Fall 2024 Exam 2 Review Notes PDF

**Fall 2024 Exam 2 Review Notes** **NOTE: I include MOST of these concepts in the Kaltura voiceovers housed in the announcements of your canvas course but may not touch on some if fairly straight forward. [However, review ALL of these concepts.] -- PLEASE REACH OUT TO YOUR COURSE FACULTY IF YOU HAV...

**Fall 2024 Exam 2 Review Notes** **NOTE: I include MOST of these concepts in the Kaltura voiceovers housed in the announcements of your canvas course but may not touch on some if fairly straight forward. [However, review ALL of these concepts.] -- PLEASE REACH OUT TO YOUR COURSE FACULTY IF YOU HAVE ANY QUESTIONS!!! This exam covers weeks 4, 5, 6, and 7 content -- (Chapters 16-20; 7-14)** **[Nervous System]** **Pain, Temperature Regulation, Sleep, and Sensory Function** ***[Pain]*** **Nociceptors can be defined as sensory receptors that are activated by noxious stimuli that damage or threaten the body\'s integrity.** ** They are located in the skin, muscles, joints, bones, and internal organs (Peripheral Nervous System).** ** Nociceptors are activated by a painful stimuli and send electrical signaling messages to the dorsal horn of the spinal cord.** ** Not evenly distributed throughout the body. Fingertips extremely abundant; cartilage none** **Acute versus Chronic Pain** +-----------------------+-----------------------+-----------------------+ | **CHARACTERISTIC** | **ACUTE PAIN** | **CHRONIC PAIN** | +=======================+=======================+=======================+ | **Source** | **Acute Pain is a | **Unknown; if known, | | | protective mechanism | treatment is | | | to warn of actual or | prolonged or | | | impending injury.** | ineffective** | | | | | | | **External agent or | | | | internal disease | | | | usually known** | | +-----------------------+-----------------------+-----------------------+ | **Duration** | **Transient (up to 6 | **Prolonged and | | | months)** | persistent (months to | | | | years)** | +-----------------------+-----------------------+-----------------------+ | **Clinical signs** | **Sympathetic | **Response patterns | | | response: Increased | vary; fewer overt | | | pulse rate, elevated | signs, \*sympathetic | | | blood pressure (B/P), | unresponsiveness | | | increased respiratory | (adaptation). | | | rate, diaphoresis, | Usually, no increase | | | dilated pupils** | in pulse or B/P, | | | | calm** | +-----------------------+-----------------------+-----------------------+ | **Prognosis** | **Likelihood of | **Complete relief | | | eventual complete | usually not | | | relief** | possible** | +-----------------------+-----------------------+-----------------------+ **\*Chronic Pain: Due to adaptation, the sympathetic response is no longer activated. The patient may even look calm with no increase in pulse or respiratory rate.** ***[Temperature Regulation]* -- Protective mechanism: Moderate fever helps the body respond to infectious processes. However, extreme, prolonged hyperthermia can produce complications such as nerve damage, coagulation of proteins, convulsions, and even death.** **Pyrogens: a substance that can cause a fever. Exogenous pyrogens are produced by pathogens. Endogenous pyrogens are produced primarily by phagocytic cells (prostaglandin, interleukins)** **Benefits of Fever** **1. Raising of body temperature kills many pathogens and adversely affects their growth and replication.** **2. Higher body temperatures decrease serum levels of iron, zinc, and copper---minerals needed for bacterial replication.** **3. Increased temperature causes lysosomal breakdown and auto destruction of cells, preventing viral replication in infected cells.** **4. Heat increases lymphocytic transformation and motility of polymorphonuclear neutrophils, facilitating the immune response.** **5. Phagocytosis is enhanced, and production of antiviral interferon is augmented.** **Infection and fever responses in older adult persons and children may vary from those in normal adults.** **Box 16.2 from Textbook: Effects of Fever at the Extremes of Age** ***Older Adult Persons*** **Subtle or atypical responses to infectious fever are often accompanied by dehydration, and in severe systemic infection there may be no fever. Symptoms can include feeling cold or warm, having strange body sensations, headache, vivid dreams, and hallucinations.** **Severe systemic infections may cause alternating hypothermia and high fever in a 24 h period.** ***Infants and Children*** **Infected babies may not develop infectious fever in the first few days of life.** **Young infants (less than 60--90 days of age) often present with fever and no other symptoms, making differential diagnosis difficult.** **Children develop higher temperatures than adults for relatively minor infections, and any skin vasoconstriction can lead to a rapid increase in body temperature.** **Severe systemic infections may cause alternating hypothermia and high fever in a 24 h period, the same as elderly adults.** ***[Sleep]*** ***[Obstructive sleep apnea syndrome]* (OSAS) is the most commonly diagnosed sleep disorder and occurs in all age groups. However, the incidence of OSAS increases with age beyond 60 years. Major risk factors include obesity, male sex, older age, and postmenopausal status (not on hormone therapy) in women, craniofacial anomalies, and increased size of tonsillar and adenoid tissue. OSAS results from partial or total upper airway obstruction to airflow recurring during sleep with continuous respiratory efforts made against a closed airway. It is often accompanied by excessive loud snoring, gasping, and multiple apneic episodes that last 10 seconds or longer. Central sleep apnea is the temporary absence or diminution of ventilatory effort during sleep with decreased sensitivity to carbon dioxide and oxygen tensions, and decreased airway dilator muscle activation. It may be associated with heart failure, neurologic disease, high altitude, or narcotic medications. Obesity hypoventilation syndrome is a combination of obesity, daytime hypercapnia, and sleep disordered breathing not caused by other disorders of hypoventilation. The periodic breathing eventually produces arousal, which interrupts the sleep cycle, reducing total sleep time and producing sleep and REM deprivation. Sleep apnea produces hypercapnia and low oxygen saturation and if left untreated, eventually leads to polycythemia, pulmonary hypertension, systemic hypertension, stroke, right-sided congestive heart failure, dysrhythmias, liver congestion, cyanosis, and peripheral edema.