances
- Potassium depletion (e.g. diuretics)
What are the 3 central principles of antibiotic use?
- Anti-bacterials target processes that humans do not possess (e.g. bacterial cell well)
- Anti-bacterials target processes that humans possess by the bacterial versions are sufficiently different
- The toxicity of anti-bacterials is greater to bacteria than it is to humans (selective toxicity)
What are the 5 main classes of antimicrobial drugs?
- Beta-lactam and cephalosporin
- Glycopeptide
- Cyclic peptide
- Phosphonic acid
- Lipopeptides
Beta-lactam and cephalosporin:
Target?
Mechanism?
Example?
Target: Penicillin binding proteins
Mechanism: Preventing peptidoglycan cross-linking
Example: Penicillin G, flucloxacillin
Glycopeptide:
Target?
Mechanism?
Example?
Target: C-terminal D-Ala-D-Ala
Mechanism: Prevents transglycolation and transpeptidation
Example: Vancomycin, Teicoplanin
Glycopeptide:
Target?
Mechanism?
Example?
Target: C-terminal D-Ala-D-Ala
Mechanism: Prevents transglycolation and transpeptidation. Inhibits synthesis of peptidoglycan
Example: Vancomycin, Teicoplanin
What 3 drugs act as bacterial cell wall inhibitors? What does this cause?
Drugs:
- B-lactams
- Vancomycin
- Bacitracin
Inhibiting bacterial cell wall synthesis normally leads to the death of the bacteria.
The osmotic pressure in the cytoplasm of bacteria is high and the cytoplasmic membrane does not remain intact when the other rigid cell wall is damaged
What 3 drugs act as bacterial cell wall inhibitors? What does this cause?
Drugs:
- B-lactams
- Vancomycin
- Bacitracin
Inhibiting bacterial cell wall synthesis normally leads to the death of the bacteria.
The osmotic pressure in the cytoplasm of bacteria is high and the cytoplasmic membrane does not remain intact when the other rigid cell wall is damaged
Health hazards associated with being in hospital
HIA infections: Can be reduced by the implementation of hospital infection control guidelines
Bed rest: Highly unphysiologic, PE, bed sores, muscle loss (particular issue in elderly)
Effect of hospitalisation on adults
- Unfamilar environment: Limited privacy, stressful, staff wear uniforms
- Entering into the “role of a patient”
- Loss of control: Reactance (anger) due to restrictions placed upon inpatients. RLOC
- Depersonalisation
- Institutionalisation occurs in patients with long hospital stay
Issues related to hospitalisation of children
- Separation anxiety or distress:
- Stages of separation: Protest -> despair -> Detachment
- Height of distress seen at 15 months - Illness misconception: Illness as punishment for being “bad”
- Faulty illness representation e.g. a haemophilia bug
What is the RLOC?
Recovery Locus Of Control scale.
Higher score boosts recovery
What is depersonalisation?
Why does depersonalisation happen?
Depersonalisation is when your patient is treated as though he or she were either not present or not a person
Why?
-Distancing mechanism of doctor
-Due to burnt out doctors
What is institutionalisation
Institutionalisation: Number of roles of person can adopt is reduced when in hospital
When leaving hospital there is a fear of not being able to adapt to different roles
Strategies to improve hospital experience for children?
- Outpatient treatment when feasible
- Preparation for hospitalisation
- Unrestricted parental visits
- Nursing staff provide support and education to parents about care
- Reduce number of staff dealing with one child
- Communicate with the child as well as the parents
Impacts on behaviour of hospitalisation of children? (3)
- May regress sharply
- Nightmares
- Irritable
Explain some of the reasons why the NHS has become overstretched, year on year
- Increase in life expectancy
- Increasing costs of treatments
- Patient’s expectations increase
- Increase cost of admin and salaries
- Free means less constraints on demand
- Increase in negligence cases
Explain different strategies that could be used in NHS resource allocation
Rationing: The discretionary allocation of scare resources
- Equal access to treatment
- Rationing according to clinical need
- Maximising health gains (QALY)
- Discriminating according to age
- Taking individual responsibility for ill health into account
- Rationing according to ability to pay
- Singling out certain types of excluding treatment
- Dilution of care
- Random allocation
Outline the role of NICE
National Institute for Health and Clinical Excellence
Produce evidence-based guidance and advice for health, public heath and social care practitioners
Outline the role of SMC and describe its involvement in NHS rationing
SMC= Scottish Medicines Consortium
Ensures all new drugs are god value for money
Describe what a ‘QALY’ is?
