Acute Respiratory Failure 2'to BACTERIAL Meningitis
Transcript of Acute Respiratory Failure 2'to BACTERIAL Meningitis
PATHOPHYSIOLOGY
ACUTE RESPIRATORY FAILURE S/T BACTERIAL MENINGITIS
A. ETIOLOGY
PREDISPOSING FACTORS
Rationale/Justification
Age It is most common in the extremes of age such
as greater than 69 years old and less than 5
years old.
Gender Prevalence is greater in the male gender.
Race It is most common among Blacks and Native
Americans due to genetic factors that merely
exist in these racial groups.
Immunosuppression Immunosuppression increases risk of
opportunistic infections and acute bacterial
meningitis. Examples of conditions include HIV
infection and malignancy/cancer. It increases
susceptibility on encapsulated organisms,
primarily S, pneumoniae, and opportunistic
pathogens.
Pathoanatomy Congenital cranial or dural defect causes
leakage allowing the pathogen to effectively pass
through the external covering of leptomeninges
and skull, and then invade the CNS.
History of infection Bacteria (usually S. pneumoniae) caused by
previous infection (e.g. sinusitis and mastoiditis)
may remain dormant inside the body. The
moment the body decreases its immunity (due to
stress or other immune-suppressing
circumstances), there will be activation of the
dormant bacteria, and it travels through the
bloodstream, crosses the CSF, and then enters
the brain causing bacterial meningitis.
Past history of meningitis Relapse can always occur due to easy
susceptibility on the infection and due to possible
remaining dormant bacteria in the bloodstream or
CSF.
Intracranial exposure
through manipulation
during surgery or trauma
Open exposure of the intracranial compartments
due to injury or surgery may predispose a person
to infection. Dormancy of the infection inside the
PRECIPITATING FACTORS
Rationale/Justification
Environment Exposure to the pathogen may trigger infectious
process then leading to inflammation of the
meninges, especially if it enters the vascular
system and invades the CNS surviving from the
detection of the body’s immune system. More
importantly, exposure to others with meningitis,
with or without prophylaxis, is at high risks in
harbouring the bacteria causing meningitis.
Underlying disease conditions
Underlying diseases such as diabetes mellitus,
renal or adrenal insufficiency, hypothyroidism,
cystic fibrosis, sickle cell disease, and cirrhosis
may trigger meningitis. The presence of multiple
diseases causes decrease in the immune system
function of the individual.
Alcohol Use Alcohol has direct effect unto the nervous
system; thus, triggering possible alterations in
CNS. On the other hand, since alcoholism
damages the liver Kupffer cells which causes
decrease in chemotactic activity of neutrophil
leukocytescontributing to increased susceptibility
to infections.
Smoking Smoking cigarettes causes decreased immune
response by suppressing Th1 cytokine
production.
Drug Abuse Intravenous drug abuse may lead to meningitis
especially if there are multiple users
Crowding Exposure to a lot of people carrying the infectious
pathogens (e.g. college students living in
dormitories and personnel in military barracks)
increases risk for harbouring infection-causing
meningitis.
B. SYMPTOMATOLOGY
Signs/Symptoms Rationale
Nuchal Rigidity Upon flexing the neck, the spinal canal elongates
and the meninges stretch, causing pain
especially if there is inflammation due to
meningitis.
Brudzinski’s Sign Flexing the head towards the chin causes
pressure against the infected meningeal lining
leading to pain sensation.
Kernig’s Sign Upon extending the leg fully with hips flexed, it
stretches the peripheral nerves, which pulls the
inflamed meninges, causing pain.
Prostration/ opisthotonus This hyperextension and spasticity causing an
“arching” position is caused by the spasm of axial
muscles along the spinal column. However, it is
more pronounced in infants than in adults.
Fever Presence of bacterial infection stimulates the
production of Intraleukin-1 which is an
endogenous pyrogen causing fever.
Chills This is in response to hyperthermia as a way of
compensating the body to achieve homeostasis.
Increased Intracranial
Pressure
This is due to the imbalance in the three brain
compartments namely: brain tissue, CSF, and
blood. Inflammation may cause edema leading to
swelling of the brain tissues, pus formation, toxin
accumulation, and among others which causes
increased in intracranial pressure.
