Chapter 6: Common Neurological Complaints
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Dementia- chronic, progressive cognitive decline
Delirium- an acute confusional state
Patients with Hx of dementia have higher incidence of delirium.
Delirium may exist by itself, without evidence of dementia.
Causes of delirium: fever, infection, sepsis, cerebral event, organic brain sydrome, distended
bladder, constipation, actively dying, alcohol withdrawal delirium, hypoxemia, and metabolic
disorders.
Symptoms:
Hallmark—inattention (73%)
Sleep–wake cycle disturbance (73%)
Memory problems
Psychomotor retardation (37%)
Agitation (27%)
Perceptual disturbances and hallucinations (26%)
Language disturbance (25%)
Screening tools: MMSE, MOTYB screening tool, CAM
Treatment: antipsychotics (haloperidol, olanzapine) if sedation is required for acute agitation.
Causes of dementia:
→ Neurodegenerative diseases: Alzheimer’s disease, Dementia with Lewy bodies,
Parkinson’s disease dementia, Frontotemporal dementia, Huntington disease, Chronic
traumatic encephalopathy
→ Nonneurodegenerative causes: Alcohol-related dementia, Vascular dementia, Normal
pressure hydrocephalus, Chronic subdural hematoma, CNS infections (syphilis, HIV,
prion disease, etc.)
o Symptoms: aphasia, apraxia, agnosia, A failing sense of direction, Being
repetitive, Requiring help with activities of daily living, incontinence
o Screening tools: SLUMS, MoCA, AD8 informant interview, MC-FAQ, MMSE
o Treatment: Cholinesterase inhibitors, Antidepressants, Antipsychotics
Parkinson’s Disease: Parkinson’s disease is a chronic, progressive, degenerative disorder of the
basal ganglia in the CNS. Idiopathic, atypical, and secondary types.
♦ Atypical parkinsonian syndromes cause more widespread neurodegeneration.
o Examples in this category include progressive supranuclear palsy, multiple
systems atrophy, DLB, and corticobasal degeneration.
o Common causes of secondary parkinsonism include exposure to dopamineblocking medications, such as antipsychotics or certain antiemetics.
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o One of the more common causes of parkinsonism is Wilson’s disease, which
causes an abnormal accumulation of copper.
Symptoms: rest tremor, rigidity, bradykinesia, and postural instability.
PD is the second most common neurodegenerative disorder in older adults after AD.
PD causes abnormal accumulation of Lewy bodies and degeneration of the pigmented
dopaminergic cells of the substantia nigra (located in the brainstem).
PD depletes the dopaminergic neurons of the substantia nigra. Dopamine has both
excitatory effects in the direct pathway and inhibitory effects in the indirect pathway.
The major manifestations of Tremor at rest, Rigidity, Akinesia (or bradykinesia), and
Postural disturbances form the mnemonic “TRAP.”
Presenting symptoms: cognitive decline, anxiety, depression, apathy, orthostatic hypotension,
overactive bladder, fatigue, drooling, constipation, loss of sense of smell, and REM sleep
behavior disorder (an abnormal acting out of dreams during REM sleep). Constipation, REM
sleep behavior disorder, and anosmia frequently predate symptoms of PD by several years.
Progressive bradykinesia.
stooped posture. The head is bowed, the trunk is bent forward, and the back posture is
kyphotic. Extreme truncal flexion is called camptocormia; “striatal hand” deformity including
ulnar deviation, fingers flexed at the metacarpophalangeal joints, and extension of
interphalangeal joints. Freezing, also called “motor block,”, “masklike” face (hypomimia); soft
speech (hypophonia); and small, slow handwriting (micrographia).
Headaches:
♦ Three types of primary headaches- tension, cluster, and migraine.
o Tension- bilateral pressure, band-like
o Cluster- Periorbital nighttime unilateral, nonpulsatile pain, Photophobia, Tearing,
Nasal stuffiness
o
♦ Migraines have 2 subtypes- with and without aura.
o Migraine symptoms: Unilateral pulsating episodic pain, Nausea and vomiting,
Photophobia and phonophobia.
Migraine treatments:
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Abortive: triptans, NSAIDs, antiemetics,
Prophylactic: propranolol, nortriptyline, topiramate, CGRP inhibitors,
Botox
 In familial hemiplegic migraine, the cause is associated with mutations in calcium,
sodium, or potassium channel genes. In women, menstrual migraines are triggered by
hormonal fluctuations typically occurring around the time of menstruation.
 black people and nonwhite people of Hispanic or other nonspecified ethnic origin are at
least twice as likely as White or Asian people.
 Prevalence of migraine is highest in adults younger than age 40 and lowest in those older
than age 60.
Box 6.1 Common Triggers of Migraine Headaches
Diet- Alcohol, sodium nitrate, caffeine, chicken livers, yogurt, avocado, sour cream,
artificial sweeteners, Tyramine (bananas, ripe cheese, nuts, pods of broad beans [Italian
pole, lima, or butter beans]), Phenylethylamine (some cheeses, red wine, chocolate),
Monosodium glutamate.
Environmental- High-pitched noises, excessive sun, bright lights, weather changes,
strong odors, video display terminals.
Other triggers: Stress, fatigue, cigarette smoking, changes in sleep patterns,
dehydration.
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Migraine aura also tends to cause “positive” symptoms (e.g., extra sensations) such
as flashing lights or tingling, in contrast to a TIA, which tends to cause “negative”
symptoms (e.g., loss of sensation), such as numbness or visual field cut.
Drugs Commonly Prescribed 6.1: Migraine Headache: Adults
1) Triptans (serotonin receptor agonists): Contraindicated in ischemic heart disease or
other significant cardiovascular disease or cerebrovascular disease. There is a risk of
rebound headache if triptans are used more than twice a week.
2) Ergot derivatives: (Ergotamine/Caffeine) Cafergot; Contraindicated in peripheral
vascular disease, coronary heart disease, hypertension, and hepatic or renal disease.
3) Combination analgesics: Butalbital 50 mg/acetaminophen 325 mg/caffeine 40 mg
(Fioricet), Butalbital 50 mg/ASA 325 mg/caffeine 40 mg (Fiorinal)- Use of butalbitalcontaining medications is not recommended as first-line treatment for migraine
headaches; avoid if possible.
4) Beta Blockers: Contraindicated in asthma, sinus bradycardia, second or third
atrioventricular block.
5) Calcium Channel Blockers (Verapamil)- May take several months to be effective.
Contraindicated in pregnancy.
6) CGRP antagonists- (Erenumab (Aimovig), Fremanezumab (Ajovy), Galcanezumab
(Emgality), Eptinezumab (Vyepti))- Newer medications approved for migraine
prevention. Monoclonal antibodies that block calcitonin gene-related peptide (CGRP)
activity. Injectable medications given every 1 to 3 months.
7) Botulinum toxin injections- For chronic migraine. Injected into the muscles of the face
and neck every 3 months.
8) NSAIDs, Opiates, Anticonvulsants, Antidepressants
Cluster Headaches
➢ fall under the category of trigeminal autonomic cephalalgias, a group of primary
headache disorders associated with severe, unilateral head pain accompanied by
ipsilateral autonomic symptoms.
➢ pattern of occurrence: span of several weeks or months,
➢ one of the most painful types of headaches
➢ typically occur in middle-aged men
➢ A dysfunction of the hypothalamus may account for the periodicity and clocklike
regularity of cluster headaches.
➢ triggered by an abnormality in the ipsilateral circadian pacemaker, which is located in the
ventral hypothalamus. concurrent excitation of parasympathetic fibers.
Seizures
1) Focal onset seizures:
a. Focal onset seizures are typically caused by an underlying focal lesion or
abnormality in the brain that acts as an epileptogenic seizure focus.
b. Focal impaired awareness seizures, previously called complex partial seizures, are
the most common type of seizure in adults with epilepsy.
c. associated with repetitive behaviors called automatisms.
d. Focal onset seizures may progress to a generalized seizure, called a focal to
bilateral tonic-clonic seizure.
2) General onset seizures:
a)
b)
c)
d)
often associated with childhood onset generalized epilepsy syndromes.
consciousness is typically transiently impaired (except in myoclonus).
Motor manifestations are bilateral.
The EEG shows bilateral and widespread seizure activity in both hemispheres.
3) Tonic-clonic seizures, which used to be referred to as grand mal seizures, are the most
frequently encountered generalized seizures. sudden tonic stiffening of muscles. The patient
lies rigid; during this state, tonic contraction inhibits respiration, and cyanosis may occur.
4) An absence seizure is a nonmotor seizure- sudden interruption of ongoing activities, typically
with a blank stare.
5) Atonic seizures cause a sudden loss of muscle control. associated with generalized epilepsy
syndromes and cause “drop attacks” (sudden falls without warning). typically begin in
childhood.
6) Psychogenic nonepileptic seizures (PNES) are paroxysmal seizure-like events that arise
from psychological disturbances rather than abnormal electrical brain activity. PNES are often
comorbid with epilepsy and can be considered to be a type of conversion disorder.
psychotherapy and psychiatric medications are used to treat this condition.
♦ Todd’s paralysis- a transient hemiparesis following some seizures
Differential Diagnosis 7.1: Seizures
 Cerebrovascular disorders- TIA, ischemic stroke, ICH, vasculat malformations
 Diencephalic and brainstem disorders- Decorticate and decerebrate posturing,
diencephalic attacks, nonepileptic paroxysmal laughter, peduncular hallucinosis, KleineLevin syndrome.
 Movement disorders- Hemifacial spasm, tic, paroxysmal kinesigenic dyskinesia,
dystonia, paroxysmal ataxia, tremor, chorea.
 Nonepileptic myoclonus- Hypnic jerks; myoclonus and asterixis in toxic metabolic
encephalopathy.
 Psychiatric disorders- PNES, psychogenic fugue, intermittent explosive disorder
(episodic dyscontrol), schizophrenia
 Startle disorders- Startle reaction, startle disease (hyperekplexia), jumping Frenchman,
Malay latah, etc
 Syncope disorders- convulsive syncope; cardiac syncope (Stokes-Adams attack,
tachyarrhythmias, prolonged QT syndrome aortic stenosis, Shy-Drager syndrome,
autonomic neuropathy
 Toxic metabolic or infectious disorders- Alcoholic blackouts, hallucinogen ingestion
(Lysergic acid diethylamide [LSD], mescaline), strychnine and camphor poisoning,
tetanus, rabies, hypoglycemia, porphyria, pheochromocytoma, carcinoid syndrome,
mastocytosis
Drugs Commonly Prescribed 7.1: Seizure Disorders (Monotherapy Only)
♦ Benzodiazepines, Lamotrigine, Levetiracetam, Phenobarbital, Topiramate (Topamax),
Valproic acid (Depakote), Zonisamide (Zonegran)- Focal and generalized onset
seizures.
♦ Carbamazepine, Gabapentin, Lacosamide, Oxcarbazepine, Phenytoin/fosphenytoin
(Dilantin)- focal onset seizures
Alzheimer’s Disease (AD)
✓ AD is a progressive neurodegenerative condition and the most common form of dementia
(60% to 80%) in the older population.
✓ The prevalence of AD dementia is higher in people of color than in whites.
✓ The rare familial form of AD typically has an earlier onset. Inheritance is autosomal
dominant; if a parent has the familial form of AD, offspring have a 50% chance of
developing the disease.
✓ Cortical areas that are preferentially affected include the hippocampus, the amygdala, the
temporal cortex, the olfactory system, and intercortical connections.
