SUNY Downstate Medical Center NRMS 5190/ NRMS5190 | Pathophysiology Final Exam Study Guide - A+ 100% updated Fall 2026.

Somatosensory function Somatosensory Component of the Nervous System ● Function → provides an awayness of the body sensations such as touch, temperature, limb position, and pain ● Information is transmitted over 1st, 2nd, and 3rd order neurons Pathways from the Spinal Cord to the Thalamic Level of Sensation ● Discriminative Pathway → relays precise information regarding spatial orientation. There is input from multiple receptors. ○ Used for perception, arousal, and motor control ● ****Anterolateral pathway → sends signals for pain, thermal sensation, crude touch, and pressure. ● **Stereognosis → is the ability to sense the shape and size of an object in the absence of visualization. This is based on precise information from muscle, tendon and joint receptors. This is a complex process that requires both the discriminative system and higher order parietal association cortex to be functioning properly. For example, you can find your cell phone in your bag without seeing it, or you can feel a screwdriver in your hand and know what it is without actually seeing it. Mechanisms of Pain ● First order neurons → detect stimuli that threaten integrity of innervated tissue ● Second order neurons → process information ● Third order neurons → project pain information to the brain ● Nociceptors = pain receptors ○ Types ■ A Delta Fibers → fast pain ■ C Fibers → smaller and slower wave pain Transmission of Pain ● Neospinothalamic tract → sharp stabbing pain ● Paleospinothalamic Tract → dull aching pain commonly associated with chronic and visceral pain All types of pain TYPES OF PAIN ● Nociceptive Pain → Nociceptors are sensory receptors that are activated by noxious insults to periphery tissue. The endings of the peripheral pain fibers are free nerve endings - These receptive endings are widely distributed in the skin, dental pulp, periosteum (tissue that covers bones), meninges, and some internal organs. The nociceptors translate noxious stimuli into action potentials that are transmitted by a dorsal root ganglion to the dorsal horn of the spinal cord. Advanced Pathophyisology (NRMS 5190) Final Exam Study Guide (A+) Latest Updated Fall 2026 -SUNY Downstate Medical Center.○ **occurs when nociceptor (pain receptors) are activated in response to actual or impending tissue injury - when it occurs in internal organs it is known as visceral pain ● Neuropathic Pain → arises from direct injury Acute vs Chronic Pain ● Acute pain → self limiting pain that lasts less than 6 months ● Chronic pain → persistent pain lasting longer than 6 months ○ Lacks autonomic and somatic responses associated with acute pain ○ Is accompanied by debilitating responses Types of Pain ● Cutaneous → sharp pain with burning, can be abrupt or slow in onset. Origin in skin and subcutaneous tissues ○ Perceived as sharp and intense ● Deep Somatic Pain → originates in deep body structures (periosteum, muscles, tendons, joints, blood vessels). – More diffuse than cutaneous pain. Can be produced by strong pressure on bone, ischemia to a muscle, and tissue damage can produce deep somatic pain. Sprained ankle is an example of deep somatic pain. ● Visceral Pain → has origins in the visceral organs and is the most common pain produced by disease ● Referred Pain → originates at a visceral site but perceived as originating in part of the body wall that is innervated by neurons entering the same segment of the nervous system Painful Sensations ● Allodynia → extreme sensitivity to touch (wind, sheets, water) - can’t let the sheets touch area Pain and Pain Syndromes ● Neuropathic pain → pain that is widespread and otherwise unexplainable, there is evidence of sensory deficit (numbness or paresthesias) – Can be caused by nerve entrapment, compression of nerve by tumor mass, and various neuralgias. Can be caused by Diabetes, long term alcohol use, hypothyroidism, rash or trauma. ● Trigeminal neuralgia → Sharp, stabbing pain without numbness – ***Affects Cranial Nerve V *** There is demyelination of axons in the ganglion, root and nerve. ● Postherpetic neuralgia → after the shingles – there can be burning, aching, throbbing, intermittent stabbing shooting pain, or allodynia ● Complex regional pain syndrome → chronic arm or leg pain after an injury, surgery or heart attack. Pain is greater than would be expected from the injury that causes it Phantom Limb Pain ● Follows amputation of a limb or part of a limb ● Pain often begins as sensation of tingling, heat and cold, or heaviness, followed by burning, cramping, or shooting painLasting effects of pain All types of headaches TYPES OF HEADACHES ● Tension-Type Headache ○ Causes are unknown but may be due to oromandibular dysfunction, psychogenic stress, anxiety, depression, and muscular stress. These headaches are dull, aching, nondescript, occur in the hatband distribution. Not associated with N/V or worsened with activity. ● Cluster Headache ○ uncommon. Occur more in men than women. This is a primary neurovascular headache that includes severe, unrelenting, unilateral pain. Headaches tend to occur in clusters over weeks or months, followed by a long, headache free period of remission. Believed to have heredity component, the hypothalmus is believed to play a key role, as well as circadian biologic changes and neuroendocrine disturbances. ● Chronic Daily Headache ○ headaches that occur 15 or more days per month for more than 3 months. Characteristics can be like migraines for some, others more of a tension type. Temporomandibular Joint Pain ● ** Major causes of headaches, usually caused by an imbalance in joint movement due to poor bite, grinding of the teeth (mostly at night) or joint problems. ● Presents as facial muscle pain, headache, neck pain or earache. ○ Some patients don’t even know they are grinding their teeth. ● Treatment → NSAIDs Categories of Migraine Headaches ● Migraine → Stimulation of the trigeminal nerve. Can be due to hormonal variations, certain foods such as MSG, aged cheese, chocolate can trigger migraines – the chemicals in the foods trigger the migraine – it is NOT due to food allergy. ● Types of Migraines ○ Without aura → usually pulsing, throbbing unilateral headache that lasts 1-2 days, and can be accompanied by N/V, sensitivity to light and sound, visual disturbances (visual hallucinations) - seeing stars, sparks, and flashes of light. ○ With Aura → similar to migraine without but pt can see flickering lights, spots, or lines, or may have loss of vision. Can feel pins and needles, or have numbness, may have speech disturbances or neurologic symptoms that precede the headache. The aura develops over 5-20 minutes and lasts 5 minutes to an hour. These patients know the migraine is going to happen. ● Subtypes of Migraines ○ **Retinal Migraine → fully reversible visual disturbances (sparks, scotomas, temporary blindness of 1 eye)● Treatment → Some people know their triggers and have to avoid them. There are preventive treatments for migraines – some people who have frequent migraines get low dose beta blockers and see a reduction in occurrences. Temperature regulation Body Temperature and Regulation ● Mechanisms of Heat Production ● Mechanisms of Heat Loss ○ Radiation ○ Conduction ○ Convection ○ Evaporation ● Increased Body Temperature - Fever ● Increased Body Temperature → Hyperthermia ○ Heat cramps ○ Heat exhaustion ○ Heatstroke ○ Drug fever ○ Malignant hyperthermia ○ Neuroleptic malignant syndrome ● Decreased Body Temperature → Hypothermia ○ Accidental hypothermia ○ Systemic hypothermia ○ Neonatal hypothermia ○ Perioperative hypothermia ○ Diagnosis/treatment ○ Therapeutic hypothermia Know about neuropathies Know about pathophysiology of