Increased Systolic Blood
Pressure with Widened
Pulse Pressure
Due to increased ICP, the brain compensated by
stimulating the heart to pump more blood with
longer refractory period to enhance perfusion.
Bradycardia This is in response to increase in blood pressure
with prolonged refractory period.
Decreased and Irregular
Respirations
Increased ICP compresses the brain stem
leading to alterations in respirations.
Pupil Dilation Pressure on the optic nerves caused by
increased ICP leads to dilatation of the pupils.
Papilledema This is an optic disc edema secondary to proven
elevated intracranial pressure.
Photophobia The mechanism of photophobia is thought to be a
feeling of discomfort generated by irritation of the
rich innervation to the eye supplied by the first
division of the trigeminal nerve.
Cranial Nerve Palsy (III,
IV, VI)
Due to the surrounding inflammation, the cranial
nerves may be injured, inflamed, compressed, or
compromised causing alteration in function
mainly on the extraocular muscles.
Neutrophilic Pleocytosis This increased in WBC count in the CSF is due to
the migration of leukocytes over the areas of
injury at the CNS.
Headache Headache is usually severe and is due to the
inflammation of the infected lining of the brain.
Also, cerebral hypoperfusion and anoxia may
facilitate anaerobic metabolism causing lactic
acid formation.
Vomiting (Projectile) This is due to irritation unto the vomiting center of
the brain which is the medulla oblongata.
Irritability Mood lability is the most common initial
manifestation in ongoing CNS depression. Due to
compression in the brain compartments, there is
alteration in the emotional center (hypothalamus)
of the CNS.
Seizure Infection in the CNS causes impaired neuronal
activity causing abnormal electrical activity
leading to seizure episodes.
Altered Level of
Consciousness leading
to Stupor/Coma
As the CNS function depresses, the patient’s
level of consciousness deteriorates, probably due
to the compression over the brainstem where the
Reticular Activating System (RAS), responsible
for wakefulness, resides.
Increased Protein in
CSF
Normal protein levels in CSF should be less than
500 mg/L. Increased levels suggests
accumulation of proteinaceous factors that
manages inflammation over the meninges.
Increased Glucose in
CSF
Normal glucose levels in CSF ranges from 40-80
mg/dL. This may be due to increasing capillary
permeability across the CSF.
Increased WBC in CSF Normal white blood cell count in CSF is within 0-5
cells/mm3. This indicates leukocyte action against
existing infection/inflammation.
PaO2 <60 mmHg Decreased partial oxygen indicates hypoxemia
due to poor ventilation and perfusion of oxygen
into the capillaries.
PaCO2 > 50 mmHg Increased partial carbon dioxide indicates
hypercapnia due to increased ventilation with
impaired perfusion causing air trapping of CO2.
Hyperventilation
(Tachypnea)
In response to hypoxemia, the body
compensates by increasing the ventilation of the
lungs.
Respiratory Alkalosis Further hyperventilation causes increased levels
of oxygen in the lungs, leading to respiratory
alkalosis.
Dyspnea Still, increased O2 levels don’t assure good
ventilation; hence, the patient will still manifest
difficulty in breathing.
Metabolic Acidosis In response to respiratory alkalosis, the kidneys
will conserve bicarbonate ions and in turn,
release hydrogen ions to increase acidity and
nullify the alkaline environment in the respiratory
system. However, excessive H+ ions can also
cause systematic acidosis.
Hypoventilation This may be in response to the acidic
environment caused by metabolic acidosis, or
due to increased carbon dioxide concentration
during Hypercapnic periods.
Respiratory Acidosis Decreasing ventilation during Hypercapnic phase
leads to carbon dioxide settlement and
accumulation in the alveoli, thus contributing to
the acidity of the respiratory environment.
Hypoxemia may also occur simultaneously as
response to the increased CO2 levels
overpowering oxygen.
Pulmonary Edema Poor perfusion to the heart causes damage to its
parts especially the valves in each chamber.
Sclerosis or calcification in the valves may cause
regurgitation of the blood back to the lungs
causing pooling of fluids (pulmonary edema). On
the other hand, further injury to the capillary walls
brought about by extensive damage caused by
the infectious bacteria, may lead to increased
capillary permeability allowing entrance of fluids
to the lungs.
