Pathophysiology Exam 3

leukemia

-Cancer of white blood cells
-Acute is rapid onset, chronic is usually noticed via blood count
-can occur at different locations along the differentiation cascade
-produces immature cells

acute lymphocytic leukemia

-most common in children
-affect the lymphocytic line in the bone marrow
-majority are B cell in origin in young adults and children (80%)
-20% is T cell in origin

acute myelocytic leukemia

-often associated with deletion of 5q
-petechiae is usually present
-echymoses
-orificial bleeding (abnormal bleeding causes low platelets and RBC with elevated WBC)
-at risk for infection because WBC are immature

Chronic Myelocytic Leukemia

-philadelphia chromosome translocation between chromosome 9 and 22
-abnormal and excessive accumulation and overgrowth of mature granulocytes in the bone marrow
-predominantly a disorder of adults, but can affect children

Chronic Myelocytic Leukemia stages

-chronic (2-8 years)
-accelerated (granulocytes increase)
-acute or blast crisis (orificial bleeding, fatigue, ineffective WBC)

Chronic Lymphocytic Leukemia

-incompetent lymphocytes
-usually a disease of older males
-75% survival rate, usually involves lymph nodes like spleen/liver

etiology of leukemia

-exact cause is unknown (idiopathic)
-chemical: exposure to benzene, chemotherapy medications, methyl methacrylate
-viral (retroviruses)
-radiation: hiroshima, chernobyl have increased incidence (radiation eliminates bones)
-genetic (Philadelphia chromosome, trisomy 21)

leukemia pathogenesis

excessive production of one cell line decreases production of other cell lines producing erythrocytes, leukocytes, and platelets

Leukemia manifestations

-anemia (pallor, fatigue, malaise, dyspneic, decreased activity tolerance
-thrombocytopenia (petechiae, easy bruising, bleeding gums, occult hematuria, retinal hemorrhages, intracerebral hemorrhage, epistaxis)
-Leukopenia (infection, abscesses)
-weight loss, anorexia, possible CNS involvement (altered LOC)

platelets

thrombocytes

thrombocytopenia etiology

-Decreased production in bone marrow
-Increased destruction of platelets (d/t antibodies)
-Increased consumption (by the spleen)

thrombocytopenia manifestations

Petechiae, ecchymosis, bleeding from mucous membranes, cutaneous sites, internal organs.

Red Blood Cells

-no nucleus, mitochondria, or ribosomes
-life cycle is 80-120 days
-biconcave disc, allowing for large amounts of O2 to be carried
-produced in the red bone marrow

Iron deficiency anemia

-iron is essential for hemoglobin development
-occurs when you lose RBC chronically (blood loss from heavy menstrual cycles, colon cancer)
-weakness, pallor, fatigue
-RBCs are microcytic, hypochromic

pernicious anemia

-(type of megaloblastic anemia) vitamin B12 deficiency
-B12 is absorbed in the terminal ileum and requires intrinsic factor secreted by parietal cells in the stomach
-can be caused by a bowel resection surgery and stomach issues
-diarrhea, fatigue, weakness, bleeding/swollen gums, dyspnea, jaundice

sickle cell disease

Genetic disorder in which red blood cells have abnormal hemoglobin molecules and take on an abnormal shape.

sickle cell etiology

-genetic, autosomal recessive, chromosome 7
-heterozygous carriers can have some symptoms that present at low O2 environments (high altitude, cold)

sickle cell pathogenesis

-change in the molecular structure of hemoglobin
-decreases the RBC lifespan
-occludes vasculature
-development of venous thrombosis

sickle cell manifestations

-pain, splenomegaly, stroke
-retinal vessel destruction, blindness
-hepatomegaly, tachycardia
-myocardial ischemia

Multiple Myeloma

-abnormal proliferation of plasma cells (lesions on skull or spine)

multiple myeloma population characteristics

-greater than 40 years of age
-peak incidence is 60s
-greater incidence in males

multiple myeloma etiology

-viral
-genetic

multiple myeloma pathogenesis

-excess number of abnormal plasma cells infiltrate the bone marrow
-produce abnormal immunoglobulin called bence jones protein
-demineralization of bone in skull and spine

multiple myeloma manifestations

-destruction of bine leading to bone pain and pathological fractures
-hypercalcemia
-renal insufficiency due to hypercalcemia and increased blood viscosity
-acute renal failure
-anemia- fatigue
-leukopenia (repeated infections)
-thrombocytopenia (bleeding tendencies)