Diagnostic tests:
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Structural magnetic resonance imaging (MRI) of the brain can rule out alternate
diagnoses, as well as evaluate for radiological biomarkers of AD such as generalized
cortical atrophy and focal hippocampal atrophy.
Functional brain imaging with 18-F fluorodeoxyglucose positron emission
tomography (FDG-PET) or single-photon emission computed tomography (SPECT)
can look for regions of hypometabolism (PET) and hypoperfusion (SPECT) seen in
AD.
Positron emission tomography (PET) imaging using amyloid tracers may be used to
detect amyloid deposits.
Cerebrospinal biomarkers including beta-amyloid and tau, (Amyloid precursor
protein [APP] on chromosome 21; Presenilin 1 [PSEN1] on chromosome 14;
andPresenilin 2 [PSEN2] on chromosome 1),
Multiple Sclerosis:
 Multiple sclerosis (MS) is a chronic and potentially disabling demyelinating disease
of the CNS that begins most commonly in young adulthood. Common symptoms
include visual changes (unilateral vision loss, double vision), weakness and
numbness, and loss of balance.
There are three classifications of MS that differ with patterns of progression:
1.
Relapsing–remitting MS is characterized by acute attacks, with recovery (either partial
or full between episodes).
2. Primary progressive MS has a steady disease progression from onset, with possibly some
plateaus and remissions.
3. Secondary progressive MS is a combination of the first two types, beginning as a
relapsing–remitting disease but then transitioning to a progressive course.
→ The disease affects two to three times more women than men.
→ The major histocompatibility complex (MHC) on chromosome 6 has been identified as
one genetic determinant for MS.
→ Areas of MS damage form sharply defined plaques, which are typically found around
venules. MS plaques tend to be large (greater than 6 mm in diameter) and oval shaped;
over time, the plaques become more widely distributed.
→ The most common presenting symptoms in MS include weakness of the legs, bladder and
bowel dysfunction, ataxic gait, paresthesias in the extremities, and optic neuritis.
Seventy-five percent to 95% of patients with MS experience MS-related fatigue.
→ A sensation of “electricity” down the back after passive or active neck flexion, called
Lhermitte’s sign, is indicative of a lesion in the posterior column in the cervical spinal
cord.
Diagnostic Tests:
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MRI is a sensitive, objective measure of plaques and is used to diagnose MS and measure
the outcomes of treatment.
Patients with evidence of demyelinating plaques consistent with MS on MRI but no
clinical symptoms are described as having radiologically isolated syndrome.
Differential Diagnosis:
Other CNS diseases may resemble MS clinically or radiologically, including
▫ cerebral small vessel disease;
▫ tumors such as lymphoma or glioma;
▫ infections such as Lyme, HIV, and other causes of encephalitis and/or myelitis;
▫ collagen vascular disease such as systemic lupus erythematosus,
▫ Behçet’s disease, and sarcoidosis; other leukoencephalopathies;
▫ other autoimmune demyelinating diseases of the CNS such as neuromyelitis optica
spectrum disorders and acute disseminated encephalomyelitis.
 Behcet's (beh-CHETS) disease, also called Behcet's syndrome, is a rare disorder that
causes blood vessel inflammation throughout your body. The disease can lead to
numerous signs and symptoms that can seem unrelated at first. They can include mouth
sores, eye inflammation, skin rashes and lesions, and genital sores.
Drugs Commonly Prescribed 10.1: Multiple Sclerosis
1. IV Methylprednisolone (Depo-Medrol) -Acute exacerbation
2. IV Interferon therapies- Relapsing–remitting multiple sclerosis (RRMS), active
secondary progressive (SPMS)
3. Monoclonal Antibody infusions- Ocrelizumab (Ocrevus), Natalizumab (Tysabri),
Alemtuzumab (Lemtrada): used for RRMS and active SPMS.
4. Oral meds: Cladribine (Mavenclad), Teriflunomide (Aubagio), Fumarates (dimethyl
fumarate, diroximel fumarate, monomethyl fumarate), Sphingosine 1P receptor
modulators (fingolimod, siponimod, ozanimod, ponesimod)- used for RRMS and active
SPMS.
5. Meds to reduce spasticity; Tizanidine (Zanaflex) ,Diazepam (Valium), Baclofen
(Lioseral)- infusion pump may be used to administer baclofen intrathecally.
6. Botox injections- may be beneficial for localized spasticity in a single muscle or limb.
♦ The tremors associated with MS are usually cerebellar outflow tremors. Medications such
as propranolol (Inderal), clonazepam (Klonopin), and primidone (Mysoline) may be
effective.
♦ Neuropathic pain may be treated with antiepileptics such as gabapentin and/or
antidepressants such as duloxetine and nortriptyline.
♦ complementary therapies for patients with MS: acupuncture, hypnotherapy and imagery,
massage, biofeedback, tai chi, therapeutic touch, Reiki, bioelectromagnetic therapy, and
chiropractic therapy.
Chapter 9: CVA/STROKE
Causes:
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Cerebral ischemia is caused by a reduction in blood flow to the brain.
o Thrombosis refers to local obstruction of an artery.
o Embolism refers to fragments of debris that travel downstream and occlude
smaller arteries and arterioles, producing areas of ischemia. Occlusive emboli can
be generated upstream some distance from the cerebral arteries.
o Decreased Brain Perfusion- involving the ACA, MCA, and/or PCA due to
shock or cardiac arrest.
o Subdural hematoma- Subdural bleeding is usually caused by blunt trauma that
knocks the brain against the skull.
o Intracerebral Hemorrhage- Also known as intraparenchymal hemorrhage
(IPH), intracerebral hemorrhage refers to bleeding within the brain parenchyma.
One of the most common causes of IPH is hypertension. Hypertensive IPHs most
often develop from ruptures of arteries to the basal ganglia and thalamus. Other
etiologies include trauma, amyloid angiopathy, underlying tumor, clotting
disorders, low platelet counts, anticoagulant drugs, vasoconstrictors (including
amphetamine or cocaine use), and eclampsia during pregnancy.
o Subarachnoid Hemorrhage- Subarachnoid hemorrhages (SAHs) are caused by
tears in the arteries running along the subarachnoid space at the surface of the
brain. Typically occur at branch points of the large arteries, especially in the circle
of Willis. A subarachnoid hemorrhage will spread quickly throughout the CSF
coating the brain and spinal cord. In SAH, a lumbar puncture (LP) produces CSF
mixed with red blood cells. In this case, the CSF often assumes a yellowish tinge
referred to as xanthochromia. Xanthochromia occurs as a result of the
breakdown of hemoglobin in the CSF by enzymes producing yellow-pigmented
bilirubin.
Diagnostic Tests
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noncontrast CT of the head
If the patient is a candidate for mechanical thrombectomy, then CT-angiography should
be performed as well
Some early infarct signs on head CT include hyperdensity in a segment of a blood vessel
(representing clot at that location), loss of the “insular ribbon,” loss of gray-white matter
differentiation, hypoattenuation of the deep nuclei, and cortical edema.
MRI is generally recommended for patients with stroke because it is more sensitive than
CT for identifying small ischemic lesions, particularly in the acute period. It also can help
identify the etiology of ischemic and hemorrhagic strokes.
Magnetic resonance angiography, CT angiogram, color duplex ultrasound, and
transcranial Doppler are acceptable noninvasive techniques to screen patients for vascular
abnormalities in the setting of stroke.
A cardiac echocardiogram should be obtained, preferably with a bubble study (which
helps evaluate for a PFO), in patients with ischemic stroke to assess for cardioembolic
source.
Management of ischemic strokes:
 Thrombolytic therapy with TPA
o Contraindications - recent head trauma or stroke in the last 3 months, previous
ICH, recent intracranial or intraspinal surgery, untreated HTN with > 185/110 mm
Hg, active internal bleeding, known brain tumor, evidence of intracranial bleed on
CT scan, INR > 1.7, PTT >40, platelet count < 100,000/mm3, infective
endocarditis, and use of anticoagulants (unless on warfarin with (INR) of 1.7 or
less).
o thrombolytic therapy carries a 6.4% risk of intracerebral hemorrhage
o Edema with “large territory infarcts”, causing herniation- hyperosmolar therapy
and decompressive surgery. The use of corticosteroids is not indicated in the
management of cerebral edema and increased intracranial pressure due to stroke.
Chapter 10: Infectious and Inflammatory Neurological Disorders
Meningitis:
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Meningitis is an inflammation of the meninges (pia, arachnoid, and dura)
Acute bacterial meningitis is a life-threatening infection. The most common organisms
are Strep pneumoniae, N. meningitidis, and H. influenzae type B.
When routine bacterial cultures are negative, meningitis is called aseptic meningitis.
TABLE 10.1 Types of Meningitis
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lumbar puncture (LP) in bacterial meningitis produces CSF with a high WBC count.
CSF in bacterial meningitis is typically cloudy with elevated WBCs, elevated pressure,
greater than 80% polymorphonuclear neutrophils, low glucose, and elevated protein.
Bacterial meningitis can cause hydrocephalus, altered level of consciousness, and
seizures.
elevation of WBCs (neutrophils) in bacterial meningitis or mild elevation in viral
meningitis. Electrolytes should be monitored. Hyponatremia may occur from a common
complication of meningitis, the syndrome of inappropriate antidiuretic hormone secretion
(SIADH).
Objective signs/symptoms:
▫ fever, tachycardia, and tachypnea.
▫ photophobia, pain with eye movement, Brudzinski’s sign, and Kernig’s sign
▫ opisthotonos (severe back spasm, causing arching).
▫ diplopia, deafness, facial weakness, and pupillary abnormalities.
Diagnostic Tests:
 a CT or magnetic resonance imaging (MRI) may reveal meningeal enhancement, basilar
exudate, hydrocephalus, and associated focal lesions.
 A CT of the head should be performed before LP in cases of an abnormal neurological
examination (alteration of consciousness, focal findings, papilledema) to assess risk for
herniation with LP.
 Gram stain and culture of CSF may assist in detecting causative organisms.
Bell’s Palsy- is an idiopathic cranial nerve VII palsy causing lower motor neuron facial
paralysis, typically occurring on one side of the face.
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most likely viral, typically from HSV infection.
A higher incidence is seen in individuals with DM, HTN, trauma, toxin exposure, Lyme
disease, HIV, pregnancy, and those with upper respiratory ailments.
Patient may present with loss of taste (dysgeusia) on their ipsilateral tongue,
postauricular pain, abnormal sensitivity to sound (hyperacusis), and a heavy feeling
in the face.
Objective findings: absence of forehead wrinkles on the affected side, wider
palpebral fissure of the eye with weakness of eye closure, decreased corneal reflex,
Bell’s phenomenon (the eyeball turns upward when the patient tries to close the
eyelid), flattening of the nasolabial fold, and loss of taste on the anterior two-thirds
of the tongue.
Differential Diagnosis: Tumors, infections (HIV, infectious mononucleosis, Lyme disease),
Guillain-Barré syndrome (GBS), trauma, stroke, sarcoidosis, and other inflammatory conditions
can cause unilateral facial weakness that may appear similar to Bell’s palsy. A Bell’s palsy–like
facial paralysis is the most common neurological problem caused by Lyme disease, although this
is often bilateral.
GUILLAIN-BARRÉ SYNDROME:
→ Guillain-Barré Syndrome (GBS) is an acute monophasic immune-mediated
polyradiculoneuropathy. It is usually an ascending paralysis most often beginning in the
legs and then progressing in an ascending fashion. Sensation can be involved, and
patients usually report tingling in the extremities. Back pain and autonomic dysfunction
are also common.
→ The Miller Fisher variant causes brainstem symptoms such as ataxia and eye-movement
abnormalities, in addition to loss of reflexes. GBS is often postinfectious, and there is a
strong association with gastric Campylobacter infection.
