Fever, Body Weakness. Easy Fatigability, Pain, Headache, Weight loss, Dyspnea, Cough, Edema Flashcards
an unpleasant sensation localized to a part of the body. It is often described in terms of a penetrating or tissue-destructive process (e.g., stabbing, burning, twisting, tearing, squeezing) and/or of a bodily or emotional reaction (e.g., terrifying, nauseating, sickening)
Pain
These properties illustrate the duality of pain
both sensation and emotion
Peripheral nerve consists of the
axons of three different types of neurons:
primary sensory afferents, motor neurons, and sympathetic postganglionic neurons
The cell bodies of primary sensory afferents
are located in
the dorsal root ganglia
within the vertebral foramina.
The largest diameter afferent fibers, respond maximally to light touch and/or moving stimuli; they are
present primarily in nerves that innervate the skin
A-beta (Aβ)
These fibers are present in nerves to the
skin and to deep somatic and visceral
A-delta (Aδ) and the unmyelinated (C) axons
primary afferent nociceptors (pain receptors)
Innervated only by Aδ and C fiber afferents
Cornea
When intense, repeated, or prolonged stimuli are applied to damaged or inflamed tissues, the threshold for activating primary afferent nociceptors is lowered, and the frequency of firing is higher for
all stimulus intensities
Sensitization
Sensitization occurs at the level of the
peripheral nerve terminal (peripheral sensitization) as well as at the level of the dorsal horn of the spinal cord (central sensitization).
occurs in damaged or inflamed tissues,
when inflammatory mediators activate intracellular signal transduction in nociceptors, prompting an increase in the production, transport, and membrane insertion of chemically gated and voltage-gated ion channels.
These changes increase the excitability of nociceptor
terminals and lower their threshold for activation by mechanical, thermal, and chemical stimuli
Peripheral sensitization
occurs when activity, generated by nociceptors during inflammation, enhances the excitability of nerve cells in the dorsal horn of the spinal cord
Central sensitization
Following injury and resultant sensitization, normally innocuous stimuli can produce pain
Allodynia
increased pain intensity in response to the same noxious stimulus
hyperalgesia
play a significant role in sensitization
Low pH, prostaglandins, leukotrienes
inflammatory mediators such as bradykinin
is released from primary afferent nociceptors and
has multiple biologic activities. It is a potent vasodilator, degranulates mast cells, is a chemoattractant for leukocytes, and increases the production
and release of inflammatory mediators
Substance P
When primary afferents are activated by noxious stimuli, they release neurotransmitters from their terminals that excite the spinal cord neurons. The major
neurotransmitter released is
glutamate
The convergence of sensory inputs to a single spinal pain-transmission neuron is of great importance because it underlies the phenomenon of
referred pain
Inflammation near the central diaphragm
is often reported as
shoulder discomfort.
This spatial displacement of
pain sensation from the site of the injury that produces it is known as
referred pain
causes vasodilation and neurogenic edema with further accumulation of bradykinin (BK).
also causes the release of histamine
(H) from mast cells and serotonin (5HT) from platelets
Substance P
pathway is crucial for pain sensation in humans
The spinothalamic
This projection mediates the purely sensory aspects of pain, i.e., its location, intensity, and quality
somatosensory cortex.
According to this hypothesis, visceral afferent nociceptors converge on the same pain-projection neurons as the afferents from the somatic structures in which the pain is perceived. The brain has no way of knowing the actual source of input and mistakenly “projects” the sensation to the somatic structure
convergence-projection hypothesis of referred
pain
The suggestion that pain will worsen following administration of an inert substance can increase its perceived intensity
(the nocebo effect)
typically has an unusual burning, tingling, or
electric shock like quality and may be triggered by very light touch
Neuropathic pain
a greatly exaggerated pain sensation to innocuous
Hyperpathia
This constellation of spontaneous pain and signs of sympathetic dysfunction following injury has been termed
complex regional pain syndrome (CRPS)
complex regional pain syndrome (CRPS) occurs after an identifiable nerve injury, it is termed
(CRPS) II also known as posttraumatic neuralgia
or, if severe, causalgia
complex regional pain syndrome (CRPS) occurs without obvious nerve injury, it is termed
CRPS type I (also known as reflex sympathetic dystrophy)
Effective for patients with postherpetic neuralgia who have prominent allodynia
topical preparation of 5% lidocaine in patch form
The ideal treatment for any pain is to
remove the cause
Gastric irritation is most severe
with this drug , which may cause erosion and ulceration of the gastric mucosa leading to bleeding or perforation
aspirin
irreversibly acetylates platelet cyclooxygenase and thereby interferes with coagulation of the blood, gastrointestinal bleeding is a particular risk
aspirin
two major classes of COX:
COX-1 is constitutively expressed, and COX-2 is induced in the inflammatory state.
have similar analgesic potency and produce less gastric irritation than the nonselective COX inhibitors
COX-2– selective drugs
COX-2 inhibitors, including celecoxib (Celebrex), are
associated with increased risk of ?
It appears that this is a class effect of NSAIDs, excluding aspirin.
cardiovascular risk
These drugs are contraindicated in patients in the immediate period after coronary artery bypass surgery and should be used with caution in elderly patients and those with a history of or significant risk factors for cardiovascular disease.
Side effects of opiods
Nausea, vomiting, pruritus, and constipation are the most frequent and bothersome side effects.
Respiratory depression is uncommon at standard analgesic doses, but can be life threatening.
Opioid-related side effects can be reversed rapidly with the narcotic antagonist
naloxone
Opioids produce analgesia by actions in
CNS. They activate pain-inhibitory neurons and directly inhibit pain-transmission neurons. Most of the commercially available opioid analgesics act at
the same opioid receptor (μ-receptor)
metabolite of meperidine. At higher doses of meperidine, typically greater than 1 g/d, accumulation
of this drug can produce hyperexcitability and seizures that are not reversible with naloxone. accumulation is
increased in patients with renal failure
normeperidine
The most common error made by physicians in managing severe pain with opioids is to?
Because many patients are reluctant to complain, this practice leads to needless suffering. In the absence of sedation at the expected time of peak effect
prescribe an inadequate dose
Useful for the management of chronic
pain
The tricyclic antidepressants (TCAs), particularly nortriptyline and desipramin
TCAs potentiate opioid analgesia, so they may be useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors
TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia
block both serotonin and norepinephrine reuptake, appear to retain most of the pain-relieving effect of TCAs with a side effect profile more like that of the selective serotonin reuptake inhibitors
These drugs may be particularly useful in patients who cannot tolerate the side effects of TCAs.
nontricyclic antidepressants (SNRI) venlafaxine (Effexor) and duloxetine (Cymbalta),
The most common causes of abdominal pain on admission are
acute appendicitis, nonspecific abdominal pain, pain of urologic origin, and intestinal obstruction.