neuropathies NEUROPATHIES Peripheral Neuropathy ● Definition → any primary disorder of peripheral nerves ● Results → muscle weakness, with or without atrophy and sensory changes ● Involvement → can involve a single nerve (mononeuropathy) or multiple nerves (polyneuropathy) Mononueropathies ● Causes → localized conditions such as trauma, compression, or infections that affect a single spinal nerve, plexus, or peripheral nerve trunk ○ Fractured bones may lacerate or compress nerves○ Excessively tight tourniquets ○ Infections such as herpes zoster (shingles) ○ Carpal tunnel due to repetitive wrist motion Polyneuropathy ● Involves demyelination or axonal degeneration of multiple peripheral nerves that leads to symmetric sensory, motor, or mixed sensorimotor deficits ● Causes ○ Immune mechanisms (guillain-barre syndrome) ■ Guillain-Barre Syndrome – acute immune-mediated polyneuropathy. Starts rapidly with limb weakness and loss of tendon reflexes ○ Toxic agents (arsenic polyneuropathy, lead polyneuropathy, alcoholic polyneuropathy) ○ Metabolic diseases (diabetes mellitus, uremia) Nerve Root Injuries → ruptured intervertebral disk ● Cause paresthesia and numbness of leg and foot ● Knee and ankle reflexes also may be diminished or absent ● Can cause motor weakness Pathophysiology of autoimmune disease Neurological diseases - Parkinson’s, MS, Alzheimers, Huntingtons - know pathophysiology PARKINSON’S DISEASE ● Definition → A degenerative disorder of basal ganglia function that results in variable combinations of tremor, rigidity, and bradykinesia ● Pathophysiology → The nuclei in the substantia nigra project fibers to the corpus striatum. The nerve fibers carry dopamine to the corpus striatum. The loss of dopamine nerve cells from the brain’s substantia nigra is thought to be responsible for the symptoms of parkinsonism. ● Characteristics → There is progressive destruction of the nigrostriatal pathway, with subsequent reduction in striatal concentrations of dopamine ● Clinical Manifestations → tremor is most visible ○ Tremor affects the distal segments of the limbs, mainly hands feet, head, neck, face lips, tongue or jaw ○ They will have pill-rolling movements of the forefinger and thumb ○ Tremor is usually unilateral, occurs when limb is supported and at rest and disappears with movement or sleep ○ Tremor eventually progresses to both sides. ○ Bradykinesia is characterized by slowness in initiating and performing movements, and difficulty with sudden, unexpected stopping of voluntary movements. Amyotrophic Lateral Sclerosis (ALS)● also known as Lou Gehrig’s disease. Devastating neurological disorder that selectively affects motor function. ● ** The mean survival period of 2 to 5 years from the onset of symptoms ● starts with weakness, spasticity or stiffness, impaired fine motor control. Progresses over time, and eventually cause dysphagia with recurrent aspiration and weakness of the respiratory muscles. Multiple Sclerosis (MS) ● Pathophysiology → Demyelination of the nerve fibers in the white matter of the brain, spinal cord, and optic nerve. It is caused by an autoimmune attack on the oligodendrocytes of the CNS. ● Most common non traumatic cause of neurologic disability among young and middle-age adults ● *** Characterized by exacerbations and remissions over many years in several different sites in the CNS. Initially, there is normal or near-normal neurologic function between exacerbations. As the disease progresses, there is less improvement between exacerbations and increasing neurologic dysfunction ● Types ○ Relapsing remitting form → episodes of acute worsening neuro involvement with recovery, and stable course between relapses ○ Secondary progressive disease → involves gradual neurologic deterioration with or without superimposed acute relapses in a person with previous relapsing-remitting disease. ○ Primary progressive → nearly continuous neurologic degeneration from onset of symptoms. ○ Progressive relapsing → gradual neurologic deterioration from onset of symptoms but with subsequent superimposed relapses Spinal Cord Injury (SCI) ● Definition → damage to the neural elements of the spinal cord ● Causes → motor vehicle crashes, falls, violence, and sporting activities ● Involvement → most SCIs involve damage to the vertebral column and/or supporting ligaments as well as the spinal cord ○ Commonly involve both sensory and motor function ● Types of Incomplete Spinal Cord Injuries ○ **Central Cord Syndrome → injury in the white matter of the cord. motor function of upper extremities affected, lower extremities to a lesser degree – This usually occurs in the cervical cord – occurs in elderly with narrowing or stenosis related to arthritis, or people with congenital stenosis○ Anterior cord Syndrome → damage from infarction of the anterior spinal cord. There is loss of motor function and loss of pain and temperature sensation from the damage. ○ Brown-Sequard Syndrome → damage to a hemisection of the cord – causing ipsilateral loss of voluntary motor function ○ **Conus medullaris syndrome → there is damage to the sacral cord and lumbar nerve roots. Functional deficits result in flaccid bowel and bladder and altered sexual functions. Know different types of Alzheimer DEMENTIA ● Impairment of short- and long-term memory, associated with abstract thinking, impaired judgment, other higher cortical functions, or personality change ● Caused by any disorder that permanently damages large association areas serving memory and learning ○ D - Drugs ○ E - emotional (depression) ○ M - metabolic (thyroid function) ○ E - ears or eyes declining ○ N - normal pressure hydrocephalus ○ T - tumor or other space occupying lesion ○ I - infection (HIV or syphilis) ○ A - Anemia (Vit B 12 or folate deficiency) ● Types of Dementia ○ Alzheimers – there is about 8-10 year survival rate after diagnosis of Alzheimer’s ○ Vascular dementia: caused by injury resulting in ischemic or hemorrhagic damage to the brain. Damage to large vessels - dementia may occur suddenly, and small vessel damage leads to a slower onset. ○ Frontotemporal dementia: progressive deterioration of the frontal and anterior lobes of the brain. There is strong familial tendencies and starts before age 65 years of age. ○ Creutzfeldt-Jakob disease - extremely rare. There is degeneration of the pyramidal and extrapyramidal systems, causing cognition changes within 6 months of onset. There is extreme cognitive decline, insomnia, blindness, and ataxia follow as disease progresses. Death often occurs within a few months, although some people have survived a few years. . ○ Wernick-Korsakoff syndrome ○ Huntington disease ● Alzheimer's Histology ○ Neuritic (senile) plaques ○ Neurofibrillary tangles ○ Amyloid Angiopathy○ ** Alzheimers is characterized by cortical atrophy and loss of neurons, particularly in the parietal and temporal lobes. Thought to be a combination of neurotransmission disruption, oxidative stress, neuroinflammation and other factors. ○ Diagnosis is made by microscopic examination of cerebral biopsy or at autopsy. Diagnosis is based on clinical findings. Wernicke Disorders ● ****Please know that Wernicke-Korsakoff syndrome is due to chronic alcoholism ○ there can be memory impairment with confabulation, in addition to the symptoms on the slide ■ Symptoms ● Weakness ● Paralysis ● Nystagmus ● Ataxia ● Confusion ○ When you see a patient on Thiamine you should keep in mind that thiamine deficiency is caused by poor diet or alcoholism. ● ***** Thiamine deficiency interferes with production of glucose, which is the brain’s main nutrient. Know different types of seizures - be able to differentiate Seizures and Convulsions ● Seizures → The abnormal behavior caused by an electrical discharge from neurons in the cerebral cortex ○ discrete clinical event with associated signs and symptoms that vary according to the site of neuronal discharge in the brain ○ Manifestations → sensory, motor, autonomic, or psychic phenomenon ● Convulsion → specific seizure type of a motor seizure involving the entire body ● TYPES OF SEIZURES ○ FOCAL ONSET → seizure begins in a specific or focal area of one cerebral hemisphere ○ GENERALIZED ONSET → begin simultaneously in both cerebral hemispheres ■ Most common type of seizure ■ MOTOR SEIZURES: ● Tonic-Clonic – formerly grand mal seizures. Most common major motor seizure – person may have a vague warning, then experiences a sharp tonic contraction of muscles with extension of the extremities and immediate loss of consciousness. Incontinence is common● Atonic seizure = sudden, split second loss of muscle tone leading to the slackening of the jaw, drooping of limbs, or falling to the ground – also known as drop attacks. ● Myoclonic seizures: involves brief involuntary muscle contractions induced by stimuli of cerebral origin. Involves bilateral jerking of muscles, generalized or confined to face, trunk, or one or more extremities. ● Tonic seizures: sudden onset of increased tone, often associated with falling. ■ NONMOTOR: ● ****Absence Seizure –(petit mal) generalized, nonconvulsive events that are expressed mainly as disturbances in consciousness. Typically occur in children and cease in adulthood or may evolve to generalized motor seizures. Characterized as a blank stare, motionless and unresponsiveness, can have lipsmacking, - there is a brief loss of contact with the environment. Usually lasts only a few seconds and person is able to resume normal activity. STATUS EPILEPTICUS **life threatening** ● Continual seizure ● Do not stop spontaneously ● Many types ● If untreated or not stopped can lead to death due to respiratory failure Meningitis MENINGITIS ● *** Please know the etiology of Meningitis: Inflammation of the pia mater, the arachnoid, and the CSF-filled subarachnoid space, ● Manifestations: Fever and chills; headache; stiff neck; back, abdominal, and extremity pains; and nausea and vomiting Sleep wake disorders Prankeria for acute and chronic insomnia Chapter 17 → Sleep Wake Disorders Dyssomnias ● Circadian Rhythm Disorders ○ Non–24-hour sleep–wake syndrome – common in blindness ○ Acute shifts in the sleep–wake cycle – jet lag, shift work ○ Change in sleep phase disorders ○ Advanced sleep phase syndrome ● Insomnia○ Insomnia criteria → difficulty initiating and/or maintaining sleep with adequate opportunity and circumstances for sleep, and daytime consequences such as fatigue, daytime sleepiness, irritability, and impaired attention or memory. More common in females, advancing age, anxious and worry prone temperament. ○ ***Acute → symptoms do not last more than 3 months. Can be caused by emotional stressors and physical stressors. ○ ***Chronic → difficulty initiating or maintain sleep despite adequate opportunity with daytime impairment that has occurred at least 3 x a week for at least 3 months. Some causes are pain, immobility, hormonal changes in pregnancy or menopause. Drugs commonly related to insomnia: caffeine, nicotine, stimulating antidepressants, alcohol, and recreational drugs. ○ Treatment ■ Education and counseling regarding better sleep habits (sleep hygiene) ■ Behavioral therapy aimed at changing maladaptive sleep habits ■ The judicious use of pharmacologic interventions Sleep Disorders ● Narcolepsy → disorder of daytime sleep attacks, cataplexy, hallucinations at the onset of sleep and sleep paralysis ● Motor disorders of sleep ○ Periodic limb movement disorder ○ Restless legs syndrome ○ Obstructive sleep apnea Sleep Apnea ● Types ○ Central sleep apnea → rare disorder involving CNS ○ Obstructive apnea → upper airway obstruction (commonly due to obesity)( ○ Apnea-hypopnea - periods per hour ● Signs and Symptoms ○ Noisy snoring ○ Insomnia ○ Abnormal movements during sleep ○ Morning headaches ○ Excessive daytime sleepiness ○ Cognitive and personality changes ○ Sexual impotence ○ Systemic hypertension ○ Pulmonary hypertension, cor pulmonale ○ Polycythemia **obesity is most likely the cause of obstructive apnea Parasomnias ● Nightmares ● Sleep walking ● Sleep terrors ● Teeth grinding● Bed wetting (enuresis) All types of head injuries Medical Documentation of Brain Death ● Cause and irreversibility of the condition ● Absence of brain stem reflexes and motor responses to pain ● Absence of respiration with a PCO2 of 60mmHg or more ● The justification for use of confirmatory tests and their results ● ** Brain death there is absence of brain stem reflexes and motor responses to pain, Absence of respiration with a PCO2 of 60 mm Hg or more Hypoxia and Ischemia ● Hypoxia → deprivation of oxygen with maintained blood flow ● Ischemia → reduced or interrupted blood flow ○ Focal cerebral ischemia → stroke ○ Global cerebral ischemia → MI Common cause of Neural Injury ● Ischemia ● Excitatory amino acids ● Cerebral edema ● Increased ICP ● **NOT recreational drug use Intracranial Pressure ● Increased ICP is a common pathway for brain injury ○ Can obstruct cerebral blood flow, destroy brain cells, displace brain tissue, and damage delicate brain structures ● Cranial Cavity ○ 10% blood, 80% brain tissue, 10% CSF ○ Normal ICP 0 to 15 mmHg ● Monro-Kellie hypothesis of normalization of ICP Brain Herniation ● Cingulate → involves cerebral artery ○ Clinical Sign → leg weakness ● Central Transtentorial ○ Involves the reticular activating system and corticospinal tract ○ Clinical signs → altered level of consciousness, decorticate posturing, rostralcaudal deterioration ● Uncal○ Involves the cerebral peduncle, oculomotor nerve, posterior cerebral artery, cerebellar tonsil, respiratory center ○ Clinical signs → hemiparesis, pupil dilation, visual field loss, respiratory arrest Hydrocephalus ● Definition ○ An abnormal increase in CSF volume in any part or all of the ventricular system ○ Enlargement of CSF compartment occurs ● Types ○ Communicating → decreased absorption of CSF ○ Noncommunicating → overproduction of CSF Types of Brain Injuries ● Primary or Direct Injury → **damage caused by impact** ○ Includes diffuse axonal injury and local lesions of laceration, contusion, and hemorrhage ● Secondary injury → **most common cause is ischemia** ○ Damage results of subsequent brain swelling, infection, and cerebral hypoxia ○ Often diffuse or multifocal, including, infection, and hypoxic brain injury Coup-Contrecoup Injuries ● **Coup injury – direct contusion of the brain at the site of external force is referred to as a coup injury, ● Contrecoup Injury → rebound injury on opposite side of brain ○ The brain floats in the CSF, blunt force can cause the brain to strike the rough surface of the cranial vault and brain tissue, blood vessels, nerve tracts, and other structures are bruised and torn resulting in contusions and hematomas. Post Concussion Syndrome ● Concussion refers to “an immediate and transient loss of consciousness accompanied by a brief period of amnesia after a blow to the head.” ● Recovery usually takes place in 24 hours ● Mild s/sx may persist for months ○ Headache ○ Irritability ○ Insomnia ○ Poor concentration and memory Risk Factors and Deficits of Stroke ● Risk factors ○ Age, sex, race ○ Family history ○ Hypertension ○ Smoking○ SM ○ Asymptomatic carotid stenosis ○ Sickle cell disease ○ Hyperlipidemia ○ Atrial fibrillation ● Stroke-Related Deficits ○ Motor deficits ○ Dysarthria and aphasia ○ Cognitive and other deficits Two Main Types of Strokes (Brain Attack) ● Ischemic stroke → Caused by an interruption of blood flow in a cerebral vessel and are the most common type of strokes, accounting for 70% to 80% of all strokes. ○ Ischemic strokes are caused by obstruction by thrombosis or emboli ● Hemorrhagic Stroke → Caused by bleeding into brain tissue usually from a blood vessel rupture caused by hypertension, aneurysms, arteriovenous malformations, head injury, or blood dyscrasias Warning Signs and Danger Zones ● Ischemic penumbra – this is the central core of dead or dying cells surrounded by an ischemic band or area of minimally perfused cells - if there is a successful timely return of adequate circulation the cells of the penumbra may continue to survive ● ****** Transient Ischemic Stroke (TIA) – transient episodes of neurologic dysfunction caused ischemia – without acute infarction There is a temporary disturbance in cerebral blood flow which reverses before the infarction occurs. This is a warning about possible impending stroke. 