Crackles/Rales These bronchial sounds occur in response to
obstructed airway caused by pooling of
secretions.
Hypotension Poor perfusion towards the cardiovascular
system causes decreased in cardiac contractility
producing lesser pressure against the vascular
walls.
Hypertension During the vasodilation process, there is
increased flow of poorly oxygenated blood to the
peripheral organs. Due to the increased oxygen
demand by the peripheral tissues, this stimulates
the blood vessels to constrict in order to distribute
oxygen-concentrated blood throughout the
system.
Arrhythmia Variations in the heart’s contractility cause
arrhythmia.
Cyanosis/Pallor This is due to ineffective perfusion to the
peripheries causing cyanosis (due to hypoxia) or
pallor (due to decreased blood flow).
Decreased Urine Output This is one of the manifestations whenever the
renal system is already involved in
hypoperfusion.
C. SCHEMATIC DIAGRAM
PREDISPOSING FACTORSAge; Gender; Race; Immune Status;
Pathoana.; Hx of Infection; Past hx of Meningitis; Intracranial Exposure
PRECIPITATING FACTORSEnvironment; underlying disease
condition; Alcohol Use; Smoking; Drug Abuse; Crowding
Presence of bacteria
Nasopharyngeal colonization
Bacterial fimbriae adheres to upper respiratory tract host cells
Resistance against body’s immune function
Virulence factor: polysaccharide capsuleStimulates IgA, blocks IgG & IgM; produces IgA1 proteases that cleave IgA
Multiplication and formation of microcolonies on the epithelial surface
Invasion of the epithelium by intracellular or intercellular routes
Passage of organisms to the submucosa
Local invasion
Bacteria crosses over the mucosal barrier
Bacteria in bloodstream
Hematogenous Spread
Bloodstream Survival
Capsule inhibits neutrophil phagocytosisBacteria resists classic complement-mediated bactericidal activity
Intravascular replication
Bacteremia
Bacteria engulfed by circulating monocytes
Monocytes contained with phagocytised bacterium particles migrate into the CSF via choroid plexus(TROJAN HORSE Hypothesis for CNS invasion)
Meningeal Invasion
MENINGITIS
Subarachnoid space inflammation
Stimulates endothelial cells, leukocytes, microglia, astrocytes, & meningeal macrophages
TNF-ɑNO PGE2 IL-1 PAF
Cytotoxicity Regulation of immune cellBBB permeability
Neutrophil migration
Neutrophilic pleocytosis
Release of toxic factors
Swelling of cellular elements of the brain
Vasogenic EdemaCytotoxicEdema
FeverChills
Formation of thrombi and activation of clotting factors within vasculature
Vascular endothelial injury
Cerebral vasculitis
Cerebral infarction
Influx of plasma components in the subarachnoid space
↑CSF viscosity
InterstitialEdema
↑ICP
↓ Cerebral blood flow
A
B
Cerebral Edema
Problems to cranial nerves
Photophobia; palsy
Meningeal irritation:Nuchal rigidity
Brudzinski’s SignKernig’s SignProstration
Dxcs: (CSF GSCS) ↑ICP, ↑CHON, ↑glucose, ↑WBC; LP; CT; MRI; CBC; Biopsy
Meds:Corticosteroids (dexamethasone); Antibiotics (ampicillin, ceftriaxone); NSAIDs (indomethacin)
↑SBP w/ wide pulse pressure, bradycardia, ↓& irreg. RR ; pupil dilation; papilledema
Meds: Diuretics
Meds: steroids
Cerebral cortical hypoperfusion
Cerebral anoxia
A B
CNS impairment/ depression
Altered ANS function
Further bacteremia
Invasion to other organs (e.g.lungs)
Compression of brainstem (medulla)
Compromised respiration function
Impaired ventilation and perfusion in the alveolar capillaries
Impaired ventilationGood ventilation; poor perfusion
Low V/Q(Shunting)
High V/Q(Dead Space)
Hypoperfusion in the respiratory system
ACUTE RESPIRATORY FAILURE
PaO2 < 60mmHg PaCO2 > 50mmHg
I: Hypoxemic RF II: Hypercapnic RF
Excessive ventilation Hypoventilation
Respiratory alkalosis
Dyspnea
Metabolic acidosis
Respiratory acidosis
Further hypoxemia
Anaerobic metabolism
Lactic acid formation
SevereHeadache
VomitingSeizureStupor/Coma