Pain is steady and aching in character and is located directly over the inflamed area, its exact reference being possible because it is transmitted by somatic nerves
The pain of parietal peritoneal
inflammation
Exposure of blood and urine to the peritoneal cavity may go unnoticed unless it is sudden and massive
Blood is normally only a mild irritant and the response to urine can be bland
Invariably accentuated by pressure or changes in tension of the peritoneum, whether produced by palpation or by movement such as with coughing or sneezing
Characteristically lies quietly in bed, preferring
to avoid motion, in contrast to the patient with colic, who may be thrashing in discomfort
tonic reflex spasm of the abdominal musculature, localized to the involved body segment
The pain of peritoneal inflammation
Classically elicits intermittent or colicky abdominal pain that is not as well localized as the pain of parietal peritoneal irritation.
Intraluminal obstruction
often presents as poorly localized, intermittent
periumbilical or supraumbilical pain. As the intestine progressively dilates and loses muscular tone, the colicky nature of the pain may diminish. With superimposed strangulating obstruction, pain
may spread to the lower lumbar region if there is traction on the root of the mesentery.
Small-bowel obstruction
colicky pain of colonic obstruction is of lesser
intensity, is commonly located in the infraumbilical area, and may often radiate to the lumbar region
usually causes pain in the right upper quadrant with radiation to the right posterior region of the thorax or to the tip of the right scapula, but it is also not uncommonly found near
the midline.
Acute distention of the gallbladder
Often causes epigastric pain that may radiate to the upper lumbar region.
Distention of the common bile duct
Abdominal pain with radiation to the sacral region,
flank, or genitalia should always signal the possible presence of a
rupturing
abdominal aortic aneurysm.
Often accompanied by splinting
of the involved hemithorax with respiratory lag and decrease in excursion more marked than that seen in the presence of intraabdominaldisease.
Referred pain of thoracic origin
Hallmark of familial Mediterranean fever
Abdominal pain
associated with angioneurotic edema is often associated with episodes of severe abdominal pain.
C1 esterase deficiency
Should also be considered, especially when evaluating
patients with left upper quadrant or left flank pain.
Splenic abscesses due to Candida or
Salmonella infection
Clinically important weight loss is defined as the loss of
10 pounds (4.5 kg) or >5% of one’s body weight over a period of 6–12 months
IWL is encountered in up to
8% of all adult outpatients and
27% of frail persons age 65 years and older.
Significant weight loss is associated with increased mortality, which can range
from 9% to as high as 38% within 1 to 2.5 years in the absence of clinical awareness and attention
Among healthy aging people, total body weight peaks in the
sixth decade of life and generally remains
stable until the ninth decade, after which it gradually falls
lean body mass (fat-free mass) begins to decline at a rate of
0.3 kg per year in the third decade, and the rate of decline increases further beginning at age 60 in men and age 65 in women.
These changes in lean body mass largely reflect the age-dependent decline in growth hormone secretion and, consequently, circulating levels of
insulin-like growth factor type I (IGF-I) that occur with normal aging.
In the healthy elderly, an increase in fat tissue balances the loss in lean body mass until
very old age, when loss of both fat and skeletal muscle occurs
Between ages 20 and 80, mean energy intake is reduced by
up to 1200 kcal/d in men and 800 kcal/d in women
Half of all patients with cancer lose some body weight;
one-third lose more than 5% of their original body weight, and up to 20% of all cancer deaths are caused directly by cachexia (through immobility and/or cardiac/respiratory failure).
The greatest incidence of weight loss
is seen among patients with
solid tumors
Hyperthyroidism in the elderly may have less prominent sympathomimetic, features and may present as
“apathetic hyperthyroidism” or T3 toxicosis
may be one of the earliest manifestations
of Alzheimer’s dementia.
Involuntary weight loss
The four major manifestations of IWL are
(1) anorexia (loss of appetite),
(2) sarcopenia (loss of muscle mass)
(3) cachexia (a syndrome that combines weight loss, loss of muscle and adipose tissue, anorexia, and weakness), and
4) dehydration
Assessment and Testing for Involuntar y Weight Loss
5% weight loss in 30 d= Complete blood count
10% weight loss in 180 d =Comprehensive electrolyte andmetabolic panel, including liver and
renal function tests
Body mass index <21 =Thyroid function tests
25% of food left uneaten after 7 d =ESR
Change in fit of clothing= CRP
Change in appetite, smell, or taste =Ferritin
The first priority in managing weight loss
to identify and treat the underlying causes systematically. Treatment of underlying metabolic, psychiatric, infectious, or other systemic disorders may
be sufficient to restore weight and functional status gradually.
Refers to an inherently subjective human experience of physical and mental weariness, sluggishness, and exhaustion.
In the context of clinical medicine, it is
most typically and practically defined as difficulty initiating or maintaining voluntary mental or physical activity
Fatigue
is a cardinal manifestation of some neuromuscular disorders such as myasthenia gravis and can be
distinguished from fatigue by finding clinically apparent diminution of the amount of force that a muscle generates upon repeated contraction
Fatigability of muscle power
On confrontational testing, they are able
to generate full power for only a brief period before suddenly giving way to the examiner. This type of weakness is often referred to as
breakaway weakness
is a reduction in the power that can be exerted by one or more muscles.
Weakness
It must be distinguished from increased fatigability (i.e., the inability to sustain the performance of an activity that should be normal for a person of the same age, sex, and size), limitation in function due to pain or articular stiffness, or impaired motor activity because severe proprioceptive sensory
loss prevents adequate feedback information about the direction and power of movements
also distinct from bradykinesia (in which increased time is required for full power to be exerted) and apraxia,
a disorder of planning and initiating a skilled or learned movement unrelated to a significant motor or sensory deficit
or the suffix “-plegia” indicates weakness so severe that a muscle cannot be contracted at all, whereas paresis refers to less severe weakness.
Paralysis
Weakness from involvement of
occurs particularly in the extensors and abductors of the upper limb and the flexors of the lower limb.
upper motor neurons
weakness depends on whether
involvement is at the level of the anterior horn cells, nerve root, limb plexus, or peripheral nerve—only muscles supplied by the affected structure are weak
Lower motor neuron
is generally most marked in
proximal muscles
Myopathic weakness
is the resistance of a muscle to passive stretch
Tone
is the increase in tone associated with
disease of upper motor neurons. It is velocity-dependent, has a sudden release after reaching a maximum (the “clasp-knife” phenomenon), and predominantly affects the antigravity muscles (i.e., upper-limb flexors and lower-limb extensors).