** ***[Circadian rhythm sleep disorders]* are common disorders of the 24-hour sleep-wake schedule with disruption in the timing of sleep. These disorders can result from extrinsic causes, such as rapid time zone changes (or jet-lag syndrome), alternating the sleep schedule (rotating work shifts) involving 3 hours or more in sleep time, or changing the total sleep time from day to day. The disruption of circadian rhythms may cause problems in the short term, such as cognitive deficits, poor vigilance, difficulty concentrating, and inadequate performance of psychomotor tasks. However, long-term health consequences of shift work sleep disorder may be quite serious and include depression/anxiety, increased risk for cardiovascular disease, and increased all-cause mortality.** ***[Sensory ]*** [ **Hearing**] ***[Conductive hearing loss]* occurs when there is interference in air conduction. Conditions that commonly cause a conductive hearing loss include impacted cerumen, foreign bodies lodged in the ear canal, benign tumors of the middle ear, carcinoma of the external auditory canal or middle ear.** **Symptoms of conductive hearing loss include diminished hearing and soft speaking voice. The voice is soft because often the individual hears his or her voice, conducted by bone, as loud. In addition, although the cause is unknown, the individual often hears better in a noisy environment than in a quiet one. Treatment of the underlying cause generally improves hearing and a hearing aid can improve quality of life.** ***[Sensorineural hearing loss]* is caused by *impairment of the organ of Corti* or its central connections. There are many conditions that commonly cause sensorineural hearing loss: congenital and hereditary factors, noise exposure, aging, ototoxicity, and systemic disease (syphilis, Paget disease, collagen diseases, diabetes mellitus).** **[*Presbycusis*] is age-related hearing loss usually in the high frequencies. It is the most common form of sensorineural hearing loss and is especially common in older adults. Presbycusis may occur because of atrophy of the basal end of the organ of Corti, a loss in the number of auditory receptors, changes in vasculature, or stiffening of the basilar membranes. Because of the slow progression of hearing loss, onset of symptoms is gradual. In addition, drug ototoxicity (drugs that cause destruction of auditory function) can be observed after exposure to a variety of chemicals, for example, antibiotics, and chemicals such as salicylate, mercury, tobacco, and alcohol.** *[**Vision** ]* ***Glaucoma*: leading cause of visual impairment and blindness. Outflow obstruction of aqueous humor at the trabecular meshwork or canal of Schlemm. Family history is a risk factor and can be inherited. Open-angle glaucoma is the most common: chronic increased intraocular pressure causes death of retinal ganglions and optic nerve degeneration with myopia and loss of peripheral vision, followed by central vision impairment & blindness. Loss of visual acuity results from pressure on the optic nerve.** ***Age-related macular degeneration (AMD)* accumulation of waste products from photoreceptors in the macula and choriocapillary loss**. **AMD** **is a severe and irreversible loss of vision and a major cause of blindness in older individuals. Hypertension, cigarette smoking, diabetes mellitus, and a family history of AMD are risk factors. The degeneration usually occurs after the age of 60 years. The cause of AMD is unknown and complex because of the many components of eye structure, genetic diversity, and variable environmental factors. There are two forms: dry or non-neovascular (atrophic) and wet or exudative (neovascular). The dry form is more common and is slowly progressive with accumulation of drusen (waste products from photoreceptors) in the macula, choriocapillary loss, accumulation of lipofuscin (a lysosomal pigmented residue) in the retinae, and atrophy, leading to permanent central vision loss. Early symptoms include limited night vision and difficulty reading. The wet form includes abnormal choroidal blood vessel growth within the macula (neovascularization), leakage of blood or serum, retinal tears or detachment, fibrovascular scarring, loss of photoreceptors, and more severe and rapid loss of central vision.** *[**Presbyopia**]* **Loss of accommodation with advancing age is termed presbyopia, a condition in which the ocular lens becomes larger, firmer, and less elastic. The major symptom is reduced near vision, causing the individual to hold reading material at arm\'s length. Treatment includes corrective forward, contact, and intraocular lenses, corneal inlays, or laser refractive surgery for monovision.** ***[Retinal detachment]*** **is a common cause of visual impairment and blindness. Fluid (exudate, hemorrhage, or liquid vitreous) separates the retinal pigment epithelium from the photoreceptors in the neuroepithelium. The separation deprives the outer retina of oxygen and nutrients because the diffusion distance is increased. Communication is also disrupted between the pigment epithelium and photoreceptors. There is retinal degeneration and fibrosis with loss of vision.** ***[Proprioception]*: One of the main causes of falls in the elderly is decreased awareness of the position of the body (proprioception). For example, *[vestibular nystagmus]* is the constant, involuntary movement of the eyeball and develops when the semicircular canal system is overstimulated. It is a dysfunction of the semi-circular canal in the ear that can cause an unsteady gait.** **Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function** **[Multiple sclerosis (MS)] -- destruction of myelin sheath -- signals do not get sent down nerve properly -- leads to motor-type symptoms, weakness, slurred speech, autoimmune inflammatory disorder. *A chronic inflammatory disease involving degeneration of central nervous system myelin, scarring or formation of plaque, and loss of axons.