The pathophysiology of covid 19

1. The mystery
behind
pandemic’s
Happy
hypoxia…

2. ● Disconnect
between
the severity of hypoxemia and
the relatively mild
respiratory discomfort reported
by the patients.
Happy hypoxemia…

3. ● Among the many surprises of the new
coronavirus, the one that seems to defy
basic biology is happy hypoxia : infected
patients with extraordinarily low blood-
oxygen levels, or hypoxia, scrolling on their
phones, chatting with doctors, and
generally describing themselves as
comfortable !

4. Dr Levitan, with 30 years of emergency medicine experience, notes “A vast majority of Covid pneumonia
patients I met had remarkably low oxygen saturations at triage—seemingly incompatible with life—but they were using their
cellphones . . . they had relatively minimal apparent distress, despite dangerously low oxygen levels” . Despite this extensive
coverage in the news media, the topic has not been addressed in medical journals.

5. Dyspnea as a sensation
Conscious awareness of the activation of respiratory
muscles is absent in healthy breathing.
However, when the respiratory muscles are fatigued or
weakened due to altered lung mechanics, breathing may
be perceived as a substantial effort

6. Tachypnea Hyperpnea Dyspnea
The output of the respiratory center can be divided into rhythm-
(e.g. respiratory rate) and pattern generating (e.g. depth of
breathing effort) signals

7. Tachypnea Hyperpnea Dyspnea
Rapid breathing Increased ventilation
sensation of ‘uncomfortable,
difficult, or labored’ breathing
and occurs, in general, when
the demand for ventilation is
out of proportion to the
patient’s ability to respond

8. Dyspnea
Input from the
mechanoreceptors
In the respiratory tract
and the chest wall.
Vagal irritant
receptors
(Bronchoconstriction,
breathing through an
external resistance)
Changes in partial gas
pressure of dissolved
carbon dioxide in the
blood (paco2)
Causing shifts in pH at
the level Of both the
peripheral and central
chemoreceptors
Hypoxemia itself rather plays a limited role
The normal response to hypoxemia is a rise in minute ventilation, primarily by increasing
tidal volume and respiratory rate. Increased respiratory rate (tachypnea) and tidal
volume (hyperpnea) -and not dyspnea…

9. Hypoxia
Decreased PaCO2
Respiratory
Alkalosis

10. Factors contributing to Happy Hypoxia
Intrapulmonary shunting
Loss of lung perfusion regulation
Intravascular thrombi
Changes in HBO2 dissociation curve
Reduced compliance, consolidation,
aetelectais, CO2 retention and frank
ARDS
Dyspnea
Happy
hypoxia

11. 1.Intrapulmonary shunting

12. 1.Intrapulmonary
shunting

13. 1.Intrapulmonary shunting

14. SARS CoV 19….pulmonary involvement
Local subpleural interstitial edema
Vasoplegia
Intravascular thrombosis
Endothelial injury
Fibrin deposition, diffuse alveolar damage, vascular wall thickening, and frequently occurring
complement-rich microthrombi occluding lung capillaries and larger thrombi causing pulmonary artery
thrombosis and embolism
virus-linked pyroptosis
denuded basement membrane to be
covered with debris, consisting of
fibrin, dead cells

15. ● Hypoxic pulmonary vasoconstriction constriction of small intrapulmonary
arteries in response to alveolar hypoxia
● This phenomenon is abolished by SARS CoV 2 by following mechanisms
● Vasoplegia
● Diminished levels of ACE 2 causing increase in Ang II(Ang II levels were
linearly associated with viral load and lung injury in COVID-19)
2.Loss of lung perfusion
regulation – Abolition of HPV

16. Hypoxic Pulmonary
Vasoconstriction
Bradykinins
Degradation
of Bradykinins
by Ang 1-7

17. ● Endothelial injury is emerging as a central hallmark of COVID-19
pathogenesis
● Intravascular microthrombi are the net result of an imbalance
between procoagulant and fibrinolytic activity in the presence of
acute inflammation and endothelial injury
3.Intravascular microthrombi

18. 4. Preservation of lung mechanics -
Lung compliance

19. v
4. Preservation of lung mechanics - Lung
compliance

20. ● Shift to the left, due to induced respiratory
alkalosis (drop in PaCO2) because of
hypoxemia-driven tachypnea and hyperpnea.
● During hypocapnic periods, (the affinity of
hemoglobin for oxygen )/oxygen saturation
increases for a given degree of PaO2,
5.Changes in oxyhemoglobin dissociation
curve
Explaining why SpO2 can be well-preserved in the face of a profoundly low PaO2…

21. Sebastiaan Dhont , Eric Derom, Eva Van Braeckel, Pieter Depuydt and Bart N. Lambrecht.
The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respiratory Research (2020)
21:198.