Hodgkin's lymphoma

-70% cure rate, even better with early diagnosis
-Half of cases occur between 20 and 40; Incidence is higher in males
-Etiology: Genetic, Exposure to chemical agents, Epstein barr virus
-Starts in single lymph node and spreads to other lymph nodes; Contains Reed-Sternberg cell
-Invades other tissues late in disease process; Prognosis for treatment
-Lymph node enlargement (cervical nodes most common), continuous spread through lymph nodes, Fever, Night sweats, Pruritus, Weight loss, Malaise

Non-Hodgkin's lymphoma

-older adults, greater incidence in males
-etiology: viral infection, radiation, exposure to chemicals
-Pattern of development less defined than Hodgkin’s (More spread early on)
-May invade non-lymph tissue early in disease process (Organ involvement like GI bleeds)
-Prognosis ominous for diffuse disease
-Non Contiguous spread of disease, Involvement of gastrointestinal tract (GI bleed, Perforation, Malabsorption), Testes (Testicular mass), Bone marrow

sleep-wake cycles

-part of normal biological fluctuations known as "circadian rhythms"
-circadian rhythms are under control of the suprachiasmatic nucleus of the hypothalamus (SCN)
-a wide variety of pharmacological agents influence sleep cycles

circadian rhythm disruption

-due to phase shift
-jet lag (sleep cycle changes first, then temp cycle, then cortisol 10-12 days later)
-shift work causes an increased risk of chronic health problems (especially DM and weight gain)
-cortisol spikes in the early morning and then later in the afternoon (Max about 1-2 hours before waking)

sleep and temperature

temperature spikes in the evening hours

REM sleep

-Rapid eye movement sleep, a recurring sleep stage during which vivid dreams commonly occur.
-Psychologically restorative
-about 90 minutes into the cycle
-the older you get, the harder it is to get REM
-serotonin needed for priming of REM sleep, loss of muscle tone, loss of ability to thermoregulate, eye movements

stage 1 sleep

-Light sleep
-The brain emits alpha waves--> consistent with a relaxed state of wakefulness

stage 2 sleep

A sleep deeper than that of stage 1, characterized by a slower, more regular wave pattern, along with momentary interruptions of "sleep spindles."

stage 3 sleep

third stage of sleep; deep sleep characterized by low frequency, high amplitude delta waves

stage 4 sleep

-the deepest stage of sleep, during which we are least responsive to outside stimulation
-absent in individuals over 70

physiological changes during sleep

-decreased clearance of respiratory secretions
-cough reflex diminished
-decreased swallowing and esophageal motility
-decreased glomerular filtration rate
-increased aldosterone production
-decreased temp

sleep deprivation

-causes immune system malfunction
-cognitive decline
-hospitalized patients, anxiety, depression, poor sleep hygiene

sleep changes across the lifespan

-sleep stage is 50-60 minutes in infants
-sleep stage is 90 minutes in adults
-decreased sleep requirement over time
-stage 4 sleep is absent in adults over 70
-changes like dementia may be linked to sleep (cognitive functioning)

Restorative function of sleep

This theory proposes that the purpose of sleep is to allow the body and nervous system to grow and repair any damage that may have occurred to tissues during the day.

fever manifestations

-increased heart rate
-increased cardiac output
-increased oxygen consumption
-increased respiratory rate
-each 1º rise in temp causes a 10% increase in metabolic rate
-decreased production of albumin
-increased production of acute phase proteins
-altered drug metabolism
-enhanced immune function (fever increases interferon response to kill pathogens)

hypothermia manifestations

-decreased heart rate
-decreased cardiac output
-development of coagulants
-depressed CNS

pain

-it is whatever the patient says it is
-subjective
-best way to regulate pain assessment is numerical scale

spinothalamic tract

nerve pathway from the spine to the thalamus along which pain impulses are carried to the brain

manifestations of pain

-increased heart rate
-increased blood pressure
-increased respiratory rate
-dilated pupils
-pallor and perspiration
-nausea and vomiting
-urine retention
-elevated blood glucose

fast pain

-myelinated A delta fibers
-quick, sharp, stabbing pain
-well localized

slow pain

-Unmyelinated C fibers
-dull, achy, diffuse pain

nocioreceptors

-pain receptors stimulated by tissue injuries
-distribution is mostly in skin

cutaneous pain

superficial pain usually involving the skin or subcutaneous tissue

somatic pain

Pain that originates from skeletal muscles, ligaments, or joints.