* MS is caused by an autoimmune response to self-antigens in genetically susceptible individuals.** **B-cells produce myelin specific antibodies. Plaques form when T-cells recognize myelin as autoantigens.** ***[Guillain-Barré syndrome (GBS):]* An autoimmune response triggered by a preceding bacterial or viral infection. Vaccinations can trigger Guillain-Barre syndrome. The disorder usually appears days or weeks after a bacterial or viral infection. Vaccinations can trigger Guillain-Barre syndrome. Normally the immune system uses antibodies (molecules produced in an immune response) and special white blood cells to protect us by attacking infecting bacteria and viruses. In GBS, however, the immune system mistakenly attacks the healthy nerves in the *peripheral nervous system*. This attack may start as a fight against an infection. One possible reason for this is that some chemicals seen on bacteria and viruses resemble those on nerve cells. The immune system may not be able to distinguish bacteria and viruses from healthy nerve cells which also become targets of attack. In most cases of GBS, the immune system damages the myelin sheath; it also may damage the axons themselves. As a result, the nerves cannot transmit signals efficiently and the muscles begin to lose their ability to respond to the brain\'s commands, which causes weakness.** **[Amyotrophic lateral sclerosis (ALS]) is a motor neuron disease! Originates in the cortical motor neurons. Formerly known as Lou Gehrig\'s disease, is degeneration and death of upper and lower motor neurons, including the neuromuscular junction (NMJ).** **Amyotrophic (without muscle nutrition and progressive muscle wasting) refers to the lower motor neuron (LMN) component. The Lateral Sclerosis, scarring of the spinal cord, refers to the upper motor neuron component of the disease. As motor neurons degenerate and die, they stop sending messages to the muscles, which causes the muscles to weaken, start to twitch (fasciculations), and waste away (atrophy). Eventually, in people with ALS, the brain loses its ability to initiate and control voluntary movements. Risk factors include a family history.** **Bulbar onset disease has a more rapid and progressive course. Bulbar symptoms: difficulty speaking, swallowing, and saliva production (Bulbar refers to the region of the brain that controls the muscles in the face and neck, as well as swallowing and speech.) Most people with ALS die from being unable to breathe on their own (known as respiratory failure,) usually within three to five years from when the symptoms first appear. However, about 10% survive for a decade or more.** **[Parkinson's disease (PD):] The pathogenesis of primary PD is unknown. The primary pathology is degeneration of the basal ganglia (corpus striatum, globus pallidus, subthalamic nucleus, and substantia nigra). The hallmark pathologic features of PD is dopaminergic deficiency in the striatum, brainstem, and cortex. Secondary PD is caused by other neurodegenerative and acquired disorders (Exposure to pesticides, heavy metals, and herbicides; Drugs such as antipsychotics; Repeated head trauma such as boxing), Specific gene panels and imaging studies are evolving for early diagnosis, but currently, definitive diagnosis is made post-mortem.** **The classic motor manifestations of PD are resting tremor, pill-rolling tremors, bradykinesia/akinesia (poverty of movement), rigidity (muscle stiffness), and postural abnormalities. The combination of all the parkinsonian symptoms gives the individual a characteristic appearance: a wide-eyed, unblinking, staring expression with the facial muscles smoothed out and almost immobile. Saliva frequently drools from the corners of the slightly open mouth. The gait is pathognomonic: the individual walks with slow, short, shuffling steps; the arms are flexed, abducted, and held stiffly at the side; and the trunk is bent slightly forward. The person may break into a run spontaneously or when pushed forward or backward. Because of the disorder of postural fixation, the tendency is to fall to the side.** **[Myasthenia Gravis]: is a chronic autoimmune disease mediated by acetylcholine receptor (AchR) antibodies that act at the neuromuscular junction. Pathophysiology: an autoimmune response to acetylcholine receptors. Myasthenia gravis typically has an insidious onset. Clinical manifestations may first appear during pregnancy, during the postpartum period, or in conjunction with the administration of certain anesthetic agents. Hallmark symptoms are exertional fatigue and weakness that worsens with activity, improves with rest, and recurs with resumption of activity. The individual often complains of fatigue after exercise and has a recent history of recurring upper respiratory tract infections. The muscles of the eyes, face, mouth, throat, and neck usually are affected first. The extraocular (eye) muscles and the levator muscles are most affected. Manifestations include diplopia, ptosis, and ocular palsies. The muscles of facial expression, mastication, swallowing, and speech are the next most involved. Respiratory distress and difficulty breathing are later signs of disease progression.** ***[Dementia versus Delirium]*** **FEATURE** **DELIRIUM** **Dementia** --------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------- ---------------------------------- **Age** **Usually, older** **Usually, older** ***Onset*** ***Acute---common during hospitalization*** ***insidious*** **Associated conditions** **Urinary tract infection, thyroid disorders, hypoxia, hypoglycemia, toxicity, fluid-electrolyte imbalance, renal insufficiency, trauma, multiple medications** **May have no other conditions** **Course** **Fluctuating; remits with treatment** **Chronic slow decline** **Alertness** **Impaired** ***Normal*** **Orientation** **Impaired** **Intact early; impaired late** ***[Alzheimer disease]* (dementia of Alzheimer type \[DAT\], senile disease complex) is the leading cause of dementia and one of the most common causes of severe cognitive dysfunction in older adults. There is deterioration of judgment, cognition, and memory. The greatest risk factors are age and family history. More common in males. The exact cause of AD is unknown and there is no clear understanding of this complex disease process. FIRST, rule out ALL other causes of dementia with a thorough clinical history, behavior changes, cognitive testing, course of the illness, laboratory tests, and brain imaging.