What is its use in the decision-making process to purchase health care resources?
Strengths and weaknesses?
QALY= Quality of adjusted life year
Theory = consequentialism (utilitarianism)
Quality of life x life expectancy (before + after) then cost it
Use:
- Beneficial healthcare activity = positive No. of QUALs
- Efficient healthcare activity = cost per QALY is low
- Quantity + quality = Overall welfare of patient
Weaknesses:
- How do you define QOL
- Only welfare?
Describe the work of NICE in their technology appraisals and their role in NHS rationing
4 technology appraisal recommendations possible:
- Recommended for use in NHS
- Restricted use to certain categories of patients
- Use confined to clinical trials
- Should not be used in NHS
What are the different branches of penicillins?
- Penicillins G&V
- Gram positive and gram negative Cocci
- Gram positive rods
- Spirochaetes - B-lactams-resistant penicillins
- Broad-spectrum penicillins
- Extended-spectrum penicillins
Structure and function of carbapenems?
Structure:
- Broad antibacterial spectrum (broader than other penicillins and cephalosporins)
- Resistant to the typical B-lactamases
Function:
- Active against both gram positive and gram negative bacteria and anaerobes
- Poorly active against MRSA
- Targets bacteria cell wall
Mechanisms of bacterial resistance to the b-lactam antibiotics
- Destruction by B-lactamase e.g. S. aureus
- Failure to reach target enzyme e.g. Pseudomonas
- Failure to bind to the transpeptidase e.g. S. pneumoniae
B-lactamase inhibitors
Classes?
Inhibitors?
Use?
3 classes of B-lactamases (A.B and C)
B-lactam compounds, Clavulanic acid and sulbactam, are strong inhibitors of Class A
Use: Co-administration of B-lactamase inhibitors with B-lactam antibiotic is an alternative to B-lactam-resistant antibiotics
Cepholasporins:
Uses?
Examples?
Uses: Similar to penicillin and are often alternatives.
Used to treat: Septicaemia, pneumonia, meningitis, biliary tract infections, urinary tract infections, sinusitis
Examples: Cefalexin, cefuroxime, cefotaxime, cefadroxil
Vancomycin: Drug class? Mechanism? Development of resistance? Uses?
Drug class: Glycopeptide antibiotic
Mechanism: Binds to the peptide chain of peptidoglycan (in bacterial cell wall). Interferes with the elongation of the peptidoglycan backbone.
Resistance development: Very specific interaction with D-Ala-D-Ala which leads to minimal resistance development
Uses: MRSA, resistant streptococci and enterococci
Bacitracin:
Drug class?
Mechanism?
Clinical uses?
Drug class: Cyclic peptide
Mechanism: Interferes with the dephosphorylation of the lipid carrier which moves the early cell wall components through the membrane
Clinical uses: In an ointment to treat infections of the skin and eye by streptococci and staphylococci
Bacterial folate antagonists:
- Name 2 examples
- Mechanism?
- Therapeutic uses?