visceral pain

-a poorly localized, dull, or diffuse pain that arises from the abdominal organs, or viscera
-can manifest as referred pain

referred pain

-shared pathways cause this
-pancreas to back
-heart to chest, neck, jaw, arms
-gallbladder to right shoulder

Autoregulation

-mechanism that attempts to maintain supply of necessary metabolic substrates
-protective mechanism that maintains blood pressure
-blood flow remains constant as long as blood pressure is normal
-A MAP (perfusion pressure) lower than 60 and higher than 140 can cause the brain to lose autoregulation
-traumatic brain injury can cause swelling, blood loss which alters blood pressure and can cause a loss of autoregulation
-dehydration can cause altered blood pressure

factors that affect blood flow

-blood pressure
-carbon dioxide concentration (increased CO2 causes vasodilation and increased blood flow)
-oxygen concentration (decreased O2 concentration causes blood vessel vasodilation)

Monroe Kellie hypothesis

-brain, blood, CSF
-intracranial space is limited; increase in volume causes increase in intracranial pressure; to maintain same intracranial pressure, when there is an increase in one component, there must be a decrease in another component
-if there is no compensation, the increased ICP will cause brain death
-ex. breathing faster to decrease CO2 and vasoconstriction to shunt blood

Cerebral perfusion

-should be greater than 50mmHg
-(MAP-intracranial pressure)

intracranial pressure

-the amount of pressure inside the skull
-norm is 0-15 mmHg
-if too high, drain CSF

reticular activating system

-Located in the upper brain stem; responsible for maintenance of consciousness, specifically one's level of arousal
-in a coma, the reticular activating system goes off and stays off

etiology of intracranial hypertension

-anything that causes closed head pathology
-brain swelling causes increased brain tissue volume (traumatic injury) which interferes with cerebral blood flow
-epidural hematoma
-subdural hematoma
-subarachnoid hemorrhage
-intracerebral hematoma
-hydrocephalus

manifestations of elevated ICP

-decreased LOC is the earliest indicator
-coma
-if obtunded: posturing (decorticate or decerebrate) is a poor indicator
-lower than 8 on the Glasgow coma scale
-projectile vomiting
-pupils non reactive to light
-visual disturbances (delusions, hallucinations)
-Motor Dysfunction (hemiplegia, hemiparesis)
-Headache
-Aphasia
-Changes in respiratory pattern (Cheyne Stokes, apnea)
-Cushing's Reflex (late sign)
-brainstem death
-brain herniation

Cushing's Reflex

decreased heart rate, increased blood pressure (trying to maintain CPP), widened pulse pressure
-pulse pressure means that the systolic and diastolic get farther apart
-systolic increases to try and force blood through the brain

Decorticate posturing

characterized by upper extremities flexed at the elbows and held closely to the body and lower extremities that are externally rotated and extended. occurs when the brainstem is not inhibited by the motor function of the cerebral cortex.

Decerebrate posturing

posturing in which the neck is extended with jaw clenched; arms are pronated, extended, and close to the sides; legs are extended straight out; more ominous sign of brain stem damage. Most Severe.

brain death

-loss of brainstem (only "alive" from hospital measures)
-requires multiple criteria: no perfusion, flat EEG, Apnea test

Uncal Herniation

-Uncus of the temporal lobe is displaced downward
Creates pressure on CN III, posterior cerebral artery, and RAS
-temporal lobe moves through the tentorial notch
-causes fixed, blown pupils from CN III pressure

uncal herniation manifestations

-symptoms of ICP (headache, nausea, vomiting, altered mental status)
-Cushing's Sign
-altered respiratory pattern
-loss of brainstem reflexes
-one pupil blown out, other normal; pupils nonreactive to light
-altered balance

Epidural Hematoma

-arterial bleeding in the space between the skull and dura layer
-arterial bleeds are more quick moving than venous because each heart beat prevents clotting by pushing blood through the arteries

epidural hematoma etiology

-arterial bleed (85% are associated with skull fractures)
-occurs quickly
-baseball to the head, MVA

epidural hematoma mechanism

tear in the middle meningeal artery pushes the brain toward midline

epidural hematoma manifestations

-Lucid interval
-ipsilateral pupil change
-contralateral hemiparesis
-increased ICP

subdural hematoma

-usually venous in origin between the dura and arachnoid layer

Subdural hematoma stages

Acute- symptoms come in 24 hours (elevated ICP symptoms)