** **Alterations of the Brain** **Focal injury: Focal brain injury is a traumatic brain injury (TBI) that affects a specific location of the brain. TYPES: Direct impact - for example a contusion: A direct impact trauma (blow to the head, gunshot wound) that may or may not involve a loss of consciousness. This is the most common type of TBI. It is often mild, but it can be fatal**. ***[Acute Ischemic stroke]* - *Focal brain ischemia with infarction*. Strokes are considered a type of focal brain injury. Types: embolic, hemorrhagic, transient ischemic attacks (TIA) Focal brain ischemia can lead to cell death, sensory, motor, and cognitive impairments, and infarction. Infarction can occur when blood flow drops below 25% of normal, or when focal brain ischemia lasts more than 30--60 minutes. Risk factor:** **According to the CDC, *high blood pressure, or hypertension* is the leading cause of stroke. High blood pressure can cause arteries to become blocked or weaker, which can lead to a stroke.** ***[Diffuse axonal injuries]* are caused by widespread damage to axons, vascular injury, and brain swelling or edema. The main cause of diffuse brain injuries is rapid acceleration-deceleration of the head (Example -- whiplash), such as in motor vehicle accidents. This acceleration-deceleration motion causes shearing forces on the brain\'s white matter tracts, which damages the axons at the junction of the gray and white matter. This is known as diffuse axonal injury (DAI).** ***[Closed head injuries]* are specific, grossly observable skull and brain lesions that occur in a precise location. Of blunt trauma injuries, 75% to 90% are mild. Injury to the cranial vault, vessels, and supporting structures can produce more severe damage. The dura mater remains intact, and brain tissues are not exposed to the environment. The injury may be a coup injury (injury at site of impact) or a contrecoup injury (injury from brain rebounding and hitting the opposite side of skull or forces being transmitted through the cerebrospinal fluid \[CSF\])** ***[Secondary brain injury]* is caused by inflammatory mediators and decreased cerebral perfusion pressure. Secondary brain injury is an indirect result of primary brain injury, including trauma and stroke syndromes. It occurs as a consequence of primary injury; a cascade of cerebral and molecular events initiated at the time of trauma and lasts for hours to days. Both systemic and cerebral processes are contributing factors. Systemic processes include hypotension, hypoxia, anemia, ischemia, hypercapnia, and hypocapnia. Cerebral contributions include inflammation, cerebral edema, increased intracranial pressure (IICP), microthrombosis, decreased cerebral perfusion pressure, cerebral ischemia, and brain herniation** **Definition: An epidural (extradural) hematoma (EDH) is bleeding between the dura mater and the skull.** **Definition: A subdural hematoma (SDH) is bleeding between the dura mater and the arachnoid membrane covering the brain and is caused by tearing of veins. It is the most common cause of a traumatic intracranial mass lesion.** **[Headaches]** *[Migraines] Activation of the trigeminovascular system and associated changes in brain metabolism and blood flow*. Current theories include neurologic, vascular, hormonal, and neurotransmitter components. Release of inflammatory mediators with sterile meningeal inflammation, edema of blood vessels, and release of neurotransmitters may be important components of migraine pain. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- *[Cluster]* Group of disorders referred to as *trigeminal autonomic cephalalgias*. The trigeminovascular system is activated with release of pain-producing vasoactive peptides and neuroinflammation similar to migraine. Trigeminal-autonomic reflex activation occurs, characterized by sympathetic underactivity and parasympathetic activation geminal autonomic cephalalgies. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- *[Tension]* Both central and peripheral mechanisms operate in causing tension headache. It is not a vascular headache. The peripheral sensitization of myofascial nociceptors may contribute to muscular hypersensitivity and the development of episodic TTH. Pericranial muscle tenderness may develop from the activation of peripheral nociceptors around the blood vessels in striated muscle, tendon insertions, and fascia. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CHARACTERISTICS OF COMMON HEADACHES ----------------------------------- **MIGRAINE WITH OR WITHOUT AURA** **CLUSTER HEADACHE** **TENSION TYPE OF HEADACHE** --------------------------------- ----------------------------------- ---------------------------------------------- ----------------------------------- **Gender** **Female** **Male** **Not gender specific** **Family history of headaches** **Yes** **No** **Yes** **Onset and evolution** **Slow to rapid** **Rapid** **Slow to rapid** **Time course** **Episodic** **Clusters in time** **Episodic, may become constant** **Quality** **Usually throbbing** **Steady** **Steady** **Location** **Variable, often unilateral** **Orbit, temple, cheek** **Variable** **Associated features** **Prodrome, vomiting** **Lacrimation, rhinorrhea, Horner syndrome** **None** **Neurobiology of Schizophrenic, Mood Disorders, Anxiety Disorders** ***[Schizophrenia]* Multifactorial, genetic component. [Neuroanatomic alteration:] Lateral and third ventricle enlargement, abnormal amygdala connectivity -- the amygdala plays a central role in the social brain emotional processing network. This lack of connectivity makes it difficult to make appropriate social judgements. There is a progressive loss of frontal lobe volume thus further decline in cognitive functioning. Neurotransmitter alterations: used to believe there was high concentrations of dopamine, however, still under investigation: but new evidence suggests that it is an alteration of dopamine pathways (dopamine hypothesis).