Oral care is one of the fundamental basic Nursing Care to maintain personal hygeine both in hospital setting and home care for all patient. Oral health is a good step to understand your health status, and any possibility of bacteria in your mouth which can affect the rest of your body causing psychological and pathophysiological changes to your health. Many organ systems in our body can be affected if oral care is poorly handled. The mouth can be affected though most bacteria can be harmless, however, the body has natural defense against bacteria which can prevent penetration of bacteria into our blood system if care is taking to maintain good health and good immume system. Daily brushing and flossing is recommended by the Dentist to keep bacteria under control. However, poor oral hygiene can reach the level of acquiring oral infection causing tooth decay, gum disease, pain and offensive breadth.
Physiologically, oral infection and inflammation caused by periodontitis can have severe role to play in some diseases such as Cardiovasuclar, HIV (AIDS), Osteoporosis, Dementia, Mental illness, Mental Health, Diabetes, Alzheimer. Some other conditions that might be linked to oral health include eating disorders, rheumatoid arthritis, head and neck cancers, and Sjogren’s syndrome.
In contrast some medication can reduce saliva flow and saliva washes away food and neutralises acid that is produced by bacteria in the mouth. Pain killers, diurectic and antidepressants can reduce saliva flow, it is essential to visit your dentist on time, early intervention in medicine leads to early recovery. While you can, visit your Dentist and acknowledge your appointments.
Personal Care: Saint Alexandra Nurses take this aspect of care very seriously. Oral care enhances refreshment of the mouth, but most especially it nourishes and refreshes the body and mind leading to a sound positive pschological state. Brushing out teeth daily as we were told by the Dentist to brush twice a day, however, some people with certain types of job are likely to brush their teeth after every meal. Our patients are critically ill and some are ventilated and in need of a good oral care to prevent Ventilator and Endotracheal Tube acquired infection while tracheostomy care becomes equally extremely important, some are elderly and need support to achieve this aspect of activities of daily living, whle some are too ill receiving palliative care.
Oral care is an essential part of Nursing Care adding to over-all Personal Care. We cherish our patients cleanliness, we give total personal care, we are able to wash your hair, dry and style, cut the gentman’s hair, eye lids, eyes brows, hair in the nose and ears, shaving, brush your teeth and offer mouth wash and lip balm, keeping your mouth moisture and fresh. We also get fully involve in your activities of daily living, we can wash your feet, massage and oil them giving you total skin care. We will feed you to your satisfaction no hurry at all, we will keep you company and read your favourite books to you, be your new best friend giving you bundle of generous care because you deserve it!
Care is beautiful once it comes from the inner-most heart. It is a privilleage to be able to care for others. We have passion in doing this at Saint Alexandra as Care is Life to Us!
Accepting help might mean loosing privacy and independence to the new life changing routines. As a result, your loved one might feel frightened and vulnerable, and may also be angry that he or she needs help or feeling guilty of becoming a burden to the family and friends.
Professional caregivers include home health visiting nurses, rehabilitation therapists and healthcare social workers. The therapies comprise physical therapy, speech and language pathology and occupational therapy services. Professional caregivers deliver services at the elder patient’s home to help them develop independence with activities of daily living in a convenient and comfortable setting while allowing families to be closely involved in the rehabilitation process. This is what Saint Alexandra Healthcare does best!
Intensive Care Unit can be very remarkable my patient was looked after for two days in a row and was discharged to the ward. Handover was given to the ward Nurse and thereafter returned to the Intensive Care Unit to look after my other patient. At the end of my shift just about to go home met with discharged patient’s sister at the corridor the lady told me her brother is sick and have sent for me so l went to the ward.
I assessed him and realised he has declined medical advice to have only sips of water after major pelvic exenteration, he has been drinking and even had a small amount of soup and this has caused nausea and vomiting as the bowels are yet to function actively. The abdomen was distended and firm tapping like a drum.
Pelvic exenteration is a radical surgical treatment that removes all organs from a person’s pelvic cavity. The urinary bladder, urethra, rectum, and anus are removed. The procedure leaves the person with a permanent colostomy and urinary diversion.
I spoke with my colleagues on the ward and looked for the ward doctor to inform them of my assessment. The doctor came with me straight away and assessed the patient agreed a replacement of the Nasal Gastric Tube (Free Drainage) is needed.
I inserted the NG and aspirated over 470mls at one time and stayed with patient for another 45 minutes and aspirated the NG again and this gentleman is now feeling better and abdomen is less distended. Going to see this patient on the ward has prevented the possibility of readmission to Intensive care Unit.
Patient and family happy and smiling, bedside teaching given to patient and family not to exceed sips of water as Surgeons have advised and to wait until Surgeons approve eating and drinking.
Patient agreed to follow Surgeons directives and was much better which made me happy too. Patient said thank you Anita you’re one in a Million.
The fact that patient has been discharged from the ICU does not mean compassion should not be shown to patients wherever they are admitted or homecare going extra mile is what Saint Alexandra does best!
Tinnitus is the perception of sounds in the head or the ears. The term tinnitus derives from the Latin word tinnire, meaning to ring. Typically, an individual perceives the sound in the absence of outside sounds, and the perception is unrelated to any external source. Sound that only the patient hears is subjective tinnitus, while sound that others can hear as well is called objective tinnitus. Estimates of patients with tinnitus range from 10-15% of the population (30-40 million people). Of patients presenting with ear-related symptoms, 85% report experiencing tinnitus as well. Both adults and children report experiencing tinnitus. Development of tinnitus increases in incidence with age, although the rate of tinnitus in children has been reported as high as 13%.
Many people experience tinnitus after exposure to a gunshot or a loud concert with modern amplification. This type of tinnitus can be annoying, but it usually resolves in a matter of hours. Tinnitus is a symptom (not a disease) and therefore reflects an underlying abnormality. Most typically, tinnitus is associated with a sensorineural hearing loss, but tinnitus types such as pulsatile tinnitus, tinnitus with vertigo, fluctuating tinnitus, or unilateral tinnitus should be investigated thoroughly.
Most of the knowledge and therapeutic options available to those who experience tinnitus have been encapsulated above. Individuals have placed advertisements in major otolaryngology, audiology, and neurology journals seeking therapeutic help. Such advertisements have yielded a great deal of interest but little substantive therapy. Unfortunately, because so little is known about the causes of tinnitus, little therapy is available to eliminate the problem. Frequently, therapy that is helpful to one person is not helpful to the next. Thus, many have adopted the philosophical outlook that tinnitus is a chronic or psychologic disease and is managed and not cured.
That philosophic approach to the problem of chronic tinnitus is apparent throughout this discussion of tinnitus. Because so few patients are cured, the emphasis should be on helping each individual cope with what is likely to be a chronic problem. As always, areas of active research are focused on developing a better understanding and therapy of tinnitus, and these are of importance for those interested in academic or investigative pursuits.
Such investigations have recently focused around the quantification of tinnitus, the medical and legal aspects of the problem, and the source of tinnitus. Many of these treatments are pioneered by a dedicated few. Most are described in a journal committed to the investigation, understanding, and treatment of tinnitus.