10%-15% people have stroke within 3 months, with 50% of those occurring within 48 hours of the TIA. PLEASE KNOW ABOUT TIA ○ Brain angina ● Water shed Zone Signs and Symptoms of Cerebral Aneurysms ● Most small aneurysms are asymptomatic. ● Large aneurysms may cause chronic headache, neurologic deficits, or both. ● Other manifestations include signs of meningeal irritation, cranial nerve deficits, stroke syndrome, cerebral edema and increased ICP, and pituitary dysfunction. ● Hypertension and cardiac dysrhythmias result from massive release of catecholamines triggered by the subarachnoid hemorrhage. - this is a complication after hemorrhage ● **** Please know that Hypertension and cardiac dysrhythmias result from massive release of catecholamines triggered by the subarachnoid hemorrhageAneurysmal Subarachnoid Hemorrhage ● Bleeding into the subarachnoid space ● Causes ● Congenital Defects → **risk factors for aneurysmal subarachnoid hemorrhage** ○ Acute increases in ICP ○ Cigarette Smoking ○ Hypertension ○ Excessive alcohol intake Typical Problems Arising from Stroke ● Motor deficits are most common ● Followed by deficits of language, sensation, and cognition Know what you would expect with injury to each lobe Functions of the Frontal Lobe ● *** Frontal lobe is responsible for decision-making as well as motivation, reasoning, and numerous other functions. ● Abstract versus concrete reasoning ● Motivation/volition ● Concentration ● Decision-making ● Purposeful behavior ● Memory, sequencing, making meaning of language ● Speech organization and production ● Aspects of emotional response Functions of the Temporal Lobe ● Attention ● Motivation ● Impulse and aggression control ● Interpretation and meaning of social contact Functions of the Parietal Lobe ● Sensory integration and spatial relations ● Bodily awareness ● Personality factors ● Memory and nonverbal memory● Concept formation Functions of Occipital Lobe ● Vision ● Possible information holding area Schizophrenia - clinical manifestations, presentation SCHIZOPHRENIA ● Chronic debilitating psychotic disorder that involves the disconnection between thought and language - it affects the thinking, feeling, perceiving, behaving, and experiencing the environment. ● Onset is between 17 and 25 years ● Men and women seem to be affected equally ● First degree relatives of a person with schizophrenia have a 10-fold greater prevalence of the illness Diagnosis of Schizophrenia ● Two or more of the following symptoms must be present for a significant portion of 1 month. ○ Delusions ○ Hallucinations ○ Disorganized speech ○ Grossly disorganized or catatonic behavior ○ Negative symptoms ■ Absence of normal social and interpersonal behaviors ■ Alogia ■ Avolition ■ Apathy ■ Affective flattening ■ Anhedonia ■ Blunted response to pain ● One or more areas of functioning must be significantly impaired and continuous signs of the disturbance must persist for at least 6 months. Types of Delusions in Schizophrenia ● Delusions of persecution ● Delusions of influence ● Delusions of ill health ● Delusions of grandeur ● Delusions of poverty● Delusions of possession Major Groups of Antipsychotic Agents for Schizophrenia ● Typical Antipsychotics → Include the phenothiazines (chlorpromazine), butyrophenones (haloperidol), and thioxanthenes (chlorprothixene) ● Atypical Antipsychotics → Exemplified first by clozapine are more effective in treating the negative symptoms of schizophrenia and produce fewer extrapyramidal effects ● **always need a psych referral** Hemovascular disorders DIC - other clotting disorders Bleeding disorders Five Stages of Hemostasis ● Vessel Spasm ● Formation of the platelet plug ● Blood coagulation or development of an insoluble fibrin clot ● Clot retraction ○ Clot retraction occurs within 20-60 minutes after a clot has formed, contributing to hemostasis by squeezing serum from the clot and joining the edges of the broken vessel. Platelets also contribute to clot retraction through the action of actin and myosin filaments. Clot retraction requires a large number of platelets, and failure of clot retraction is indicative of a low platelet count. ● Clot dissolution ○ Clot dissolution begins shortly after its formation. The process of by which a clot dissolves is called fibrinolysis which is a sequence of steps controlled by activators and inhibitors. Plasminogen, the proenzyme for the fibrinolytic process, normally is present in the blood in its inactive form. It is converted to its active form, plasmin, by plasminogen activators formed in the vascular endothelium, liver, and kidneys **These processes (retraction and dissolution) involve the interaction of substrates, enzymes, protein cofactors, and calcium ions that circulate in the blood or are released from platelets and cells in the vessel wall. Categories of Disorders of Hemostasis ● Thrombosis → inappropriate formation of clothes within the vascular system ● Bleeding → failure of blood to clot in response to appropriate stimulus Vascular Constriction ● Vessel spasm constricts the vessel and reduces blood flow. It is a transient event that usually lasts minutes or hours. ● Vessel spasm is initiated by endothelial injury and caused by local and humoral mechanisms.● Injury to a blood vessel causes vascular smooth muscle in the vessel wall to contract. This instantaneously reduces the flow of blood from the vessel rupture. Both local nervous reflexes and local humoral factors such as TXA2, which is released from platelets, contribute to the vasoconstriction. Platelet plug formation ● Adhesion and Aggregation ○ 1.Attracted to a damaged vessel wall ○ 2.Activation by subendothelial tissue ○ 3.Change from smooth disks to spiny spheres ○ 4.Exposing glycoprotein receptors on their surfaces ● **** Seconds after vessel injury, von Willebrand factor released from the endothelium, binds to platelet receptors causing adhesion of the platelets to the exposed collagen fibers. As the platelets adhere to the collagen fibers of the damaged vessel wall, they become activated and release ADP and TXA, which attract additional platelets, leading to platelet aggregation (clumping together to form a clot). Clot Retraction and Dissolution ● Clot retraction and clot dissolution are also significant to hemostasis. ● The process involves the interaction of substrates, enzymes, protein cofactors, and calcium ions that circulate in the blood or are released from platelets and cells in the vessel wall. ● Clot retraction → occurs within 20-60 minutes after a clot has formed ○ Contributing to hemostasis by squeezing serum from the clot and joining the edges of the broken vessel ○ Platelets also contribute to clot retraction through the action of actin and myosin filaments ○ Clot retraction requires a large number of platelets, and failure of clot retraction is indicative of a low platelet count. ● Clot dissolution → begins shortly after its formation ○ The process by which a clot dissolves is called fibrinolysis which is a sequence