Spasticity
is hypertonia that is present throughout the range of motion (a “lead pipe” or “plastic” stiffness)
and affects flexors and extensors equally; it sometimes has a cogwheel quality that is enhanced by voluntary movement of the contralateral limb (reinforcement)
Rigidity
is increased tone that varies irregularly in a manner seemingly related to the degree of relaxation, is present throughout the range of motion, and affects flexors and extensors equally; it usually results from disease of the frontal lobes
Paratonia (or gegenhalten)
Weakness with decreased tone (flaccidity) or normal
tone occurs with disorders of motor units. A motor unit consists of
a single lower motor neuron and all the muscle fibers that it innervates
Generally is not affected by upper motor neuron lesions, although mild disuse atrophy eventually may occur.
Muscle bulk
By contrast, atrophy is often conspicuous when a lower motor neuron lesion is responsible for weakness and also may occur with advanced muscle disease
are usually increased with upper motor neuron lesions, but may be decreased or absent for a variable period immediately after onset of an acute lesion
Muscle stretch (tendon) reflexes
The muscle stretch reflexes are
depressed with
lower motor neuron lesions directly involving specific
reflex arcs. They generally are preserved in patients with myopathic weakness except in advanced stages, when they sometimes are attenuated.
In disorders of the neuromuscular junction, reflex responses may be affected by preceding voluntary activity of affected muscles; such activity may lead to enhancement of initially depressed reflexes in
Lambert-Eaton myasthenic syndrome
and, conversely, to depression of initially normal reflexes in myasthenia gravis
Lambert–Eaton myasthenic syndrome is caused by autoantibodies to the presynaptic membrane. Myasthenia gravis is caused by autoantibodies to the postsynaptic acetylcholine receptors
distal weakness is likely to be
neuropathic,
and symmetric proximal weakness
myopathic
distal muscle groups are affected more severely than proximal ones, and axial movements are spared unless the lesion is severe and bilateral.
Spasticity is typical but may not be present acutely. Rapid repetitive movements are slowed and coarse, but normal rhythmicity is maintained.
Upper motor neuron lesion
(EMG) shows that with weakness of the upper motor neuron type, motor units have a diminished maximal
discharge frequency.
Bilateral corticobulbar lesions produce a
pseudobulbar palsy: dysarthria, dysphagia, dysphonia, and emotional lability accompany bilateral facial weakness and a brisk jaw jerk
disorders brainstem motor nuclei and the anterior
horn of the spinal cord or from dysfunction of the axons of these neurons as they pass to skeletal muscle
Weakness is due to a
decrease in the number of muscle fibers that can be activated through a loss of α motor neurons or disruption of their connections to muscle. Loss of γ motor neurons does not cause weakness but decreases tension on the muscle spindles, which decreases muscle tone and attenuates
the stretch reflexes
Lower Motor Neuron lesion
When a motor unit becomes diseased, especially in anterior horn cell diseases, it may discharge spontaneously, producing
fasciculations
Atrophy
Fasciculations
Tone Decreased
Distal/segmental Distribution of weakness
Hypoactive/absent Muscle stretch reflexes
Absent Babinski
Lower Motor Neuron
Tone Spastic Atrophy Absent Fasciculations Absent Hyperactive Babinski sign Present
Upper Motor Neuronn
The bulbospinal system sometimes is referred to as the
extrapyramidal upper motor neuron system
The larger α motor neurons are more numerous and innervate the extrafusal muscle fibers of the motor unit.
Loss of α motor neurons or disruption of their axons produces
Lower motor neuron weakness
The smaller, less numerous γ motor neurons innervate the _
and contribute to normal tone and stretch reflexes
intrafusal muscle fibers of the muscle spindle
is produced by a decrease
in the number or contractile force of muscle fibers activated within motor units
Myopathic weakness
On EMG, the size of each motor
unit action potential is decreased, and motor units must be recruited more rapidly than normal to produce the desired power.
Some myopathies produce weakness through loss of contractile force of muscle fibers or through relatively selective involvement of type II (fast)
Weakness may occur without a recognizable
organic basis. It tends to be variable, inconsistent, and with a pattern
of distribution that cannot be explained on a neuroanatomic basis
Psychogenic Weakness
Causes of Episodic Generalized Weakness
- Electrolyte disturbances, e.g., hypokalemia, hyperkalemia, hypercalcemia,
hypernatremia, hyponatremia, hypophosphatemia, hypermagnesemia - Muscle disorders
a. Channelopathies (periodic paralyses)
b. Metabolic defects of muscle (impaired carbohydrate or fatty acid utilization;
abnormal mitochondrial function) - Neuromuscular junction disorders
a. Myasthenia gravis
b. Lambert-Eaton myasthenic syndrome - Central nervous system disorders
a. Transient ischemic attacks of the brainstem
b. Transient global cerebral ischemia
c. Multiple sclerosis - Lack of voluntary effort
a. Anxiety
b. Pain or discomfort
c. Somatization disorder
results from an upper motor neuron lesion
above the midcervical spinal cord; most such lesions are above the foramen magnum.
Hemiparesis
reflect either a cortical or a subcortical hemispheric lesion.
Homonymous visual field defects
produce “crossed paralyses,” consisting of ipsilateral cranial nerve signs and contralateral hemiparesis
brainstem lesions
The absence of cranial nerve signs or facial weakness suggests that a hemiparesis is due to a lesion in the high cervical spinal cord, especially if associated with the
Brown-Séquard syndrome
usually results from focal structural lesions, particularly rapidly expanding lesions, or an inflammatory
process
Acute or episodic hemiparesis
that evolves over days or weeks may relate to subdural hematoma, infectious or inflammatory disorders (e.g., cerebral abscess, fungal granuloma or meningitis, parasitic infection, multiple sclerosis, sarcoidosis), or primary and metastatic
neoplasms.
Subacute hemiparesis
that evolves over months usually is due to a neoplasm
or vascular malformation, a chronic subdural hematoma, or a degenerative disease
Chronic hemiparesis
If weakness is predominantly distal and of upper
motor neuron type and is not associated with sensory impairment or pain, focal cortical ischemia is likely
Acute monoparesis
often produces symmetric weakness
of the pelvic or shoulder girdle muscles
Myopathy
may present with symmetric proximal weakness often associated with ptosis, diplopia, or bulbar weakness and fluctuating in severity during the day
Diseases of the neuromuscular junction, such as myasthenia gravis
proximal weakness is usually
asymmetric, but it may be symmetric if familial
anterior horn cell disease
suggests Guillain-Barré syndrome
Bilateral facial palsy with areflexia
Body temperature is controlled by the
hypothalamus
Neurons in both the preoptic anterior hypothalamus and the posterior hypothalamus receive two kinds of signals: one from peripheral nerves that transmit
information from warmth/cold receptors in the skin and the other from the temperature of the blood bathing the region
In a neutral temperature environment, the human metabolic rate produces more heat than is necessary to maintain the core body temperature in the range of
36.5–37.5°C (97.7–99.5°F)
According to studies of healthy individuals 18–40 years of age, the mean oral temperature is
36.8° ± 0.4°C (98.2° ± 0.7°F), with
low levels at 6 a.m. and higher levels at 4–6 p.m.