Tinnitus is classified in many cases into 2 categories. Tinnitus is either objective (ie, audible to anyone in addition to the affected individual) or subjective (ie, audible only to the affected individual). Even though this classification system is used quite frequently, focusing on the etiology of tinnitus is often more useful. The classification is discussed, and then this article focuses primarily on the various etiologies of tinnitus and their respective therapies.
Objective tinnitus is relatively rare. It is sound created somewhere in the body, usually in the ear, head, or neck, and has a muscular or vascular etiology. Muscular tinnitus is observed in several degenerative diseases of the head and neck, including amyotrophic lateral sclerosis. In this entity, the neuromuscular control over the muscles in the ear occasionally deteriorates in an individual with perfect sensory perception. Occasionally, the loss of control results in a repetitive flutter or myoclonus of either the stapedius or tensor tympani muscles. The result is an observable and audible flutter coming from the ear.
Lysis of the tensor or stapedius muscle via a tympanotomy incision is uniformly successful in relieving the symptoms in these cases. However, attention must be paid to the contralateral side. Often, the problem is bilateral, but attention is directed to the louder side. If in fact contralateral problems are present, both muscles should be cut at the same time. This is one of the few cases in otology where operating on both sides at the same time may be considered, decreasing the anesthesia risk and attendant logistic problems for the patient who frequently has problems with anxiety.
Palatal myoclonus is a rare cause of muscular-induced clicking tinnitus. It results from rhythmic discharges from the inferior olivary nucleus by a lesion in the triangle of the Guillain-Mollaret (brainstem). The lesion is usually due to stroke, trauma, encephalitis, multiple sclerosis (MS), or degenerative disease. Some success has been reported with botulinum toxin injection therapy.
The other disturbance that is more frequently observed is an aberrance or abnormality of the carotid artery. Aberrances of the carotid artery are documented multiple times in the literature. The carotid artery can also become ectatic as a person ages or as operations are performed on the carotid. The end result is an artery that often takes a tortuous route through the neck and the ear to reach the brain. Such tortuosity produces turbulent flow in the artery, which can be auscultated by the examiner with each heartbeat.
Similarly, the jugular bulb and the jugular vein can produce a type of tinnitus that is characterized as a venous hum. Often described by the patient as a vibration or a low-pitched sound rather than as a ringing, these sounds seem to be slightly more frequent than the other 2 types of objective tinnitus. Many operations have been described for the treatment of venous hum tinnitus and carotid arterial tinnitus all of these operations have initially met with success but limited long-term control of the symptom.
Clinically, subjective tinnitus is the perception of sound in the absence of auditory stimulation. In terms of neurophysiology, tinnitus is the consequence of the brain’s response to input deprivation from the auditory periphery. In the healthy auditory system, there is an ordered tonotopic frequency mapping from the auditory periphery (cochlea), through the midbrain, to the auditory cortex. When a region of the cochlea is damaged, the subcortical and cortical projections adjust to this chronic lack of output (plasticity), and the tonotopic organization is altered. In the auditory cortex, the region that corresponds to the area of cochlear damage is termed the lesion projection zone (LPZ). After cochlear damage, neurons in the LPZ show 2 important changes: an increase in the spontaneous firing rate and an increase in the frequency representation of the neurons that border the region of damage (the so-called lesion edge frequencies).
These findings are explained in terms of a) the loss of central inhibition on the regions that are damaged and b) cortical plasticity of the neighboring regions of the cortex that are still active. Hence, tinnitus neurophysiology is related to detrimental cortical adaptation to input deprivation from the sensory periphery.
Additional data from animal and human studies have suggested that tinnitus may be associated with neuronal hyperactivity at different levels of the central auditory pathways, including the dorsal cochlear nucleus, the inferior colliculus, auditory cortex, and the striatum.
A literature review, by Tegg-Quinn et al, indicated that tinnitus can cause cognitive difficulties in adults by affecting executive control of attention.
Measurement and quantification
Volumes are devoted to the quantification and measurement of tinnitus. One of the more successful and useful mechanisms for the quantification of tinnitus has been the matching of tinnitus to a tone presented to the patient in a sound-treated room, using an audiometer. Such procedures, types of tinnitus matching, are used to provide a measure of tinnitus for reevaluation of symptoms before, during, and after therapy. Although those who experience tinnitus often describe their match as exact, they quickly point out that such a match does not adequately reflect the severity of the problem affecting their daily lives.
Tinnitus is a symptom that requires further investigation to determine origin. Often, the origin may be a sensorineural hearing loss. Certain types of tinnitus signify other problems. Unilateral or pulsatile tinnitus and tinnitus associated with vertigo or conductive hearing losses are examples. Tinnitus therapy is as multifaceted as the origins of tinnitus. Choose therapy, therefore, with individual symptoms and problems in mind. A combination of sound-based therapy with medical therapy of anxiety, depression, or insomnia will help most patients. By applying the best of the multiplicity of available therapies, patients need never again hear the old adage, “you’ll just have to live with it.”
Moller AR. Sensorineural Tinnitus: Its Pathology and Probable Therapies. Int J Otolaryngol. 2016. 2016:2830157.
Tegg-Quinn S, Bennett RJ, Eikelboom RH, Baguley DM. The impact of tinnitus upon cognition in adults: a systematic review. Int J Audiol. 2016 May 31. 1-8.
Bhatt JM, Bhattacharyya N, Lin HW. Relationships between tinnitus and the prevalence of anxiety and depression. Laryngoscope. 2017 Feb. 127 (2):466-9.
Kim HJ, Lee HJ, An SY, et al. Analysis of the prevalence and associated risk factors of tinnitus in adults. PLoS One. 2015. 10 (5):e0127578.
Yang P, Ma W, Zheng Y, Yang H, Lin H. A Systematic Review and Meta-Analysis on the Association between Hypertension and Tinnitus. Int J Hypertens. 2015. 2015:583493.
Alcohol use disorder (which includes a level that’s sometimes called alcoholism) is a pattern of alcohol use that involves problems controlling your drinking, being preoccupied with alcohol, continuing to use alcohol even when it causes problems, having to drink more to get the same effect, or having withdrawal symptoms when you rapidly decrease or stop drinking. Unhealthy alcohol use includes any alcohol use that puts your health or safety at risk or causes other alcohol-related problems. It also includes binge drinking — a pattern of drinking where a male consumes five or more drinks within two hours or a female downs at least four drinks within two hours. Binge drinking causes significant health and safety risks. If your pattern of drinking results in repeated significant distress and problems functioning in your daily life, you likely have alcohol use disorder. It can range from mild to severe. However, even a mild disorder can escalate and lead to serious problems, so early treatment is important.
The most common and costly form of drug abuse, is a major contributing factor to many disease categories. The alcohol-attributable disease burden is closely related to the average volume of alcohol consumption, with dose-dependent relationships between amount and duration of alcohol consumption and the incidence of diabetes mellitus, hypertension, cardiovascular disease, stroke, and pneumonia. The frequent occurrence of alcohol use disorders in the adult population and the significant and widespread detrimental organ system effects highlight the importance of recognizing and further investigating the pathophysiological mechanisms underlying alcohol-induced tissue and organ injury.
