Theme 2:
Shortness of
Breath
Summary
1
,Content
Week 5: Infections................................................................................................................................... 5
History of infectious diseases .............................................................................................................. 5
Epidemics......................................................................................................................................... 5
Political consequences .................................................................................................................... 5
Infection .............................................................................................................................................. 5
Bacterial infections .......................................................................................................................... 6
Viral infections ................................................................................................................................. 6
Prions ............................................................................................................................................... 7
Tuberculosis......................................................................................................................................... 7
Syphilis ................................................................................................................................................. 8
COVID-19 ........................................................................................................................................... 10
GI-tract infections .............................................................................................................................. 11
Spread of hepatitis ............................................................................................................................ 12
Prevention of infection...................................................................................................................... 12
Isolation and obligation to report disease .................................................................................... 12
Hemostasis ........................................................................................................................................ 12
Disseminated intravascular coagulation ....................................................................................... 14
Pulmonary embolism..................................................................................................................... 14
Week 6: Shortness of breath and chronic heart failure ........................................................................ 15
The heart ........................................................................................................................................... 15
Anatomy of the heart .................................................................................................................... 15
The circulation ............................................................................................................................... 15
The heart as a pump ...................................................................................................................... 16
Coronary circulation ...................................................................................................................... 17
Regulation of cardiac function ...................................................................................................... 18
Cardiac hypertrophy ...................................................................................................................... 18
The systemic circulation .................................................................................................................... 19
Compliance .................................................................................................................................... 19
Resistance ...................................................................................................................................... 20
Venous return................................................................................................................................ 20
Cardiac output and atrial pressure in situations ........................................................................... 20
Microcirculation ............................................................................................................................ 20
Changes during a cardiac arrest .................................................................................................... 21
THE curves ......................................................................................................................................... 21
Venous function curves (in vitro = outside of the body) ............................................................... 21
2
, The venous function curves (in vivo = in the thoracic cavity) ....................................................... 22
The arterial heart function curve (in vivo)..................................................................................... 23
Venous vascular function curve .................................................................................................... 24
The venous return curve ............................................................................................................... 24
Arterial vascular function curves ................................................................................................... 25
Venous coupling ............................................................................................................................ 26
Blood pressure regulation ................................................................................................................. 27
Local control loops ........................................................................................................................ 27
Systemic regulation ....................................................................................................................... 27
Pharmacology .................................................................................................................................... 28
Heart disease ..................................................................................................................................... 29
Common symptoms & their cause ................................................................................................ 29
Heart failure .................................................................................................................................. 29
Physiology of heart failure............................................................................................................. 31
Week 7: Shortness of breath – Chronic pulmonary disease ................................................................. 33
Histology ............................................................................................................................................ 33
Nasal passages ............................................................................................................................... 33
Larynx ............................................................................................................................................ 34
Trachea .......................................................................................................................................... 34
Microscopic anatomy of the bronchus.......................................................................................... 34
Microscopic build-up of bronchioles ............................................................................................. 35
Microscopic structure of the alveoli.............................................................................................. 35
Pathology........................................................................................................................................... 36
Obstructive vs restrictive lung diseases ........................................................................................ 36
Asthma........................................................................................................................................... 36
Chronic obstructive pulmonary disease ........................................................................................ 37
Bronchiectasis................................................................................................................................ 38
Cystic fibrosis ................................................................................................................................. 39