** ***[Anxiety disorders]*** **when fear and anxiety become too intense and undermine the ability to function on a daily basis, the individual may develop an anxiety disorder. Associated with EXCESSIVE AND PERSISTENT WORRIES. Anxiety disorders are the most prevalent psychiatric illness, occurring in approximately 10% to 30% of the general population. Notably, many individuals with anxiety disorders also exhibit symptoms of major depression, and the high comorbidity of anxiety disorders and depression suggests a common neural pathophysiologic basis linking these two illnesses. Anxiety disorders include panic disorder (PD), social anxiety disorder (SAD), generalized anxiety disorder (GAD), and posttraumatic stress disorder. A notable complication of anxiety disorders, particularly prevalent in panic disorders, is the development of agoraphobia or phobic avoidance of places or situations where escape or help is not readily available. The agoraphobic individual will avoid being away from home, standing in line or in a crowd, or traveling in a train, plane, or automobile. Severely agoraphobic individuals become housebound.** **Alterations of Neurologic Function in Children** **Hydrocephalus: Too much cerebrospinal fluid in ventricles -- can be caused by too much production or an obstruction of flow. Remember the brain is within the skull -- a "fixed container"---edema of brain or increased fluid in ventricles will affect blood flow, oxygen delivery, nerve transmission due to pressure from skull on the swelling brain.** **Neural Tube Defects (NTD): No gene has been identified. Present, seems to be multifactorial as a combination of genetics and environment. Folic acid in early pregnancy is important for normal neural tube development. Folic acid deficiency prompted United States (1996) to mandate folate fortification in many foods -- causing a significant decrease of NTDs.** **Definitions of 3 types of NTDS:** ***Meningocele*: a birth defect where there is a sac protruding from the spinal column. The sac includes spinal fluid, but does not contain neural tissue. It may be covered with skin or with meninges (the membranes that cover the central nervous system).** ***Myelomeningocele*:** **is a severe form of NTD in which the meninges, spinal cord, spinal fluid, and nerves develop outside of the body and are contained in a fluid-filled sac that is visible outside of the back area. These babies typically have weakness and loss of sensation below the sac. This can result in muscle weakness and/or paralysis, bowel and bladder problems, excessive fluid on the brain (hydrocephalus).** ***Encephalocele:* a rare birth defect that occurs when part of the baby\'s skull does not close completely during pregnancy, allowing some brain tissue to protrude through the skull. This creates a sac-like bulge containing brain tissue and spinal fluid.** **Seizures: Seizures can be caused by structural abnormalities of the brain, hypoxia, intracranial hemorrhage, CNS infection, traumatic injury, electrolyte imbalance, or inborn metabolic disturbances. Febrile Seizures are benign and the most common type of childhood seizure *[BUT DO NOT LEAD or CAUSE EPILEPSY]*. Seizures are sometimes clearly familial. Often the cause of epilepsy is unknown and presumed to have a genetic basis.** ***[Childhood epilepsy.]* Cause unknown.** **When a sufficient number of neurons become overexcited, they discharge abnormally, which sometimes results in clinical manifestations (seizures) with alterations in motor function, sensation, autonomic function, behavior, and consciousness. The manifestations depend on the site and spread of abnormal electrical activity within the brain. If a child has more than *two unprovoked seizures more than 24 hours apart*.** [ ***Immunity, Inflammation, Infectious Disease***] **Overview: Purpose of the inflammatory process.** **Innate immunity includes two lines of defense: natural barriers and inflammation. Natural barriers are physical, mechanical, and biochemical barriers at the body\'s surfaces and are in place at birth to prevent damage by substances in the environment and thwart infection by pathogenic microorganisms. If the surface barriers are breached, the second line of defense, the inflammatory response, is activated to protect the body from further injury, prevent infection of the injured tissue, and promote healing.** **The inflammatory response is a rapid activation of biochemical and cellular processes that is relatively nonspecific, with similar responses being initiated against a wide variety of causes of tissue damage.** **Inflammation is the immediate response to injury ( "first responder") that contains the initial injury and slows the spread of infection.** **Four (4) Cardinal signs: Inflammation occurs in tissue that has a blood supply (vascularized) and results in a group of easily observable characteristics: *redness, heat, edema (swelling)*, and *pain*.** ***[Edema (swelling)]*: Increased capillary permeability. Vasodilation increases local blood flow to the injured site causing swelling (edema) in the surrounding tissue.** ***[Warmth and redness]*: The increased blood flow and increasing concentration of red cells at the site of inflammation cause locally increased warmth and redness.** ***[Pain:]* Biochemical mediators (e.g., histamine, bradykinins, leukotrienes, prostaglandins).