of steps controlled by activators and inhibitors ○ Plasminogen, the proenzyme for the fibrinolytic process, normally is present in the blood in its inactive form. It is converted to its active form, plasmin, by plasminogen activators formed in the vascular endothelium, liver, and kidneys General Forms of Hypercoagulability ● Hypercoagulability causes excessive clotting and contributes to thrombus formation. It results from conditions that foster an increase in platelet numbers or function or accelerated activity of the coagulation system. Thrombocytosis, an elevation in the platelet count, can occur as a reactive process (secondary thrombocytosis) or an essential process (primary thrombocytosis). Increased platelet function usually results from disorders such as atherosclerosis that damage the vascular endothelium and disturb blood flow or from conditions such as smoking that increase sensitivity of platelets to factors that promote adhesiveness and aggregation. ● Conditions that create INCREASED platelet function○ Atherosclerosis ○ Diabetes mellitus ○ Smoking ○ Elevated blood lipoid and cholesterol levels ○ Increased platelet levels ● Conditions that cause accelerated activity of the coagulation system ○ Pregnancy and the puerperium → 6 weeks after delivery ○ Use of oral contraceptives ○ Postsurgical state ○ Immobility ○ Congestive heart failure ○ Malignant diseases ● ** The risk of stroke, thromboemboli, and MI is greater in women who use oral contraceptives, particularly over 35 and those who are smokers. ● Some malignant tumors are thought to release tissue factor molecules, which along with increased immobility and sepsis seen in people with malignant disease, contribute to thrombosis in people with these conditions. HyperCoagulability States ● Increase the risk of clot or thrombus formation in the arterial or venous circulations ○ Arterial thrombi are associated with conditions that produce turbulent blood flow and platelet adherence. ○ Venous thrombi are associated with conditions that cause stasis of blood flow with increased concentrations of coagulation factors. Atherosclerotic Plaques and Platelets ● Atherosclerotic plaques disturb blood flow, causing endothelial damage and promoting platelet adherence. ● Platelets that adhere to the vessel wall release growth factors, which cause proliferation of smooth muscle and thereby contribute to the development of atherosclerosis. ● Smoking, elevated levels of blood lipids and cholesterol, hemodynamic stress, and diabetes mellitus predispose to vessel damage, platelet adherence, and eventual thrombosis. Causes of Bleeding ● Decrease in number of circulating platelets → Depletion of platelets must be relatively severe before hemorrhagic tendencies of spontaneous bleeding occur. ● Impaired platelet function → Bleeding resulting from platelet deficiency commonly occurs in small vessels and is characterized by petechiae and purpura. Platelet Defects ● Thrombocytopenia ○ Results in decrease in platelet production, increased sequestration of platelets in spleen, or decreased platelet survival○ Thrombocytopenia = decreased circulating platelets of less than 150K/uL ■ The lower the number of circulating platelets, the higher the risk of bleeding ■ **There is decreased platelet production if there is loss of bone marrow function which occurs in aplastic anemia** ■ Treatment of cancer depresses bone marrow function and reduces platelet formation ○ Causes of Thrombocytopenia ■ Autoantibodies ■ Drug hypersensitivities ■ Bacterial infections that decrease platelet production ○ Types of Thrombocytopenia ■ Drug induced thrombocytopenia → this can be caused by aspirin, atorvastatin and some antibiotics ● Once drug is discontinued, platelet count rises. ■ ***ITP (Idiopathic or immune thrombocytopenic purpura) → There is platelet antibody formation and excess destruction of platelets ● There may be bruising, bleeding of gums, epistaxis, melena, abnormal menstrual bleeding ● There can be purpura or petechiae as a first sign. ■ Thrombotic Thrombocytopenic Purpura (TTP) → is marked by sudden and severe thrombotic involvement and is rooted in an enzyme deficiency → RARE ○ Manifestations of Thrombocytopenia ○ Bleeding ■ Mucous membranes → nose mouth GI tract, and uterine cavity ■ Commonly occurs in small vessels ● petechiae → pinpoint purplish-red spots ○ Seen almost exclusively in conditions of platelet deficiency ● Purpura - purple areas of bruising Coagulation and Vitamin K ● Vitamin K is an essential cofactor for synthesis of clotting factors ○ Fat-soluble vitamin synthesized by intestinal bacteria ○ In vitamin K deficiency, the liver produces an inactive clotting factor resulting in abnormal bleeding. ○ Coagulation Defects ● Deficiencies can arise because of defective synthesis, inherited disease, or increased consumption of the clotting factors ○ Hereditary disorders○ Hemophilia A – (Factor VIII & vWF deficiency) - Hem A must avoid trauma – Factor VIII replacement therapy at home reduces typical musculoskeletal damage. ○ Hemophilia B (Factor IX deficiency) ○ Von Willebrand (Factor VIII-vWF complex defects which cause platelet dysfunction) - Only treatment is to avoid aspirin ■ Von Willebrand disease is the most frequently inherited coagulopathy and affects 1-2% of the population. ● Manifestations → bleeding into soft tissue, GI tract, joint spaces. ● **Von Willebrand Disease is caused by → deficiency of VIII and poor platelet function Vascular disorders That Cause Bleeding ● Hemorrhagic telangiectasia → An uncommon autosomal dominant disorder characterized by thin-walled, dilated capillaries and arterioles ● Vitamin C deficiency (scurvy) → Results in poor collagen synthesis and failure of the endothelial cells to be cemented together properly, causing a fragile wall ● Cushing disease → Causes protein wasting and loss of vessel tissue support because of excess cortisol ● Senile purpura (bruising in elderly persons) → Caused by the aging process Conditions Associated with DIC ● Obstetric conditions ● Cancers ● Infections ● Shock ● Trauma or surgery ● Hematologic conditions ● DIC → a paradox in the hemostatic sequence and is characterized by widespread coagulation and bleeding in the vascular compartment ○ It begins with a massive activation of the coagulation sequence as a result of unregulated generation of thrombin, resulting in systemic formation of fibrin ○ In addition, levels of all the major anticoagulants are reduced ○ The microthrombi that result cause vessel occlusion and tissue ischemia ○ Multiple organ failure occurs ○ Clot formation consumes all available coagulation proteins and platelets, and severe bleeding occurs ● DIC is initiated by activation of the intrinsic or extrinsic pathway or both ○ The extrinsic pathway is associated with obstetric complications, trauma, bacterial sepsis and cancers. ● Only about ½ people survive, and some may have organ dysfunction or may have had to have amputations. ● DIC is associated with → endothelial damage, activation of factor x, and release of tissue factor as well as other factors.