Obstructive sleep apnea ................................................................................................................ 39
Idiopathic pulmonary fibrosis........................................................................................................ 39
Pulmonary hypertension ............................................................................................................... 40
Hypoxia .......................................................................................................................................... 40
Pneumonia .................................................................................................................................... 40
Pharmacology: drugs for asthma and COPD ..................................................................................... 41
Drug delivery to the lungs ............................................................................................................. 41
Drugs.............................................................................................................................................. 42
3
, Asthma management strategy ...................................................................................................... 43
Management of COPD ................................................................................................................... 43
Breathing ........................................................................................................................................... 43
Spirometry ..................................................................................................................................... 44
Ventilation ..................................................................................................................................... 45
Work of breathing ......................................................................................................................... 48
Ventilation – perfusion ...................................................................................................................... 49
From 1 to multiple breaths............................................................................................................ 49
Diffusion ........................................................................................................................................ 49
The A-a gradient ............................................................................................................................ 50
Disturbances in ventilation-perfusion ratio .................................................................................. 51
Oxygen transport in the blood ...................................................................................................... 51
Carbon dioxide transport in the blood .......................................................................................... 52
Regulation of ventilation ................................................................................................................... 52
Hyper- and hypoventilation........................................................................................................... 52
Factors determining the result of gas exchange ........................................................................... 53
GP medicine....................................................................................................................................... 53
Diagnostics in pulmonary diseases ................................................................................................ 53
Week 8: A spot on the X-ray .................................................................................................................. 55
Pulmonology...................................................................................................................................... 55
Pulmonary metastasis ................................................................................................................... 56
TNM cancer staging ....................................................................................................................... 56
Pleural effusion.............................................................................................................................. 57
Sarcoidosis ..................................................................................................................................... 57
Mediastinal lesions ........................................................................................................................ 59
Radiotherapy ..................................................................................................................................... 59
Radiotherapy for lung metastases ................................................................................................ 60
Radiology ........................................................................................................................................... 61
Normal lungs ................................................................................................................................. 61
Lung diseases and their X-rays ...................................................................................................... 62
Pathology........................................................................................................................................... 66
The cell cycle.................................................................................................................................. 66
Neoplasia ....................................................................................................................................... 66
4
,Week 5: Infections
History of infectious diseases
Epidemics
Pandemic = worldwide spread of infectious disease
Epidemic = collective disease → requires common explanation
➔ An event with a widespread threat response by society
Configuration Contamination
Holism: unique configuration of Person-to-person transmission
circumstances
(Dis)balance More general sense
Multifactorial Monocausal
Predisposition: some people are more susceptible to epidemic disease
Dramaturgic event in 4 acts (comparable to a play):
1. Progressive revelation: unwilling and slow acceptance and acknowledgement →
acceptance leads to the consequences of the threat
2. Managing randomness: creation of explanatory framework (mixture of medical
knowledge and moral/social assumptions)
3. Negotiating public response: pressure to be decisive (measures reflect cultural
attitudes and rituals)
4. Epilogue: gradual decline of incidence or becomes part of normal life → evaluation
Political consequences
Until mid-19th century: emphasis on configuration
➔ Industrial and urban populations vs happier conditions in rural areas (poor people
were often blamed)
Tuskegee study: black, African men with syphilis was done research on, but they were not
helped, even though penicillin was already on the market for 15 years
Medical revolution: better hygiene
Second half of the 19th century: germ theory → more emphasis on contamination
(configuration is still relevant!)
Two important morals:
- Both models mirror and imply policy choices
- Emphases, not answers
Infection
Entry of microbes in the body:
5
, - Skin
- Biting arthropods
- Conjunctiva: eyes
- Respiratory tract
Spread:
- Spread to lymph and blood
o Tissue fluids
o Local macrophages
o Lymphatic system
- Spread from blood
o Free
o Attached to other cells
- Spread via nerves
- Spread via cerebrospinal fluid
- Spread via peritoneal and pleural cavity
Transmission:
- Endogenous: from the body’s own microbiome
- Air-borne: aerosols and droplets
- Faeco-oral route
- Vector-borne: most important is Malaria caused by mosquitos
- Direct person-to-person spread: by actual contact
- Indirect person-to-person spread: by indirect contact (fomites: e.g. door handle)
- Direct inoculation: goes into internal environment directly (e.g. because of an open
fracture)
- Consumption of infected material
- Zoonosis: from animals (e.g. rabies, Q-fever and Creutzfeldt-Jakob disease)
Bacterial infections
Virulence factors: proteins that aid bacteria in entering the cell, evade the immune system
and exit the host
- Adherence proteins: to adhere to the cells
- Invasion proteins
- Capsules: to avoid opsonization
- Endotoxins (on gram negative bacteria): cause inflammation
- Exotoxins: protein toxins
- Siderophores: to take away host’s iron
Viral infections
Course of a viral infection:
6
, - Incubation: period between infection and onset of symptoms
- Prodrome: period of initial symptoms
- Invasion: period of multiplication and disease
- Convalescence: period of healing
Viremia: when the virus enters the bloodstream → systemic infection
Common symptoms of a viral infection:
- Malaise
- Muscle ache
- Fatigue
- Sore throat
- Coughing
- Runny nose
- Fever
Viruses must enter host’s cell in order to survive and replicate
➔ Penetrate or fuse with the membrane of the cell → releases viral DNA or RNA into