Dxcs: ABG; CBC; S. Elec. (K, Mg, PO4); PFT; CXR; ECG; Right cardiac catheterization
Mgt: ETT; O2; MV; CBR; Diuretics; Nitrates; Analgesics; Inotropics; Bronchodilators; Corticosteroids
Meds: Anticonvulsants
O2
Ineffective perfusion to multiple systems
Further CNS Depression CVS hypoperfusion
↓cardiac contractility
↓cardiac output
Arrythmia
Inadequate distribution of oxygenated blood into system
Cyanosis/Pallor
↑cardiac contractility as compensation
Renal hypoperfusion
Renal damage
Renal failure
Decompensation
Ischemia/Infarction/Heart Failure
Ischemia to Necrosis
↓UO
Valvular dysfunction;Left ventricular dysfunction
Blood regurgitation from left chambers to the lungs
Pulm. edema
If Managed, FAIR PROGNOSIS
If Not, DEATH
Hypotension
Hypertension
(+) Crackles/Rales
Respiratory Failure
D. NARRATIVE PATHOPHYSIOLOGY
Bacterial meningitis is an inflammation of the meninges caused by the invasion of
infectious pathogens. This however may lead to complication not only specific to the
CNS but also towards the system, e.g. respiratory system.
The factors predisposing the client to be a candidate for bacterial meningitis are:
(1) extremes of age; (2) males than females; (3) Blacks and Native Americans; (4)
immunosuppression; (5) congenital anatomical defects in the nervous system; (6)
history of infection; (7) past history of meningitis (or relapse); and (8) intracranial
exposure through surgery or injury.
Moreover, triggering factors may include: (1) environment, especially those
infectious ones; (2) underlying disease condition, e.g. Diabetes Mellitus which provides
a favourable environment for the bacteria, or even diseases causing
immunosuppression; (3) alcohol use, and (4) smoking, which causes decreased
immune responses; (5) intravenous drug abuse; and (6) crowding, especially to those
areas with increased incidence of meningitis and infection.
Having any among the abovementioned factors present, the client is easily
susceptible to bacterial infection. The usual route is the nasopharynx via inhalation of
infectious airborne particles. These pathogenic bacteria possess fimbriae which are
proteinaceous appendages similar to the pili but shorter than a flagellum. With these
fimbriae, the bacterium can easily attach itself to the respiratory tract host cells. The
immediate reaction of the body is the initiation of the immune response; however, the
bacteria, wise as they are, have resistance against the body’s immunity due to its
virulence factor. Being coated with a polysaccharide capsule, the bacterium survives
phagocytosis. Moreover, it also stimulates attraction of IgA and blocks IgG and IgM
while producing IgA1 proteases that cleave and deactivate the function of IgA.
Surviving the first attack, the bacterium multiplies in the epithelial surfaces and
form microcolonies which further invade the submucosa passing through intracellular
and intercellular routes. This leads to local invasion.
However, the bacteria do not settle in a single area forever, hence they cross
over the mucosal barrier and enter the blood stream, termed as “hematogenous
spread”. Still, the bacteria survive after inhibiting phagocytosis and resisting the classic
complement-mediated bactericidal activity of the body’s immune system. Herein, the
bacterium replicates causing bacteremia.
However, the circulating monocytes arrive taking charge of disabling the bacteria
from the spread. As a result, the bacteria are phagocytised. Normally, a bacterium
cannot survive too long resisting the body’s immune system, however, due to the
specialization of meningitis-causing bacteria such as Haemophilus influenzae, Neisseria
meningitides, Streptococcus pneumoniae, Escherichia coli, and Streptococcus
agalactiae, they are able to survive being engulfed by the monocytes. Thanks to the
polysaccharide encapsulation.