The maximal normal oral temperature is
37.2°C (98.9°F) at 6 a.m. and 37.7°C (99.9°F) at 4 p.m
what would define a fever.
an a.m. temperature of >37.2°C (>98.9°F) or a
p.m. temperature of >37.7°C (>99.9°F)
The normal daily temperature variation is typically
0.5°C (0.9°F)
in some individuals recovering from a febrile illness, this daily variation can be as great as 1.0°C.
Rectal temperatures are generally
0.4°C (0.7°F) higher than oral readings
that unadjusted-mode tympanic membrane values are
0.8°C (1.6°F) lower than rectal temperatures
In women who menstruate, the a.m. temperature is generally lower in the 2 weeks before ovulation; it then rises by
∼0.6°C (1°F) with ovulation and remains at that level until menses occur
is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point
Fever
A fever of >41.5°C (>106.7°F) is called
hyperpyrexia
extraordinarily high fever can develop in patients with severe infections but most commonly occurs in patients with central nervous system (CNS) hemorrhages
The term hypothalamic fever is sometimes used to describe elevated temperature caused by abnormal hypothalamic function. However, most patients with hypothalamic damage have subnormal, not supranormal, body temperatures
is characterized by an uncontrolled increase in body temperature that exceeds the body’s ability to lose heat.
Hyperthermia
The setting of the hypothalamic thermoregulatory
center is unchanged
In contrast to fever in infections, hyperthermia does not involve pyrogenic molecules. Exogenous heat exposure and endogenous heat production are two mechanisms by which hyperthermia can result in dangerously high internal temperatures
Hyperthermia is often diagnosed on the basis of the
events immediately preceding the elevation of core temperature— e.g., heat exposure or treatment with drugs that interfere with thermoregulation
Antipyretics do not reduce the elevated temperature in hyperthermia, whereas in fever—and even in hyperpyrexia—adequate doses of either aspirin or acetaminophen usually result in some decrease in body temperature
is used to describe any substance
that causes fever.
pyrogen (Greek pyro, “fire”)
Exogenous pyrogens are derived from outside the patient; most are microbial products, microbial toxins, or whole microorganisms (including viruses).
The classic example of an exogenous pyrogen is the lipopolysaccharide (endotoxin) produced by all gram-negative bacteria.
Pyrogenic products of gram-positive organisms include the enterotoxins of Staphylococcus aureus and the groups A and B streptococcal toxins, also called superantigens
are small proteins (molecular mass, 10,000–20,000 Da) that regulate immune, inflammatory, and hematopoietic processes.
Cytokines
the elevated leukocytosis seen in several infections with an absolute neutrophilia is attributable to the cytokines
interleukin (IL) 1 and IL-6
Some cytokines also cause fever; formerly referred to as endogenous pyrogens, they are now called pyrogenic cytokines
The pyrogenic cytokines include
IL-1, IL-6, tumor necrosis factor (TNF), and ciliary neurotropic factor, a member of the IL-6 family
Interferons (IFNs), particularly , also are pyrogenic cytokines
IFN-α
fever is a prominent side effect of IFN-α
During fever, levels of prostaglandin are elevated in hypothalamic tissue and the third cerebral ventricle
E2 (PGE2
cells are the primary cell types that produce pyrogenic cytokines. Pyrogenic cytokines such as IL-1, IL-6, and TNF are released from these cells and enter the systemic circulation
Myeloid and endothelial
PGE2 in the periphery accounts for
the nonspecific myalgias and arthralgias that often accompany fever. It is thought that some systemic PGE2 escapes destruction by the lung and gains access to the hypothalamus via the internal carotid. However, it is the elevation of PGE2 in the brain that starts the process of raising the hypothalamic set point for core temperature
Cytokines produced in the brain may account for the hyperpyrexia of CNS hemorrhage, trauma, or infection
There are four receptors for PGE2, and each signals the cell in different ways. Of the four receptors,
the third (EP-3) is essential for fever
PGE2 is not a neurotransmitter
the release of PGE2 from the brain side of the hypothalamic endothelium triggers the PGE2 receptor
on glial cells, and this stimulation results in the rapid release of
cyclic adenosine 5′-monophosphate (cAMP), which is a neurotransmitter
The elevation of _ is thought to account for changes
in the hypothalamic set point either directly or indirectly (by inducing the release of neurotransmitters)
cAMP
The workup should include a complete blood count; a differential count should be performed manually or with an instrument sensitive to the identification of juvenile or band forms, toxic granulations, and Döhle bodies, which are suggestive
bacterial infection
in patients with low-grade fevers or possible disease, the most valuable measurements are
the C-reactive protein level and the erythrocyte sedimentation rate
Measurement of circulating IL-6 is useful because
IL-6 induces
C-reactive protein
Even when the results of tests for latent Mycobacterium
tuberculosis infection are negative, active tuberculosis can develop in patients receiving
anti-TNF therapy
Temperature-pulse dissociation (relative bradycardia) occurs in
typhoid fever, brucellosis, leptospirosis, some drug-induced fevers, and factitious fever.
fever may not be present despite infection in the ff conditions
in newborns, elderly patients, patients with chronic liver or kidney failure, and patients taking glucocorticoids,
relapsing fever is related
to Borrelia infection, with days of fever followed by a several-day afebrile period and then a relapse into additional days of fever
fever lasting 3–10 days is followed by afebrile periods of 3–10 days; this pattern can be classic for Hodgkin’s disease and other lymphomas.
Pel-Ebstein pattern
fevers occur every 21 days and accompany the neutropenia
cyclic neutropenia
The reduction of fever by lowering of the elevated hypothalamic set point is a direct function of reduction of the PGE2 level in the thermoregulatory center. The synthesis of PGE2 depends on the constitutively expressed enzyme
cyclooxygenase.
this release is the rate-limiting step in the synthesis of PGE2.
The substrate for cyclooxygenase is arachidonic acid released from the cell membrane
Therefore, inhibitors of cyclooxygenase are potent antipyretics
is a poor cyclooxygenase inhibitor in peripheral tissue and lacks noteworthy anti-inflammatory activity; in the brain, however, acetaminophen is oxidized by the p450 cytochrome system, and the oxidized form inhibits cyclooxygenase activity. Moreover, in the brain, the inhibition of another enzyme, COX-3, by acetaminophen may account for the antipyretic effect of this agent.
Acetaminophen
However, COX-3 is not found outside the CNS.