Alcoholism is a chronic remitting and relapsing condition; its aetiology and pathophysiology remains largely obscure despite recent advances. This review summarises the current knowledge about the causation (biological or psychological) of alcohol addiction. This involves heredity, candidate genes, alcohol metabolism regulation and the influence of alcohol in the pathophysiology of the different neurotransmitter systems. Alcohol addiction is a multifactorial phenomenon where personality structure, individual state of mind and social influences are in constant interaction with brain neurobiology and pathophysiology. This disorder influences different sexes in different ways and causes major problems, especially in developed societies. It is well established that alcoholism is a chronic condition and a major public health issue. Alcoholism presents as a continuum with different presentations among different individuals. This continuum starts from habitual consumption, to problematic use/abuse, to severe abuse with physical problems and finally addiction. It is certain that the physical and psychological problems that accompany the pathological relationship with alcohol increase with the quantity consumed and the frequency of use. Alcohol addiction is a multifactorial disorder that runs transgenerationally. Genetics have an important and critical contribution in the development of alcohol abuse. Despite significant indications for the involvement of the genetic factor the risk that is inherited remains unknown.
Alcohol depresses your central nervous system. In some people, the initial reaction may be stimulation. But as you continue to drink, you become sedated.Too much alcohol affects your speech, muscle coordination and vital centers of your brain. A heavy drinking binge may even cause a life-threatening coma or death. This is of particular concern when you’re taking certain medications that also depress the brain’s function.
Impact on your safety
Excessive drinking can reduce your judgment skills and lower inhibitions, leading to poor choices and dangerous situations or behaviors, including:
Motor vehicle accidents and other types of accidental injury, such as drowning
Poor performance at work or school
Increased likelihood of committing violent crimes or being the victim of a crime
Legal problems or problems with employment or finances
Problems with other substance use
Engaging in risky, unprotected sex, or becoming the victim of sexual abuse or date rape
Increased risk of attempted or completed suicide
Impact on your health
Drinking too much alcohol on a single occasion or over time can cause health problems, including:
Liver disease. Heavy drinking can cause increased fat in the liver (hepatic steatosis), inflammation of the liver (alcoholic hepatitis), and over time, irreversible destruction and scarring of liver tissue (cirrhosis).
Digestive problems. Heavy drinking can result in inflammation of the stomach lining (gastritis), as well as stomach and esophageal ulcers. It also can interfere with absorption of B vitamins and other nutrients. Heavy drinking can damage your pancreas or lead to inflammation of the pancreas (pancreatitis).
Heart problems. Excessive drinking can lead to high blood pressure and increases your risk of an enlarged heart, heart failure or stroke. Even a single binge can cause a serious heart arrhythmia called atrial fibrillation.
Diabetes complications. Alcohol interferes with the release of glucose from your liver and can increase the risk of low blood sugar (hypoglycemia). This is dangerous if you have diabetes and are already taking insulin to lower your blood sugar level.
Sexual function and menstruation issues. Excessive drinking can cause erectile dysfunction in men. In women, it can interrupt menstruation.
Eye problems. Over time, heavy drinking can cause involuntary rapid eye movement (nystagmus) as well as weakness and paralysis of your eye muscles due to a deficiency of vitamin B-1 (thiamine). A thiamine deficiency also can be associated with other brain changes, such as irreversible dementia, if not promptly treated.
Birth defects. Alcohol use during pregnancy may cause miscarriage. It also may cause fetal alcohol syndrome, resulting in giving birth to a child who has physical and developmental problems that last a lifetime.
Bone damage. Alcohol may interfere with the production of new bone. This bone loss can lead to thinning bones (osteoporosis) and an increased risk of fractures. Alcohol can also damage bone marrow, which makes blood cells. This can cause a low platelet count, which may result in bruising and bleeding.
Neurological complications. Excessive drinking can affect your nervous system, causing numbness and pain in your hands and feet, disordered thinking, dementia, and short-term memory loss.
Weakened immune system. Excessive alcohol use can make it harder for your body to resist disease, increasing your risk of various illnesses, especially pneumonia.
Increased risk of cancer. Long-term excessive alcohol use has been linked to a higher risk of many cancers, including mouth, throat, liver, colon and breast cancer. Even moderate drinking can increase the risk of breast cancer.
Medication and alcohol interactions. Some medications interact with alcohol, increasing its toxic effects. Drinking while taking these medications can either increase or decrease their effectiveness, or make them dangerous.
Although we now know much more about the influence of alcohol on the central nervous system, the mechanisms of action remain under discussion. One of the main problems is related to the fact that alcohol influences more than one neurochemical system of the brain. These influences are different if the quantity of alcohol consumed is large or small. In some cases, this leads to contrasting effects (toxicity versus withdrawal syndrome). Chronic alcohol exposure may lead to changes in many significant brain functions. In addition, psychological factors and mechanisms are in constant interaction with the biological background, the genetic influence and the sociocultural environment, creating new clinical results and various study areas.
Updated: Sep 12, 2017
Author: Warren Thompson, MD, FACP; Chief Editor: Randon S Welton, MD
CDC. Alcohol-Related Disease Impact (ARDI). Centers for Disease Control and Prevention. Available at http://nccd.cdc.gov/DPH_ARDI/default/default.aspx. Accessed: March 4, 2016.
Stahre M, Roeber J, Kanny D, Brewer RD, Zhang X. Contribution of excessive alcohol consumption to deaths and years of potential life lost in the United States. Prev Chronic Dis. 2014 Jun 26. 11:E109 Medline
Sacks JJ, Gonzales KR, Bouchery EE, Tomedi LE, Brewer RD. 2010 National and State Costs of Excessive Alcohol Consumption. Am J Prev Med. 2015 Nov. 49 (5):e73-9. Medline
This unique study describes how Paediatric ICU nurses in Australia empower the families of the dying children in two hospitals. (1). Previous studies have investigated the families’ perspective (2, 3), but this is the first to explore the nurses’ viewpoint.
The authors utilise their extensive experience in this field and make rigorous use of qualitative methods to investigate a subject not suitable for quantitative analysis. Convenience sampling produced nurses from 2 Neonate ICU’s and 2 Paediatric ICU’s in 2 Australian hospitals. Six focus groups and four individual interviews were conducted using a semi-structured conversational approach. These were audiotaped and transcribed verbatim for analysis. Inductive content analysis was used to limit subjective interpretation by researchers.
Four themes emerged:
1) Respecting the child as a person
2) Creating opportunities for family involvement and connection
3) Collecting mementoes
4) Planning for death
The study notes several initiatives undertaken by individual nurses, such as working to make the PICU welcoming and comfortable – with the goal of making memories for the family, or even arranging for the death to happen outside of the unit. There were several points not noted in the paper related to these initiatives, which might be interesting for readers:
Are these nurses part of a unit culture with written guidelines?
Are nurses supported emotionally after these events?
In this article, nurses share what they do; it would be interesting to also hear how that makes them feel.
This paper is part of a larger study; so perhaps the nurses’ experience and feelings will be explored a follow up article. Additionally, the sampling is taken from nurses that volunteered to take part. Investigation of nurses with more ambivalent attitudes towards engaging with dying patients and their families might prove worthwhile. It would also be interesting to know how the hospital management views and/or supports these initiatives. Are nurses given time and legitimacy from both unit and institution management?
Caring for dying children may be the greatest challenge to ICU nurses. This article makes a moving contribution to the literature on how nurses care for dying patients and bereaved families. Dissemination of initiatives undertaken by these Australian nurses provide ICU teams everywhere with insight and inspiration into how nurses can honour the dying of all ages.
