PATHOPHYSIOLOGY ACUTE RESPIRATORY FAILURE S/T BACTERIAL MENINGITIS

A. ETIOLOGY

PREDISPOSING FACTORS Age

Rationale/Justification It is most common in the extremes of age such as greater than 69 years old and less than 5 years old.

Gender Race

Prevalence is greater in the male gender. It is most common among Blacks and Native Americans due to genetic factors that merely exist in these racial groups.

Immunosuppression

Immunosuppression opportunistic infections

increases and acute

risk

of

bacterial

meningitis. Examples of conditions include HIV infection and malignancy/cancer. It increases susceptibility primarily S, on encapsulated and organisms, opportunistic

pneumoniae,

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 through exposure Open exposure of the intracranial compartments manipulation due to injury or surgery may predispose a person to infection. Dormancy of the infection inside the brain parenchyma may be triggered by various stress factors that may suppress the bodys immune function. PRECIPITATING FACTORS Environment Rationale/Justification 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 bodys 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,

during surgery or trauma

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 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 by suppressing Th1 cytokine

dormitories and personnel in military barracks) increases risk for harbouring infection-causing meningitis.

B. SYMPTOMATOLOGY

Signs/Symptoms Nuchal Rigidity

Rationale Upon flexing the neck, the spinal canal elongates and the meninges stretch, causing pain

especially if there is inflammation due to meningitis. Brudzinskis Sign Flexing the head towards the chin causes pressure against the infected meningeal lining leading to pain sensation. Kernigs 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 Pressure Intracranial 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 Due to increased ICP, the brain compensated by Pressure with Widened stimulating the heart to pump more blood with Pulse Pressure Bradycardia longer refractory period to enhance perfusion. This is in response to increase in blood pressure with prolonged refractory period. Decreased and Irregular Increased ICP compresses the brain stem Respirations Pupil Dilation leading to alterations in respirations. 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, Due to the surrounding inflammation, the cranial IV, VI) 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 As the CNS function depresses, the patients

Consciousness to Stupor/Coma

leading level of consciousness deteriorates, probably due to the compression over the brainstem where the Reticular Activating System (RAS), responsible for wakefulness, resides.

Increased CSF

Protein

in Normal protein levels in CSF should be less than 500 mg/L. Increased of levels suggests that

accumulation

proteinaceous

factors

manages inflammation over the meninges. Increased CSF Glucose in 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 dont 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 secretions. Hypotension Poor perfusion towards the cardiovascular airway caused by pooling of

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 hearts 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 FACTORS Age; Gender; Race; Immune Status; Pathoana.; Hx of Infection; Past hx of Meningitis; Intracranial Exposure Presence of bacteria Nasopharyngeal colonization Bacterial fimbriae adheres to upper respiratory tract host cells Resistance against body s immune function Virulence factor: polysaccharide capsule Stimulates IgA, blocks IgG & IgM; produces IgA1 proteases that cleave IgA PRECIPITATING FACTORS Environment; underlying disease condition; Alcohol Use; Smoking; Drug Abuse; Crowding

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 phagocytosis Bacteria resists classic complementmediated 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 irritation: Nuchal rigidity Brudzinski s Sign Kernig s Sign Prostration Dxcs: (CSF GSCS) ICP, CHON, glucose, WBC; LP; CT; MRI; CBC; Biopsy Meningeal Invasion MENINGITIS Meds: Corticosteroids (dexamethasone); Antibiotics (ampicillin, ceftriaxone); NSAIDs (indomethacin)

Subarachnoid space inflammation Stimulates endothelial cells, leukocytes, microglia, astrocytes, & meningeal macrophages

NO Cytotoxicity Release of toxic factors Swelling of cellular elements of the brain

Meds: steroid s

TNFRegulation of immune cell Influx of plasma components in the subarachnoid space CSF viscosity Interstitial Edema Cerebral Edema

PGE2 BBB permeability Neutrophil migration

IL-1 Fever Chills

PAF Formation of thrombi and activation of clotting factors within vasculature Vascular endothelial injury

Neutrophilic pleocytosis

Cerebral vasculitis Cerebral infarction

Cytotoxic Edema

Vasogenic Edema

Problems to cranial nerves

SBP w/ wide pulse pressure, bradycardia, & irreg. RR ; pupil dilation; papilledema

B ICP
Meds: Diuretics

Photophobia; palsy

Cerebral blood flow

Cerebral cortical hypoperfusion Anaerobic metabolism Lactic acid formation Severe Headache

Cerebral anoxia A CNS impairment/ depression Altered ANS function Further bacteremia B Compression of brainstem (medulla) Compromised respiration function

Invasion to other organs (e.g.lungs)

O2

Vomiting Seizure Stupor/ Coma

Impaired ventilation and perfusion in the alveolar capillaries Impaired ventilation Low V/Q (Shunting) Good ventilation; poor perfusion High V/Q (Dead Space)

Meds: Anticonvulsants

Dxcs: ABG; CBC; S. Elec. (K, Mg, PO4); PFT; CXR; ECG; Right cardiac catheterization

Hypoperfusion in the respiratory system ACUTE RESPIRATORY FAILURE

Mgt: ETT; O2; MV; CBR; Diuretics; Nitrates; Analgesics; Inotropics; Bronchodilators; Corticosteroids

PaO2 < 60mmHg

PaCO2 > 50mmHg

I: Hypoxemic RF Excessive ventilation Respiratory alkalosis Dyspnea Metabolic acidosis

II: Hypercapnic RF Hypoventilation Respiratory acidosis Further hypoxemia

Ineffective perfusion to multiple systems

Further CNS Depression

CVS hypoperfusion

Renal hypoperfusion Renal damage Arrythmia Renal failure cardiac contractility as compensation Hypertension

Valvular dysfunction; Left ventricular dysfunction Blood regurgitation from left chambers to the lungs Pulm. edema (+) Crackles/Rales Respiratory Failure

cardiac contractility Hypotension cardiac output

Inadequate distribution of oxygenated blood into system

Decompensation Ischemia/ Infarction/ Heart Failure UO

Cyanosis/Pallor Ischemia to Necrosis

If Managed, FAIR PROGNOSIS If Not, DEATH

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 bodys 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 bodys 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 bodys 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) Brudzinskis sign; (3) Kernigs 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- ) 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 Cushings 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 bodys 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 doesnt follow though that an increased in O2 levels mean good oxygenation; thats 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.