Subacute- 2-10 days before symptoms

Chronic- 2 weeks to 2 months later (common in the elderly because they are on anticoagulants and atrophy of brain allows more time before symptoms); sometimes symptoms are mistaken for dementia

subdural hematoma mechanism

tear in the bridging veins

subdural hematoma etiology

72% falls, MVAs

Subdural hematoma manifestations

-headache
-altered levels of consciousness
-no lucid interval
-signs of increased ICP
-drowsy, confusion, agitation, ipsilateral pupil changes (sign of herniation), contralateral hemiparesis

Subarachnoid hemorrhage

-bleeding into the subarachnoid space (blood mixes with CSF)
-50% mortality

subarachnoid hemorrhage etiology

-ruptured cerebral aneurysm
-trauma

subarachnoid hemorrhage mechanisms

-irritation of the dura can cause signs of meningitis
-decreased absorption of CSF because the blood plugs up arachnoid villi
-can cause communicating hydrocephalus

subarachnoid hemorrhage manifestations

-fever
-photophobia
-nuchal rigidity
-communicating hydrocephalus
-severe headache, blurred vision, diplopia
-sensory and motor deficits
-projectile vomiting
-vasospasm (constricts vessels and causes lack of blood flow and potential stroke)

signs of meningial irritation

-photophobia
-nuchal rigidity

Intracerebral Hemorrhage

-hemorrhagic stroke
-bleeding in the brain tissue

intracerebral hemorrhagex etiology

often uncontrolled hypertension (usually in the daytime because BP is higher)

intracerebral hemorrhage manifestations

-elevated ICP symptoms
-coma if pressure gets too high

hydrocephalus

accumulation of fluid in the spaces of the brain, causes increased ICP

communicating hydrocephalus

-difficulty reabsorbing CSF because the arachnoid villi are plugged up
-arachnoid villi may eventually work again
-causes headache nausea, downward deviation of the eyes, impaired balance, increased ICP symptoms

noncommunicating hydrocephalus

-blockage in the CSF drainage system (something obstructs the flow between the ventricles)
-congenital defect between the third and fourth ventricles, tumor
-requires a shunt
-increased ICP symptoms

compression force

-tissue is compressed on impact
-ex. brain hits the front of the skull

tension force

-less common
-tissue is pulled apart

shearing force

-brain moves at two different rates, causing a shift and tearing down the corpus callosum

Diffuse axonal injury

-due to shearing force (tears corpus callosum)
-damage to nerve cells in the connecting fibers of the brain
-poor prognosis, people generally do not recover/wake up

pattern of head injuries

-damage to frontal lobe and temporal tips

concussions

-shake the brain; momentary interruption of brain function without loss of consciousness
-can occur from any kind of mechanical force that impacts the brain

concussion manifestations

-repeated concussions can cause residual effects
-momentary loss of reflexes
-arrest of respirations
-amnesia
-headache
-dizziness
-confusion
-visual disturbance
-gait disturbances

post concussion syndrome

-can last six months to never ending
-headache, dizziness, insonnia, decreased cognitive abilities

cerebral contusions

-focal injury
-bruising of the temporal tips and frontal lobe (usually)

contusion etiology

-head injury

contusion mechanism

-anatomic site often involved is frontal and temporal lobes

contusion manifestations

-loss of consciousness
-loss of reflexes
-stop breathing for a few seconds
-bradycardia
-hemiparesis
-hypotension
-aphasia

basilar skull fracture

-base of the skull through the sinuses
-transverse sinuses have a risk for infection (meningitis)

basilar skull fracture manifestations

-CSF leak out of ears and nose
-potential for meningitis
-racoon's eyes (bruising)
-battle sign (mastoid process bruising)

meningitis

inflammation of the meninges

bacterial meningitis etiology

-2/3 of cases are under 5 years old
-haemophilus influenza (not common because children are vaccinated)
-neisseria meningitides (triggered by respiratory/ear infections; common in college; manifests as petechiae on chest/wrist, sepsis)
-streptococcus pneumoniae (older adults)
-E. coli in infants