Sulphonamides and trimethoprim
Mechanism:
- Inhibition of the folate pathway in bacteria which is key in cell metabolism
- Bacteria make it, we receive in our diet
- Bacteria are susceptible targets … “selective toxicity”
Therapeutic uses:
- Urinary tract infections
- Co-trimoxazole (combination of sulphamethoxazole and trimethoprim)
- In combination with other drugs to treat opportunistic infections in AIDS
Macrolides e.g. Erythromycin and clarithromycin:
- Inhibitors of…
- Uses as an alternative to…
- Clinical uses
- Side effects
- Inhibitors of bacterial ribosomal actions
- As an alternative to penicillin where patients are penicillin sensitive
Clinical uses:
- Chlamydia Legionella
- Lower respiratory tract infections
- Diphtheria
- Diarrhoea
- Limited gram-neg spectrum
- H. influenza
- Helicobacter pylori (in combo)
Side effects:
Erythromycin- Gut disturbances, hypersensitivity reactions, hearing disturbances, GT prolongation
Clindamycin:
-Drug class?
-Uses?
Side effects?
Lincosamide class
Uses:
- Gram-pos Cocci inc staphylococci
- In combo against anaerobic sepsis and necrotising fasciitis
- Staphylococcal infections of joints and bones
- In eye drop to treat staphylococcal conjunctivitis
Side effects:
-GI disturbances
-Psuedomembraneous colitis
(due to clindamycin-resistant C. diff)
Aminoglycoside:
- Inhibitors of…
- Uses?
- Side effects?
- Pharmacokinetics?
- Caution in use?
Inhibitors of bacterial ribosomal actions
Uses: -UTIs -Septicaemia -Pneumonia -Respiratory and intra-abdominal infections (Due to pseudomonas)
Side effects:
- Renal toxicity
- Ototoxicity (damage and destruction of the sensory cells of the cochlea and vestibular organ of the ear)
- Neuromuscular block
Pharmacokinetics:
- Polar agent confined to extracellular fluid
- Doesn’t cross BBB
- Excreted by kidney
- Administered intravenously
Cautions:
- Elderly
- With renal failure or other renal toxic drugs
- In severe sepsis (that is causing acute renal failure)
Tetracyclines:
Inhibitors of …..
Uses?
Side effects?
Inhibitors of bacterial ribosomal actions
Uses:
- COPD
- Chronic acne
- Rickets
- Mycoplasma and chlamydial infections
- Brucellosis
- Cholera
- Resistant gram neg infection
Side effects:
- Gut upsets
- Hepatic and renal dysfunction
- Photosensitivity
- Binding to bone and teeth causing staining; dental hypoplasia and bone deformities
- Vestibular toxicity (dizziness and nausea)
Chloramphenicol:
Inhibitors of…
Risk?
Only used in?
Inhibitors of bacterial ribosomal actions
Risk: Aplastic anaemia
Only used in serious infection e.g. meningitis and brain abscess
What is topoisomerase IV?
Tetrameric enzyme involved in chromosomal partitioning.
Catalyses relaxant of supercoiled DNA and unknotting of duplux
What is DNA gyrase?
A tetrametic enzyme which forms a transient covalent bond with DNA.
- Breaks the DNA
- Passes the DNA through break
- Repairs break
DNA gyrase = type II topoisomerase
Target for quinolone antibacterial which make lethal DNA breaks
Fluroquinolones:
Main action?
Most common?
Uses?
Antibiotics which affect Topoisomerase II.
Ciprofloxacin is most commonly used
- Gram neg bacteria
- H. influenza
- N. gonorrhoea
- Diarrhoea
- Salmonella
Metronidazole
Main function?
Action?
Uses:
Antibiotics which affect Topoisomerase II.
Under anaerobic conditions it generates toxic radicals that damage bacterial DNA
Uses:
- Sepsis secondary to bowel disease
- Pseudomembraneous colitis
- In combo to Helicobacter pylori which gives rise to peptic ulceration
Nitrofurans
- Useful feature
- Clinical use?
Broad spectrum so resistance is rare
Treats UTIs
Polymixins:
Mechanisms?
Clinical use?
Mechanism: Interacts with phospholipids of cell membrane and disrupts its structure. Eventually cell membrane is breached and there is loss of its intracellular constituents
Use: Topical use for cutaneous Pseudomonas infections
Describe the main types of vaccine preparations in use
LAKERD
Live: Organisms capable of normal infection and replication. Not used against pathogens that can cause severe disease.