** ***[Neutrophils]* - The neutrophil, or polymorphonuclear neutrophil (PMN), is a granulocyte named for its characteristic staining pattern as well as its multilobed nucleus. Neutrophils circulate in the blood in large numbers and are attracted to the area of injury by chemotactic factors, such as mast cell cytokines, chemokines, and complement. Neutrophils are the predominant phagocytes in early inflammation. The primary role of the neutrophil is to phagocytize pathogenic microbes and remove cellular debris and dead cells from lesions. The neutrophil is a mature cell incapable of division. It is short-lived** ***[Inflammation and adaptive immunity differ in several keyways. ]*** **Inflammation** **Adaptive Immunity** ------------------- -------------------------------------- **Immediate** **Inducible** **Same response** **Exquisitely specific; has memory** **Short-lived** **Long-lived** **First, the components of innate immunity and [ ] inflammation are activated immediately after tissue damage. Adaptive immunity is inducible; the effectors of the immune response, lymphocytes, and antibodies, do not preexist in large numbers but are produced in response to infection or other abnormal molecules. Thus, adaptive immunity develops more slowly than inflammation.** **Second, the inflammatory response is similar regardless of differences in the cause of tissue damage. The adaptive immune response is exquisitely specific. For example, the lymphocytes and antibodies induced in response to infection are extremely specific to the particular strain of the infecting microbe.** **Third, the residual mediators of inflammation must be removed quickly to limit damage to surrounding healthy tissue and allow healing. The effectors of the adaptive immune response are long-lived and provide long-term protection against specific invaders.** **Despite the differences, the innate and adaptive immune systems are highly interactive and complementary.** **[Immunity: 3^rd^ line of defense -- Adaptive Immunity ]** **Adaptive immunity (active immunity) "remembers the pathogen and acts more rapidly on subsequent exposure" and is produced by an individual either after natural exposure to an antigen or after immunization.** **Passive immunity - does not involve the host's immune response at all. Passive immunity occurs when preformed antibodies or T lymphocytes are transferred from a donor to the recipient (breast milk). This can occur naturally, as in the passage of maternal antibodies across the placenta to the fetus. [ ]** ***[Two types of adaptive immunity:]*** ***[Humoral immunity]*:** **B-lymphocytes (B-cells) produce antibodies.** ***Antibody circulates in the blood and binds to antigens on infectious agents.* This** **interaction can result in direct inactivation of the microorganism or activation of a variety of inflammatory mediators (e.g., complement, phagocytes) that will destroy the pathogen. Antibody is primarily responsible for protection against many bacteria and viruses. This arm of the immune response is termed humoral immunity.** ***[Antibodies:]*** **Immunoglobulin E (IgE): When IgE is produced against relatively innocuous environmental antigens, it is also the primary cause of common allergies (e.g., hay fever, dust allergies, bee stings). High levels of Interleukin-4 promote production of IgE. (FYI:** **Interleukins (ILs) are a group of proteins that act as chemical signals between white blood cells and other cells in the body to regulate immune responses.** **FYI: Cytokines are small proteins that are crucial in controlling the growth and activity of other immune system cells and blood cells. When released, they signal the immune system to do its job. Cytokines affect the growth of all blood cells and other cells that help the body\'s immune and inflammation responses. Cytokines signal the immune system to fight off pathogens like viruses and bacteria, as well as allergens and other harmful substances. Some examples of cytokines include interleukins, interferons, and colony-stimulating factors. An overproduction or inappropriate production of cytokines can lead to disease. For example, in rheumatoid arthritis, the body produces excess interleukin-1 (IL-1), interleukin-6 (IL-6), and TNF-α, which are involved in inflammation and tissue destruction.)** **Immunoglobulin A (IgA): IgA is the dominant secretory immunoglobulin. The primary role of IgA is to prevent the attachment and invasion of pathogens through mucosal membranes, such as those of the gastrointestinal, pulmonary, and genitourinary tracts. Protects against a variety of pathogens as well as helps to maintain a healthy microbiome in the gut.** **Immunoglobulin M (IgM): First antibody produced during the initial response to antigens. The immune response to antigen has classically been divided into two phases---primary and secondary responses. After a single initial exposure to most antigens, there is a latent period, or lag phase, during which clonal selection occurs. After approximately 5 to 7 days, IgM antibody is detected in the circulation. This is the primary immune response, typically characterized by IgM\'s initial production.** **Immunoglobulin G (IgG) A second challenge by the same antigen results in the secondary immune response, characterized by the more rapid production of a larger amount of antibody compared with the primary response. The rapidity of the secondary immune response is the result of memory cells that are already differentiated. IgM may be transiently produced in the secondary response, but IgG production is increased considerably, making it the predominant antibody class. Natural infection (e.g., rubella) may result in measurable levels of protective IgG for the individual\'s life.** ***[Cellular immunity]*:** **T-lymphocytes (T- cells) also undergo differentiation during an immune response and develop into several subpopulations of cells that react directly with antigen on the surface of infectious agents. Some develop into T cells (T-helper) that can stimulate the activities of other leukocytes via cell-to-cell contact or through the secretion of cytokines. Others** **develop into T-cytotoxic cells (Tc cells) that attack and kill targets directly. Targets for Tc cells include cells infected by a variety of viruses and cells that have become cancerous (need these to function properly as one component to protect against cancer).** *[Invasion and Evasion of Organisms]* ------------------------------------------------- ***[Bacteria Invasion:]* results in direct confrontation with the individual's primary defense mechanisms against bacteria. Bacterial survival and growth depend on the effectiveness of the body's defenses and on the bacterium's capacity to resist those defenses and obtain nutrients and multiply.