(1) Bloomer MJ, Endacott R, Copnell B, O’Connor M. Something normal in a very, very abnormal environment. Nursing work to honour the life of dying infants and children in neonatal and paediatric intensive care in Australia. Intensive Crit Care Nurs, 2016
(2) Butler AE, Hall H, Willetts G, Copnell B. Family Experience and PICU Death: A Meta-Synthesis. Pediatrics. 2015 Oct;136(4):e961-73. doi: 10.1542/peds.2015-1068. Epub 2015 Sep 14. Review.
(3) Falkenburg JL, Tibboel D, Ganzevoort RR, Gischler S, Hagoort J, van Dijk M. Parental Physical Proximity in End-of-Life Care in the PICU. Pediatr Crit Care Med. 2016 May;17(5)
Article review prepared and submitted by Maureen Ben-Nun, member of the N&AHP
Schizophrenia is a psychotic disorder (or a group of disorders) marked by severely impaired thinking, emotions, and behaviors. Schizophrenic patients are typically unable to filter sensory stimuli and may have enhanced perceptions of sounds, colors, and other features of their environment. Most schizophrenics, if untreated, gradually withdraw from interactions with other people, and lose their ability to take care of personal needs and grooming.
The prevalence of schizophrenia is thought to be about 1% of the population around the world; it is thus more common than diabetes, Alzheimer’s disease, or multiple sclerosis. In the United States and Canada, patients with schizophrenia fill about 25% of all hospital beds. The disorder is considered to be one of the top ten causes of long-term disability worldwide.
The course of schizophrenia in adults can be divided into three phases or stages. In the acute phase, the patient has an overt loss of contact with reality (psychotic episode) that requires intervention and treatment. In the second or stabilization phase, the initial psychotic symptoms have been brought under control but the patient is at risk for relapse if treatment is interrupted. In the third or maintenance phase, the patient is relatively stable and can be kept indefinitely on antipsychotic medications. Even in the maintenance phase, however, relapses are not unusual and patients do not always return to full functioning.
The English term schizophrenia comes from two Greek words that mean “split mind.” It was observed around 1908, by a Swiss doctor named Eugen Bleuler, to describe the splitting apart of mental functions that he regarded as the central characteristic of schizophrenia.
Recently, some psychotherapists have begun to use a classification of schizophrenia based on two main types. People with Type I, or positive schizophrenia, have a rapid (acute) onset of symptoms and tend to respond well to drugs. They also tend to suffer more from the “positive” symptoms, such as delusions and hallucinations. People with Type II, or negative schizophrenia, are usually described as poorly adjusted before their schizophrenia slowly overtakes them. They have predominantly “negative” symptoms, such as withdrawal from others and a slowing of mental and physical reactions (psychomotor retardation).
There are five subtypes of schizophrenia:
The key feature of this subtype of schizophrenia is the combination of false beliefs (delusions) and hearing voices (auditory hallucinations), with more nearly normal emotions and cognitive functioning (cognitive functions include reasoning, judgment, and memory). The delusions of paranoid schizophrenics usually involve thoughts of being persecuted or harmed by others or exaggerated opinions of their own importance, but may also reflect feelings of jealousy or excessive religiosity. The delusions are typically organized into a coherent framework. Paranoid schizophrenics function at a higher level than other subtypes, but are at risk for suicidal or violent behavior under the influence of their delusions.
Disorganized schizophrenia (formerly called hebephrenic schizophrenia) is marked by disorganized speech, thinking, and behavior on the patient’s part, coupled with flat or inappropriate emotional responses to a situation (affect). The patient may act silly or withdraw socially to an extreme extent. Most patients in this category have weak personality structures prior to their initial acute psychotic episode.
Catatonic schizophrenia is characterized by disturbances of movement that may include rigidity, stupor, agitation, bizarre posturing, and repetitive imitations of the movements or speech of other people. These patients are at risk for malnutrition, exhaustion, or self-injury. This subtype is presently uncommon in Europe and the United States. Catatonia as a symptom is most commonly associated with mood disorders.
Patients in this category have the characteristic positive and negative symptoms of schizophrenia but do not meet the specific criteria for the paranoid, disorganized, or catatonic subtypes.
This category is used for patients who have had at least one acute schizophrenic episode but do not presently have strong positive psychotic symptoms, such as delusions and hallucinations. They may have negative symptoms, such as withdrawal from others, or mild forms of positive symptoms, which indicate that the disorder has not completely resolved.
The risk of schizophrenia among first-degree biological relatives is ten times greater than that observed in the general population. Furthermore the presence of the same disorder is higher in monozygotic twins (identical twins) than in dizygotic twins (nonidentical twins). The research concerning adoption studies and identical twins also supports the notion that environmental factors are important, because not all relatives who have the disorder express it. There are several chromosomes and loci (specific areas on chromosomes which contain mutated genes), which have been identified. Research is actively ongoing to elucidate the causes, types and variations of these mutations.
Most patients are diagnosed in their late teens or early twenties, but the symptoms of schizophrenia can emerge at any age in the life cycle. The male/female ratio in adults is about 1.2:1. Male patients typically have their first acute episode in their early twenties, while female patients are usually closer to age 30 when they are recognized with active symptoms.
Schizophrenia is rarely diagnosed in preadolescent children, although patients as young as five or six have been reported. Childhood schizophrenia is at the upper end of the spectrum of severity and shows a greater gender disparity. It affects one or two children in every 10,000; the male/female ratio is 2:1.
Causes and symptoms and Theories of causality:
One of the reasons for the ongoing difficulty in classifying schizophrenic disorders is incomplete understanding of their causes. It is thought that these disorders are the end result of a combination of genetic, neurobiological, and environmental causes. A leading neurobiological hypothesis looks at the connection between the disease and excessive levels of dopamine, a chemical that transmits signals in the brain (neurotransmitter). The genetic factor in schizophrenia has been underscored by recent findings that first-degree biological relatives of schizophrenics are ten times as likely to develop the disorder as are members of the general population.
Prior to recent findings of abnormalities in the brain structure of schizophrenic patients, several generations of psychotherapists advanced a number of psychoanalytic and sociological theories about the origins of schizophrenia. These theories ranged from hypotheses about the patient’s problems with anxiety or aggression to theories about stress reactions or interactions with disturbed parents. Psychosocial factors are now thought to influence the expression or severity of schizophrenia rather than cause it directly.
As of 2004, migration is a social factor that is known to influence people’s susceptibility to psychosis. Psychiatrists in Europe have noted the increasing rate of schizophrenia and other psychotic disorders among immigrants to almost all Western European countries. Black immigrants from Africa or the Caribbean appear to be especially vulnerable. The stresses involved in migration include family breakup, the need to adjust to living in large urban areas, and social inequalities in the new country.
Another hypothesis suggests that schizophrenia may be caused by a virus that attacks the hippocampus, a part of the brain that processes sense perceptions. Damage to the hippocampus would account for schizophrenic patients’ vulnerability to sensory overload. As of 2004, researchers are focusing on the possible role of the herpes simplex virus (HSV) in schizophrenia, as well as human endogenous retroviruses (HERVs). The possibility that HERVs may be associated with schizophrenia has to do with the fact that antibodies to these retroviruses are found more frequently in the blood serum of patients with schizophrenia than in serum from control subjects.