Attenuated: Organisms is live, but ability to replicate and cause disease reduced by chemical treatment or growth-adaptation in non-human cell lines (MMR)
Killed: Organism killed by physical or chemical treatment. Incapable of infection or replication, but still able to provoke strong immune response (B.pertussis, typhoid)
Extract: Materials derived from disrupted or lysed organism. Used when risk of organism surviving inactivation steps (Flu, pneumococcal, diptheria, tetanus)
Recombinant: Genetically engineering to alter critical genes. Often can infect and replicate but does not induce associated disease
DNA: Naked DNA injected. Host cells pick up DNA and express pathogen proteins that stimulate immune response
Essential characteristics of vaccines
Stimulate neutralised antibodies to prevent re-infection
Essential characteristics of vaccines
Stimulate correct arm of immune response i.e. antibodies or effector T cells
Stimulate neutralised antibodies to prevent re-infection
In general which vaccines are the most effective?
Live or attenuated
Why? These organisms express proteins and stimulate the immune response in a manner which most closely resembles normal infection
What is herd immunity?
Reason for occurance?
Example
When a pool of unimmunised individuals is created that cab become victim to disease.
Why? Vaccinations create unawareness of risks of disease. Leads to vaccination rates fallen. Plus public debate on side effects
E.g. Measles
Why is ‘reverse vaccinology” offered?
For MenB vaccine
The capsular polysaccharide antigen (that is normally a good target) is similar is structure to a sugar found on NCAM (an important neuronal membrane protein)
Hence antibodies could cause autoimmunity
Role of dendritic cells in vaccination?
- On activation, they migrate to lymph nodes and activate T cells
- Express Pattern Recognition Receptors (PRR) , members of the Toll-Like Receptor family (TLR)
- Activation increases their ability to capture and process antigen and immunogens
[Activate when DC encounters antigens in periphery]
Describe the normal host defence mechanisms of the respiratory tract and how these influence infection
Saliva Mucus Cilia Nasal secretions Antimicrobial peptides
Common cold: Transmission? Causative agents? Clinical features? Treatment?
Transmission: Aerosol, virus-contaminated hands
Causative agents: Rhinoviruses, Coronaviruses
Clinical features:
- Tiredness
- Pyrexia
- Malaise
- Sore nose and pharynx
- Nasal discharge
- Secondary bacterial infection
Treatment: No vaccine
Acute pharyngitis and tonsillitis:
Causative agents
Causative agents:
Viruses: Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
Bacteria: Streptococcus pyogenes
Cytomegalovirus: Transmission? Causative agents? Clinical features? Diagnosis? Treatment?
Transmission: Body secretions and organ transplants
Causative agents: Virus can reactivate and cause disease when cell-mediated immunity is compromised
Clinical features: Asymptomatic
Diagnosis:
- 2’ infection= IgM in blood
- CMV pneumonitis =CMV antigen in BAL (Broncho-Alveolar Lavage)
Treatment: Ganciclovir, foscarnet, cidofovir
Epstein-Barr Virus (EBV) (Glandular fever): Transmission? Pathophysiology? Incidence? Causative agents? Clinical features? Diagnosis? Treatment? Complications?
Transmission: Saliva and aerosol
Pathophysiology: Replicates specifically in B lymphocytes
Incidence: Occurs in 2 peaks, illness lasts 4-14 days
Clinical features
- Occurs in 2 peaks, illness lasts 4-14 days
- Causes glandular fever (Fever, headache, malaise, sore throat, anorexia, swollen tonsils, red dots on soft palate, pus)
- Splenomegaly
Diagnosis:
-Detection of heterophile antibodies (IgM) specific for RBV in monospot test
Treatment?
- No antibiotics
- No contact sports or heavy lifting
Complications:
- Burkitt’s lymphoma
- Nasopharngeal carcinoma
- Guillain- Barre syndrome
Tonsillitis: Transmission? Incidence? Causative agents? Clinical features? Diagnosis? Treatment?