the cell
Bacteriophage: virus that infects and replicated in bacteria
Prions
= proteins that can make healthy proteins in the body (e.g. the brain) fold the wrong way →
widespread, fatal damage
➔ Causes Creutzfeldt-Jakob disease
Transmission:
- (in)direct person-to-person contact
- Faeco-oral route
- Ingestion of infected material
Tuberculosis
= from Mycobacterium Tuberculosis
Transmission: air-borne
Pathophysiology:
1. Bacteria enters the lungs, where it gets phagocytosed
2. Produces enzymes that inhibit lysosomes and phagocytic vacuole fusion
3. Bacteria survives and proliferates → local infection = primary tuberculosis
4. Infection mostly gets killed by the immune system or walled off in granulomas and
becomes latent (when the person has a competent immune system)
7
, Symptoms:
- Mostly asymptomatic (90-95%)
- Mild flu-like symptoms
- Rarely pleural effusion
Reactivation tuberculosis: when the immune system is not competent enough to fight the
infection → more necrotic areas → cavity formation → reactivation of the bacteria
Symptoms:
- Fever
- Chills
- Night sweats
- Malaise
- Fatigue
- Appetite loss
- Weight loss
- Pleuritic chest pain
- Cough
- Crepitations during lung auscultation
Extrapulmonary tuberculosis: involves other organs (e.g. the kidneys, meninges and lymph
nodes)
➔ Miliary tuberculosis: systemic infection that can affect any organ
Symptoms:
- Depends on the organ
- Dyspnea
- Weight loss
- Fever
- Chills
Treatment:
- Prophylaxis: BCG vaccine
- Latent TB: isoniazid
- Active: isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin
- Multiple drug-resistant TB: amikacin, kanamycin, capreomycin
Prevention: extensive screening (Mantoux test) and immunization (BCG vaccine)
Syphilis
= from treponema pallidum
Transmission: sexually and perinatally (bacteria crosses the placenta)
8
Shortness of
Breath
Summary
1
,Content
Week 5: Infections................................................................................................................................... 5
History of infectious diseases .............................................................................................................. 5
Epidemics......................................................................................................................................... 5
Political consequences .................................................................................................................... 5
Infection .............................................................................................................................................. 5
Bacterial infections .......................................................................................................................... 6
Viral infections ................................................................................................................................. 6
Prions ............................................................................................................................................... 7
Tuberculosis......................................................................................................................................... 7
Syphilis ................................................................................................................................................. 8
COVID-19 ........................................................................................................................................... 10
GI-tract infections .............................................................................................................................. 11
Spread of hepatitis ............................................................................................................................ 12
Prevention of infection...................................................................................................................... 12
Isolation and obligation to report disease .................................................................................... 12
Hemostasis ........................................................................................................................................ 12
Disseminated intravascular coagulation ....................................................................................... 14
Pulmonary embolism..................................................................................................................... 14
Week 6: Shortness of breath and chronic heart failure ........................................................................ 15
The heart ........................................................................................................................................... 15
Anatomy of the heart .................................................................................................................... 15
The circulation ............................................................................................................................... 15
The heart as a pump ...................................................................................................................... 16
Coronary circulation ...................................................................................................................... 17
Regulation of cardiac function ...................................................................................................... 18
Cardiac hypertrophy ...................................................................................................................... 18
The systemic circulation .................................................................................................................... 19
Compliance .................................................................................................................................... 19
Resistance ...................................................................................................................................... 20
Venous return................................................................................................................................ 20
Cardiac output and atrial pressure in situations ........................................................................... 20
Microcirculation ............................................................................................................................ 20
Changes during a cardiac arrest .................................................................................................... 21
THE curves ......................................................................................................................................... 21
Venous function curves (in vitro = outside of the body) ............................................................... 21
2
, The venous function curves (in vivo = in the thoracic cavity) ....................................................... 22
The arterial heart function curve (in vivo)..................................................................................... 23
Venous vascular function curve .................................................................................................... 24
The venous return curve ............................................................................................................... 24
Arterial vascular function curves ................................................................................................... 25
Venous coupling ............................................................................................................................ 26
Blood pressure regulation ................................................................................................................. 27
Local control loops ........................................................................................................................ 27
Systemic regulation ....................................................................................................................... 27
Pharmacology .................................................................................................................................... 28
Heart disease ..................................................................................................................................... 29
Common symptoms & their cause ................................................................................................ 29
Heart failure .................................................................................................................................. 29
Physiology of heart failure............................................................................................................. 31
Week 7: Shortness of breath – Chronic pulmonary disease ................................................................. 33