→ The treatment involves IV gamma globulin or plasmapheresis.
Myasthenia Gravis:
♦ Myasthenia gravis (MG) is a disorder of the neuromuscular junction. It is an autoimmune
disease in which an antibody targets the receptor for acetylcholine at the neuromuscular
junction.
♦ MG causes muscle fatigue and weakness that worsens with use. Eye movements and
speech are commonly affected. Weakness is usually worse later in the day, and the
symptoms will usually ameliorate with rest.
♦ Tensilon test, in which use of edrophonium chloride results in resolution of the weakness.
♦ The presence of autoantibodies against the acetylcholine receptor supports the diagnosis,
and electromyography can confirm the diagnosis.
♦ Immunosuppressant drugs, IV immunoglobulins, and plasmapheresis are also used to
reduce antibody levels.
♦ MG is associated with thymoma- in some patients, thymectomy can be curative.
Abdominal Pain
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Visceral pain is caused by distention or spasm of a hollow viscus and is usually
generalized and dull.
parietal pain, described as sharp and well localized, is caused by irritation of the
peritoneum.
Colicky- means that it comes and goes
Burning pain, caused by irritation of the gastric ucosa by gastric contents, is associated
with peptic ulcers and esophagitis.
•
Acute Viral Gastroenteritis
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Rotavirus- Very common cause of gastroenteritis in industrialized areas. Organism most
often implicated in deaths from diarrhea. Frequently involves small bowel. Incubation
period 24 to 36 hours. Duration is 4 to 6 days. Common in children younger than age 3.
Peak incidence at age 6 to 24 months. Uncommon in adults. Symptoms include lowgrade fever and copious watery diarrhea.
Norwalk virus- It can cause large epidemics when spread by contaminated water. It is
transmitted by the fecal–oral route. Incubation is 18 to 48 hours. Duration is 48 to 72
hours. Symptoms are mild and brief and include vomiting, frequent watery diarrhea,
diffuse myalgias, chills, and sometimes fever. No known antiviral therapy is available.
Fluid and electrolyte replacement is the treatment of choice.
Chapter 39: Infectious Gastrointestinal disorders
Gastroenteritis- Gastroenteritis is an inflammation of the stomach and intestine that
manifests as anorexia, nausea, vomiting, and diarrhea. Gastroenteritis can be acute or chronic
and can be caused by bacteria, viruses, parasites, injury to the bowel mucosa, inorganic poisons
(sodium nitrate), organic poisons (mushrooms or shellfish), and drugs.
♦ The most common mode of transmission for acute infectious gastroenteritis is the fecal–
oral route from contaminated food or water. Person-to-person transfer of the
disease is more common within the hospital setting, long-term care facilities, and daycare centers where there are larger groups of people capable of transmitting the disease.
 the most common cause of acute infectious diarrhea are viruses (norovirus, rotavirus,
adenovirus, and others).
 Other than norovirus, important causes of watery diarrhea include Clostridium perfringens,
and enterotoxigenic Escherichia coli (ETEC).
 Among these severe bacterial causes, nontyphoidal Salmonella and Campylobacter spp are
the most common causes in the United States.

Diverticulitis-
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Diverticular disease is the term used to describe the inflammatory changes that occur
within the diverticular mucosa of the intestine (diverticulitis), as well as the
asymptomatic, uninflamed outpouchings called diverticulosis.
There are two types, congenital and acquired. Congenital diverticula are situated on the
antimesenteric margin of the bowel and consist of the intestinal wall layers. Acquired
diverticula occur on the mesenteric margin of the bowel, where the blood vessels enter
the bowel wall.
Inflammation occurring around the diverticular sac is often caused by the retention of
undigested food and bacteria, which when formed into a hardened mass is called a
fecalith.
Fistula formation may follow acute diverticulitis... colovesicular fistulas (urinary
bladder), colovaginal fistulas (vagina), entero-enteric fistulas (loop of bowel), and
colocutaneous fistulas (peritoneal tissue).
Subjective symptoms- LLQ pain, sometimes worse after eating, abd distention, alternating
between diarrhea & constipation. ubjective symptoms- LLQ pain, sometimes worse after eating,
abd distention, alternating between diarrhea & constipation.
Objective findings: tenderness in the LLQ, a firm, fixed mass may be identified in the area of
the diverticula. rebound tenderness with involuntary guarding and rigidity.
Diagnostic tests: CT ABD w/contrast, for acute attacks, is a much more sensitive and accurate
test to diagnose suspected diverticulitis, particularly in patients with fever, leukocytosis, or other
indicators of peritonitis or sepsis. A colonoscopy may be needed 4-8 weeks after resolution of
symptoms.
Management:
♦ antibiotics should not be routinely used because acute diverticulitis is more of an
inflammatory process rather than an infectious one.
♦ If ABX needed, amoxicillin and clavulanate potassium 875/125 mg PO BID or
metronidazole (Flagyl) 500 mg TID with trimethoprim/sulfamethoxazole (Bactrim DS)
160/800 mg PO BID for 7-10 days.
♦ The choice of antibiotics will depend on the severity of the disease process and should
cover both gram-negative bacteria and anaerobic organisms.
♦ For ABD spasms; antispasmodics such as hyoscyamine (Levsin) 0.125 mg q4h
dicyclomine (Bentyl) 20 to 40 mg 4x/day, or buspirone (BuSpar) 15 to 30 mg/day.
♦
✓ Patients whose cases are complicated by bleeding that does not subside will require
angiography to locate the site of bleeding; they may also require infusion of vasopressin
(Pitressin) 0.2 to 0.3 units/min via an intra-arterial catheter placed during the radiographic
procedure.
✓ Surgery is usually required for patients who have had several episodes of diverticulitis
within 2 years or for those who have had a single episode of diverticulitis with
complications.
Inflammatory Bowel Disease (IBD)
 Inflammatory bowel disease describes a group of chronic, heterogeneous, immunological
diseases that manifest in intestinal inflammation.
 The two most common IBDs are Ulcerative Colitis UC and Chron’s Disease CD, but MC
is increasing in prevalence and includes collagenous colitis (CC) and lymphocytic colitis
(LC).
o UC involves only the mucosal surface of the colon, which ultimately results in
friability, erosions, and bleeding. Typically involving the rectosigmoid area.
o CD is characterized by segmental or patchy transmural inflammation of the bowel
wall involving any portion of the GI tract from the mouth to the anus.
 The age at onset for UC and CD is frequently in early adulthood but can be anywhere
from age 10 to 40 years, whereas microscopic colitis is more common in people over 40
years of age.
.
✓ In UC, inflammatory and erosive changes most often occurs in the rectum and
sigmoid colon. The muscularis mucosa becomes edematous and thickened, narrowing the
lumen of the colon. Bleeding, cramping pain, and the urge to defecate result from the
mucosal destruction. frequent bloody bowel movements (six to 10 per day); Fecal
leukocytes are always present with active colitis. steatorrhea (foul-smelling, fatty stools).
Patients diagnosed with severe UC are at risk for a perforated colon.
✓ Diagnosis of acute UC is best made by sigmoidoscopy. Barium enema should not be
performed because of the risk of precipitating toxic megacolon
✓ In CD, any portion of the GI tract can be affected, but 80% of patients have small bowel
involvement. areas of tissue damage. skip lesions. Peyer’s patches. “cobblestone”
appearance.
✓ Clinical findings suggest that carcinoma is less common in patients with CD than with
UC and is attributed to the treatment of CD with colectomy.
✓ CD tends to present in one of four patterns:
o (1) inflammation, RLQ abdominal pain, and tenderness, often presenting as
appendicitis;
o (2) obstruction, fibrosis, and stenotic changes within the bowel, causing recurrent
obstruction associated with severe colic, abdominal distention, constipation, and
vomiting;
o (3) diffuse jejunoileitis involving the jejunum and ileum and characterized by
both inflammation and obstruction, which can result in malnutrition and chronic
debility; and
o (4) abdominal fistulas and abscesses normally occurring late in the disease
process and causing fever, generalized wasting, and abdominal masses.
✓ Patients with CD who have small intestine involvement may also require evaluation for
anemia secondary to bleeding, iron deficiency and macrocytic anemia, from poor
absorption of folate, hypocalcemia and vitamin D deficiency, hypoalbuminemia, and
steatorrhea resulting from bile salt deficiency.
✓ Primary sclerosing cholangitis (PSC) is most common in males aged 20 to 40 and is
associated with inflammatory bowel disease (75%).
PEPTIC ULCER DISEASE
•
•
Peptic ulcer disease (PUD) is a generic name for both gastric ulcers and duodenal ulcers.
A peptic ulcer is a break in the surface mucosa of the stomach or duodenum.
The hallmark of PUD is a complaint of a burning or gnawing (hunger) sensation or pain
(dyspepsia) in the epigastrium, which is often relieved by food or antacids.
•
•
•
•
•
A peptic ulcer penetrates the muscularis mucosa and is usually larger than 5 mm in
diameter.
Most ulcers are located in the duodenum, and approximately 95% occur within 3 cm of
the pylorus.
Nocturnal pain is present in two-thirds of patients with duodenal ulcers and one-third of
those with gastric ulcers.
Cigarette smoking, aspirin and other NASIDs, increase risk of ulcer development.
As many as 70% to 90% of patients with duodenal ulcers are infected with H. pylori, and
the bacterium is present in most gastric ulcer patients
o There are four tests used to detect H. pylori: (1) fecal antigen assay, (2) urea
breath test, (3) biopsy with histological examination, and (4) serological antibody
(enzyme-linked immunosorbent assay [ELISA]) test (not as sensitive or specific
as the three other tests).
CHOLECYSTITIS
 Cholecystitis is an acute inflammation of the gallbladder wall, which is usually the result
of an impacted calculus within the cystic duct.
 Cholecystitis without gallstones, acalculous cholecystitis, is a very serious disease with
high morbidity and mortality rates. It usually occurs in patients who are already critically
ill because of trauma, burns, surgery, or sepsis, and who have had no oral intake or have
been supplemented with hyperalimentation.
 Cholesterol stones are the most common form and account for 75% of all gallstones. The
remaining 25% are pigmented stones, which are categorized as black or brown.

♦ Biliary cholesterol is increased by ingestion of estrogen and oral contraceptives,
multiparity, and inflammatory terminal ileal disease, which decreases the bile acid pool.
♦ Black-pigmented stones are formed within the gallbladder and are commonly associated
with hemolytic diseases, cirrhosis, and long-term parenteral hyperalimentation.
♦ Brown pigmented stones are composed of alternating layers of calcium bilirubinate and
calcium fatty acids. Chronic bacterial infections are believed to be partly responsible for
the formation of brown pigmented stones because the enzymes the bacteria produce
predispose the patient to this type of stone formation. Brown stones are typically found
within the intrahepatic ducts and are rarely found within the gallbladder.
♦ The earliest pathological findings are erythema, edema, and a fibrinosuppurative exudate.
Subjective symptoms: RUQ or epigastric pain, indigestion, nausea, and vomiting, especially
after consuming a high-fat meal. Acute cholecystitis usually begins with acute, colicky-type
pain. Patients may complain of referred pain that radiates to the middle of the back, infrascapular
area, or right shoulder.
Objective findings: As the pain over the RUQ becomes severe, there is often involuntary
guarding of the abdominal muscles over the right side. A positive Murphy’s sign is elicited when
the right subcostal region is so tender that there is painful splinting with deep inspiration or when
palpation over the RUQ area causes transient inspiratory arrest. Patients may develop mild
jaundice from edema of the common bile duct. Hyperbilirubinemia should raise the suspicion of
choledocholithiasis.