Transmission: Aerosol
Causative agents: Streptococcus pyogenes (gram pos)
Incidence: Mainly in children
Clinical features:
- Susceptible to treatment with penicillin
- Fever, pain in throat, enlargement of tonsilts, tonsillar lymphadenopathy
Diagnosis?
Treatment?
What are the 6 complications than can occur with Streptococcus pyogenes?
- Scarlet fever
- Peritonsillar abscess
- Otitis media/ sinusitis
- Rheumatic heart disease
- Glomerulonephritis
- Tonsillitis
Parotitis: Transmission? Incidence? Causative agents? Clinical features? Diagnosis? Treatment? Prevention? Complications?
Transmission: Droplet spread and fomites
Incidence: School-aged children and young adults
Causative agents: Mumps virus
Clinical features:
- Fever
- Malaise
- Headache
- Malaise
- Anorexia
- Trismus
- Pain and swelling of parotid gland
Diagnosis:
- Based on clinical features
- IgM serology can be performed from saliva, CSF or urine
Treatment:
- Mouth care
- Nutritional
- Analgesia
Prevent: MMR vaccine
Complications: CNS involvement
What is trismus?
The reduced opening of the jaws caused by spasm of the muscles of mastication
Acute epiglottitis: Transmission? Incidence? Causative agents? Clinical features? Diagnosis? Treatment?
Transmission?
Incidence: Young children
Causative agents: Haemophilus influenza (gram neg)
Clinical features:
- High fever
- Oedema of epiglottis
- Airflow obstruction = breathing difficulties
- Bacteraemia
Diagnosis:
- DO NOT examine throat or take throat swabs (precitates complete airway obstruction)
- Blood cultures to isolate H. influenza
Treatment:
- Life threatening emergency
- Requires urgent endotracheal intubations
- IV antibiotics
Diphtheria: Transmission? Incidence? Causative agents? Clinical features? Diagnosis? Treatment? Prevention?
Transmission: Aerosol
Incidence: Rarely in developed countries. Childhood
Causative agents: Corynebacterium diphtheria (Only toxin producing strains cause disease) Clinical features: -Sore throat -Fever -Formation of pseudomembrane -Lymphadenopathy -Oedema of anterior cervical tissue
Diagnosis:
-Clinical features
Treatment:
- Prompt anti-toxin therapy administered intramuscularly
- Concurrent antibiotics (penicillin or erythromycin)
- Strict isolation
Prevention:
- Childhood immunisation with toxoid vaccine
- Booster when traveling to endemic areas
Laryngitis and tracheitis:
- Viral origin
- Symptoms in adults and chidlren
Viral origin:
- Parainfluenza virus
- Respiratory syncytial virus
- Influenza virus
- Adenovirus
Symptoms in adults: Hoarseness, retrosternal pain
Symptoms in children: Dry cough, inspiratory stridor
Whooping cough: Transmission? Incidence? Causative agents? Clinical features? Diagnosis? Treatment? Prevention? Complications?
Transmission: Aerosol
Incidence: In children <5 yrs. In developed countries.
Causative agents: Bordetlla pertussis (Gram neg) in cilia
Clinical features:
- Catarrhal stage (1 week): Highly contagious, malaise, mucoid rhinorrhoea, conjunctivitis
- Paraoxysmal stage (1-4 weeks): Inspiratory whoop, Mucus secretion and oedema compromises RT
Diagnosis:
- “Whoop”
- Bacterial isolation
- NAAT
Treatment:
- In catarrhal stage = Erythromycin
- In paroxysmal stage: Not antibiotics. Isolation and supportive care
Prevention:
-Vaccine
Complications?
What is rhinorrhea?
Rhinorrhea or rhinorrhoea is a condition where the nasal cavity is filled with a significant amount of mucus fluid
Difference between centrilobular and panacinar emphysema?
Centrilobular emphysema: Begins in the respiratory bronchioles and spreads peripherally.
Panacinar: Destroys the entire alveolus uniformly and is predominant in the lower half of the lungs.
Name 3 interstitial lung diseases?