** **Evasion: Bacterial survival and growth depend on the effectiveness of the body's defenses and on the bacterium's capacity to resist those defenses and obtain nutrients and multiply. In order to replicate and cause disease, they must evade (resist) the inflammatory and immune defense mechanisms.** - **They typically replicate extremely fast; some are known to double in number every 4 -- 20 minutes. E. Coli can divide every 20 minutes.** - **Develop proteases that digest immunoglobulins, cytokines** - **Develop capsules -- encapsulated bacteria are difficult for macrophages and neutrophils to phagocytose. Pseudomonas has a "slimy" capsule.** - **Increase virulence -- they can change (mutate)** - **Antibiotic resistance is associated with both inappropriate prescribing of antibiotics and an organism changing in response to exposure to antibiotic** ***[Virus Invasion]*** **Viruses are extremely simple microorganisms that do not possess any of the metabolic organelles found in prokaryotes (e.g., bacteria) or eukaryotes (e.g., human cells). Viral replication depends on their ability to infect a permissive host cell. The basic viral structure (virion) consists of nucleic acid protected by a protein shell, the capsid. Many viruses also are surrounded by a protective envelope, which contains the viral proteins needed for attachment to host cells. Viruses also contain enzymes that drive viral replication. Viral pathogens directly destroy or damage cells as part of their replication in infected cells.** **The effects of a virus on an infected cell vary greatly and often result in destruction of the cell. These destructive processes can include such mechanisms as the cessation of DNA, RNA, and protein synthesis, and even disrupt lysosomal membranes.** **Viruses also can elude the immune system by making small changes to the genes that produce viral surface antigens, a process known as antigenic variation. Antigenic drift is a minor form of antigenic variation and results from mutations in the viral genome. For example, antigenic drift can lead to changes in the surface proteins that allow the influenza virus to attach to human cells.** **When an antigenic shift occurs*, previous protection by vaccination may not exist*, resulting in a major pandemic (an epidemic that spreads over a large area, such as a continent or worldwide) and much more severe disease. Such an event occurred in 2009 with the emergence of H1N1 influenza ("swine flu").** **Some viruses can "hide"** **Some viruses bypass intracellular defenses and hide within cells and away from normal inflammatory or immune responses in a process called viral latency (e.g., varicella zoster virus, HPV, and HIV). Varicella zoster virus (which causes chickenpox) will enter a latency phase and spread from mucosal and epidermal sites to remain dormant in the dorsal root ganglion. Later in life and in response to stimuli, such as stress, hormonal changes, or disease, the virus may exit latency and enter a productive cycle causing herpes zoster (shingles) or postherpetic neuralgia** ***[Human immunodeficiency virus (HIV]*):** **After transmission from one person to another, HIV replication begins with attachment to the target cell. The virus first attaches to macrophages and to dendritic cells, which then carry the virus into the lymph nodes where it can infect its primary target cell, the Th lymphocyte. While the killing of infected Th cells is essential for suppressing HIV replication, this process causes the destruction of billions of Th cells each day. The HIV virus takes some of the host cell membrane with it, making the virus less vulnerable to adaptive immune attack. The effects of HIV on the body extend beyond immune suppression. Chronic inflammation, recurrent opportunistic infections, and changes in the gut microbiome contribute to long-term effects on organ function.** ***[Hypersensitivity Reactions]*** ***[Type I reactions]* are mediated by antigen-specific IgE and the products of tissue mast cells. Most common allergies (e.g., bee sting, nuts, pollen allergies) are type I reactions. In addition, most type I reactions occur against environmental antigens and are therefore allergic. Usually, symptoms are mild. HOWEVER, the most life-threatening complication of Type I hypersensitivity is anaphylaxis, which can increase the risk of mortality. During an anaphylactic reaction, the patient may experience hypotension, difficulty in breathing or hypoxia, and/or circulatory failure (distributive shock).** ***[Type II hypersensitivity reaction:]* Type II hypersensitivity reactions are generally characterized by a specific cell or tissue being the target of an immune response. Antibodies bind to the antigens on the cell surface. Some antigens are called tissue-specific antigens because they are expressed on the plasma membranes of only certain cells in specific tissues. The symptoms of many type II diseases are determined by which tissue or organ expresses the particular antigen. *For example, alloimmune reaction to ABO-mismatched transfused blood cells.* Because individuals with type O blood lack both types of antigens, they are considered universal donors, meaning that anyone can accept their red blood cells. Similarly, type AB individuals are considered universal recipients because they lack both anti-A and anti-B antibodies and can be transfused with any ABO blood type. Antibodies in the donor's blood can bind to antigenic determinants on the recipient's erythrocytes, causing agglutination of the recipient's own cells. Agglutination and lysis cause harmful transfusion.** **Another Example: Graves Disease - Antireceptor antibodies do not destroy the target cell but rather cause the cell to malfunction. These autoantibodies change the function of the target receptor by blocking, overstimulating, or destroying it. For example, in Graves disease, autoantibodies called thyroid-stimulating immunoglobulins (TSIs) bind to and activate receptors for thyroid-stimulating hormone (TSH) on thyroid gland cells. TSH normally stimulates thyroid hormone secretion but is under the control of feedback mechanisms. When TSIs bind to the TSH receptors, they stimulate the thyroid cells to overproduce thyroxine, thus producing symptoms of hyperthyroidism.