Diagnostics Tests: ABD x-ray, CT (useful if gangrene or perforation is suspected), US
(sensitive for cholelithiasis but less so for acute cholecystitis), hepatobiliary imaging
(cholescintigraphy) aka- HIDA scan (best way to identify an obstructive cystic duct).
Management: rehydration with IV fluids, antibiotics, analgesics, and GI rest. If vomiting is
persistent, a nasogastric (NG) tube is inserted.
✓ A second or third generation cephalosporin (i.e., ceftriaxone 1 g IV every 24 hours) is
started once the diagnosis is made. If the patient has a severe case or is septic, then a
fluoroquinolone (ciprofloxacin 400 mg IV every 12 hours) plus metronidazole should
added to the antibiotic coverage.
✓ The most common complications of acute cholecystitis are empyema and perforation.
✓ Patients who have persistent symptoms after removal of the gallbladder
(postcholecystectomy syndrome) may have a mistaken diagnosis, a functional bowel
disorder, retained or recurrent common bile duct stones, or spasm of the sphincter of
Oddi.
ACUTE PANCREATITIS: approximately 80% of all hospital admissions for acute pancreatitis are
the result of biliary tract disease (passing of a gallstone) or alcohol use disorder
Subjective symptoms:
•
•
•
•
abrupt onset of severe, deep epigastric pain that persists for hours to days and may
radiate straight through to the back.
It is aggravated by any vigorous activity, such as coughing, and by lying supine; it
improves when the patient is seated and leaning forward.
The patient appears acutely ill, often with intractable nausea and vomiting.
The patient may report a history of ingestion of alcohol or a big meal before onset of
symptoms or mild biliary colic preceding the episode.
Objective findings:
•
•
•
severe abdominal tenderness, particularly over the epigastric area, which may be
accompanied by guarding but without rigidity or rebound tenderness.
Fever. Abdominal distention. hypoactive or absent bowel sounds. Tachycardic with
rapid, shallow respiration. Inspiratory effort is poor because deep inspiration causes
pain.
Uncommon findings that can result from the pancreatic inflammatory process include
left-sided pleural effusion, bluish discoloration over the flanks (Grey Turner’s sign) or
around the umbilicus (Cullen’s sign), jaundice caused by impingement on the common
bile duct, and epigastric mass secondary to pseudocyst development.
Diagnostic Tests: CT ABD... Endoscopic retrograde cholangiopancreatography (ERCP) with
sphincterotomy and stone extraction can be performed and has been proved to decrease
morbidity and mortality.
 The gold standard for diagnosis is an elevated serum amylase level (up to three times
the normal value); however, in one-third of patients with pancreatitis from alcohol use
disorder, the serum amylase level may be normal.
 A decrease in serum calcium may indicate saponification and is indicative of the severity
of the pancreatitis. Calcium levels less than 7 mg/dL (with normal serum albumin) can
cause tetany and are associated with poor prognosis.
 When alanine aminotransferase is up to three times the normal limit, the positive
predictive value is 95% that the pancreatitis is caused by biliary disease (gallstones).
Concomitant increases in the aspartate aminotransferase, alkaline phosphatase, and
bilirubin suggest gallbladder disease.

Management: IV fluids, IV pain meds, NPO status (for bowel rest), antiemetics, tylenol for
fever, NG tube for persistent vomiting.
 The use of empiric antibiotics, H2-receptor antagonists, and pancreatic enzyme inhibitors
have not been proved effective and are not recommended.
 Patients with severe pancreatitis must be maintained in a fasting state for prolonged
periods of time, often for 2 to 4 weeks.
 In febrile patients, cultures of blood, urine, and sputum should be obtained, as well as
CT-guided needle aspiration of necrotic areas of the pancreas with initiation of
appropriate broad-spectrum antibiotic coverage as necessary to prevent increased
morbidity and mortality.
 Surgical intervention is normally reserved for a pancreatic pseudocyst that has persisted
for more than 6 weeks with ongoing symptomatology, necrotizing pancreatitis, pancreatic
abscess, or severe hemorrhagic pancreatitis.
Chronic Pancreatitis:
✓ Chronic pancreatitis is defined as a slowly progressive inflammatory process that
results in irreversible fibrosis of the pancreas with destruction and atrophy of the
exocrine and endocrine glandular tissue.
✓ Chronic relapsing pancreatitis is defined as acute attacks that occur in the setting of
chronic pancreatitis and are usually precipitated by a specific event such as binge
drinking or the passage of a stone.
✓ Other causes of chronic pancreatitis include autoimmune disease, genetic mutations,
hereditary predisposition, hypertriglyceridemia, severe malnutrition (especially proteincalorie deficiency in developing countries), tropical pancreatitis, and obstruction of the
main pancreatic duct caused by stenosis, stones, tumor, or cystic fibrosis.
✓ patients are divided into two groups: (1) those who present with abdominal pain (usually
between ages 15 and 30) and (2) older individuals (ages 50 to 70) who present, often
without pain, with pancreatic calcifications, glandular insufficiency, and diabetes.
✓ Patients often complain of “oil leakage” from the rectum or an “oil slick” in the toilet
bowl, which is indicative of pancreatic insufficiency.
✓ Pancreatic insufficiency can be confirmed by the bentiromide (nitroblue tetrazolium–
para-aminobenzoic acid [NBT-PABA]) test, which measures urinary excretion of
pancreatic chymotrypsin.
✓ Magnetic resonance cholangiopancreatography, safer procedure than ERCP.
Management:
▪
▪
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pancreatic enzyme supplementation. Pancrelipase formulations (Viokase or Cotazym),
(Pancrease or Creon) or pancreatin (Donnazyme)... Fat-soluble vitamin (A, D, E, and K)
replacement may be required.
the Whipple procedure is performed when the disease is most extensive at the head of the
pancreas.
In patients with pancreatitis from alcohol use disorder, ERCP examination often reveals
alternating stricture and dilation (“chain of lakes”) of the pancreatic duct. Treatment is a
modified Puestow procedure (lateral pancreaticojejunostomy), which relieves pain in
70% to 80% of patients.
Wilson’s Disease- Wilson disease is an inherited disorder in which excessive amounts of copper
accumulate in the body, particularly in the liver, brain, and eyes. Liver disease is typically the initial
feature of Wilson disease in affected children and young adults.
Signs and symptoms of these problems can include clumsiness, tremors, difficulty walking, speech
problems, impaired thinking ability, depression, anxiety, and mood swings.
Copper deposits in the front surface of the eye (the cornea) form a green-to-brownish ring, called
the Kayser-Fleischer ring, that surrounds the colored part of the eye.
Cirrhosis: The most common causes of cirrhosis are
♦ alcoholic liver disease—damage to the liver and its function due to alcohol abuse
nonalcoholic fatty liver disease
♦ chronic hepatitis C
♦ chronic hepatitis B
Less common causes
Some of the less common causes of cirrhosis include
♦ autoimmune hepatitis
♦ diseases that damage, destroy, or block bile ducts, such as primary biliary cholangitis and
primary sclerosing cholangitis
♦ inherited liver diseases—diseases passed from parents to children through genes—that
affect how the liver works, such as Wilson disease, hemochromatosis, and alpha-1antitrypsin deficiency
♦ chronic heart failure NIH external link with liver congestion, a condition in which blood
flow out of the liver is slowed
♦ Manifestations of cirrhosis that are nonspecific but suggestive of CLD include spider
nevi, which are normally found over the anterior chest; pectoral alopecia; generalized
muscle wasting; Dupuytren’s (palmar) contractions; parotid gland enlargement; palmar
erythema; hair loss; and testicular atrophy. Patients may have dilated cutaneous veins
called caput medusae (Medusa’s head) radiating from around the umbilical area.
Box 42.2 Complications of Alcohol-Induced Liver Disease
♦ Portal hypertension and varices. Portal hypertension is a common complication of
cirrhosis and, less commonly, alcoholic hepatitis. ...
♦ Ascites. ...
♦ Hepatic encephalopathy. ...
♦ Infection. …
♦ Fatty liver
♦ Esophageal varices
♦ Spontaneous Bacterial Peritonitis
♦ Hepatorenal syndrome
♦ Liver cancer.
BOWEL OBSTRUCTION
♦
♦
Can be partial or complete, simple (blood supply not compromised), or strangulated (blood
supply compromised).
Metabolic acidosis or alkalosis:
o Alkalosis occurs early in intestinal obstruction or if the obstruction is in the proximal
portion of the small bowel.
o later in the course of obstruction, or if the obstruction is more distal, acidosis occurs
because alkaline pancreatic secretions and bile cannot be reabsorbed.
Subjective symptoms:
♦ sudden onset of colicky abdominal pain accompanied by nausea and vomiting.
♦ Patients with obstruction at the jejunum or below may have emesis that has changed to a
brownish, feculent type of material.
Objective findings:
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Abd distention & tenderness, signs of dehydration, including poor skin turgor, dry
mucous membranes, sunken eyeballs, and tachycardia. Blood pressure may be elevated,
depending on the degree of pain and if there is evidence of strangulation and subsequent
ischemia.
Bowel sounds are high-pitched and hyperactive; they may be accompanied by rushes.
Sometimes a mass is palpable. If perforation has occurred, there may be a short period of
pain relief, which is soon followed by increased pain, rebound tenderness, and fever, all
suggestive of peritonitis.
Vomiting occurs if there is an incompetent ileocecal valve or if there is a resultant
superimposed small bowel obstruction. The most common cause of large bowel
obstruction is carcinoma of the sigmoid colon or diverticulosis.
✓ Diagnosis of small bowel obstruction is usually confirmed by supine and upright
abdominal x-ray films that reveal a ladder-like distention of the small bowel.
✓ Upright films show multiple air-fluid levels within the loops of small bowel, which are
the hallmark of small bowel obstruction.
✓ Oral contrast with small bowel follow-through can identify areas of partial obstruction
(not recommended unless large bowel obstruction has been ruled out).
Management:
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NG tube to suction, IV fluid & electrolyte replacements, Foley catheter.
If strangulation is suspected, the patient should be started on broad-spectrum antibiotic
therapy, which provides coverage for anaerobic and gram-negative organisms.
All medications that can decrease intestinal motility, including anticholinergics,
narcotics, and calcium channel blockers, should be discontinued.
Laparotomy is indicated for all patients with complete bowel obstruction.
Treatments for Hep C infection
♦ 1st lineo Elbasvir/Grazoprevir (Zepatier)
o Glecaprevir/Pibrentasvir (Mavyret)
o Sofosbuvir/Ledipasvir (Harvoni)
o Sofosbuvir/Velpatasvir (Epclusa)
♦ Second line hepatitis C medications:
o Sofosbuvir/Velpatasvir/Voxelaprevir (Vosevi)
 Treatment is usually 8-12 weeks long but can be as much as 16 weeks long in
certain situations.
Irritable Bowel Syndrome (IBS)•
•
•
The official definition according to the new Rome IV Criteria is that IBS is a disorder
of gut-brain interaction.
IBS is linked with other functional GI disorders and is classified by a combination of GI
symptoms that include motility disturbances, visceral hypersensitivity, altered mucosal
and immune function, altered gut microbiota, and altered central nervous system
processing.
A diagnosis of IBS must include recurrent abdominal pain of at least 1 day per week
for the previous 3 months and be associated with at least two of the following
additional features: related to defecation, associated with a change in stool frequency,
and/or associated with a change in stool appearance or form.