PGE2 appears to play no role in
normal thermoregulation
glucocorticoids act at two levels
First, similar to the cyclooxygenase inhibitors, glucocorticoids reduce PGE2 synthesis by inhibiting the activity of phospholipase A2, which is needed to release arachidonic acid from the cell membrane
Second, glucocorticoids block the transcription of
the mRNA for the pyrogenic cytokines
ibuprofen and COX-2 inhibitors reduce
IL-1- induced IL-6 production and may contribute to the antipyretic activity of NSAIDs
In children, acetaminophen or oral ibuprofen must be used because aspirin increases the risk of
Reye’s syndrome
Fever increases the demand for oxygen (i.e., for every increase of 1°C over 37°C, there is a
13% increase in oxygen consumption
are flat lesions defined by an area of changed
color (i.e., a blanchable erythema).
Macules
are raised, solid lesions <5 mm in diameter; plaques are lesions >5 mm in diameter with a flat, plateau-like surface;
Papules
are lesions >5 mm in diameter with a more rounded configuration
Nodules
are papules or plaques that are pale pink and may appear annular (ringlike) as they enlarge;
Wheals (urticaria, hives)
classic (nonvasculitic) wheals are transient, lasting only 24 h in any defined area.
are circumscribed, elevated lesions containing fluid
Vesicles (<5 mm) and bullae (>5 mm)
is a flat lesion that is due to bleeding into the skin
<3 mm in diameter, the purpuric lesions are
termed petechiae; if >3 mm, they are termed ecchymoses.
an illness of >3 weeks’ duration with fever of ≥38.3°C (101°F) on two occasions and an uncertain diagnosis despite 1 week of inpatient evaluation
FUO
- Fever >38.3°C (101°F) on at least two occasions
- Illness duration of ≥3 weeks
- No known immunocompromised state
- Diagnosis that remains uncertain after a thorough history-taking, physical examination, and the following obligatory investigations:
determination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level; platelet count; leukocyte count and differential; measurement of levels of hemoglobin, electrolytes, creatinine, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, ferritin, antinuclear antibodies, and rheumatoid factor;protein electrophoresis; urinalysis; blood cultures (n = 3); urine culture; chest x-ray; abdominal ultrasonography; and tuberculin skin test (TST).
In general, what accounts for about 20–25% of cases of FUO in Western countries
infection
next in frequency are neoplasms and noninfectious inflammatory diseases (NIIDs), the latter including “collagen or rheumatic diseases,” vasculitis syndromes, and granulomatous disorders
In geographic areas outside the West, infections are a much more common cause of FUO (43% vs 22%), while the proportions of cases due to NIIDs and neoplasms are similar. Up to 50% of cases caused by infections in
patients with FUO outside Western nations are due to tuberculosis
(defined as repeated episodes of fever interspersed with fever-free intervals of at least 2 weeks and apparent remission of the underlying disease), the chance of attaining an etiologic diagnosis is <50%.
recurrent fever
is often accompanied by eosinophilia and also by lymphadenopathy, which can be extensive
Drug-induced fever, including DRESS (drug reaction with eosinophilia and systemic symptoms
More common causes of drug induced
fever are
allopurinol, carbamazepine, lamotrigine, phenytoin,
sulfasalazine, furosemide, antimicrobial drugs (especially sulfonamides, minocycline, vancomycin, β-lactam antibiotics, and isoniazid), some cardiovascular drugs
is characterized by an elevated body temperature that is associated with moderate to strenuous exercise lasting from half an hour up to several hours without an increase in CRP level or ESR; typically these patients sweat during the temperature elevation
Exercise-induced hyperthermia
(fever artificially induced by the patient—for example, by IV injection of contaminated water) should be considered in all patients but is more common among young women in health care professions
Factitious fever
the patient is normothermic but manipulates the thermometer
fraudulent fever
Another clue to fraudulent fever is a dissociation between pulse rate and temperature.
Tuberculosis is the most common infectious
disease associated with FUO in elderly patients, occurring much more often than in younger patients.
Tuberculosis
the CSF typically has elevated
protein and lowered glucose concentrations, with a mononuclear pleocytosis. C
CNS tuberculosis
SF protein levels range from 100 to 500 mg/dL in most
patients, the CSF glucose concentration is <45 mg/dL in 80% of cases, and the usual CSF cell count is between 100 and 500 cells/μL.
should be avoided in FUO except when a patient’s condition is rapidly deteriorating after the aforementioned diagnostic tests have failed to provide a definite diagnosis
Empirical therapeutic trials with antibiotics, glucocorticoids, or antituberculous agents
is highly effective in preventing attacks of familial
Mediterranean fever but is not always effective once an attack is well under way.
Colchicine
a recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra), blocks the activity of both IL-1α and IL-1β.
Anakinra
are those in which headache
and its associated features are the disorder in itself,
Primary headaches
whereas secondary headaches are those caused by exogenous disorders (HeadacheClassification Committee of the International Headache Society, 2013)
Most Common Primary Headache
Tension-type 69%
Migraine 16%
Idiopathic stabbing 2%
Most Common Secondary Headache
Systemic infection 63%
Head injury 4%
Most common pain-producing structures in head
the scalp, middle meningeal artery, dural sinuses, falx cerebri, and proximal segments of the large pial arteries.
NOT pain-producing structures in head
The ventricular ependyma, choroid plexus, pial veins, and much of the brain parenchyma
Cranial autonomic symptoms
lacrimation, conjunctival injection, nasal congestion, rhinorrhea, periorbital swelling, aural fullness,
and ptosis, are prominent in the trigeminal autonomic cephalalgia
including cluster headache and paroxysmal hemicrania, and may also be seen in migraine, even in children.
Headache Symptoms That Suggest a Serious Underlying Disorder
Sudden-onset headache First severe headache “Worst” headache ever Vomiting that precedes headache Subacute worsening over days or weeks Pain induced by bending, lifting, cough Pain that disturbs sleep or presents immediately upon awakening Known systemic illness Onset after age 55 Fever or unexplained systemic signs Abnormal neurologic examination Pain associated with local tenderness, e.g., region of temporal artery
Acute, severe headache with stiff neck and fever suggests
Often there is striking accentuation of pain with eye movement
Meningitis.
LP is mandatory
Meningitis can be easily mistaken for migraine in that the cardinal symptoms of pounding headache, photophobia, nausea, and vomiting are frequently present, perhaps reflecting the underlying biology of some of the patients
Acute, severe headache with stiff neck but without fever suggests
Subarachnoid hemorrhage
A ruptured aneurysm, arteriovenous malformation,
or intraparenchymal hemorrhage may also present with
headache alone. Rarely, if the hemorrhage is small or below the foramen magnum, the head CT scan can be normal.
Therefore, LP may be required to definitively diagnose subarachnoid hemorrhage
Approximately 30% of patients with brain tumors consider headache to be their chief complaint.