** ***[Type III hypersensitivity reactions:]* Type III hypersensitivity disease reactions are caused by antigen-antibody (immune) complexes that are formed in the circulation and are deposited in vessel walls or other tissues. The primary difference between type II and type III mechanisms is that in type II hypersensitivity, antibody binds to antigen on the cell surface, whereas in type III, antibody binds to soluble antigen that was released into blood or body fluids. Immune complexes are likely to be deposited in certain target tissues, where they have severe pathologic consequences, such as inflammation in the kidneys (glomerulonephritis), the vessels (vasculitis), or the joints (arthritis or degenerative joint disease).** **Raynaud phenomenon, a condition caused by the temperature-dependent deposition of immune complexes in the capillary beds of the peripheral circulation. Certain immune complexes precipitate at temperatures less than normal body temperature, particularly in the tips of the fingers, toes, and nose, and are called cryoglobulins. The precipitates block the circulation and cause localized pallor and numbness, followed by cyanosis (a bluish tinge resulting from oxygen deprivation) and eventually gangrene if the circulation is not restored.** ***[Type IV hypersensitivity reactions:]* Whereas types I, II, and III hypersensitivity reactions are mediated by antibody, type IV reactions are mediated by T lymphocytes and do not involve antibodies. Clinical examples of type IV hypersensitivity reactions include contact with such substances as poison ivy and metals. *Intradermal injection screening for TB is a delayed response Type IV.*** ***[Stress and Disease]*** ***[General adaptation syndrome (GAS).]* GAS involves three successive stages: the alarm, the resistance or adaptation, and the exhaustion stages. *The alarm stage* is the emergency reaction that prepares the body to fight or flee from threat. *Signals the release of catecholamines and hormones!* *The resistance or adaptation stage* requires continued mobilization of the body\'s resources, such as cortisol and adrenaline, to cope and overcome a sustained challenge. However, prolonged use of these resources may weaken the IS and increase the risk of developing diseases. *The exhaustion stage* occurs when the body\'s physiologic resources are depleted and the IS no longer is able to cope with the stressor. The body now becomes vulnerable to psychosomatic and physical diseases, and mental disorders (diseases of adaptation). That is, when stress continues unabated, body organs, such as the heart and kidney, may no longer function normally, and disease may develop followed by premature death.** **[*Chronic Stress--Induced Effects of Glucocorticoids (cortisol)*.]** **Chronic elevation of cortisol is linked to a wide variety of disorders, including obesity, sleep deprivation, lipid abnormalities, hypertension, diabetes, atherosclerosis, and loss of bone density.** **Contribute to the development of metabolic syndrome and the pathogenesis of obesity by directly causing insulin resistance and influencing genetic variations that predispose to obesity. Chronic stress-induced secretion of GCs stimulates food intake and increases fat storage. As obesity develops*, inflammatory cytokine levels increase*, as do lipoproteins and free fatty acids. The resulting low-grade inflammation is associated with an increased risk for diabetes, heart disease, cancer, disability, and early death.** ***[Pathophysiologic Effects of Catecholamines (CA)]*: CA secretion increases proinflammatory cytokine production, which elevates heart rate and blood pressure and impairs wound healing. Chronic stress-induced release in norepinephrine contributes to the production of inflammatory leukocytes that adhere to vessel walls and promote the development of plaque. Proteases released from these inflammatory leukocytes increase the risk of myocardial infarction and stroke by weakening the fibrous cap of the plaque, which can promote plaque rupture. In addition to a stress-induced risk of cardiovascular disease, the effects of stress on elevated inflammatory cytokine production also influence the onset of depression and autoimmune disorders and may facilitate functional decline that leads to frailty, disability, and untimely death. Stress-induced excessive levels of inflammatory cytokines during infection or inflammatory illness. Finally, stress-induced CAs may promote tumor development by modulating the microenvironment** ***Cancer Biology: Cancer cells are considered immortal because they can grow and multiply without limit, unlike normal cells that have a lifespan and die when they become damaged or old. Cancer cells can achieve immortality because they can grow and multiply without limit.** **Cancer cells can ignore signals that tell them to self-destruct when they should. They have unlimited proliferation signaling. Tumor initiation is dependent on mutational and epigenetic changes.*** ***[Tumor Markers -] Both benign and malignant cells can have tumor markers. These markers include hormones, enzymes, and antigens. Although these markers can help to screen for cancer, they do not provide a definitive diagnosis.*** ***[Benign versus Malignant cells]*** **Characteristic** **Benign** **Malignant** ---------------------------- ------------------------- --------------------------------------------- **Appearance of cells** **Well differentiated** **Poorly differentiated** **Usual rate of growth** **Slow** **Rapid with variability in size/shape** **Vascularization** **Slight** **Neovascularization through angiogenesis** **Tissue structure** **Maintained** **Changed** **Ability to metastasize** **No** **Yes** ***[Staging of Cancer:]* Stage 1: confined to the organ of origin; Stage 2: cancer that is invasive locally; Stage 3: cancer that has spread to regional structures, such as lymph nodes; and Stage 4: cancer that has spread to distant sites (e.g., a liver cancer that has spread to a lung or a prostate cancer that has spread to bone).**