The monocytes further travel in the circulation containing with them the
phagocytised yet surviving bacterium particles. Because of this, they are able to enter
the cerebrospinal fluid (CSF) via the choroid plexus without detection. This is known as
the “Trojan Horse Hypothesis of CNS Invasion”.
Upon entering the CNS, there will be immediate invasion of the meninges
causing inflammation to it, thus termed as meningitis. Since, the CNS is isolated from
the conventional immune system due to the blood-brain-barrier (separates CNS from
outside organs to prevent the immune system from directly attacking it), there is high
chance of survival of the bacteria.
The classical signs of meningeal irritation (which indicates meningeal
inflammation) are the following: (1) Nuchal rigidity; (2) Brudzinski’s sign; (3) Kernig’s
sign; and (4) Prostration/Opisthotonus – all working in the same principle: stretching the
meninges by flexion or extension elicits a painful reaction.
Laboratory tests that may denote meningitis are the following: (1) increased ICP
(mechanism explained later in this study); (2) increased protein; (3) increased glucose;
(4) increased WBC – all four taken via CSF Gram-Staining Culture and Sensitivity
(GSCC) through lumbar puncture. Other diagnostic procedures include CT scan, MRI,
CBC monitoring of WBC differential, and meningeal biopsy.
In managing the inflamed meninges, corticosteroids (e.g. dexamethasone) are
used as anti-inflammatory agents, or even non-steroidal anti-inflammatory drugs
(NSAIDs) such as indomethacin. Adjunct to this therapy is the administration of
antibiotics to limit bacterial growth such as ampicillin, cefotaxime, ceftriaxone, and
vancomycin.
Following meningeal invasion is the subarachnoid space – which contains the
CSF and is bounded by the spinal meninges. This stimulates the endothelial cells,
leukocytes, microglia, astrocytes, and meningeal macrophages to secrete the following.
(1) Nitric oxide (NO) causes cytotoxicity towards the bacterium. Bacterial death
leads to the release of its toxic factors causing inflammation and further swelling of the
cellular elements of the brain. This leads to cytotoxic edema. This can be managed by
administration of steroids such as dexamethasone, since it reduces the inflammation
caused by the toxins released after bacterial death.
(2) Tumor Necrosis Factor – alpha (TNF-ɑ) initiates regulation of the immune
cells responsible for the cytotoxicity together with NO. Also, it sets off the influx of
plasma components in the subarachnoid space causing hyperviscosity of the CSF
leading to interstitial edema.
(3) Prostagalandin E2 (PGE2) causes vasodilation thus increasing the blood
brain barrier (BBB) permeability. This causes influx of plasma to the subarachnoid
space while at the same time enhances neutrophil migration leading to “neutrophilic
pleocytosis” or increased WBC count within the CSF. This is termed as vasogenic
edema.
Eventually, summing up the three sources of fluid accumulation: cytotoxic,
interstitial, and vasogenic edema; these sum-up to cerebral edema that causes an
increase in intracranial pressure (ICP). Excessive increase of ICP will manifest the
Cushing’s Triad namely: increased systolic blood pressure (SBP) with widened pulse
pressure, bradycardia, and decrease or irregular respiratory rate. All of which is due to
the body’s compensation over the increased ICP. Other signs include pupil dilation (due
to the compression on the optic nerve) and papilledema (due to ocular edema).
Other immune factors are: (1) Interleukin-1 (IL-1) which is an endogenous
pyrogen responsible for hyperthermia; and (2) Platelet-activating factor (PAF) which
initiates formation of thrombi and activation of clotting factors within vasculature –
especially to those severely damaged by the infection. This caused vascular endothelial
injury leading to a complication – cerebral vaculitis, then to cerebral infarction. This
injury can also affect the cranial nerves resulting to photophobia (due to irritation on the
first division of the trigeminal nerve) and palsy (especially in the cranial nerves
responsible for extraocular muscles: Oculomotor (III), Trochlear (IV), and Abducens
(VI).
An increase in ICP causes decreased in cerebral blood flow (CBF). This ICP can
be decreased by administering diuretics which promotes fluid excretion, e.g. Mannitol or
Lasix. Also, decreased CBF causes ischemia then cerebral infarction.