The head pain is usually nondescript—an
intermittent deep, dull aching of moderate intensity, which may worsen with exertion or change in position and may be associated with nausea and vomiting.
Vomiting that precedes the appearance of headache by weeks is highly characteristic of
posterior fossa brain tumors.
A history of amenorrhea or galactorrhea should lead one to question
whether a prolactin-secreting pituitary adenoma (or the polycystic ovary syndrome) is the source of headache
is an inflammatory disorder of arteries that frequently involves the extracranial carotid circulation. It is a common disorder of the elderly
Temporal (giant cell) arteritis
The average age of onset is 70 years, and women account for 65% of cases
About half of patients with untreated temporal arteritis develop blindness due to involvement of the ophthalmic artery and its branches; indeed, the ischemic optic neuropathy induced by giant cell arteritis is the major cause of rapidly developing bilateral blindness in patients >60 years
glucocorticoids is effective
Typical presenting symptoms include headache, polymyalgia rheumatica, jaw claudication, fever, and weight loss. Headache is the dominant symptom and often appears in association with malaise and muscle aches. Head pain may be unilateral or bilateral
and is located temporally in 50% of patients but may involve any and all aspects of the cranium.
Pain usually appears gradually over a few hours before peak intensity is reached; occasionally, it is explosive
in onset. The quality of pain is only seldom throbbing; it is almost invariably described as dull and boring, with superimposed episodic stabbing pains similar to the sharp pains that appear in migraine.
Most patients can recognize that the origin of their head pain is superficial, external to the skull, rather than originating deep within the cranium (the pain site for migraineurs). Scalp tenderness is present, often to a marked degree; brushing the hair or resting the head on a pillow may be impossible because of pain. Headache is usually worse at night and often aggravated by exposure to cold
reddened, tender nodules or red streaking of the skin overlying the temporal arteries, and tenderness of the temporal or, less commonly, the occipital arteries
The erythrocyte sedimentation rate (ESR) is often, although not always, elevated
Diagnosis and Tx of Temporal Arteritis
A temporal artery biopsy followed by immediate treatment with prednisone 80 mg daily for the first 4–6 weeks should be initiated when clinical suspicion is high.
may present with a prostrating headache associated with nausea and vomiting. The headache often starts with severe eye pain
On physical examination, the eye is often red with a fixed, moderately
dilated pupil.
Glaucoma
Classiification of Chronic Daily Headache
> 4 h Daily
Chronic migraine Headace
<4 h Daily
Chronic cluster headache
when a patient experiences headache on 15 days or more per month.
chronic daily headache (CDH)
are also useful in migraine
Tricyclics are started in low doses (10–25 mg) daily and may be given 12 h before the expected time of awakening in order to avoid excess morning sleepiness. Anticonvulsants, such as topiramate,
valproate, flunarizine (not available in the United States), and candesartan
(SUNA), (SUNCT)
short-lasting unilateral neuralgiform
headache attacks with cranial autonomic symptoms
short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing
Overuse of analgesic medication for headache can aggravate headache frequency, markedly impair the effect of preventive medicines, and induce a state of refractory daily or near-daily headache called
medication-overuse headache
One approach is to reduce the medication dose
by 10% every 1–2 weeks. Immediate cessation of analgesic use is possible for some patients, provided there is no contraindication
small dose of a nonsteroidal anti-inflammatory drug (NSAID) such as naproxen, 500 mg bid
is used for opioid withdrawal symptoms
clonidine
Tx for substance withdrawal causing headache
Three to 5 days into the admission, as the effect of the withdrawn substance wears off, a course of IV dihydroergotamine (DHE) can be used. DHE, administered every 8 h for 5 consecutive days, can
induce a significant remission that allows a preventive treatment to be established
presents with headache on most if not all days, and the patient can clearly, and often vividly, recall the moment of onset. The headache usually begins abruptly, but onset may be more gradual; evolution over 3 days has been proposed as the upper limit for this syndrome.
NDPH New Daily Persistent Headache
head pain is positional: it begins when the patient sits or stands upright and resolves upon reclining.
The pain, which is occipitofrontal, is usually a dull ache but may be throbbing.
Patients typically present with a history of headache from one day to the next that is generally not present
on waking but worsens during the day.
Recumbency usually improves the headache within minutes, and it can take only minutes to an hour for the pain to return when the patient resumes an upright position
Low CSF Volume Headache
The most common cause of headache due to persistent low CSF volume is
CSF leak following LP
Post-LP headache usually begins within
48 h but may be delayed for up to 12 days
Beverages with caffeine may provide temporary
relief. Besides LP, index events may include epidural injection or a vigorous Valsalva maneuver, such as from lifting, straining, coughing, clearing the eustachian tubes in an airplane, or multiple orgasms.
Symptoms appear to result from low volume rather than low pressure: although low CSF pressures, typically 0–50 mmH2O, are usually identified, a pressure as high as 140 mmH2O has been noted with a documented leak
Postural orthostatic tachycardia syndrome (POTS) can present with orthostatic headache similar to low CSF volume headache and is a diagnosis that needs consideration in this setting
Initial treatment for low CSF volume headache is
bed rest.
For patients with persistent pain, IV caffeine (500 mg in 500 mL of saline administered over 2 h) can be very effective
An electrocardiogram (ECG) to screen for arrhythmia should be performed before administration
It is reasonable to administer at least two infusions of caffeine before embarking on additional tests to identify the source of the CSF leak
If unsuccessful, an abdominal binder may be helpful. If a leak can be identified, an autologous blood patch is usually curative. A blood patch is also effective for post-LP headache; in this setting, the location is empirically determined to be the site of the LP.
In patients with intractable pain, oral theophylline is a useful alternative; however, its effect is less rapid than caffeine
increased ICP
Initial treatment is with acetazolamide (250–500 mg bid); the headache may improve within weeks. If ineffective, topiramate is the next treatment of choice
as a “subjective experience
of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.
dyspnea
in the carotid bodies and medulla
are activated by hypoxemia, acute hypercapnia, and acidemia. Stimulation of these receptors and of others that lead to an increase in ventilation produce a sensation of “air hunger
Chemoreceptors
chest radiograph in cardiogenic pulmonary edema typically
shows
an enlarged cardiac silhouette, vascular redistribution, interstitial thickening, and perihilar alveolar infiltrates; pleural effusions are common.
In noncardiogenic pulmonary edema, heart size is normal, alveolar infiltrates are distributed more uniformly throughout the lungs, and pleural effusions are uncommon
The American Thoracic Society defines__ as a “subjective experience of breathing discomfort that consists of qualitatively distinct
sensations that vary in intensity
dyspnea
Chemoreceptors in the__
are activated by hypoxemia, acute hypercapnia, and acidemia. Stimulation of these receptors and of others that lead to an increase in ventilation produce a sensation of “air hunger.”
carotid bodies and medulla
__ in the lungs, when stimulated by bronchospasm, lead to a sensation of chest tightness.
Mechanoreceptors
__which are sensitive to interstitial edema,
and pulmonary vascular receptors, which are activated by acute changes in pulmonary artery pressure, appear to contribute to air hunger.