22. PULMONARY
PATHOPHYSIOLOGY
OF COVID 19

23. INVOLVEMENT OF THE LOWER RESPIRATORY TRACT AND PROGRESSION TO Acute
RESPIRATORY DISTRESS SYNDROME (ARDS)
About one fifth patients develop severe symptoms. Involvement of type 2 alveolar cells
via ACE 2 receptors, cytokine storm, immune response-ARDS
INVASION AND INFECTION OF THE UPPER RESPIRATORY TRACT
Involves upper airways, and manifests as fever, malaise and dry cough. Greater immune
response and majority do not progress beyond this stage
ASYMPTOMATIC PHASE
SARS-CoV-2 binds to nasal epithelial cells via ACE-2 receptors, replicates and
propagates via ciliated cells in conducting airways, lasts for a couple of days.

24. COVID-19 presentation in the emergency department depend on the interaction between
three factors:
1. the severity of the infection, the host response, and comorbidities;
2. the ventilatory responsiveness of the patient to hypoxemia;
3. the time elapsed between the onset of the disease and the observation in hospital.
The interaction between these factors leads to the development of a time-related disease
spectrum within two primary “phenotypes”: Type L, characterized by Low elastance
(i.e., high compliance), and Type H, characterized by High elastance.*
*Luciano Gattinoni, Davide Chiumello, Pietro Caironi, Mattia Busana, Federica Romitti, Luca Brazzi and Luigi
Camporota. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med
(2020) 46:1099–1102.

25. AT THE BEGINNING, COVID-19 PNEUMONIA PRESENTS WITHTHE FOLLOWING
CHARACTERISTICS:
COVID-19
pneumonia
Type L
Low elastance
nearly normal
compliance.
Low ventilation-to-
perfusion (VA/Q) ratio.
hypoxemia explained by
the loss of regulation of
perfusion and loss of
hypoxic
vasoconstriction.
Low lung weight
Only ground-glass densities are
present on CT scan, primarily
located subpleurally and along the
lung fissures
Low lung
recruitability
The amount of
non-aerated
tissue is very
low.

26. ● The Type L patients may remain unchanging for a period and then improve
or worsen.
● Over time, the increased edema increases lung weight, superimposed
pressure and dependent atelectasis.
● When lung edema reaches a certain magnitude, the gas volume in the lung
decreases, and the tidal volumes generated for a given inspiratory
pressure decrease.
● At this stage, dyspnea develops and patient progresses to type H.
TRANSITIONING BETWEEN PHENOTYPES

27. COVID-19
pneumonia
Type H
High elastance
The decrease in
gas volume due to
increased edema
High right-to-left shunt..
fraction
cardiac output
perfusing the non-
aerated tissue
developing in the
dependent lung regions
due to the increased
edema
High lung weight
Increase in lung weight
(> 1.5 kg), on the order of magnitude of
severe ARDS
High lung
recruitability
The increased
amount of
non-aerated tissue
is associated, as
in severe ARDS,
with increased
recruitability

28. ● Non ventilatory
● Proning
● Steroids
● Mucolytics
● Physiotherapy
Management
Ventilatory devices
• Nasal prongs
•
• Face mask
• NRM
• HFNC
• NIV
• Invasive ventilation

29. ● The main reason for happy hypoxia seem to be the presence of hypocapnia, our brain
senses the CO2 levels with various sensors,” but, “We don't sense our oxygen levels.”
● Also, intrapulmonary shunting act as a key factor in patients with COVID-19
accounting for both the presence of hypoxia and the absence of dyspnea in many of
them. Happy Hypoxia has been described as Sadly Ignored “Acute Vascular
Distress Syndrome” in Patients with COVID-19.*
To conclude…

30. ● Normal compliance till late in the disease.
● Inaccuracy of pulse oximeters below 85%.
● Apart from happy hypoxia, covid made us realize that ARDS may actually present with
normal compliance.
● It taught us, for the first time to use oxygen as a drug with proper indication, dosage,
flow rate, route, along with its escalation and deescalation.
*Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit
Care Med 2020;202:356–360.
To conclude…