IBS triggers- Specific foods reported to cause symptoms are legumes, vegetables, foods
containing lactose, foods high in fat, stone fruits, and artificial sweeteners. Any food that
contains fermentable oligosaccharides, disaccharides, monosaccharides, and polyols
(FODMAP) worsens symptoms because of the fermentation and osmotic effects.
 The gut microbiota in patients diagnosed with IBS show a lower microbial variety and
lower numbers of Methanobacteriales and Prevotella species. Other studies have
shown lower numbers of the beneficial bacteria Lactobacillus and Bacteroides with
increased numbers of Streptococcus pathogens.
Symptoms- Many patients report the passage of large volumes of mucus within the stool. This
differs from the mucus occurring with colitis because there is no associated inflammatory
process nor is there any blood in the stool.
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There are no definitive tests for IBS.
Patients with IBS have no abnormalities seen on colonoscopy.
Differential Diagnoses
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Abdominal Angina.
Acute Cholecystitis and Biliary Colic.
Acute Intermittent Porphyria.
Anxiety Disorders.
Bacterial Gastroenteritis.
Bacterial Overgrowth Syndrome.
Biliary Disease.
Celiac Disease (Sprue).
▪
There is a moderate level of evidence indicating the use of probiotics is effective for
patients with IBS.
Some research has shown that some Lactobacilli strains may induce the expression of
μ-opioid and cannabinoid receptors in the intestinal mucosal barrier, thereby
modulating intestinal pain.
The probiotic that seems to have the best results in multiple clinical trials is VSL#3, one
packet orally twice a day and Bifidobacterium infantis, one tablet orally twice a day.
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Celiac Disease- also known as gluten-sensitive enteropathy or celiac sprue, is a gluten-sensitive
autoimmune disorder that affects the small intestinal villous epithelium. The cereal protein
gluten (gliadin) in wheat, rye, and barley.
→ Risk factors for celiac disease include a family history of celiac disease, Down syndrome,
HLA-DQ2 or HLA-DQ8, Turner’s syndrome, or another genetic-based autoimmune
disease such as type 1 diabetes mellitus and thyroiditis.
→ Antigliadin, antiendomysium, and anti-tTG IgA antibodies develop in the presence of
gluten.
→ It should be noted that patients with celiac disease have a threefold increased risk of
developing non-Hodgkin’s lymphoma.
→ Objective signs include diarrhea, weight loss, dyspepsia, and flatulence. Atypical
symptoms are Fatigue, joint pain, depressed mood. Females may have amenorrhea and
difficulty to become pregnant.
→ Subjective signs- malabsorption such as muscle wasting, pallor (anemia), reduced
subcutaneous fat, ataxia, and peripheral neuropathy (vitamin B12 deficiency).
Dermatitis herpetiformis occurs as a cutaneous variant of celiac disease in less than 10%
of patients. Patients presenting with dermatitis herpetiformis almost always have signs
of celiac disease on intestinal biopsy.
Management- A strict gluten-free diet. The risk of developing non-Hodgkin’s lymphoma is
reduced if the patient can maintain the strict gluten-free diet for more than 5 years.
Patients should be monitored for the development of complications or other diseases
associated with celiac disease, including Addison’s disease, Graves’s disease, type 1 diabetes
mellitus, myasthenia gravis, scleroderma, atrophic gastritis, and pancreatic insufficiency.
Renal Problems
▪
Hematuria- Transient hematuria occurs on a single occasion, whereas persistent
hematuria occurs on two or more consecutive voidings. Urine color may go from light
pink to dark red and is sometimes characterized as “smoky.”
o there is a greater positive correlation between underlying malignancy and gross
hematuria versus microscopic hematuria, especially in patients with a history of
cigarette smoking.
→ β-Lactam antibiotics (e.g., amoxicillin with clavulanic acid [Augmentin]), sulfonamides
(e.g., sulfamethoxazole/trimethoprim [Bactrim]), NSAIDs, rifampin (Rifadin),
ciprofloxacin (Cipro), allopurinol (Zyloprim), cimetidine (Tagamet), and phenytoin
(Dilantin) can all cause nephritis (typically allergic interstitial nephritis), which can result
in destruction of nephrons and subsequently lead to impaired renal function and
hematuria.
→ Suprapubic tenderness is suggestive of a bladder etiology, whereas urethral discharge
indicates urethritis.
→ Hematuria accompanied by colicky flank pain suggests a ureteral stone.
→ If the dipstick is positive for heme but the number of RBCs on the microscopic
examination is within normal limits, myoglobinuria and hemoglobinuria should be
suspected.
→ When hematuria of renal origin is suspected, laboratory tests should include an
antinuclear antibody test, immunoglobulins, cryoglobulins, antiglomerular basement
membrane antibodies, a full serum chemistry panel including creatinine clearance and
blood urea nitrogen, a complete blood count and platelet count, an antistreptolysin O
titer (to rule out past streptococcal infection), and a Venereal Disease Research
Laboratory test (VDRL) (to rule out syphilis).
Proteinuria- Proteinuria is usually indicative of renal pathology, most often of glomerular origin.
Proteinuria can be functional as a result of acute illness, emotional stress, or excessive exercise.
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Abnormalities in the glomerular basement membrane produce glomerular proteinuria,
and damage to the proximal tubule where filterable proteins are reabsorbed can result
in tubular proteinuria.
The most accurate way to quantify the amount of protein in the urine is with a 24-hour
urine collection, although cumbersome.
A spot urine albumin to urine creatinine ratio can be measured as a close
approximation of the 24-hour urine collection assessment.
Orthostatic proteinuria occurs when the urinary protein level is elevated only when the
patient has been standing for a prolonged time, but not while they have been reclining.
Exercise-induced proteinuria is related more to intensity, rather than duration, of
exercise and may occur in athletes such as runners or boxers, sometimes accompanied
by elevated catecholamines, hemoglobinuria, or hematuria.
When proteinuria is identified in a low-risk (nondiabetic or nonpregnant) patient, the
urine should be tested for Bence Jones proteins via electrophoresis, the presence of
which suggests multiple myeloma.
•
•
•
•
50% of people with CHF experience incontinence.
A transrectal ultrasound can provide evidence of prostatic disease, and a pelvic
ultrasound may demonstrate pelvic pathology. A cystogram may show abnormal
sphincter pressure or bladder pathology.
Injuries to the sacral spinal cord, which controls reflex bladder filling and emptying, may
lead to an acontractile bladder and overflow incontinence.
OAB is an overarching term used to describe urine storage symptoms such as urgency,
frequency, and nocturia, which may or may not be accompanied by urge incontinence.
Drugs Commonly Prescribed 44.1: Urinary Incontinence
Overactive Bladder
♦ The term overactive bladder is often used interchangeably with the term urge
incontinence; however, they are different conditions. OAB is a syndrome of symptoms
that include urgency, frequency, and nocturia, all of which are associated with
involuntary contractions of the detrusor muscle. Urge incontinence (the sudden intense
urge to urinate and an involuntary loss of urine) may or may not be a feature of this
syndrome, as about one-third of patients with OAB have urge incontinence.
♦ Botulinum toxin A injection into the detrusor muscle is effective for patients with
refractory OAB.
Lower Urinary Tract Infections
✓ A UTI is considered recurrent when it occurs again within 2 weeks of the original
infection.
✓ A complicated UTI is either an acute or chronic infection that is accompanied by factors
that predispose a patient to the infection or make treatment more difficult, such as
instrumentation (e.g., indwelling, suprapubic, or intermittent catheterization),
underlying chronic disease, systemic symptoms, or pregnancy.
✓ Interstitial cystitis (IC) is commonly found in females, aka- bladder pain syndrome (BPS).
✓ IC/BPS is not an infection, but it may feel like a UTI.
✓ some researchers theorize that an abnormality in the bladder surface allows potassium
and urea to leak into the bladder interstitium. May also be related to lymphatic,
infectious, neurological, autoimmune, and vasculitic mechanisms.
♦ urease gene, expressed by certain gram-negative bacteria such as Proteus, Klebsiella,
Ureaplasma, Providencia, and Pseudomonas species. This enzyme splits urea molecules
within the urinary tract, creating ammonium and hydroxyl ions that produce an alkaline
microenvironment. This higher pH facilitates survival of these bacteria.
♦ asymptomatic bacteriuria and dysuria–pyuria syndrome. In asymptomatic bacteriuria,
patients experience no obvious clinical symptoms or signs of UTI (including altered
mental status in older adults), yet urinalysis and urine culture yield findings consistent
with bacteriuria. In contrast, dysuria–pyuria syndrome (also called “acute urethral
syndrome”) is characterized by painful urination with WBCs on microscopic urinalysis in
the absence of a positive bacterial culture.
Objective findings of UTI
•
•
•
•
Enterobacteriaceae convert urinary nitrates to nitrites, producing positive results on
urine dipstick analysis if present in adequate numbers (i.e., greater than 100,000
organisms/mL).
In contrast, however, Staphylococcus does not convert this substrate and is not
detectable by this test.
false-positive urinary nitrite tests may result from the urinary tract analgesic
phenazopyridine.
Hematuria is common in UTI but not with urethritis or vaginitis; however, blood in the
urine is not a marker of complicated infection.
 Fosfomycin is a broad-spectrum antibiotic also used to empirically treat uncomplicated
lower UTI and has the advantage of being given as a single dose.
 The cost-effective single-day treatment regimen with fosfomycin for uncomplicated
lower UTI reduces the risk of nonadherence and the development of Candida vaginitis
due to clearance of normal urogenital flora.
 Ciprofloxacin (Cipro) and other fluoroquinolones are reserved for when no other viable
choice is available due to development of resistant uropathogens; the risk of tendon
rupture and other connective tissue abnormalities; and the potential for severe,
permanent, and disabling peripheral neuropathy.
 Empirical treatment of UTI in male patients (by definition, a complicated UTI) should be
extended to at least 7 days.
 The management of asymptomatic bacteriuria deserves special mention. This condition
should be treated with antibiotics in pregnancy because it increases the risk of
premature delivery.
 Although asymptomatic bacteriuria may be a harbinger of future UTI, antibiotic therapy
has not been shown to persistently eradicate bacteriuria or urinary tract colonization in
these populations.
 Chronic or recurrent UTI- prophylactic treatment either on a daily basis or after sexual
intercourse. Females- postcoital prophylaxis with a single oral dose of nitrofurantoin 50
mg or cephalexin 250 mg has been shown to be highly effective.
 IC does not respond to antibiotics. However, this condition may be treated with
pentosan polysulfate sodium (Elmiron), which tends to reduce the bladder wall
inflammation. This drug has been shown to improve symptoms in 38% of patients with
IC.
 If UTI recurs frequently (e.g., monthly), prophylactic therapy should be prescribed. After
a course of 10 to 14 days of a suitable antibiotic for recurrent infection, the patient
should begin low-dose antimicrobial prophylaxis every other day at bedtime over a 4- to
6-month period, which has proved as effective as daily dosing. Nighttime therapy is
recommended because the patient generally does not void for a prolonged period, thus
giving the bacteria the opportunity to adhere to the bladder wall.
 cranberry supplements (300 to 400 mg twice daily) or drink pure cranberry juicedecrease the bacteria’s ability to adhere to the epithelial cells that line the bladder.
 double voiding (i.e., completely emptying the bladder two times in 5 minutes),
especially if recurrent infections are a problem.
PYELONEPHRITIS - a kidney infection characterized by infection within the renal pelvis, tubules,
or interstitial tissue that may be unilateral or bilateral. In acute pyelonephritis, swelling of the
renal parenchyma occurs.