J-receptors
should be considered when the patient complains of platypnea—i.e., dyspnea in the upright position with relief in the supine position
Left atrial myxoma or hepatopulmonary syndrome
Clubbing of
the digits may be an indication
interstitial pulmonary fibrosis
___is useful in patients with intermittent symptoms suggestive of asthma but normal physical examination
and lung function
Bronchoprovocation testing
Supplemental O2 should be administered if the resting O2 saturation is
≤89% or if the patient’s saturation drops to these levels
with activity.
Early signs of pulmonary edema
include exertional dyspnea and
orthopnea.
Chest radiographs of pulmonary edema
peribronchial thickening,
prominent vascular markings in the upper lung zones, and Kerley B lines.
As the pulmonary edema worsens, alveoli fill with fluid
the chest radiograph shows patchy alveolar filling, typically in a perihilar distribution, which then progresses to diffuse alveolar infiltrates. Increasing airway edema is associated with rhonchi and wheezes
in cardiogenic pulmonary edema typically shows
an enlarged cardiac silhouette, vascular redistribution, interstitial thickening, and perihilar alveolar infiltrates; pleural effusions are common
hypoxemia of
cardiogenic pulmonary edema is due largely to V /Q to mismatch and responds to the administration of supplemental oxygen
The chest radiograph In noncardiogenic pulmonary edema
heart size is normal, alveolar infiltrates are distributed more uniformly throughout the lungs, and pleural effusions are uncommon
hypoxemia in noncardiogenic pulmonary edema is due primarily to intrapulmonary shunting and typically persists despite high concentrations of inhaled oxygen
Spontaneous cough is triggered by stimulation of sensory nerve endings that are thought to be
primarily rapidly adapting receptors and C fibers
Afferent nerve endings richly innervate the pharynx, larynx, and airways to the level of the terminal bronchioles and extend into the lung parenchyma. They may also be located in the external auditory meatus
AKA
(the auricular branch of the vagus nerve, or the Arnold nerve) and in the esophagus
in cough
Sensory signals travel via the vagus and superior laryngeal nerves to a region of the brainstem in the nucleus tractus solitarius vaguely identified as the
“cough center.”
Acute cough is most commonly due to a respiratory tract infection, aspiration, or inhalation of noxious chemicals or smoke.
duration?
(<3 weeks)
Subacute cough is a common residuum of
tracheobronchitis, as in pertussis or “postviral tussive syndrome
duration?
(3–8 weeks in duration)
Chronic cough
duration?
(>8 weeks
ACE inhibitor–induced cough occurs in__% of
patients taking these agents and is not dose dependent. ACE metabolizes
bradykinin and other tachykinins, such as substance P
5–30%
The mechanism of ACE inhibitor–associated cough may involve sensitization of sensory nerve endings due to accumulation of bradykinin.
Cough due to asthma in the absence
of wheezing, shortness of breath, and chest tightness is referred to as
“cough-variant asthma
Cough-variant asthma typically responds well to inhaled glucocorticoids and intermittent use of inhaled β-agonist bronchodilators
causes chronic cough with a normal chest radiograph.
This condition is characterized by sputum eosinophilia in excess of 3% without airflow obstruction or bronchial
hyperresponsiveness and is successfully treated with inhaled glucocorticoids
Chronic eosinophilic bronchitis
also called cough hypersensitivity syndrome,
is distressingly common. It is often experienced as a tickle or sensitivity in the throat, occurs more often in women, and is typically “dry” or at most productive of scant amounts of mucoid sputum
Chronic idiopathic cough
Most effective are narcotic cough suppressants, such as codeine or hydrocodone, which are thought to act in the “cough center” in the brainstem
Case series have reported benefit
from off-label use of gabapentin or amitriptyline for chronic idiopathic
cough.
is an over-the-counter, centrally acting
cough suppressant with fewer side effects and less efficacy than the narcotic cough suppressants
Dextromethorphan
Dextromethorphan is thought to have
a different site of action than narcotic cough suppressants and can be
used in combination with them if necessary
the expectoration of blood from the respiratory tract, can arise at any location from the alveoli to the glottis.
Hemoptysis
It is important to distinguish hemoptysis from epistaxis (bleeding from the nasopharynx) and hematemesis (bleeding from the upper gastrointestinal tract)
Worldwide, the most common cause of hemoptysis is infection with Mycobacterium tuberculosis, presumably because of the high prevalence of tuberculosis and its predilection for cavity formation.
Diffuse bleeding in the alveolar space, often referred to as may present as hemoptysis.
diffuse alveolar hemorrhage (DAH)
Causes of DAH can be inflammatory or noninflammatory. Inflammatory DAH is due to smallvessel vasculitis/capillaritis from a variety of diseases, including granulomatosis with polyangiitis and microscopic polyangiitis
Antibodies to the alveolar basement membrane, as are seen in Goodpasture’s disease, can also result in alveolar hemorrhage
DAH should be suspected in patients with sudden onset dyspnea and hypoxemia in the first 100 days after bone marrow transplantation
organisms such as___ can also result in hemoptysis
Streptococcus pneumoniae, Haemophilus influenzae,
or Moraxella catarrhalis
(a permanent dilation of the airways with loss of
mucosal integrity)
bronchiectasis
One common presentation of
patients with advanced cystic fibrosis—the prototypical bronchiectatic lung disease—is hemoptysis, which can be life-threatening.
(the dilation of a pulmonary artery in a cavity formed by previous tuberculous infection) remains
a source of massive, life-threatening hemoptysis in the developing world.
Rasmussen’s aneurysm
has been reported secondary to ingestion of crayfish or small crabs
pulmonary paragonimiasis
Malignancies that commonly
metastasize to the lungs include
renal cell, breast, colon, testicular, and thyroid cancers as well as melanoma. While hemoptysis is not a common manifestation of pulmonary metastases, the combination of multiple pulmonary nodules and hemoptysis should raise suspicion of this etiology
Patients with a__ can
present with an upper-lobe opacity on chest radiography together with hemoptysis. This finding is thought to be due to focal increases in pulmonary capillary pressure due to the regurgitant jet.
Pulmonary
arteriovenous malformations are prone to bleeding
focal jet of mitral regurgitation
Monthly hemoptysis in a woman suggests
catamenial hemoptysis from pulmonary endometriosis
Large-volume hemoptysis, referred to as massive
hemoptysis, is variably defined as hemoptysis of
> 200–600 mL in 24 h.