- Hypersensitivity pneumonitis: Type III and IV, Bird fancier, Farmer’s lung
- Sarcoidosis: Type IV (cell mediated)
Clinical features include Granulomas; Hilar lymphadenopathy, raised ACE - Idiopathic pulmonary fibrosis (UIP- Usual Interstitial Pneumonia): Presents as honeycomb lung
Main type of benign lung cancer?
Mesenchymoma
- Arising from mesenchyme
- Non-invasive
Where does primary malignant lung cancers develop?
Epithelium* and pleura
*[Importance of metaplasia and dysplasia]
Difference between metaplasia and dysplasia?
Metaplasia: The conversion of one cell type into another; e.g., squamous metaplasia, in which non-keratinised squamous epithelium replaces ciliated columnar cells in the bronchi of smokers.
Dysplasia: An abnormality of development; in pathology, alteration in size, shape, and organization of adult cells.
Where are the main locations of secondary cancers from lung cancer?
- Sarcoma
- Renal carcinoma
- Lymphoma
What are the different forms of primary epithelial cancer in the lung?
How are they diagnosis?
How are they classified?
- Squamous (NSCLC)
- Adenocarcinoma (NSCLC)- Affects glandular structure in epithelia
- Small cell undifferentiated (SCLC)
- Carcinoid; In neuroendocrine system. “Atypical” is smoking related and tends to be malignant
- Large cell undifferentiated
Diagnosis:
- Radiology (determines size change)
- Cytology
- EBUS (EndoBronchial UltraSound)
- Biopsy
Classification:
- Grade
- Stage TNM
What is the molecular pathology and treatment for epithelial cancers?
Molecular pathology:
Chromosomal rearrangements leading to oncogenic tyrosine kinase activation.
Cancers that harbour tyrosine kinase gene rearrangements express activated fusion kinases that drive the initiation and progression of malignancy
These cancers become dependent on continued signalling from the oncogenic fusion kinase
Mutations of: -EGFR (epidermal growth factor receptor) -B-RAF -RAS \+ ALK rearrangements
Treatment:
-Tyrosine-kinase inhibitors e.g. ALK (Anaplastic lymphoma kinase) inhibitors
-
How are antibodies involved in cancer immunotherapy?
They inhibit the suppressing effects of PDL (programmes death ligation). Allowing cancer cells to be killed by immune system
What is mesothelioma?
Mesothelioma is a rare cancer caused by asbestos that forms in the internal lining (pleura) of the lungs, abdomen, or heart
1kPa =
7.5mmHg
Acid-base disturbances occur when… (3)
- Ventilation problem
- Renal function problem
- Overwhelming acid or base load that they body cannot handle
What are the normal values for the following:
- pH
- pO2
- pCO2
- Bicarbonate (standard)
pH = 7.35 - 7.45
pO2 = 12 - 13kPa
pCO2 = 4.5 - 5.6 kPa
Bicarbonate (standard) = 22 - 26 mmol/l
How is standard bicarbonate calculated?
Form the actual bicarbonate but assuming 37C and pCO2 of 5.3kPa
Adverse effects of high oxygen levels
- Increases risk of hypercapnic respiratory failure in acute exacerbations of COPD
- Increased mortality in cardiac arrest survivors
- Increased mortality in intensive care patients
- Increased mortality in acute severe asthma
- Generates free radicals
- -> Lung toxicity (resulting in atelectasis and irritation of mucous membranes)
What are the British Thoracic Society guidelines for oxygen administration?
Oxygen is a treatment for hypoxia not dyspnoea alone
In an unstable medical emergency give high O2 conc then titrate to target once stable.
Targets:
-94-98% (normally)
-88-92% (in type 2 respiratory failure)
What are the therapeutic uses for high inspired conc of O2?
Pneumothorax
CO poisoning
Normal alveolar -arterial gradient is less than ____
3kPa
What is the P/F ratio?