Symptoms of schizophrenia
Patients with a possible diagnosis of schizophrenia are evaluated on the basis of a set or constellation of symptoms; there is no single symptom that is unique to schizophrenia. In 1959, the German psychiatrist Kurt Schneider proposed a list of so-called first-rank symptoms, which he regarded as diagnostic of the disorder.
These symptoms include:
hearing voices commenting on the patient’s behavior
thought insertion or thought withdrawal
Somatic hallucinations refer to sensations or perceptions concerning body organs that have no known medical cause or reason, such as the notion that one’s brain is radioactive. Thought insertion and/or withdrawal refer to delusions that an outside force (for example, the FBI, the CIA, Martians, etc.) has the power to put thoughts into one’s mind or remove them.
POSITIVE SYMPTOMS. The positive symptoms of schizophrenia are those that represent an excessive or distorted version of normal functions. Positive symptoms include Schneider’s first-rank symptoms as well as disorganized thought processes (reflected mainly in speech) and disorganized or catatonic behavior. Disorganized thought processes are marked by such characteristics as looseness of associations, in which the patient rambles from topic to topic in a disconnected way; tangentially, which means that the patient gives unrelated answers to questions; and “word salad,” in which the patient’s speech is so incoherent that it makes no grammatical or linguistic sense. Disorganized behavior means that the patient has difficulty with any type of purposeful or goal-oriented behavior, including personal self-care or preparing meals. Other forms of disorganized behavior may include dressing in odd or inappropriate ways, sexual self-stimulation in public, or agitated shouting or cursing.
NEGATIVE SYMPTOMS. Schizophrenia includes three so-called negative symptoms. They are called negative because they represent the lack or absence of behaviors. The negative symptoms that are considered diagnostic of schizophrenia are a lack of emotional response (affective flattening), poverty of speech, and absence of volition or will. In general, the negative symptoms are more difficult for doctors to evaluate than the positive symptoms.
A doctor must make a diagnosis of schizophrenia on the basis of a standardized list of outwardly observable symptoms, not on the basis of internal psychological processes. There are no specific laboratory tests that can be used to diagnose schizophrenia. Researchers have, however, discovered that patients with schizophrenia have certain abnormalities in the structure and functioning of the brain compared to normal test subjects. These discoveries have been made with the help of imaging techniques such as computed tomography scans (CT scans).
When a psychiatrist assesses a patient for schizophrenia, he or she will begin by excluding physical conditions that can cause abnormal thinking and some other behaviors associated with schizophrenia. These conditions include organic brain disorders (including traumatic injuries of the brain), temporal lobe epilepsy, Wilson’s disease, prion diseases, Huntington’s chorea, and encephalitis. The doctor will also need to rule out heavy metal poisoning and substance abuse disorders, especially amphetamine use.
After ruling out organic disorders, the clinician will consider other psychiatric conditions that may include psychotic symptoms or symptoms resembling psychosis. These disorders include mood disorders with psychotic features; delusional disorder; dissociative disorder not otherwise specified (DDNOS) or multiple personality disorder; schizotypal, schizoid, or paranoid personality disorders; and atypical reactive disorders. In the past, many individuals were incorrectly diagnosed as schizophrenic. Some patients who were diagnosed prior to the changes in categorization should have their diagnoses, and treatment, reevaluated. In children, the doctor must distinguish between psychotic symptoms and a vivid fantasy life, and also identify learning problems or disorders. After other conditions have been ruled out, the patient must meet a set of criteria specified: the patient must have two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms
decline in social, interpersonal, or occupational functioning, including self-care, disturbed behavior must last for at least six months,
mood disorders, substance abuse disorders, medical conditions, and developmental disorders have been ruled out.
The treatment of schizophrenia depends in part on the patient’s stage or phase. Psychotic symptoms and behaviors are considered psychiatric emergencies, and persons showing signs of psychosis are frequently taken by family, friends, or the police to a hospital emergency room. A person diagnosed as psychotic can be legally hospitalized against his or her will, particularly if he or she is violent, threatening to commit suicide, or threatening to harm another person. A psychotic person may also be hospitalized if he or she has become malnourished or ill as a result of failure to feed, dress appropriately for the climate, or otherwise take care of him- or herself.
A patient having a first psychotic episode should be given a CT or MRI (magnetic resonance imaging) scan to rule out structural brain disease.
The primary form of treatment of schizophrenia is antipsychotic medication. Antipsychotic drugs help to control almost all the positive symptoms of the disorder. They have minimal effects on disorganized behavior and negative symptoms. Between 60-70% of schizophrenics will respond to antipsychotics. In the acute phase of the illness, patients are usually given medications by mouth or by intramuscular injection. After the patient has been stabilized, the antipsychotic drug may be given in a long-acting form called a depot dose. Depot medications last for two to four weeks; they have the advantage of protecting the patient against the consequences of forgetting or skipping daily doses. In addition, some patients who do not respond to oral neuroleptics have better results with depot form. Patients whose long-term treatment includes depot medications are introduced to the depot form gradually during their stabilization period. Most people with schizophrenia are kept indefinitely on antipsychotic medications during the maintenance phase of their disorder to minimize the possibility of relapse.
As of the early 2000s, the most frequently used antipsychotics fall into two classes: the older dopamine receptor antagonists, or DAs, and the newer serotonin dopamine antagonists, or SDAs. (Antagonists block the action of some other substance; for example, dopamine antagonists counteract the action of dopamine.) The exact mechanisms of action of these medications are not known, but it is thought that they lower the patient’s sensitivity to sensory stimuli and so indirectly improve the patient’s ability to interact with others.
DOPAMINE RECEPTOR ANTAGONIST. The dopamine antagonists include the older antipsychotic (also called neuroleptic) drugs, such as haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks: it is often difficult to find the best dosage level for the individual patient, and a dosage level high enough to control psychotic symptoms frequently produces extrapyramidal side effects, or EPS. EPSs include parkinsonism, in which the patient cannot walk normally and usually develops a tremor; dystonia, or painful muscle spasms of the head, tongue, or neck; and akathisia, or restlessness. A type of long-term EPS is called tardive dyskinesia, which features slow, rhythmic, automatic movements. Schizophrenics with AIDS are especially vulnerable to developing EPS.
SEROTONIN DOPANINE ANTAGONISTS. The serotonin dopamine antagonists, also called atypical antipsychotics, are newer medications that include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). The SDAs have a better effect on the negative symptoms of schizophrenia than do the older drugs and are less likely to produce EPS than the older compounds. The newer drugs are significantly more expensive in the short term, although the SDAs may reduce long-term costs by reducing the need for hospitalization. They are also presently unavailable in injectable forms. The SDAs are commonly used to treat patients who respond poorly to the DAs. However, many psychotherapists now regard the use of these atypical antipsychotics as the treatment of first choice; in particular, clozapine appears to be more effective than other antipsychotics in controlling persistent aggression in some patients.