Histology ............................................................................................................................................ 33
Nasal passages ............................................................................................................................... 33
Larynx ............................................................................................................................................ 34
Trachea .......................................................................................................................................... 34
Microscopic anatomy of the bronchus.......................................................................................... 34
Microscopic build-up of bronchioles ............................................................................................. 35
Microscopic structure of the alveoli.............................................................................................. 35
Pathology........................................................................................................................................... 36
Obstructive vs restrictive lung diseases ........................................................................................ 36
Asthma........................................................................................................................................... 36
Chronic obstructive pulmonary disease ........................................................................................ 37
Bronchiectasis................................................................................................................................ 38
Cystic fibrosis ................................................................................................................................. 39
Obstructive sleep apnea ................................................................................................................ 39
Idiopathic pulmonary fibrosis........................................................................................................ 39
Pulmonary hypertension ............................................................................................................... 40
Hypoxia .......................................................................................................................................... 40
Pneumonia .................................................................................................................................... 40
Pharmacology: drugs for asthma and COPD ..................................................................................... 41
Drug delivery to the lungs ............................................................................................................. 41
Drugs.............................................................................................................................................. 42
3
, Asthma management strategy ...................................................................................................... 43
Management of COPD ................................................................................................................... 43
Breathing ........................................................................................................................................... 43
Spirometry ..................................................................................................................................... 44
Ventilation ..................................................................................................................................... 45
Work of breathing ......................................................................................................................... 48
Ventilation – perfusion ...................................................................................................................... 49
From 1 to multiple breaths............................................................................................................ 49
Diffusion ........................................................................................................................................ 49
The A-a gradient ............................................................................................................................ 50
Disturbances in ventilation-perfusion ratio .................................................................................. 51
Oxygen transport in the blood ...................................................................................................... 51
Carbon dioxide transport in the blood .......................................................................................... 52
Regulation of ventilation ................................................................................................................... 52
Hyper- and hypoventilation........................................................................................................... 52
Factors determining the result of gas exchange ........................................................................... 53
GP medicine....................................................................................................................................... 53
Diagnostics in pulmonary diseases ................................................................................................ 53
Week 8: A spot on the X-ray .................................................................................................................. 55
Pulmonology...................................................................................................................................... 55
Pulmonary metastasis ................................................................................................................... 56
TNM cancer staging ....................................................................................................................... 56
Pleural effusion.............................................................................................................................. 57
Sarcoidosis ..................................................................................................................................... 57
Mediastinal lesions ........................................................................................................................ 59
Radiotherapy ..................................................................................................................................... 59
Radiotherapy for lung metastases ................................................................................................ 60
Radiology ........................................................................................................................................... 61
Normal lungs ................................................................................................................................. 61
Lung diseases and their X-rays ...................................................................................................... 62
Pathology........................................................................................................................................... 66
The cell cycle.................................................................................................................................. 66
Neoplasia ....................................................................................................................................... 66
4
,Week 5: Infections
History of infectious diseases
Epidemics
Pandemic = worldwide spread of infectious disease
Epidemic = collective disease → requires common explanation
➔ An event with a widespread threat response by society
Configuration Contamination
Holism: unique configuration of Person-to-person transmission
circumstances
(Dis)balance More general sense
Multifactorial Monocausal
Predisposition: some people are more susceptible to epidemic disease
Dramaturgic event in 4 acts (comparable to a play):
1. Progressive revelation: unwilling and slow acceptance and acknowledgement →
acceptance leads to the consequences of the threat
2. Managing randomness: creation of explanatory framework (mixture of medical
knowledge and moral/social assumptions)
3. Negotiating public response: pressure to be decisive (measures reflect cultural
attitudes and rituals)
4. Epilogue: gradual decline of incidence or becomes part of normal life → evaluation
Political consequences
Until mid-19th century: emphasis on configuration
➔ Industrial and urban populations vs happier conditions in rural areas (poor people
were often blamed)
Tuskegee study: black, African men with syphilis was done research on, but they were not
helped, even though penicillin was already on the market for 15 years
Medical revolution: better hygiene
Second half of the 19th century: germ theory → more emphasis on contamination
(configuration is still relevant!)