PaO2 / FiO2
FiO2= Fraction of Inspired Oxygen
P/F ratio > 50 = healthy
P/F ratio < 40 = acute lung injury
P/F ratio <26.7 = ARDS
If the pH and pCO2 are changing in opposite
directions this suggests a __________
If the pCO2 and pH are changing in the same
direction, the primary problem is probably
________
Opposite direction of pH and pCO2 = RESPIRATORY PROBLEM
Same direction of pH and pCO2 = METABOLIC PROBLEM
What is compensation?
Altering of function of the respiratory or renal system in an attempt to correct an acid-base imbalance
The body will never overcompensate
If pCO2 and HCO3 - move in the \_\_\_\_ direction compensation is possibly occurring • If both values move in opposite directions more than 1 \_\_\_\_\_\_ must be present
If pCO2 and HCO3 - move in the SAME direction compensation is possibly occurring (remember pH ∞ bicarbonate/pCO2) • If both values move in opposite directions more than 1 PATHOLOGY must be present
Causes of hyperventilation
Acute severe asthma
Pulmonary embolism
Pulmonary oedema
Explain how the different forms of tuberculosis occur
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Acute bronchitis:
What is it?
Due to?
Secondary infections?
What is it? Inflammation of the tracheobronchial tree
Usually due to infection:
- Rhinovirus
- Coronovirus
- Adenovirus
- Mycoplasma pneumonia
Secondary infections:
- Streptococcus pneumonia
- Haemophilus influenzae
Chronic bronchitis:
-Characteristics?
Characterised by cough and excessive mucus secretion in tracheobronchial tree
Pneumonia:
- Definition?
- Diagnosis?
- Assess to LRT
- Difference between children and adult
- 4 different anatomical classes?
- Clinical features?
Defined as inflammation of the substance of the lungs
Confirmed on chest radiograph
Access to LRT by inhalation of microbes or by aspiration of normal flora of the URT
Age is important:
- Children is mainly viral. Neonatal pneumonia caused by Chlamydia trachmatis from moth during birth
- Adults is mainly bacterial. Aetiology varies with age, underlying disease, occupational and geographic risk factors
Classes: Lobar, broncho-, interstitial, necrotising
Clinical features: Dry cough, malaise, fever, productive sputum
What makes “atypical pneumonia” different?
Failure of patient to respond to treatment with penicillin Causes: -Mycoplasma pneumonia -Legionella pneumophilia -Chlamydia pneumoniae
- Common causes of viral pneumonia?
- Common causes of bacterial pneumonia?
Viral pneumonia causes:
- Influenza virus
- Measles
- Coronavirus
- CMV
Bacterial pneumonia causes:
- Streptococcus pneumonia
- Mycobacterium tuberculosis
- Staph. aureus
Legionnaire’s disease
- Cause
- Clinical features
- Pathophysiology?
- Transmission
- Occurrence?
- Diagnosis
Cause: Legionella pneuomophila (gram neg)
Clinical features:
- Tachypnoea
- Purulent sputum
- CXR shows consolidation
Pathophysiology:
- Secretes protease causing lung damage
- Severe systemic infection with pneumonia
Transmission: Aerosol
Occurence: In outbreaks
Diagnosis
- Gram staining of sputum
- Recognition of serotype-specific fluorescent antibody
- Culture of legionella on cysteine extract agar
- Detection of antigen in urine
- 4-fold rise in antibody
Measles:
- Clinical features
- 2’ complications?
- Cause?
- Transmission?
- Location of replication?
- Diagnosis?
- Treatment?
- Prevention?
Clinical features:
- Fever
- Runny nose
- Koplik’s spots
- Characteristic rash
Complications:
- Neurological
- Giant cell (Hecht’s) pneumonia in the immunocompromised
Cause: Paramyxovirus
Transmission: Aerosol
Replicates in LRT
Diagnosis:
- Serology for measules-specific IgM
- Virus isolation
- Viral RNA detection
Treatment:
- Ribavirin for severe cases
- Antibiotics for 2’ infection
Prevention: Immunisation with live/attenuated MMR
Define endemic?
Present in a community at all times, at a relatively low to medium frequency but at a steady state
Define epidemic?