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•
•
•
•
•
predisposing factors include anatomical abnormalities such as ureterovesical reflux,
urinary obstruction, stress incontinence, multiple or recurrent UTIs, renal disease,
kidney trauma, pregnancy, prostatic enlargement, and metabolic disorders such as
diabetes mellitus.
In acute pyelonephritis, the actual infectious insult to the kidney may be from
hematogenous seeding or urinary tract reflux, but most commonly it is an ascending
infection from the bladder.
In female patients, pyelonephritis is typically caused by fecal flora that colonize the
vaginal introitus and subsequently ascend along the urinary tract to the kidneys.
E. coli (75% to 95% of cases), P. mirabilis, Klebsiella, and Pseudomonas are the most
common gram-negative causative agents. S. saprophyticus is the second most common
cause of pyelonephritis in young females.
diagnosis and treatment in pregnancy are particularly critical because upper UTI has a
clear association with premature delivery.
The persistent unresolved infection and inflammation cause fibrosis (scarring) of the
tubulointerstitium, which may lead to hypertension as the body senses decreased renal
blood flow or eventually chronic renal insufficiency.
DIAGNOSTIC REASONING
Diagnostic Tests
•
Diagnosis of pyelonephritis is confirmed through urinalysis, which is positive for
bacteria, proteinuria, leukocyte esterase, urinary nitrites, hematuria, pyuria, and
specifically WBC casts (reflecting the passage of neutrophils through the renal tubules),
as well as urine culture, which typically demonstrates greater than 100,000 CFU/mL,
allowing for identification of the causative organism.
•
•
•
Cystoscopy with ureteral catheterization, renal ultrasound (to reveal hydroureter
and/or hydronephrosis), or an intravenous pyelogram (IVP) may be indicated; however,
the nuclear medicine–based dimercaptosuccinic acid (DMSA) scan is most sensitive for
detecting pyelonephritis and renal scarring.
Findings in chronic pyelonephritis include fibrosis, scarring, and reduction of renal
tissue, with calyceal clubbing, dilation, and distortion.
Chronic pyelonephritis can sometimes be diagnosed through IVP, DMSA scan, or renal
ultrasound, which may identify atrophied kidneys with “clubbing” of the affected
calyces.
Management
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Common oral ABX given for pyelonephritis (and UTI) are found in Table 44.2
Second-line therapy includes ceftriaxone (Rocephin) 1 g IV daily, as well as other
extended-spectrum cephalosporins or penicillins, carbapenems, monobactams (in
penicillin allergy), and aminoglycosides (except in pregnant patients) such as gentamicin
or tobramycin.
Treatment courses should typically last for 7 to 10 days for mild to moderate cases, 14
days for severe cases, or 21 days in particularly slow responders.
Nephrolithiasis- a condition in which stones (renal calculi) originate in the kidney. The stones
form from calcium salts (75% to 85%), struvite (10% to 15%), uric acid (approximately 7%), and
cystine (1% to 2%).
→ Calcium oxalate stones occur more often in males, whereas struvite stones are more
common in females.
→ increased consumption of calcium or vitamin C or D, excessive excretion of uric acid, or
vitamin A deficiency.
→ Calcium oxalate and calcium phosphate stones account for 65% to 85% of all cases of
renal calculi.
→ diet is high in salt, animal fat, animal protein, and oxalate from green leafy vegetables.
Interestingly, a low-calcium diet is also a risk factor, as it leads to increased oxaluria
because less oxalate is bound to calcium in the gastrointestinal tract.
→ Vasectomy is a risk factor too, and hypertension doubles the risk of stone formation for
unclear reasons.
→ Patients with calcium oxalate or calcium phosphate stones typically do not have
hypercalcemia except with certain disorders such as hyperparathyroidism, sarcoidosis,
and hyperuricemia, which may lead to hypercalciuria or hyperuricosuria. Loop diuretics
such as furosemide (Lasix) also promote calciuria.
→ Similarly, hypocitraturia and hyperoxaluria similarly predispose to calcium stone
formation because an increased amount of calcium is available for complexing with
oxalate or phosphate within the urinary tract.
→ IBD is associated with marked hyperoxaluria. Medullary sponge kidney disease is found
in 10% to 30% of persons with calcium stones.
→ Uric acid stones are formed from an increase in uric acid production or ineffective
elimination of uric acid, as found in gout. Foods high in uric acid, acidic urinary pH (e.g.,
type I renal tubular acidosis, significant bicarbonate loss associated with severe
diarrhea), regional enteritis, hereditary factors (including a predisposition to gout), or
ulcerative colitis.
→ Uric acid stones account for approximately 15% to 20% of all cases of nephrolithiasis.
→ Uric acid stones are radiolucent and red-orange in color, with a teardrop or flat square
shape.
→ Cystine stones are created because of a rare autosomal recessive disorder called
cystinuria.
→ Cystine stone crystals are lemon yellow, hexagonal, and sparkle under light microscopy.
→ Stones are typically anchored at the ends of collecting ducts at sites of epithelial injury.
Large stones are called staghorn calculi.
→ Staghorn calculi are more likely to be struvite stones.
→ Calcium stones are light in color; their crystals characteristically resemble RBCs in shape
and size or may be a larger “dumbbell” form.
→ Hyperoxaluria and hyperuricosuria are more associated with calcium oxalate stones,
whereas calcium phosphate stones are more associated with primary
hyperparathyroidism.
→ Struvite stones are flat and consist of hexagonally shaped crystals that are radiopaque.
→ Certain medications promote crystalluria and predispose the patient to renal stones,
including topiramate, triamterene, and sulfadiazine.
→ The protease inhibitor indinavir (Crixivan) used to treat HIV-positive patients may
actually precipitate within the renal collecting system, causing direct stone formation.
 Because hematuria may be the only presenting sign of stone formation, malignancy
(renal cell carcinoma), which is typically painless, must also be considered.
 NSAIDs are as effective as oral opiates, although they are slower-acting. In addition,
they have also been shown to relax ureteral smooth muscle, which may facilitate stone
passage.
 Flexible ureteroscopy combined with laser lithotripsy is now the preferred treatment for
proximal ureteral stones larger than 10 mm.
Patient dietary habits are crucial to reduce incidence of kidney stones.
♦ In general, caffeine, beer, and wine should be avoided. A low-oxalate diet is
recommended to prevent calcium oxalate stones, in which oxalate-rich foods are
excluded, including beets, black tea, chocolate and cocoa, lamb, nuts, rhubarb, and
spinach.
♦ A low-phosphorus diet for calcium phosphate or struvite stones should eliminate milk
products and cola drinks. A low-purine diet is often effective in reducing stones formed
from excess uric acid. This diet limits the intake of purine-rich foods, such as organ
meats, red meats, seafood (especially sardines, anchovies, and scallops), poultry,
legumes, whole grains, and alcohol (which decreases uric acid clearance).
Renal Problems- Chapter 45
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Symptoms of AKI are not usually present until the GFR falls to approximately 10% to
15% of normal. The most common symptoms, which are secondary to the accumulation
of toxic metabolites such as urea, are fatigue, malaise, nausea, vomiting, pruritus, and
mental status changes. Of note, the development of uremic syndrome symptoms bears
no direct correlation to the increases in BUN or serum creatinine. Oliguria or even
anuria may also be present in some patients.
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There are multiple signs and symptoms of AKI in its four identified stages: initiating,
oliguric, diuretic, and recovery. The initiating stage begins when the kidney is injured.
This stage is variable in length from minutes to several days (e.g., renal damage caused
by contrast dye may occur within 2 minutes).
The oliguric stage usually lasts from 5 to 15 days but can persist for weeks.
The diuretic stage, defined as beginning when urine output increases to greater than
400 mL per day and BUN begins to fall. This stage is considered to last until the BUN
level stabilizes or is in the normal range and may take from 1 to 2 weeks.
The fourth and final stage of AKI, referred to as the recovery phase, extends from the
time BUN stabilizes and urine output returns to normal to the day the patient returns to
normal activity.
Diagnostic Tests:
 Renal artery stenosis is better diagnosed via CT scan or magnetic resonance
imaging/magnetic resonance angiography (MRI/MRA), although direct renal
angiography is still considered the gold standard (albeit invasive) for diagnosis.
 biopsy is performed in cases of isolated glomerular hematuria with proteinuria to
confirm acute nephritic syndrome, better characterize nephrotic syndrome or suspected
vasculitis, and aid in the diagnosis of acute or subacute renal failure of unknown
etiology.
Chronic Kidney Disease
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The major underlying conditions leading to ESRD are DM and primary HTN, seen in
approximately 70% of cases, with GN, cystic disease, and other urological diseases
accounting for another 15% of cases.
Renal artery stenosis and chronic ischemic renovascular disease may cause up to 20%
of CKD cases in persons older than 50 years of age.
Renal artery stenosis occurs when the renal artery and its branches become thickened,
stiff, and narrow due to atheromatous plaques (two-thirds of cases) or fibromuscular
dysplasia (one-third of cases).
Analgesic overuse (e.g., NSAIDs), cigarette smoking, collagen vascular diseases, AIDSrelated nephropathies, cirrhosis, and multiple myeloma are examples of other risk
factors for the development of CKD.
Several hereditary renal diseases (e.g., polycystic kidney disease; Lowe syndrome,
which also causes congenital cataracts; Alport syndrome, which also causes congenital
deafness) can lead to CKD in children and some adults.
Diabetic nephropathy is the most common cause of ESRD and involves several
mechanisms, including hyperglycemia, hormonal imbalances, and renal hemodynamic
changes.
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After DM, hypertensive nephropathy is the second most common cause of renal
failure. The kidney is one of the major organs injured by HTN which results in
nephrosclerosis.
Glomerulonephritis GN is the third most common cause of renal failure and comprises
25% to 30% of all cases of ESRD. GN is an inflammatory process that primarily affects
the glomerular capillaries. It is also a major cause of ESRD.
poststreptococcal GN, which typically presents in a male patient aged 2 to 14 years,
with puffiness of the eyelids and facial edema, and an inadequately treated sore throat
1 to 2 weeks prior (i.e., streptococcal pharyngitis or strep throat)... A similar
presentation may also be seen in middle-aged men, most often with diabetes mellitus
and a recent history of MRSA infection.
The third National Health and Nutrition Examination Survey (NHANES) defined the stages of
CKD as follows:
Stage 1 disease is characterized by persistent albuminuria with a normal GFR greater than 90
mL/min per 1.73 m2 of body surface area (BSA).
Stage 2 disease is characterized by albuminuria with a GFR between 60 and 89 mL/min per 1.73
m2 of BSA.
Stage 3 disease is defined as a GFR between 30 and 59 mL/min per 1.73 m2 of BSA.
Stage 4 disease is defined as a GFR between 15 and 29 mL/min/1.73 m2 of BSA.
Stage 5 disease is ESRD, defined as a GFR less than 15 mL/min/1.73 m2 of BSA.
Renal Tumors
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Renal cell carcinomas originating in the renal cortex are the most common (85%) type
of malignant renal tumors. These tumors occur most often in the parenchyma of the
kidney.
renal cell carcinomas are classified as clear cell (75% to 85%), chromophilic or papillary
(15%), or chromophobic (5%).
Transitional cell carcinomas are the next most common type of renal carcinoma.
In children, nephroblastoma (Wilms’ tumor) is common, comprising 5% of primary
tumors, whereas sickle cell disease has a known, albeit rare, association with carcinoma
of the renal medulla.
Subjective symptoms: Approximately 60% of the time, asymptomatic patients present with
gross hematuria as the only outward complaint. However, 30% of patients report dull, achy
flank pain or an abdominal mass. In 10% to 15% of patients, the classic triad of flank pain,
hematuria, and an abdominal mass is observed, which is often a sign of advanced disease.