NEWER DRUGS. Some newer antipsychotic drugs have been approved by the Food and Drug administration (FDA) in the early 2000s. These drugs are sometimes called second-generation antipsychotics or SGAs. Aripiprazole (Abilify), which is classified as a partial dopaminergic agonist, received FDA approval in August 2003. Two drugs that are still under investigation, a neurokinin antagonist and a serotonin 2A/2C antagonist respectively, show promise in the treatment of schizophrenia and schizoaffective disorder.
Most schizophrenics can benefit from psychotherapy once their acute symptoms have been brought under control by antipsychotic medication. Psychoanalytic approaches are not recommended. Behavior therapy, however, is often helpful in assisting patients to acquire skills for daily living and social interaction. It can be combined with occupational therapy to prepare the patient for eventual employment.
Family therapy is often recommended for the families of schizophrenic patients, to relieve the feelings of guilt that they often have as well as to help them understand the patient’s disorder. The family’s attitude and behaviors toward the patient are key factors in minimizing relapses (for example, by reducing stress in the patient’s life), and family therapy can often strengthen the family’s ability to cope with the stresses caused by the schizophrenic’s illness. Family therapy focused on communication skills and problem-solving strategies is particularly helpful. In addition to formal treatment, many families benefit from support groups and similar mutual help organizations for relatives of schizophrenics.
One important prognostic sign is the patient’s age at onset of psychotic symptoms. Patients with early onset of schizophrenia are more often male, have a lower level of functioning prior to onset, a higher rate of brain abnormalities, more noticeable negative symptoms, and worse outcomes. Patients with later onset are more likely to be female, with fewer brain abnormalities and thought impairment, and more hopeful prognoses.
The average course and outcome for schizophrenics are less favorable than those for most other mental disorders, although as many as 30% of patients diagnosed with schizophrenia recover completely and the majority experience some improvement. Two factors that influence outcomes are stressful life events and a hostile or emotionally intense family environment. Schizophrenics with a high number of stressful changes in their lives, or who have frequent contacts with critical or emotionally over-involved family members, are more likely to relapse. Overall, the most important component of long-term care of schizophrenic patients is complying with their regimen of antipsychotic medications.
Reviews and Overviews
The Pathophysiology of Schizophrenia Disorders: Perspectives From the Spectrum:
Larry J. Siever, M.D., and Kenneth L. Davis, M.D.
Seizures are caused by paroxysmal discharges from groups of neurons, which arise as a result of excessive excitation or loss of inhibition. The key unit of neurotransmission is the synapse, and the fundamental components of synapses are ion channels. Thus, the cause of seizures boils down to malfunction of ion channels. About one third of seizures are caused by genetic abnormalities, mostly involving ion channels. A quarter or so are caused by structural lesions. Patients with such lesions usually have additional neurological abnormalities. Some of these lesions, such as brain tumors, traumatic brain injury, infections, and perinatal brain lesions, are environmentally acquired. Others, including brain malformations, genetic tumor syndromes, and metabolic disorders are genetic or have a strong genetic component. In about half of seizure disorders, no genetic or structural abnormality is evident. Perhaps many of these cases are caused by genetic or acquired channelopathies that are not yet recognized. In addition to genes and the environment, brain (synapse) development has a strong influence on seizures. Synapses are in a state of flux during childhood and adolescence; first they proliferate excessively and then they are reduced to adult levels. The dynamic state of synapses explains why most seizures begin (and often stop) for no apparent reason during childhood.
Structural lesions are frequently detected in focal seizures. The most common such lesions are cerebral changes resulting from perinatal brain damage, malformations, cerebral infarcts, trauma, brain tumors, and infections. These lesions involve the cerebral cortex and are characterized by neuronal loss and gliosis. Residual neurons in epileptogenic foci, show loss of dendritic spines, possibly due to loss of afferents. The sources of these afferents have been presumably destroyed by tumors, trauma, stroke, or other lesion. Even minute lesions of the cerebral cortex may destroy, out of proportion, small, inhibitory (GABAergic) interneurons, thus reducing the inhibition that controls large pyramidal cells.
In most generalized seizures, no primary lesions are detected by imaging or neuropathological examination.
The most common seizures in children and adults are partial complex seizures originating from the temporal lobe (temporal lobe epilepsy -TLE or psychomotor epilepsy). These seizures begin with a visceral sensation or other aura(breeze) and are followed by a state of impaired consciousness, automatic motor activities or convulsions. The EEG localizes the epileptogenic focus in the medial portion of the temporal lobe. Because TLE is refractory to drugs, it is often treated by resection of the temporal lobe including the hippocampus and surrounding area and the amygdala. Examination of temporal lobectomy specimens reveals pathology in most cases. The most common lesions are hippocampal sclerosis, tumors (gangliogliomas, gliomas), cortical dysplasias and hamartomas, vascular malformations, ischemic and traumatic lesions, and infectious-inflammatory lesions. In many cases, no pathology is found.
Hippocampal sclerosis, left Normal hippocampus, right
Hippocampal sclerosis (HS) or Ammon’s horn sclerosis consists of loss of neurons in the dentate nucleus and the pyramidal layer of the hippocampus with variable gliosis. Four patterns of HS are recognized, the most common one involving the CA4 (end folium) and CA1 (Sommer sector) subfields of the pyramidal layer. These lesions cause shrinkage of the hippocampus that can be detected by MRI. In addition to seizures, HS is seen in a significant proportion of patients with Alzheimer’s disease and other dementias.
The pathogenesis of this lesion has been the subject of a “chicken or the egg” argument for more than 100 years. Some authors propose that HS is the cause of seizures and others that it is the result of seizures. Proponents of the former view argue that the hippocampus is damaged early in life by birth injury, complicated febrile seizures, and other events, and that this damage makes it prone to seizures. Unlike the neocortex, the hippocampus continues to develop after birth and is more vulnerable to such insults. In some cases of TLE, there is a history of febrile seizures and other insults but in most cases no such history can be elicited. On the other hand, there is also strong support for the idea that HS is secondary to seizures, particularly status epilepticus. Animal experiments and observations in humans show that even a single seizure can cause neuronal damage and that this damage may occur without convulsions, is cumulative, and correlates with the duration and severity of the electrical abnormaliry. HS is also seen in patients who have seizures resulting from brain tumors, cortical dysplasias, and other brain lesions. However, some patients with seizures and status epilepticus have no HS.
The presumed mechanism of damage in HS is discharge of glutamate during the epileptic attack and the most frequent site of damage is the CA1 sector of the hippocampus. This area is also especially vulnerable to hypoxia which also initiates an excitotoxic cascade. This circular argument about HS underlines the rich connectivity and excitatory neurotransmission of certain fields of the hippocampus. However, epileptic brain damage is not limited to the hippocampus. Intractable epilepsy and status epilepticus cause also neuronal loss in the cerebral cortex, thalamus, and cerebellum (Purkinje cells). In addition, patients with epilepsy suffer brain damage from falls and have a high frequency of unexpected death.