Two important morals:
- Both models mirror and imply policy choices
- Emphases, not answers
Infection
Entry of microbes in the body:
5
, - Skin
- Biting arthropods
- Conjunctiva: eyes
- Respiratory tract
Spread:
- Spread to lymph and blood
o Tissue fluids
o Local macrophages
o Lymphatic system
- Spread from blood
o Free
o Attached to other cells
- Spread via nerves
- Spread via cerebrospinal fluid
- Spread via peritoneal and pleural cavity
Transmission:
- Endogenous: from the body’s own microbiome
- Air-borne: aerosols and droplets
- Faeco-oral route
- Vector-borne: most important is Malaria caused by mosquitos
- Direct person-to-person spread: by actual contact
- Indirect person-to-person spread: by indirect contact (fomites: e.g. door handle)
- Direct inoculation: goes into internal environment directly (e.g. because of an open
fracture)
- Consumption of infected material
- Zoonosis: from animals (e.g. rabies, Q-fever and Creutzfeldt-Jakob disease)
Bacterial infections
Virulence factors: proteins that aid bacteria in entering the cell, evade the immune system
and exit the host
- Adherence proteins: to adhere to the cells
- Invasion proteins
- Capsules: to avoid opsonization
- Endotoxins (on gram negative bacteria): cause inflammation
- Exotoxins: protein toxins
- Siderophores: to take away host’s iron
Viral infections
Course of a viral infection:
6
, - Incubation: period between infection and onset of symptoms
- Prodrome: period of initial symptoms
- Invasion: period of multiplication and disease
- Convalescence: period of healing
Viremia: when the virus enters the bloodstream → systemic infection
Common symptoms of a viral infection:
- Malaise
- Muscle ache
- Fatigue
- Sore throat
- Coughing
- Runny nose
- Fever
Viruses must enter host’s cell in order to survive and replicate
➔ Penetrate or fuse with the membrane of the cell → releases viral DNA or RNA into
the cell
Bacteriophage: virus that infects and replicated in bacteria
Prions
= proteins that can make healthy proteins in the body (e.g. the brain) fold the wrong way →
widespread, fatal damage
➔ Causes Creutzfeldt-Jakob disease
Transmission:
- (in)direct person-to-person contact
- Faeco-oral route
- Ingestion of infected material
Tuberculosis
= from Mycobacterium Tuberculosis
Transmission: air-borne
Pathophysiology:
1. Bacteria enters the lungs, where it gets phagocytosed
2. Produces enzymes that inhibit lysosomes and phagocytic vacuole fusion
3. Bacteria survives and proliferates → local infection = primary tuberculosis
4. Infection mostly gets killed by the immune system or walled off in granulomas and
becomes latent (when the person has a competent immune system)
7
, Symptoms:
- Mostly asymptomatic (90-95%)
- Mild flu-like symptoms
- Rarely pleural effusion
Reactivation tuberculosis: when the immune system is not competent enough to fight the
infection → more necrotic areas → cavity formation → reactivation of the bacteria
Symptoms:
- Fever
- Chills
- Night sweats
- Malaise
- Fatigue
- Appetite loss
- Weight loss
- Pleuritic chest pain
- Cough
- Crepitations during lung auscultation
Extrapulmonary tuberculosis: involves other organs (e.g. the kidneys, meninges and lymph
nodes)
➔ Miliary tuberculosis: systemic infection that can affect any organ
Symptoms:
- Depends on the organ
- Dyspnea
- Weight loss
- Fever
- Chills
Treatment:
- Prophylaxis: BCG vaccine
- Latent TB: isoniazid
- Active: isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin
- Multiple drug-resistant TB: amikacin, kanamycin, capreomycin
Prevention: extensive screening (Mantoux test) and immunization (BCG vaccine)
Syphilis
= from treponema pallidum
Transmission: sexually and perinatally (bacteria crosses the placenta)
8