**Please know this slide as well as slide 29 for DIC** Disorders of RBC - know pathophysiologies Causes of different types of anemias ● Know what you’ll see on a blood test for anemia ANEMIA → An abnormally low number of circulating red blood cells or level of hemoglobin, or both → results in diminished oxygen carrying capacity ● Causes ○ Excessive loss of RBCs from bleeding ○ Destruction (hemolysis) of RBC ○ Defective RBC production ○ Inadequate RBC production due to bone marrow failure ● **anemia is not a disease → it is an indication there is something wrong in the body** ● Manifestations ○ Impaired oxygen transport with resulting compensatory mechanism ○ Reduction in red cell indices the hemoglobin levels ○ s/sx associated with the pathologic process that is causing the anemia ○ Manifestations depend on severity of anemia, how quickly it develops, and the person’s age and health status. ○ In anemia, the oxygen carrying capacity of hemoglobin is reduced, causing TISSUE HYPOXIA ■ Tissue hypoxia can cause fatigue, weakness, dyspnea, and sometimes angina■ Hypoxia of brain tissue results in headache, faintness, and dim vision ■ There can be pallor of the skin, mucous membranes, conjunctiva, and nail beds ■ Tachycardia and palpitations may occur as the body tries to compensate with an increased cardiac output ■ Ventricular hypertrophy and high-output heart failure can develop in severe anemia especially if person has preexisting heart issues ● Anemias of Deficient Red Cell Production ○ Iron deficiency anemia → dietary insufficiencies ○ Megaloblastic anemias → cobalamin deficiency anemia, folic acid deficiency anemia ○ Aplastic Anemia ○ Anemia of chronic disease → Can be the result of chronic infections, inflammation, and cancer ■ Chronic renal failure almost always results in anemia due to a deficiency of erythropoietin. Sickle Cell Disease and Thalassemias ● ****Sickle cell disease is an inherited disorder in which an abnormal hemoglobin (hemoglobin S [HbS]) leads to chronic hemolytic anemia, pain, and organ failure. ● The thalassemias are a group of inherited disorders of hemoglobin synthesis leading to decreased synthesis of either the α- or β-globin chains of HbA. ● Cause of Sickling in SCD ○ The abnormal structure of HbS results from a point mutation in the β chain of the hemoglobin molecule, with an abnormal substitution of a single amino acid, valine, for glutamic acid. ○ This is inherited so you can have sickle cell trait or sickle cell disease. ○ There are 2 consequences of red blood cell sickling –chronic hemolytic anemia and blood vessel occlusion. Factors associated with sickling and vessel occlusion include cold, stress, physical exertion, infection, and illnesses that cause hypoxia, dehydration or acidosis. When there is blood vessel occlusion there is acute pain, and many areas can be affected simultaneously. Iron Deficiency Anemia ● Iron deficiency is a common worldwide cause of anemia affecting people of all ages. The anemia results from dietary deficiency, loss of iron through bleeding, or increased demands. ● Because iron is a component of heme, a deficiency leads to decreased hemoglobin synthesis and consequent impairment of oxygen delivery. ● Body iron is used for multiple mechanisms every day. When RBC are broken down the iron is released and reused in the production of new RBCs. Despite this efficiency, small amounts of iron are lost in the feces and need to be replaced by dietary uptake. ● The usual reason for IDA is chronic blood loss, because there are inadequate amounts of iron available to recycle. Blood loss can occur from GI bleeding from peptic ulcers, vascular lesions, intestinal polyps, hemorrhoids or cancer. In women of child-bearing age iron demand is increased because of losses from menstruation. In pregnancy, fetal development increases iron requirements for erythropoiesis.● You will see low Hgb and Hct, decreased iron stores and low serum iron and ferritin. CBC will show reduced MCHC and MCV. ● People with IDA may have Pica, a craving for substances lacking nutritional value such as clay or ice. Vitamin B12 Deficiency ● The hallmark of vitamin B12 deficiency is megaloblastic anemia. ● When vitamin B12 is deficient, the red cells that are produced are abnormally large because of excess cytoplasmic growth and structural proteins. ● Please know the You will see enlarged RBCs (high MCV 100) - it is ● B12 deficiency is caused by malabsorption. It can be caused by prolonged PPI use, GI diseases such as sprue or ileitis Causes of Aplastic Anemia ● Exposure to high doses of radiation, chemicals, and toxins that suppress hematopoiesis directly though immune mechanism ● There is failure of the bone marrow to replace RBCs that are destroyed and leave circulation. Can be caused by radiation, chemotherapy which cause pancytopenia. Can be caused by viral infections and HIV. ● The onset of aplastic anemia may be insidious or sudden. The initial presenting symptoms include weakness, fatigue, and pallor caused by the anemia. Petechiae and ecchymoses often occur on the skin, and bleeding from the nose, gums, vagina, or GI tract may occur due to decreased platelet levels. ● Pancytopenia: decrease in RBC, WBC, and platelets. Polycythemia → condition in which the red blood cell mass is increased ● Types ○ Relative polycythemia → results from a loss of vascular fluid and is corrected by replacing fluid ○ ***Primary polycythemia → a proliferative disease of the bone marrow with an absolute increase in total red blood cell mass accompanied by elevated white cell and platelet counts ○ Secondary polycythemia → results from increased erythropoietin levels caused by hypoxic conditions such as chronic heart and lung disease ● Manifestations → Variable and related to an increase in RBCs, hemoglobin level, and hematocrit with increased blood volume and viscosity ○ Splenomegaly ○ Depletion of iron ○ Disrupted cardiac output ○ Hypertension ○ Decreased cerebral blood flow ○ Venous stasis ○ Thromboembolism and hemorrhage Neonatal Blood ● Hemoglobin concentrations at birth are high, reflecting the high synthetic activity in utero to provide adequate oxygen delivery.○ HbF versus HbA ■ Affinity of F versus A ● Hyperbilirubinemia ○ Unconjugated versus conjugated ○ Phototherapy ● Hemolytic disease ● If there is anemia at birth, it is usually caused by hemolytic disease. Bleeding from the umbilical cord, internal hemorrhage, congenital hemolytic disease, and frequent blood sampling are other possible causes of anemia. ● Physiologic jaundice appears in term infants on the 2-3 day of life. Occurs if there is inability of the liver to conjugate bilirubin. Resolves spontaneously in a week, no treatment needed. Aging and Red Blood Cells ● Hemoglobin and RBC production decreases with age Disorders of WBCs - know about immunodeficient states, bacterial invasions, spot at which cells are responsible for defense against different types of invasions Different types of cancers of the WBCs Diseases of Deficient Blood Cell Production ● Leukopenia → deficiency of leukocytes in blood ○ Neutropenia (low neutrophils) ■ Neutrophils constitute the majority of WBCs and play a critical role in defense mechanisms against infection. They migrate to sites of infection and engulf, digest and destroy the microorganisms ■ Causes of Neutropenia ● Accelerated removal ● Drug-induced granulocytopenia ● Periodic or cyclic neutropenia ● Neoplasms involving bone marrow ● Idiopathic neutropenia occurring in the absence of other disease or provoking influence ● Felty syndrome → a disorder that includes rheumatoid arthritis, decreased WBC, swollen spleen and repeated infections. It is a rare complication of RA. ■ S/sx of neutropenia ● bacterial/fungal infections → malaise, chills, fevers, extreme weakness and fatigue ● Reduced WBC count ○ Granulocytopenia (low granulocytes) ● Aplastic Anemia ○ Anemia, thrombocytopenia, and agranulocytosis ○ Agranulocytosis → virtual absence of neutrophils. This occurs in aplastic anemia – there is anemia, thrombocytopenia (low platelets) and agranulocytosisInfectious Mononucleosis ● Definition → self limited lymphoproliferative disorder ● Causes and Characteristics ○ Caused by the B-lymphocytotropic EBV, a member of the herpes virus family; transmitted in saliva ○ Characterized by fever, generalized lymphadenopathy, sore throat, and the appearance in the blood of atypical lymphocytes and several antibodies ○ Highest incidence in adolescents and young adults ○ Treatment