Berkovic SF, Mulley JC, Scheffer IE, Petrou S. Human epilepsies: Interaction of genetic and environmental factors. TINS 2006;29:391-7. PubMed
Walker, MS. Hippocampal Sclerosis: Causes and Prevention. Semin Neurol 2015; 35: 193-200. PubMed
Updated: March, 2017
The Hunt and Hess classification system is commonly used to define the degree of neurologic injury patients incur after a subarachnoid hemorrhage. Grade I patients have minimal headache or slight nuchal rigidity, grade II patients have moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy, grade III patients are drowsy, confused, or have mild focal neurologic deficits. Patients in grade IV neurologic condition are those who are stuporous with moderate to severe hemiparesis, possibly early decerebrate rigidity, and vegetative disturbances. Grade V patients are those in deep coma with decerebrate rigidity or a moribund appearance. Patients presenting with a grade IV or V hemorrhage have typically been managed conservatively or with comfort measures for the patient only. Mortality rates of 80-90% were the rule with this type of management.
Over the past three years, we have taken a different approach to the management of these poor grade patients. In a good proportion of these patients, a reversible mechanism of neurologic impairment can be identified. Evaluation The CT scan in poor grade patients may define potentially reversible causes of coma. Patients with intraparenchymal hemorrhage (without vital brain destruction) associated with an aneurysm represent one situation where removal of the blood clot may result in neurologic improvement. Similarly, intraventricular hemorrhage or hydrocephalus associated with subarachnoid hemorrhage may be conditions where insertion of a ventricular drainage system will alleviate elevate intracranial pressure (ICP). Given these potentially reversible conditions, rapid evaluation and treatment of patients in poor neurologic condition after subarachnoid hemorrhage should proceed.
Patients presenting in poor neurologic condition undergo a head CT. If there is vital brain destruction with no hope for improvement, comfort measures only are instituted. If the head CT shows diffuse subarachnoid hemorrhage, hydrocephalus, or an intraparenchymal hemorrhage which could be removed surgically with some hope of neurologic improvement, a ventriculostomy is inserted. Once the ventricular drain is in place, the intracranial pressure can be monitored. If the ICP remains controllable (less than 20 mm Hg), and if there is improved neurologic condition with adequate brainstem function, we proceed with cerebral angiography to define the source of the hemorrhage. If the intracranial pressure remains uncontrolled or the patient makes no neurologic improvement with poor brainstem function, then no further aggressive therapy is recommended to the patient’s family. In cases where cerebral angiography is performed, the aneurysm location and size is evaluated. A decision is then made on the best treatment for the aneurysm, whether that be with direct surgery and clipping of the lesion with possible removal of intraparenchymal blood clot or possibly an endovascular approach to obliterate the aneurysm. This decision is often made through discussions between the neurosurgeon, the interventional neuroradiologist, and a neurologist. As well, discussions with the family are important at this interval to try to help family members understand the potential outcomes for a poor grade aneurysm patient.
Post-treatment care Following treatment of the aneurysm, the ventricular drain is maintained and maximal medical therapy is instituted for potential vasospasm. This involves elevated blood pressure with intravenous pressor agents, hypervolemia with central venous pressure monitoring, and hemodilution with hematocrit maintained between 30 – 32%. By using transcranial doppler monitoring in conjunction with neurologic examination, the severity of vasospasm and efficacy of treatment can be followed. Results Using the management plan outlined, we have treated 32 patients in poor neurologic condition. In 12 patients managed without treatment of the aneurysm, 2 survived. In these patients, angiogram failed to reveal an intracranial aneurysm. In the 10 other patients, uncontrolled intracranial pressure or failure to improve neurologically after placement of ventriculostomy led us to conclude that neurologic improvement was unlikely. Of 18 grade IV and V patients managed with surgery, 8 (45%) had excellent or good outcome, 2 (11%) had a fair outcome, 2 (11%) had a poor outcome, and 6 (33%) died. Although we have been able to improve the outcome of patients in poor neurologic condition after subarachnoid hemorrhage, it should be noted that of 32 patients treated, 16 were patients whose poor neurologic condition was due to a second hemorrhage from their aneurysm. This emphasizes the importance of early diagnosis and treatment of patients presenting with subarachnoid hemorrhage. It is through this type of recognition that overall improved management of aneurysm patients can be expected to occur.
- Patients presenting in poor neurologic condition after subarachnoid hemorrhage may have a reversible etiology of their impairment.
- Prompt evaluation and treatment is crucial to the overall goal of reducing the morbidity and mortality of patients in poor neurologic condition.
Christopher S. Ogilvy, M.D.
Ojemann RG, Ogilvy CS, Heros RC, Crowell RM, eds. Surgical Management of Cerebrovascular Disease.
Sepsis has been referred to as a process of malignant intravascular inflammation. Normally, a potent, complex, immunologic cascade ensures a prompt protective response to microorganism invasion in humans. A deficient immunologic defense may allow infection to become established however, an excessive or poorly regulated response may harm the host through maladaptive release of indigenously generated inflammatory compounds.
Lipid A and other bacterial products release cytokines and other immune modulators that mediate the clinical manifestations of sepsis. Interleukins, tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ), and other colony-stimulating factors are produced rapidly within minutes or hours after interactions of monocytes and macrophages with lipid A. Inflammatory mediator release becomes a self-stimulating process, and release of other such mediators, including interleukin (IL)-1, platelet activating factor, IL-2, IL-6, IL-8, IL-10, and nitric oxide (NO), further increases cytokine levels. This leads to continued activation of polymorphonuclear leukocytes (PMNs), macrophages, and lymphocytes; proinflammatory mediators recruit more of these cells. All of these processes create a state of destructive immunologic dissonance.
Sepsis is described as an autodestructive process that permits extension of the normal pathophysiologic response to infection to involve otherwise normal tissues and results in MODS. Organ dysfunction or organ failure may be the first clinical sign of sepsis, and no organ system is immune from the consequences of the inflammatory excesses of sepsis. Mortality increases as organ failure increases. Although uncontrolled, once MODS develops systemic evidence of both proinflammatory and anti-inflammatory up-regulation are usually present, suggesting that failure of host defense homeostasis is the final pathway from sepsis to MODS, rather than simple hypotension-induced end-organ injury, as may occur with hemorrhagic shock. Survival from severe sepsis with MODS is usually associated with a generalized reduction in both the proinflammatory and anti-inflammatory response. A novel hypothesis has recently emerged that survival from severe sepsis requires a generalized down-regulation of the body’s immune response, energetic functions, and associated organ performance. Thus, MODS may by the host’s adaptive response to overwhelming inflammation, allowing inflammation to clear without causing permanent end-organ harm. As discussed below, all organs reveal a generalized hyporesponsiveness that is clearly abnormal in health but may mark a survival strategy in severe sepsis.
Dysfunction of organ systems
Significant derangement in autoregulation of circulation is typical of sepsis. Vasoactive mediators cause vasodilatation and increase microvascular permeability at the site of infection. NO plays a central role in the vasodilatation of septic shock. Also, impaired secretion of vasopressin may occur, which may permit persistence of vasodilatation.
Changes in both systolic and diastolic ventricular performance occur in sepsis. Through the use of the Frank-Starling mechanism, cardiac output often is increased to maintain blood pressure in the presence of systemic vasodilatation. Patients with preexisting cardiac disease are unable to increase their cardiac output appropriately.