Sudden severe outbreak within a region or a group
Define pandemic?
Occurs when a epidemic become widespread and affects a whole region, a continent or the entre world
Influenza virus:
- Cause
- 3 types?
- What contributes to the variety of types?
- Nucleic acid structure?
- What are the genetic changes during spread?
- Diagnosis?
- Treatment?
Cause: Orthomyxovirus
3 types:
A- Epidemics and pandemics, anima reservioir
B- Epidemics, no animal hosts
C- Minor respiratory illness
Type-specific antigens on cell surface, Haemagglutinin (H) and Neuraminidase (N)
Single stranded RNA. Reassortment gives rise to novel combinations of H and N antigens
Genetic changes:
- Antigenic drift. Small point mutations in the H and N antigens occurs constantly. Allows replication despite immunity to preceding strains.
- Antigenic shift. Sudden major change based on recombination between two different virus strains when they infect the same cell. Produces virus with novel surface glycoproteins. Can cause new pandemic.
Diagnosis:
-Nasopharyngeal aspirate (Direct immunofluorescence, culture, NAAT detection)
Treatment:
- Amantadine
- Zanamavir
- Oseltamvir
4 features that make a pandemic
- Antigenic shift
- Lack of immunity
- Attack rate is high - it spreads rapidly
- Mortality can be high
What s the difference in the antigens of season swine flu and pandemic swine flu?
Seasonal flu- Different serotypes (e.g. H3, B, H1)
Pandemic flu- Almost exclusively pandemic H1N1
Influenza vaccination:
- Name
- Difference between yearly vaccine?
- Give to who?
Name: “Tamiflu”
Antigenic variation mens a new vaccine is required each year.
New vaccine is based on the predicted strains
Recombination methods speed up the process of developing a new vaccine
Given to: Elderly, immunosuppressed and those with respiratory risk
What does SARS stand for?
Severe Acute Respiratory Syndrome (SARS)
SARS:
Symptoms?
Transmission?
Symptoms:
- Sudden onset of high fever
- Dry cough
- Chills and shivering
- Muscle aches
- Breathing difficulties
Transmisson:
- Droplets
- Faeces
- Infected animals
What is SARS Co-V? How is it identified? Nucleic acid structure? Treatment Vaccine available?
SARS Co-V= SARS Coronavirus
Identified by:
- Virus isolation in cell culture
- Electron microscopy
- Molecular techniques
Nucleic acid:
- Enveloped
- RNA virus
Characteristic “halo”
Treatment:
- No specific anti-viral treatment available
- Ribavirin, corticosteroids, interferons
Whole inactivated virus vaccine and recombinant vaccine now been developed
TB Associated with? Clinical features of primary, military and post-primary TB? Causative agent? Transmission? Diagnosis? Treatment Prevention?
Associated with:
- AIDS
- Increased use of immunosuppressives
- Decreased socio-economic conditions
- Multiple drug resistance (MDR)
- Overcrowding and poor nutrition
Clinical features:
Primary- Symptomless, cough, wheeze, small transient pleural effusion may occur
Miliary- Results from acute diffuse dissemination of bacillus. Fatal without treatment
Post-primary- Malaise, fever, weight loss, sputum abnormal, pleural effusion
Causative agent: Mycobacterium tuberculosis. Neither gram neg or pos. Obliqate aerobe (found in well-aerated upper lobes of lungs)
Transmission: Spread by inhalation of organisms from dust/aerosols
Diagnosis: Mantoux test
-Detects latent TB infection
-Tuberculin injected intradermally. Immune response if individual previously exposed to bacterium
Or
-Identifying ACID-FAST BACILLI in sputum smears
Treatment:
- Combination therapy- Isoniazid, rifampicin, ethambutol, pyrazinamide. Prevents emergence of resistance
- Prolonged therapy- To eradicate slow-growing organisms
Prevention:
- Childhood immunisation
- Live attenuated BCG vaccine
- Prophylaxis with isoniazid for 1 year