Diagnostic Tests: IVP with nephrotomography... Ureteroscopy or ultrasonography with IVP
can be used to differentiate potentially neoplastic tissue from renal cyst formation. Urine
cytology.
The tumor-node-metastasis (TNM) staging of renal cell carcinoma is as follows:
Stage I is defined as a tumor confined within the kidney capsule; it is treated by nephrectomy.
The 5-year survival rate is 60% to 75%.
Stage II is defined as the invasion of the renal capsule that is confined within the Gerota’s
fascia encapsulating the kidney and adrenal gland; it is treated by nephrectomy. The 5-year
survival rate is 47% to 65%.
Stage III is defined as involvement of the regional lymph nodes ipsilaterally, the renal vein, or
the vena cava. The 5-year survival rate is 5% to 15%.
Stage IV is defined as distant metastasis, with a 5-year survival rate of less than 5%.
 Approximately 30% of patients with renal tumors have metastatic disease at diagnosis.
The most common sites of metastasis are the lung (50% to 60%), bone (30% to 40%),
regional lymph nodes (15% to 30%), brain (10%), and adjacent organs.
 Treatment for a renal neoplasm is primarily surgical with a partial or total nephrectomy,
with or without regional lymphadenectomy if no metastatic disease is present.
 Follow-up for patients with a total nephrectomy, a CT scan of the abdomen and renal
fossa should be done in 3 to 6 months. The patient may then be followed with renal
ultrasound every 6 months for 3 years and annually thereafter unless symptoms occur.
Bladder Tumors
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Bladder tumors are the most common cancer of the urinary system.
Bladder cancer is the sixth most common neoplasm in the United States.
Bladder tumors are described as papillary (90%) or nonpapillary (10%).
Primary bladder cancer tends to metastasize to the lymph nodes, liver, bones, and
lungs.
Risk Factors: cigarette smoking, the presence of renal tumors, exposure to aromatic amine
dyes known as arylamines (e.g., beta-naphthylamines, xenylamine, 4-nitrobiphenyl, and
benzidine) and arsenic, chronic use of phenacetin-containing analgesics, use of saccharin (in
rodent studies), chronic lower UTI, schistosomiasis, and recurrent nephrolithiasis. Other
predisposing factors for bladder tumors include previous radiation treatment for cervical,
ovarian, or prostate cancer, and prior cyclophosphamide chemotherapy.
Diagnostic Tests: Urine cytology, Cystoscopy, ABD or pelvic CT scan, with or without IVP.
According to the TNM system of the American Joint Committee on Cancer, the stages of
transitional cell carcinoma are as follows:
Stage 0 tumors are confined to the mucosa.
Stage I tumors invade the lamina propria.
Stage II tumors invade the muscular layer.
Stage III tumors extend to the peripelvic fat or renal parenchyma.
Stage IV indicates metastatic disease.
Endocrine and Metabolic Problems
Hyperthyroidism- Excessive secretion of T3 and/or T4, low TSH.
 thyrotoxicosis is a more general term that encompasses hyperthyroidism, as well as
exogenous thyroid hormone intake and subacute thyroiditis, in which acute
inflammation of the thyroid gland results in the rapid excretion (rather than
overproduction) of stored thyroid hormones.
 Silent thyroiditis is a form of subacute thyroiditis in which the thyroid gland is
moderately enlarged and nontender.
 Toxic multinodular goiter (Plummer’s disease) is as common as subacute thyroiditis.
Common in older adults. A complication of chronic, inactive nodular goiter.
 Thyrotoxicosis factitia is a form of thyrotoxicosis in which a patient takes excessive
amounts of either T4 or T3.
 A tumor of the pituitary gland causing hypersecretion of TSH is a rare cause of
hyperthyroidism.
 younger patients tend to have symptoms more reflective of sympathetic activation
(e.g., tremors, anxiety, and hyperactivity), whereas older patients manifest more
cardiovascular symptoms, including atrial fibrillation and dyspnea, as well as weight
loss.
 Graves’ disease is an autoimmune disorder that results from aberrantly produced thyroidstimulating immunoglobulins that activate TSH receptors
Objective signs: Whereas the goiter of Graves’ disease is typically firm, the thyroid in toxic
multinodular goiter may be softer, but with several palpable nodules.
In Graves’ disease, antithyroglobulin and antimicrosomal antibodies are elevated.
An enlarged painful thyroid is also consistent with degeneration or hemorrhage into a thyroid
nodule, or granulomatous or suppurative thyroiditis.
The skin may be moist and velvety to the touch, with increased pigmentation, spider
angiomata, and vitiligo.
hyperactive reflex is usually the Achilles tendon reflex.
Patients with longstanding hyperthyroidism may also have clubbing of the digits and signs of
new bone growth in the hands, termed thyroid acropachy.
Testing for Thyroid dysfunction.
Nuclear scintigraphy with radiolabeled iodine (123I) or technetium (99Tc) helps in assessing
the functional status of the thyroid gland. A 24-hour radioactive iodine uptake (RAIU) test can
differentiate Graves’ disease from subacute thyroiditis and toxic nodular goiters.
Patients with toxic nodular goiter and Graves’ disease have a high RAIU, whereas in subacute
thyroiditis, iodine uptake is low.
A fine-needle biopsy is the preferred initial diagnostic technique for the evaluation of thyroid
masses, particularly solid masses, to rule out malignancy.
drugs that may increase T4 levels include amiodarone (Cordarone), amphetamines, clofibrate
(Atromid-S), high-dose glucocorticoids, heparin administered during dialysis, heroin,
levothyroxine (Synthroid), methadone (Dolophine), and perphenazine (Trilafon).
Two antithyroid drugs are used—propylthiouracil (PTU) and methimazole (MMI). PTU has an
added therapeutic effect of inhibiting T3 activity and preventing peripheral conversion of T4
into T3.
Radioactive iodine 131 (131I; Iodotope) is the treatment of choice for hyperthyroidism in the
United States, especially in middle-aged or older adults.
Female patients receiving radioactive iodine therapy should not become pregnant until at least
4 months after therapy.
Subacute thyroiditis is a self-limited condition treated with beta-adrenergic blocking
medications and NSAIDs. Short-term use of oral prednisone- 40 mg daily for 1 to 2 weeks with a
gradual taper over 2 to 4 weeks.
Hypothyroidism: elevated TSH, and/or low T3 & T4...Subclinical hypothyroidism is the
presence of normal Free T4 with an elevated TSH.
♦ The most common worldwide cause of thyroid disorders is iodine deficiency.
♦ The sensitive thyrotropin assay is the most specific test for diagnosing primary
hypothyroidism.
♦ Hashimoto’s thyroiditis, a type of primary hypothyroidism, is the most common form of
autoimmune thyroid disease... four times more often in females than in males, with the
average age at onset from 30 to 60 years.
♦ Iatrogenic hypothyroidism, which occurs after treatment with radioactive iodine (for
hyperthyroidism) or surgery (for hyperthyroidism, thyroid nodules, or thyroid
carcinoma), is the next most common cause of hypothyroidism.
♦ When the thyroid dysfunction is caused by failure of the pituitary gland, the
hypothalamus, or both, it is known as central hypothyroidism. More specifically,
failure of the pituitary gland to secrete adequate amounts of TSH is known as
secondary hypothyroidism, whereas tertiary hypothyroidism results from inadequate
secretion of thyrotropin-releasing hormone (TRH) by the hypothalamus or failure of
TRH to activate its cognate receptors within the pituitary gland (peripheral resistance).
♦
▪ Destructive thyroid inflammation may occur due to immune cross reactivity after viral
infections, producing transient forms of hypothyroidism including the painful condition
called de Quervain thyroiditis.
▪ Lymphocytic thyroiditis and transient hypothyroidism also occur in up to 10% of new
mothers between 2 and 10 months postpartum.
▪ Amiodarone, an iodine-containing antiarrhythmic, can have direct inhibitory effects on
the thyroid gland. Interferon-α, thalidomide, and the antiretroviral agent stavudine have
also been associated with primary hypothyroidism. Both dopamine and lithium are
associated with central (secondary or tertiary) hypothyroidism.
▪ The most common reason for iatrogenic hypothyroidism is the therapeutic result of
previously treated hyperthyroidism.
▪ concentrated iodine therapy (Lugol’s solution, which is used in less developed
geographies) used in place of radioactive iodine.
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An insufficient amount of thyroid hormone causes abnormalities in lipid metabolism,
with an increase in total cholesterol, low-density lipoproteins (LDLs), and triglycerides.
Deficiencies in vitamin B12, iron, and folate may also occur.
A characteristic pathophysiological change of hypothyroidism is the accumulation of
hydrophilic proteoglycans within the interstitial space, which causes an increase in
interstitial fluid. Pleural, cardiac, and peritoneal effusions are a common result of this
process, as is the characteristic mucinous edema seen in longstanding hypothyroidism,
known as myxedema.
Myxedematous changes occur in the later stages of hypothyroidism, with thickened,
scaly, and “doughy” skin, an enlarged tongue, muscle weakness, joint complaints,
hearing impairment, and ascites.
Myxedema Coma- a result of severe hypothyroidism, most commonly seen in older
adult females.
o The patient is usually pale with periorbital edema, dry skin, decreased body
temperature, macroglossia, distant heart sounds, bradycardia, and delayed deep
tendon reflexes.
o administer levothyroxine (Synthroid, Levothroid) IV 300 to 500 μg over 15
minutes and then IV 100 μg every 24 hours.
o Glucocorticoids- Hydrocortisone hemisuccinate 100 mg IV bolus.
A high (1:400) antimicrosomal (anti-TPO) antibody titer is diagnostic for autoimmune
thyroiditis.
In euthyroid hypothyroxinemia, the patient is euthyroid with a decreased T4 level due
to a decreased concentration of thyroid-binding globulin caused by nephrotic
syndrome, exogenous testosterone exposure, or high-dose corticosteroids. Also, drugs
that inhibit T4 binding, such as phenytoin, phenobarbital, and salicylates, may decrease
the total T4 level.
the usual dose of thyroxine is 1.6 μg/kg per day for full replacement.
Pregnancy is also well known to increase replacement therapy requirements. Some
clinicians suggest increasing replacement dosing by 30% on confirmation of pregnancy.
Endocrinologists recommend treating subclinical disease when antithyroid antibodies
are present, when evidence of atherosclerotic cardiovascular disease exists, when heart
failure exists, or if the patient is symptomatic at the respective TSH level.
Thyroid Cancer- is classified as differentiated (papillary and follicular) or undifferentiated
(medullary and anaplastic) forms. Approximately 60% of thyroid cancers are papillary, 20%
are follicular, and the remaining 20% of cases are medullary or anaplastic.
✓ Thyroid cancer is the most common endocrine-related cancer. more common in adults
20 to 54 years.
✓ Thyroid nodules found in persons younger than 20 years of age or adults over 60 are
more likely to be cancerous.
✓ Increased incidence of follicular and anaplastic thyroid carcinoma in areas where iodine
deficiency and goiter are more prevalent.
✓ Metastatic cancer of the thyroid is less common, although renal cancer, breast cancer,
lung cancer, and malignant melanoma can all metastasize to the thyroid gland.
✓ Germline mutations in the RET proto-oncogene have been associated with the inherited
cancer syndromes of multiple endocrine neoplasia (MEN) 2A, MEN 2B, familial
adenomatous polyposis, and familial medullary thyroid carcinoma (FMTC) syndrome—
all of which are associated with medullary thyroid carcinoma.