Regionally, sepsis interferes with the normal distribution of systemic blood flow to organ systems. Consequently, core organs may not receive appropriate oxygen delivery, and the result is what is known as regional hypoperfusion. Microcirculation is the key target organ for injury in sepsis since vascular endothelium is universally affected by the circulating inflammatory mediators. Although it is unclear if microcirculatory abnormalities are the cause or an innocent bystander of the end-organ injury, clear microvascular dysfunction is seen. A decrease in the number of perfused capillaries is seen, although with application of vasodilator therapies, full microvascular recruitment occurs. Mitochondrial dysfunction also occurs and is often associated with reduced mitochondrial transmembrane potential gradients, which are necessary to drive oxidative phosphorylation. The end result is an apparent inability of end-organs to extract oxygen maximally.
Debate continues as to whether this failure of energy metabolism is an adaptive cytoprotective mechanism similar to hibernation or reflects primary mitochondrial pathology. These are areas of active research but do not presently translate into clear clinical practice guidelines. Increased capillary endothelial permeability leads to widespread protein-rich tissue edema.
Septic shock and SIRS are characterized by reversible myocardial depression, which can prove resistant to catecholamine and fluid administration. Circulating “myocardial depressant factor”—probably representing the synergistic effects of TNF-α, IL-1β, other cytokines, and NO—is implicated in pathogenesis. The two characteristics of this acute stress myocardial depression are impaired adrenergic responsiveness and diastolic dysfunction leading to relative catecholamine resistance and small rather than dilated hearts. Macrovascular myocardial ischemia and hypoperfusion are unlikely contributors. In severe sepsis and septic shock, microcirculatory dysfunction and mitochondrial depression cause regional tissue distress, and regional dysoxia therefore persists. This condition is termed microcirculatory and mitochondrial distress syndrome (MMDS). Sepsis-induced inflammatory autoregulatory dysfunction persists, and oxygen need is not matched by supply, leading to MODS.
Redistribution of intravascular fluid volume resulting from reduced arterial vascular tone, diminished venous return from venous dilation, and release of myocardial depressant substances causes hypotension.
Endothelial injury in the pulmonary vasculature leads to disturbed capillary blood flow and enhanced microvascular permeability, resulting in interstitial and alveolar edema. Neutrophil entrapment within the pulmonary microcirculation initiates and amplifies the injury to alveolar capillary membranes. Acute lung injury and acute respiratory distress syndrome (ARDS) are frequent manifestations of these effects. Indeed, sepsis and pneumonia are the most common causes of ARDS.
The gastrointestinal (GI) tract may help propagate the injury of sepsis. Overgrowth of bacteria in the upper GI tract may be aspirated into the lungs, producing nosocomial or aspiration pneumonia. The normal barrier function of the gut may be affected, allowing translocation of bacteria, endotoxins, and normal digestive proteases into the systemic circulation and extending the septic response.
Septic shock can cause paralytic ileus that can lead to a delay in the institution of enteral feeding. Excess NO production is thought to be the causative agent of sepsis-induced ileus. The optimal level of nutritional intake is interfered with in the face of high protein and calorie requirements. Narcotics and muscle relaxants can further worsen GI tract motility.
As a consequence of the role the liver plays in host defense, the abnormal synthetic functions caused by liver dysfunction can contribute to both the initiation and progression of sepsis. The reticuloendothelial system of the liver acts as a first line of defense in clearing bacteria and their products; liver dysfunction leads to a spillover of these products into systemic circulation.
Liver failure (“shocked liver”) can be manifested by elevations in liver enzymes and bilirubin, coagulation defects, and failure to excrete toxins such as ammonia, which lead to worsening encephalopathy.
Acute kidney injury (AKI) often accompanies sepsis. Different etiologies for AKI have been reported, and the cause is typically thought to be multifactorial. The mechanism of AKI is complex but likely involves a decrease in effective intravascular volume resulting from systemic hypotension, direct renal vasoconstriction, release of cytokines, and activation of neutrophils by endotoxins and other peptides, which contribute to renal injury. Still, most animal studies show that renal blood flow is increased, not decreased, in sepsis, though associated with impaired tubular function and a lack of significant histologic evidence of tubular injury.
Central nervous system dysfunction
Involvement of the central nervous system (CNS) in sepsis produces encephalopathy and peripheral neuropathy. The pathogenesis is poorly defined but is probably related to systemic hypotension, which can lead to brain hypoperfusion.
Coagulopathy and Subclinical coagulopathy, signaled by a mild elevation of the thrombin time (TT) or activated partial thromboplastin time (aPTT) or a moderate reduction in the platelet count, is extremely common; however, overt disseminated intravascular coagulation (DIC) may also develop. Protease-activated receptors (PARs), especially PAR 1, form the molecular link between coagulation and inflammation; PAR1 exerts cytoprotective effects when stimulated by activated protein C or low-dose thrombin but exerts disruptive effects on endothelial-cell barrier function when activated by high-dose thrombin.
Mechanisms of organ dysfunction and injury
The precise mechanisms of cell injury and resulting organ dysfunction in sepsis are not fully understood. MODS is associated with widespread endothelial and parenchymal cell injury, some of which can be explained by the following 4 proposed mechanisms.
The septic circulatory lesion disrupts tissue oxygenation, alters the metabolic regulation of tissue oxygen delivery, and contributes to organ dysfunction. Microvascular and endothelial abnormalities contribute to the septic microcirculatory defect in sepsis. The reactive oxygen species, lytic enzymes, and vasoactive substances (eg, NO and endothelial growth factors) lead to microcirculatory injury, which is compounded by the inability of the erythrocytes to navigate the septic microcirculation.
Endotoxin, TNF-α, and NO may cause damage to mitochondrial electron transport, leading to disordered energy metabolism. This is called cytopathic or histotoxic anoxia, an inability to utilize oxygen even when it is present.
Apoptosis (programmed cell death) is the principal mechanism by which dysfunctional cells are normally eliminated. The proinflammatory cytokines may delay apoptosis in activated macrophages and neutrophils, but other tissues (eg, gut epithelium), may undergo accelerated apoptosis. Therefore, derangement of apoptosis plays a critical role in the tissue injury of sepsis.
The interaction between proinflammatory and anti-inflammatory mediators may lead to an imbalance between them. An inflammatory reaction or an immunodeficiency may predominate, or both may be present.
Host response and other factors influencing outcome
Clinical characteristics that relate to the severity of sepsis include the host response to infection, the site and type of infection, the timing and type of antimicrobial therapy, the offending organism, the development of shock, the underlying disease, the patient’s long-term health condition, and the number of failed organs. Factors that lead to sepsis and septic shock may not be essential in determining the ultimate outcome.
The host response to sepsis is characterized by both proinflammatory responses and anti-inflammatory immunosuppressive responses. The direction, extent, and duration of these reactions are determined by both host factors (eg, genetic characteristics, age, coexisting illnesses, medications) and pathogen factors (eg, microbial load, virulence).
Inflammatory responses are initiated by interaction between pathogen-associated molecular patterns expressed by pathogens and pattern recognition receptors expressed by host cells at the cell surface (toll-like receptors [TLRs] and C-type lectin receptors [CLRs]), in the endosome (TLRs), or in the cytoplasm (retinoic acid inducible gene 1–like receptors [RLRs] and nucleotide-binding oligomerization domain–like receptors [NLRs]).
The consequence of exaggerated inflammation is collateral tissue damage and necrotic cell death, which results in the release of damage-associated molecular patterns, so-called danger molecules that perpetuate inflammation at least in part by acting on the same pattern-recognition receptors triggered by pathogens.
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