is symptomatic and supportive. ○ Most cases are caused by Epstein-Barr virus. Onset usually insidious, incubation period of 4-6 weeks. Characterized by fever, generalized lymphadenopathy and severe sore throat (which is most severe on days 5-7 and can last for 7-14 days). ○ Splenomegaly occurs in 50-60% of cases. Ruptured spleen is uncommon but can occur. Patients should avoid contact sports. Neoplastic Disorder of Hematopoietic and Lymphoid Origin ● Represents the most important of the white cell disorders ● Include somewhat overlapping categories ○ Lymphomas → hodgkin disease and non-hodgkin lymphoma ○ Leukemia ○ Plasma cell dyscrasias (multiple myeloma) Clinical Features of Neoplasms ● Largely determined by ○ Site of origin ○ Progenitor cell from which they originated ○ Molecular events involved in their transformation into a malignant neoplasm ● Chromosomal aberrations ○ Deletions ○ Polyploidy ○ Translocations ○ Hyperploidy ○ Inversions Hodgkin Disease and Non-Hodgkin Disease ● Hodgkin Lymphoma – people usually present with a painless enlargement of a single node or group of nodes. The initial lymph node involvement is typically above the level of the diaphragm (neck, supraclavicular area or axilla). Involvement of subdiaphragmatic lymph nodes at time of presentation is unusual and usually is more common in older men. Additional symptoms are fevers, chills, night sweats, weight loss. ○ **** Pruritis and intermittent fevers associated with night sweats are classic symptoms of HL. Must have Reed-Sternberg cells to have a definitive diagnosis of Hodgkin Lymphoma. ● Non-Hodgkin Lymphoma – manifestations depend on lymphoma type and stage of disease. Can be indolent (slow growing) or aggressive. Patients usually present with painless lymphadenopathy, which can be isolated or widespread. Involved nodes may be present in retroperitineum, mesentery and pelvis. Indolent lymphomas usually have spread at the time of diagnosis and bone marrow involvement is frequent.○ **** People with intermediate or more aggressive forms usually present with fever, drenching night sweats, or weight loss. There is susceptibility to bacterial, viral and fungal infections. Symptoms of Hodgkin Disease ● Stage A → lack of constitiuational symptoms ● Stage B → 40% of persons with hodgkin disease ○ Significant weight loss, fevers, pruritus, night sweats ● Advanced stages ○ Fatigue and anemia ○ Liver, lungs, digestive tract, and CNS may be involved Diagnosis of Hodgkin Disease ● **Reed-Sternberg cell present in a biopsy specimen of lymph node tissue** ● Computed tomography (CT) scans of the chest and abdomen to assess for involvement of mediastinal, abdominal, and pelvic lymph nodes ● A bipedal lymphangiogram to detect structural changes in the lymph nodes too small to visualize on CT scan ● A positron emission tomography (PET) imaging ● A bilateral bone marrow biopsy may be performed if disease is disseminated. Categories of Non-Hodgkin Lymphomas ● Low grade lymphomas → predominantly B-cell tumors ● Intermediate grade lymphomas → include B-cells and some T-cell lymphomas ● High grade lymphomas → largely immunoblastic (B cell), lymphoblastic (T cell), burkitt, and non-burkitt lymphomas ○ Just an FYI Burkitts Lymphoma – one of the most aggressive and rapidly growing tumors, is a disorder of germinal center B cells. It is endemic in regions of Africa where both Epstein Barr and malaria are common. EBV is a precursor to Burkitts lymphoma Leukemias ● Definitions → Malignant neoplasms arising from the transformation of a single blood cell line derived from hematopoietic stem cells ● Classification according to cell lineage ○ Lymphocytic (lymphocytes ○ Myelocytic (granulocytes, monocytes) Chronic Leukemias ● Definition → malignancies involving the proliferation of well-differentiated myeloid and lymphoid cells● Types of chronic leukemia ○ Chronic lymphocytic leukemia (CLL) ○ Chronic myelogenous leukemia (CML) Classifications of Leukemia Types ● Acute lymphocytic (lymphoblastic) leukemia (ALL) ● Acute myelogenous (myeloblastic) leukemia (AML) ○ ALL & AML – sudden onset with s/s of depressed bone marrow function. ALL occurs most frequently in children, accounting for 3 out of 4 cases of childhood leukemias. AML is mainly a disease of older adults, but can be seen in children and young adults, and accounts for 1 in 4 cases in children and adolescents. Both are characterized by abrupt onset of symptoms including fatigue resulting from anemia, low grade fever, night sweats, and weight loss due to the rapid proliferation and hypermetabolism of the leukemic cells, there can be bleeding from decreased platelet count, and bone pain and tenderness due to bone marrow expansion. ● Chronic lymphocytic leukemia (CLL) ○ Both involve immature lymphocytes and their progenitors in the bone marrow, the spleen, lymph nodes, CNS, and other tissue. ○ CLL is the most common form of leukemia in adults, People with indolent form may be asymptomatic at time of diagnosis and lymphocytosis is noted on routinc labs. As disease progresses, there is lymphadenopathy, hepatoslenomegaly, fever, abdominal pain, weight loss, progressive anemia, thrombocytopenia, with a rapid rise in lymphocyte count. ● Chronic myelogenous leukemia (CML) ○ Both involve the pluripotent myeloid stem cells in bone marrow and interfere with the maturation of all blood cells ○ CML – has a distinct cytogenic abnormality – the Philadelphia chromosome. Onset is slow with nonspecific symptoms of weakness and weight loss. Splenomegaly is usually present at time of diagnosis, and causes feeling of abdominal fullness and discomfort. Labs show leukocytosis, anemia and eventually thrombocytopenia. Leukemic Cells ● Are immature and poorly differentiated ● Proliferate rapidly and have a long life span ● Do not function normally ● Interfere with the maturation of normal blood cells ● Circulate in the blood stem ● Cross the blood–brain barrier ● Infiltrate many body organs Warning Signs Complications of Acute Leukemia ● s/sx ○ Fatigue○ Pallor ○ Weight loss ○ Repeated infections ○ Easy bruising ○ Nosebleeds ○ Other types of hemorrhage ● Complications ○ Leukostasis ○ Tumor lysis syndrome ○ Hyperuricemia ○ Blast crisis Multiple Myeloma ● Definition → A plasma cell dyscrasia characterized by expansion of a single clone of immunoglobulin-producing plasma cells and a resultant increase in serum levels of a single monoclonal immunoglobulin or its fragments ● Main sites involved ○ The bones and bone marrow ○ Proliferation and activation of osteoclasts that lead to bone resorption and destruction ○ Pathologic fractures ○ Hypercalcemia ● There is a high morbidity and mortality rate due to its end-organ destruction. Risk factors thought to include chronic immune stimulation, autoimmune disorders, history of radiation, and exposure to pesticides or herbicides and Agent Orange, and viruses have been associated with MM. ● Please know that MM is associated with history of radiation for cancer treatment. ● Please know that Bence jones protein in the urine is suggestive of MM. ● Clinical Features of Multiple Myeloma ○ ***** Bence Jones protein in urine suggestive of Multiple Myeloma○ AIDS - virus and criteria Phases of HIV infection AIDS Epidemic and Transmission of HIV Infection ● Transmission of HIV infection ○ Sexual contact ○ Blood to blood contact ○ Perinatally ● Transmission from mother to infant is most common way that children become infected with HIV ● HIV is a retrovirus that selectively attacks the CD4 T lymphocytes. As a result people with HIV have a deteriorating immune system and are susceptible to severe infection with ordinarily harmless organisms. HIV type 1 is the virus that leads to AIDs. ● Type 2 is endemic in West Africa, approximately 81% of the people are born with