Decreased CBF causes cerebral cortical hypoperfusion causing cerebral anoxia.
To compensate for poor oxygenation, there will be initiation of the anaerobic metabolism
whose by-product is lactic acid – a tissue irritant. This results to pain as manifested by
severe headaches. Therefore, O2 should be administered to correct hypoxia.
In cerebral anoxia, if left untreated, may result to CNS impairment or depression.
Manifestations include projectile vomiting (due to problems in the vomiting center –
medulla), seizures, stupor, and coma. Seizures can be managed through anticonvulsant
medications such as diazepam, phenytoin, and phenobarbital.
CNS depression leads to altered autonomic nervous system (ANS) function.
Together with further bacterial invasion and compression of medulla which
compromises respiration (due to increased ICP), there will be impaired ventilation and
perfusion (V/Q) in the alveolar capillaries. This may be due to impaired ANS response
to stimulate breathing, invasion of bacteria to the lungs causing damage, then
compression of medulla which compromises the respiratory center.
Impaired V/Q herein may exist into two mechanisms: impaired ventilation causing
low V/Q (a.k.a. shunting); and good ventilation/poor perfusion causing high V/Q (a.k.a.
dead space). This leads to hypoperfusion of the respiratory system leading to Acute
Respiratory failure (ARF). Diagnostics include arterial blood gas (ABG), complete blood
count (CBC), serum electrolyte monitoring; pulmonary function tests; chest x-ray;
electrocardiograph; and right cardiac catheterization.
Management includes endotracheal tubing, oxygen administration, mechanical
ventilation, complete bed rest, diuretics, nitrates, analgesics, inotropics, bronchodilators,
and corticosteroids.
ARF can be subdivided into two types depending on O2 and CO2 levels in the
body. Partial oxygen of less than 60 mmHg is the first type, Hypoxemic RF; whereas, a
partial carbon dioxide of greater than 50 mmHg cause Type II Hypercapnic RF.
In ARF-I, due to the decreased levels of O2, this stimulates the lungs to increase
ventilation in order to increase respiration of O2. Prolonged excessive ventilation will
eventually lead to entrapment of O2 in the lungs causing respiratory alkalosis. It doesn’t
follow though that an increased in O2 levels mean good oxygenation; that’s why the
patient can still manifest dyspnea. Respiratory alkalosis, then, triggers the kidneys to
buffer the basic environment by conserving bicarbonate (HOC3) and releasing hydrogen
ions, thus promoting acidity. Prolonged acidosis then causes entrapment of CO2, which
stimulates hypoventilation on the patient leading to respiratory acidosis. And the cycle
continues still ending up to further hypoxemia if not alleviated.
Meanwhile, in ARF-II, since high CO2 levels cause acidic environment, the body
was hypoventilating – thus, decreasing respiration of oxygen. This leads to CO2
overwhelming O2 levels causing respiratory acidosis. Then this leads to hypoxemia.
With poor oxygenation, there will be ineffective perfusion to the system. The most
predominant system affected will be the cardiovascular system (CVS). Due to
hypoperfusion, there will be impairment in the function of the heart causing dysfunction
of the valves or the left ventricular chamber. Poor flapping of the valves causes blood
regurgitation back to the lungs leading to accumulation of fluids or pulmonary edema.
This can be assessed by auscultation for crackles. Another is, there will be decreased
cardiac contractility (hypotension) leading to decrease in cardiac output causing
inadequate distribution of oxygenated blood throughout the system (as manifested by
cyanosis or pallor). Decreased cardiac output however stimulates the heart to increase
its contractility as a compensatory mechanism. Since there is low output, the tendency
of the heart is to contract more in order to pump more leading to hypertension.
However, this leads to decompensation due to, still, poor oxygenation which may then
on lead to ischemia, infarction, or heart failure.
In addition, due to the variances in the contractility of the heart, there will be
presence of arrhythmias halfway along. Although, the client had tachycardia, but not
irregular.
Aside from the heart, there will also be hypoperfusion to the kidneys causing
renal damage which will lead to renal failure having one particular sign – decreaed in
urinary output.
If all of the aforementioned shall be managed and intervened properly and
promptly, there will be fair prognosis, otherwise death.