✓ Several inherited cancer syndromes, including MEN 2A or Sipple’s syndrome (which may
present with concurrent pheochromocytoma and hyperparathyroidism), MEN 2B (which
may present with concurrent pheochromocytoma, a tall and slender Marfanoid body
habitus, and ganglioneuromas), or FMTC syndrome.
Diabetes Mellitus
T1DM- is a metabolic disorder characterized by severe insulin deficiency resulting from
immune-mediated pancreatic beta islet cell destruction. autoimmune infiltration of pancreatic
beta cells—a process termed insulitis.
o In nonpediatric patients, T1DM is sometimes known as latent autoimmune diabetes of
adults (LADA).
o T1DM is 1.5 to two times more common in whites of European descent than in
nonwhites.
o T1DM has two forms—immune-mediated DM (type 1A) and idiopathic DM (type 1B).
Immune-mediated DM accounts for 90% of cases.
o The most commonly identified infectious agents are congenital rubella (associated with
the development of T1DM and other autoimmune syndromes up to 5 to 20 years later),
coxsackie B4 virus, cytomegalovirus, adenovirus, and mumps virus (paramyxovirus).
o Birth weight greater than 4,000 g and higher-than-expected weight gain in the first
year of life are associated with an increased risk of T1DM, but viral antigens and certain
dietary influences appear to have the strongest impacts.
o Patients with immune-mediated DM are rarely obese and are prone to other
autoimmune diseases such as Graves’ disease, Hashimoto’s thyroiditis, Addison’s
disease, vitiligo, and pernicious anemia.
o In contrast, idiopathic type 1B DM, which accounts for less than 10% of T1DM cases,
shows no evidence of autoimmunity and has no known cause. It is a rare form of DM
that is inherited and more common in people of Asian, African, or Hispanic origin.
o T1DM is clearly associated with an increased incidence of other autoimmune disorders,
including thyroid, adrenal, and gonadal insufficiency, termed polyglandular
autoimmune disease type 2.
o autoimmune polyendocrine syndrome type 1, which results from a mutation in the
AIRE gene... IPEX syndrome, which involves mutations in foxp3—a master control gene
for regulatory T cells—that lead to DM and potentially fatal fulminant enteritis in
affected infants.
Complications of DM- retinopathy, nephropathy, with resultant HTN, neuropathy,
hyperlipidemia, micro and macrovascular disease. Autonomic involvement can affect GI,
cardiovascular, and genitourinary function. Sexual dysfunction, particularly erectile dysfunction,
occurs frequently in older patients.
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Infections that are uncommon in the general public, such as serious staphylococcal and
Klebsiella pneumoniae infections, malignant (necrotizing) otitis externa due to
Pseudomonas aeruginosa, or rhinocerebral mucormycosis, which occurs almost
exclusively in patients with DM.
Patients with DM are more likely serious complications of pyelonephritis, such as renal
papillary necrosis and emphysematous (necrotizing) pyelonephritis, or progression to
gram-negative bacterial sepsis. Female patients may also present with complaints of
vaginal pruritus or burning caused by vulvovaginitis.
chronic pyogenic infections or necrobiosis lipoidica diabeticorum, which consists of
well-demarcated granulomatous plaques with a shiny yellow surface that occur on the
anterior surfaces of the legs or dorsal aspect of the ankles.
To assess beta cell function and insulin production in a patient with T1DM is C-peptide level.
C-peptide levels are found in amounts equal to endogenous insulin. A patient with residual
pancreatic beta cell function will have decreased but nonetheless detectable levels of Cpeptide, whereas if no insulin is being produced, the levels of C-peptide will be negligible.
The A1c level roughly correlates to mean plasma glucose concentration as follows:
6% = glucose of 135 mg/dL
7% = 170 mg/dL;
8% = 205 mg/dL
9% = 240 mg/dL
10% = 275 mg/dL
11% = 310 mg/dL
12% = 345 mg/dL.
 intensive insulin regimens to achieve the following goals: plasma glucose levels of 80 to
130 mg/dL before meals, peak postprandial (1 to 2 hours after the beginning of a meal)
glucose levels of less than 180 mg/dL, and an A1c below 7% for adults with T1DM.
 The Somogyi effect- a diabetic patient develops hypoglycemia during the night with
rebound hyperglycemia in the morning.
 Charcot foot disorders occur in 9% of patients with neuropathy, leading to bony
destruction, joint subluxation, and bony remodeling of the foot.
 T1DM patients who are seriously ill and the illness is accompanied by vomiting or
diarrhea for more than 2 hours, a fever of 101°F (38.3°C) or higher, or blood glucose of
240 mg/dL or higher and if ketones continue to appear in the urine despite additional
insulin, the patient should be instructed to seek medical attention immediately, given
the risk of developing DKA.
T2DM- characterized by the abnormal secretion of insulin, resistance to the action of insulin in
the target tissues, and/or an inadequate response at the level of the insulin receptor.
♦ Insulin resistance worsens in conjunction with hyperinsulinemia, eventually resulting in
the development of fasting hyperglycemia, because hepatic gluconeogenesis increases
due to glucagon being produced by pancreatic alpha cells in response to the
hyperinsulinemia.
♦ Genetic variants have been identified that affect incretin hormones (which normally
decrease glucose levels), beta cell function, and key protein regulators of glucose
metabolism.
♦ hyperinsulinemia and hyperglycemia increase lipid synthesis, raising serum levels of
fatty acids, triglycerides (greater than 150 mg/dL), and LDL cholesterol, while lowering
HDL cholesterol. This increase in lipids is also toxic to beta cells and is referred to as
lipotoxicity.
→ The pathogenesis of T2DM has been labeled the “ominous octet,” consisting of eight
distinct factors:
o (1) beta cell failure;
o (2) insulin resistance in muscle cells;
o (3) insulin resistance in liver cells;
o (4) adipocyte resistance to the antilipolytic effect of insulin, which results in
increased plasma free fatty acids;
o (5) decreased incretin;
o (6) increased glucagon secretion and enhanced hepatic sensitivity to glucagon;
(7) enhanced renal glucose reabsorption; and
o (8) resistance of the central nervous system to the anorectic effect of insulin,
which results in appetite dysregulation and weight gain.
→ GI tissues contribute to this pathophysiology through the actions of the incretins
glucagon-like peptide-1 (GLP1) and gastric inhibitory polypeptide (GIP). These two
hormones play a significant role in glucose absorption.
▪ HHS (Hyperosmolar Hyperglycemia State) is associated with a high mortality rate and is
typically seen in older diabetic adults who have developed an infection, such as
pneumonia or other illness.
▪ Symptoms of HHS are dramatic, including severe hyperglycemia (greater than 600
mg/dL), plasma or serum hyperosmolality (more than 340 mOsm), and profound
dehydration. Although classically thought of as a nonketotic condition, ketosis may or
may not be present in HHS.
▪ Screening for prediabetes and DM should be considered in all individuals who are
overweight or obese, regardless of age, and for all adults aged 45 years and older.
▪ In T2DM, the C-peptide level is normal or elevated, but it is decreased in T1DM, given
the lack of insulin production.
 in T3cDM, there is also a loss of glucagon and pancreatic polypeptide (PP) from the
pancreatic islets, in addition to the loss of insulin specifically from the beta cells. Termed
“brittle diabetes” due to unsuppressed hepatic glucose production and exaggerated
peripheral sensitivity to insulin. patients with T3cDM are rarely overweight or obese.
patients are usually undernourished, with deficiencies in fat-soluble vitamins (e.g.,
vitamins A, D, E, and K).
 The major diagnostic criteria for T3cDM must all be present and include the following:
o Pancreatic exocrine insufficiency
o Pathological pancreatic imaging (e.g., computed tomography, magnetic
resonance imaging, ultrasound, endoscopy)
o Absence of T1DM-associated autoimmune antibodies
 No specific guidelines to manage T3cDM separately from other forms of DM.
 patients with chronic pancreatitis and T3cDM benefit from incretin-based antidiabetic
therapy, including GLP1 analogues (semaglutide [Ozempic]; dulaglutide [Trulicity]) and
DPP4-Is (sitagliptin [Januvia]; saxagliptin [Onglyza]; linagliptin [Tradjenta]).
Glandular disorders
Addison’s disease, also known as primary adrenal insufficiency, primarily caused by
autoimmune destruction of the adrenal cortex in 80% of cases in the United States.
o Primaily affects persons 30 to 50 years of age.
o Addison’s disease appears with other autoimmune diseases, which are collectively
termed autoimmune polyendocrine syndrome (APS). Type 1 APS is an inherited
autosomal recessive disease and, along with Addison’s disease, includes
hypoparathyroidism and mucocutaneous candidiasis. Type 2 APS is the more common
type, with a constellation of disorders that includes Addison’s disease, DM, celiac
disease, immune thyroid disease, and hypogonadism.
o The decreased adrenal androgen secretion associated with Addison’s disease also
results in the loss of secondary sex characteristics (e.g., loss of pubic and axillary hair) in
females, but because the adrenal glands are not a major source of androgens in males,
they do not experience any loss of secondary sex characteristics.
Diagnostic Tests:
A morning (8 a.m.) cortisol level of less than 3 μg/dL is consistent with Addison’s disease,
especially if accompanied by a plasma ACTH level greater than 200 pg/mL. The diagnosis is
confirmed by a cosyntropin stimulation test, in which a synthetic form of ACTH is given
intramuscularly (IM) and a serum cortisol level is obtained 45 minutes later. In Addison’s
disease, the exogenous ACTH dose does not result in a corresponding increase in cortisol
secretion.
Cushing’s Syndrome: can be caused by cortisol hypersecretion by the adrenal cortex due to
cortical hypertrophy or to a tumor of the adrenal gland, causing persistent and inappropriate
hypercortisolemia.
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Cushing’s disease refers to a specific form of Cushing’s syndrome caused by excess
secretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma.
Cushing’s syndrome may be classified mechanistically as ACTH-dependent or ACTHindependent hypercortisolemic states. The former mechanism results in
adrenocortical hyperplasia and is most frequently (70% of cases) due to an ACTHsecreting pituitary adenoma (Cushing’s disease), which occurs more commonly in
females.
The most frequent cause of Cushing’s syndrome, however, is prolonged administration
of exogenous glucocorticoid hormones—an iatrogenic etiology that is ACTH
independent.
Subjective symptoms: Common complaints include weight gain, back pain, headaches, skin
changes, and muscle weakness. Females may complain of menstrual irregularities and
hirsutism, and males often report decreased libido and impotence. Patients may also complain
of emotional lability, increased appetite, increased irritability, anxiety, poor concentration and
memory, and sleep disturbances.
Objective findings: “moon face”, “buffalo hump”, thinning of the skin and easy bruising. Fungal
infections of the skin, nails, and oral mucosa are common. striae (stretch marks). Striae are
typically red to purple. Hyperpigmentation, commonly found in some types of Cushing’s
syndrome, is rare in patients with Cushing’s disease. extremities are usually thin. glaucoma and
psychiatric symptoms.
Diagnostic Tests: one of four tests be used in the initial evaluation for Cushing’s syndrome:
urinary free cortisol (at least two measurements), late-night salivary cortisol (two
measurements), a 1 mg overnight dexamethasone suppression test (DST), or a longer lowdose (2 mg/day for 48 hours) DST as an alternative testing modality if the first three do not
give conclusive results.
 Transsphenoidal pituitary microsurgery is the treatment of choice for a pituitary
adenoma causing Cushing’s disease.
 In younger patients who are not surgical candidates, mitotane (Lysodren) or
alternatively ketoconazole (Nizoral) 200 mg every 6 hours to reduce cortisol levels.