About one-third of total-body water is confined to the extracellular space. Approximately __% of the latter is interstitial fluid, and the remainder is the plasma
75
The forces that regulate the disposition of fluid between these two components of the extracellular compartment frequently are referred to as the Starling forces
is defined as a clinically apparent increase in the interstitial fluid volume, which develops when Starling forces are altered so that there is increased flow of fluid from the vascular system into the interstitium.
Edema
___characteristic of states in which the effective arterial blood volume is reduced is translated by the renal juxtaglomerular cells (specialized myoepithelial cells surrounding the afferent arteriole) into a signal for increased renin release
The diminished renal blood flow
is an enzyme with a molecular mass of about 40,000 Da that acts on its substrate, angiotensinogen, an α2-globulin synthesized by the liver, to release angiotensin I, a decapeptide, which in turn is converted to angiotensin II (AII), an octapeptide.
Renin
has generalized vasoconstrictor
properties, particularly on the renal efferent arterioles.
This action reduces the hydrostatic pressure in the peritubular capillaries, whereas the increased filtration fraction raises the colloid osmotic pressure in
these vessels, thereby enhancing salt and water reabsorption in the proximal tubule as well as in the ascending limb of the loop of Henle.
Angiotensin 2
operates as both a hormonal and paracrine system. Its activation causes sodium and water retention and thereby contributes to edema formation.
Blockade of the conversion of angiotensin I to AII and blockade of the AII receptor enhance sodium and water excretion and reduce many forms
of edema.
The renin-angiotensin-aldosterone system (RAAS)
Angiotensin 2 enters the systemic circulation stimulates the production of ___ by the zona glomerulosa of the adrenal cortex.
aldosterone
Aldosterone in turn enhances sodium reabsorption (and potassium excretion) by the collecting tubule, further favoring edema formation
In patients with___, not only is aldosterone secretion elevated
but the biologic half-life of the hormone is prolonged secondary to the depression of hepatic blood flow, which reduces its hepatic catabolism and increases further the plasma level of the hormone
heart failure
Blockade of the action of aldosterone by spironolactone or eplerenone
(aldosterone antagonists) or by
amiloride (a blocker of epithelial sodium channels
The secretion of __
occurs in response to increased intracellular osmolar concentration, and, by stimulating V2 receptors,
arginine vasopressin (AVP)
AVP increases the reabsorption of free water in the distal tubules and collecting ducts of the kidneys,
thereby increasing total-body water
Circulating AVP is elevated in many patients with heart failure secondary to a nonosmotic stimulus associated with decreased effective arterial volume and reduced compliance of the left atrium. Such patients fail to show the normal reduction of AVP with a reduction of osmolality, contributing to edema formation and hyponatremia
This potent peptide vasoconstrictor is released by endothelial cells. Its concentration in the plasma is elevated in patients with severe heart failure and contributes to renal vasoconstriction, sodium retention,
and edema
ENDOTHELIN-1
Atrial distention causes release into the circulation of__, a polypeptide; a high-molecular-weight precursor of
atrial natriuretic peptide (ANP)
ANP is stored in secretory granules within atrial myocytes
___ is stored primarily in ventricular myocytes and is released when ventricular diastolic pressure rises
brain natriuretic peptide (pre-prohormone
BNP)
Released ANP and BNP (which is derived from its precursor) bind to the natriuretic receptor-A, which
causes:
(1) excretion of sodium and water by augmenting glomerular filtration rate, inhibiting sodium reabsorption in the proximal tubule, and inhibiting release of renin and aldosterone; and
(2) dilation of arterioles and venules by antagonizing the vasoconstrictor actions of AII, AVP, and sympathetic stimulation.
Thus, elevated levels of natriuretic peptides have the capacity to oppose sodium retention in hypervolemic and edematous states
Although circulating levels of ANP and BNP are elevated in heart failure and in cirrhosis with ascites, the natriuretic peptides are not sufficiently potent to prevent edema
formation.
Systems ___are responsible for a majority of patients
with generalized edema.
Cardiac, renal, hepatic, or nutritional disorders
acts as a stimulus for renal sodium retention
and causes a reduction of effective arterial blood volume.
Intrahepatic hypertension
These alterations are frequently complicated by hypoalbuminemia secondary to reduced hepatic synthesis of albumin, as well as peripheral
arterial vasodilation.
Patients with edema due to acute renal failure commonly have arterial hypertension as well as pulmonary congestion on chest roentgenogram,
often without considerable cardiac enlargement, but they may not develop orthopnea.
Patients with chronic renal failure may also
develop edema due to primary renal retention of sodium and water.
This condition is characterized in part by hepatic venous outflow blockade, which in turn expands
the splanchnic blood volume and increases hepatic lymph formation.
Hepatic Cirrhosis
Intrahepatic hypertension acts as a stimulus for renal sodium retention and causes a reduction of effective arterial blood volume. These alterations are frequently complicated by hypoalbuminemia secondary to reduced hepatic synthesis of albumin, as well as peripheral arterial vasodilation.
These effects reduce the effective arterial blood volume further, leading to activation of the RAAS and renal sympathetic nerves and to release of AVP, endothelin, and other sodium and water-retaining mechanisms
The concentration of circulating aldosterone often is elevated by the failure of the liver to metabolize this hormone.
The excess production of prostaglandins in cirrhosis
attenuates renal sodium retention.
(PGE2 and PGI2)
DRugS ASSoCiATED wiTH EDEMA foRMATion
Nonsteroidal anti-inflammatory drugs
Antihypertensive agents
Direct arterial/arteriolar vasodilators Hydralazine Clonidine Methyldopa Guanethidine Minoxidil Calcium channel antagonists α-Adrenergic antagonists
Thiazolidinediones
Steroid hormones
Glucocorticoids
Anabolic steroids
Estrogens Progestins Cyclosporine Growth hormone Immunotherapies Interleukin 2 OKT3 monoclonal antibody
The ingestion of more food may increase the quantity of sodium ingested, which is then retained along with water.
So-called___
also may be linked to increased release of insulin, which directly increases tubular sodium reabsorption
refeeding
edema
These causes include hypothyroidism and hyperthyrodism
hypothyroidism (myxedema) and hyperthyroidism (pretibial myxedema secondary to Graves’ disease), the edema in which is typically non-pitting and due to deposition of hyaluronic acid and, in Graves’ disease, lymphocytic infiltration and inflammation;
Severe heart failure may cause ascites that may be distinguished from the ascites caused
by hepatic cirrhosis by the
jugular venous pressure, which is usually
elevated in heart failure and normal in cirrhosis
Edema resulting from hypoproteinemia, as occurs in the nephrotic syndrome, characteristically is generalized, but it is especially evident in the very soft tissues of the
eyelids and face and tends to be most pronounced in the morning owing to the recumbent posture assumed
during the night.
hypoalbuminemia
serum albumin <25 g/L