it, and they tend to NOT develop AIDS. ● Spread by sexual contact with infected person, sharing IV drug paraphernalia, or blood transfusions. ● Pathophysiology and Clinical Course○ HIV 1 virus – carries its genetic information in RNA – it is surrounded by a lipid envelope, as well as a matrix protein that lies beneath the envelope. ○ *** The virus binds to CD4 T cells once it enters the blood, the virus also binds with other surface molecules. ***After virus attaches, the envelope fuses to the CD4 T cell membrane, and this results in the uncoating of the virus, allowing the contents of the viral core to enter the host cell. ○ The RNA is changed into DNA, this is done with the revers transriptase enzyme, and then new DNA enters the nucleus of the CD4 T cells (integration) , and then is transcripted to form a new mRNA with the instructions for building new viruses. ○ HIV is the virus, AIDs is a condition. When HIV causes serious damage to the immune system it becomes AIDS. ○ Initial symptoms of Primary infection phase which can last a few weeks : Fever, headaches, joint and muscle aches, rash, sore throat and sores in mouth, swollen lymph nodes in neck, cough, night sweats. May feel like they have the flu ○ Chronic latent phase - can last years – may be asymptomatic = In the US most people DO NOT develop AIDS because they are treated with antivirals. ○ **** AIDS – the CD4T cells fall below 200 or the person develops an AIDS defining complication (serious infection such as Kaposi’s sarcoma, lymphoma, Pneumocysticpneumonia (PCP), thrush, etc) ○ Phases of HIV Infection ■ Primary Infection phase ■ Chronic asymptomatic or latency phase ■ Overt AIDS phase ○ Clinical Course ■ Clinical course varies from person to person. Most (60-70%) develop to AIDS 10-11 years after infection. Some develop in less than 5 years (rapid progressors), and some it takes more than 15 years (slow progressors) - THIS IS WITHOUT TREATMENT ■ Opportunistic infections → can be fungal, protozoal, antibacterial, mycobacterial and viral. ● Bacterial pneumonia, salmonella, M. TB etc ● Fungal → candidiasis, coccidiodomycosis(fungus found in soil), cryptococcosis, histoplasmosis, pneumocystosis (pneumonia caused by fungus) ● Viral infections → CMV, herpes simplex, herpes zoster, HPV and JC virus which causes progressive multifocal leukoencophalopathy (disease of the white matter of brain). ■ Respiratory Manifestations ■ GI Manifestations ■ Nervous System Manifestations ■ Cancers and Malignancies● MANIFESTATIONS: Pneumonia, esophagitis, diarrhea, gastroenteritis, tumors, wasting syndrome, altered mental status, seizures, motor deficits, and metabolic disorders ● Prevention: AVOID EXPOSURE by use of condoms, avoiding contact with semen or vaginal secretions, avoid sharing needles or other possibly infected paraphenalia, or engaging in other unsafe behavior such as multiple partners. ● Treatment: HAART – Highly active antiretroviral therapy - This has been extremely effective in slowing progression of HIV to AIDS. The 3 medication cocktails are highly effective in decreasing viral loads and increased counts of CD4 cells. Increases life expectancies to closer to normal. Musculoskeletal disorders — sprains, strains, different types of fractures Types of Soft Tissue Injuries ● Contusion → an injury to soft tissue that results from direct trauma and is usually caused by striking a body part against a hard object ● Hematoma → large area of local hemorrhage ● Laceration → injury in which the skin is torn or its continuity is disrupted ● Strain → a stretching injury to a muscle or a musculotendinous unit caused by mechanical overloading ● Sprain → involves the ligamentous structures surrounding the joining, pain, and swelling subside more slowly than in a strain ○ Caused by abnormal or excessive movement of the joint ○ **Sprains are more severe than strains - ankle is most common, Usually occurs from twisting injury but can occur from any abnormal movement. Ligaments may be incompletely torn, or severely torn. ○ S/S: Pain, rapid swelling, heat, inability to bear weight, discoloration, limited function and ROM ● Dislocation → displacement or separation of the bone ends of a joint with loss of articulation ○ Dislocation needs to be reduced – or put back into proper position by either a reduction or by surgery ● Loose bodies → small pieces of bone or cartilage within a joint space ○ Loose bodies may need arthroscopic surgery Healing Process in Soft Tissue ● Repair is accomplished by fibroblasts from the inner tendon sheath ● Capillaries infiltrate the injured area during the initial healing process ● Formation of the long collagen bundles Fractures ● Classifications ○ Cause → sudden injury, stress fractures, pathologic fractures○ Location → proximal, midshaft, distal ○ Types → open or closed ○ Pattern of fracture line → comminuted, compression, greenstick ● S/sx ○ Pain ○ Tenderness at the site of bone disruption ○ Swelling ○ Loss of function ○ Deformity of the affected part ○ Abnormal mobility ● Treatment ○ Three objections ■ Reduction → closed manipulation or surgical reduction ■ Immobilization → immobilization through the use of external devices ■ Preservation and restoration of function → therapy ● Complications ○ Loss of skeletal continuity ○ Injury from bone fragments ○ Pressure from swelling and hemorrhage ■ Fracture blisters, compartment syndrome ○ Involvement of nerve fibers ■ Reflex sympathetic dystrophy and causalgia ○ Development of fat emboli Causes of osteonecrosis and osteomyelitis OSTEOMYELITIS ● Origin of bone infections ○ Microorganisms introduced during injury ○ Microorganisms introduced during operative procedures ○ Microorganisms from the bloodstream ● Actions of Microorganism Localized in Bone ○ Proliferate ○ Produce cell death ○ Spread within the bone shaft ○ Incite a chronic inflammatory response with further destruction of bone ● Chronic Osteomyelitis ○ HALLMARK FEATURE → presence of infected dead bone, a sequestrum, that has separated from the living bone. ○ Chronic osteomyelitis includes all inflammatory processes of bone, excluding those in rheumatic diseases that are caused by microorganisms. ○ Chronic osteomyelitis usually occurs in adults. Generally, these infections occur secondary to an open wound, most often to the bone or surrounding tissue. OSTEONECROSIS● Causes ○ Mechanical disruption of blood vessels ○ Thrombosis and embolism ○ Vessel injury ○ Increased intraosseous pressure ● Blood Flow ○ Interconnecting plexus ○ Outer cortex receives supply from surrounding blood vessels ○ Some sites have limited collateral circulation; interruption flow affects significant amount of bone tissue ● Treatment ○ **People with chronic osteonecrosis need a total joint replacement ** ○ In some cases, only short-term immobilization, nonsteroidal anti-inflammatory drugs, exercises, and limitation in weight bearing are used. ○ Osteonecrosis of the hip is particularly difficult to treat. In people with early disease, limitation of weight bearing through the use of crutches may allow the condition to stabilize. ○ Although several surgical approaches have been used, the most definitive treatment of advanced osteonecrosis of the knee or hip is total joint replacement. Difference between bone tumors - which are malignant and which are not ● Which are regressive and which are not BONE TUMORS ● Symptoms of Bone Tumors ○ Pain ○ Presence of a mass ○ Impairment of function ● Characteristics of benign tumors ○ Limited to the confines of the bone ○ Well-demarcated edges ○ Surrounded by a thin rim of sclerotic bone ● Types of benign bone tumors ○ Osteoma ○ Chondroma ○ Osteochondroma ○ Giant cell tumor ● Characteristics of malignant bone tumors ○ Tend to be ill defined ○ Lack sharp borders ○ Extend beyond the confines o