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.