Answer C: Hemangioma is the most common benign tumor in infancy and is caused by endothelial cell proliferation.

It
is often called a "strawberry mark" because of its clinical appearance (see the image below). This patient's acute onset of
symptoms, older age, and absence of a strawberry mark make hemangioma unlikely.

Answer D: Herpangina is a viral infection caused by Coxsackievirus A. It is characterized by an acute febrile illness, as
well as small ulcerative and erosive lesions in the posterior oropharynx (see the image below). The absence of these
lesions makes herpangina unlikely, and herpangina does not cause sudden-onset facial swelling.
 Summary of the Functions of Nephron Segments

Segment Function Mechanism Hormone Activity Diuretic Action

Na+/H+
exchange PTH inhibits Na
Proximal Mannitol
Reabsorption of water Na+glucose, phosphate
convoluted Carbonic anhydrase
and solute Na+amino acid, Angiotensin II stimulates
tubule inhibitors
Na+phosphate Na+, H+ exchange
cotransport

Reabsorption of NaCl
without water
Thick Dilution of tubular ADH Loop diuretics
Na+/K+/2Cl-
ascending loop fluid stimulates Na+/K+/2Cl- (furosemide, ethacrynic
cotransport
of Henle Reabsorption of cotransport acid)
calcium and
magnesium

Reabsorption of NaCl
Early distal
without water Na+/Cl- PTH stimulates calcium Thiazide diuretics
convoluted
Dilution of tubular cotransport reabsorption (hydrochlorothiazide)
tubule
fluid

Aldosterone stimulates
Late distal Na+ reabsorption K+ sparing diuretics
ENaC
tubule & Reabsorption of NaCl Aldosterone stimulates (spironolactone,
K+ channels
collecting ducts K+ excretion K+ excretion triamterene)
Aquaporins
(principal cells) ADH stimulates water
reabsorption

Late distal
tubule &
K+ sparing diuretics
collecting ducts Reabsorption of K+ Aldosterone stimulates
H+/K+ ATPase (spironolactone,
(alpha H+ secretion H+ secretion
triamterene)
intercalated
cells)

Medications For Cholinesterase Inhibitor Poisoning

Drug Mechanism of Action Adverse Effects

Dry mucous membranes

Tachycardia
Mydriasis
Atropine Muscarinic antagonist
Constipation
Urinary retention
Bronchodilation
 Muscle rigidity
Binds to nicotinic receptors
Pralidoxim Tachycardia
Reactivates cholinesterase by
e Hypertension
dephosphorylation
Seizures

Drowsiness
Benzodiazepine
Anterograde amnesia
Diazepam  frequency chloride ion conduction 
Tolerance
potentiate GABA
Addiction potential
GABA, gamma-aminobutyric acid.

Phyllodes tumor typically presents as a large, firm, rapidly enlarging breast mass. Biopsy will reveal connective tissue
and cysts with "leaf-like" lobulations.
Explanation: Phyllodes tumor, as seen here, is a fibroepithelial tumor of the breast that arises from the periductal
stromal cells of the breast. It is most commonly seen in adult women between 40 and 50 years of age prior to the onset of
menopause, and patients typically present with a large, rapidly growing breast mass without nipple discharge or skin
changes.

A diagnosis can be confirmed by biopsy, which will reveal connective tissue and cysts with "leaf-like" lobulations (seen
below). Although most cases of phyllodes tumors are benign, approximately 30% are malignant.

Microscopic evaluation of a phyllodes tumor will reveal "leaf-like" lobulations.

Answer A: Although this patient does have a history of trauma to the breast, her presentation (a rapidly enlarging breast
mass) and biopsy are not consistent with fat necrosis. Fat necrosis typically presents as a painless breast mass and is
usually caused by trauma to the breast. Biopsy will show necrotic fat and giant cells.
Fat necrosis seen on light microscopy.

Answer B: A large, rapidly growing breast mass in a 47-year-old woman is not consistent with a fibroadenoma.
Fibroadenoma is a benign breast tumor that is most commonly seen in women younger than 35 years of age. It typically
presents as a small, well-defined, mobile mass that increases in size and tenderness with increases in estrogen. As such,
patients often report that the mass changes in size throughout their menstrual cycle, and many patients will be diagnosed
during pregnancy.

A fibroadenoma is seen on light microscopy. It is characterized by an abundance of stromal cells and epithelial cells that
are arranged in a "honeycomb" pattern.

Answer C: Inflammatory breast cancer is a malignant form of breast cancer and is associated with a poor prognosis. In
most cases, patients do not present with a palpable breast mass, but they present with a painful breast and warm, swollen,
and erythematous skin. Skin dimpling (peau d'orange) may also be seen. A nontender, rapidly enlarging breast mass is
not consistent with inflammatory breast cancer.
Answer D: An intraductal papilloma should be suspected when patients present with serous or bloody nipple discharge.
Intraductal papilloma is a benign fibroepithelial tumor that occurs within the lactiferous ducts, typically beneath the
areola. In most cases, patients will present with serous or bloody nipple discharge. For the COMLEX, you should not
pick intraductal papilloma as an answer choice in the absence of nipple discharge.
Insight: Even if you were not certain as to what the biopsy was showing, the clinical presentation should have pointed
you towards a phyllodes tumor. When you are uncertain as to what is being shown in an image, try to answer the
question based on written details within the stem. In addition, even if you think that you know what the image is
showing, make sure that your answer choice still lines up with the rest of the details in the stem.
Parkinson Disease Medications

Class Examples Mechanism of Action Adverse Effects

 Muscarinic receptor  Urinary retention

 Benztropine antagonists  Tachycardia
Anticholinergic
 Trihexyphenidy  ↓ concentration of  Mydriasis
drugs
l acetylcholine  Constipation
 ↓ tremors  Delirium

 COMT inhibition
 ↓  GI side effects (eg, nausea, vomiting)
COMT  Tolcapone peripheral metabolization  Hepatotoxicity (tolcapone)
inhibitors  Entacapone of L-DOPA to 3-OMD  Dyskinesia
 Increases L-DOPA  Neuropsychiatric effects (eg, hallucinations)
reaching the CNS

 Inhibition of DOPA
decarboxylase
 ↓ peripheral conversion
Decarboxylase  Carbidopa of L-DOPA to dopamine  Can decrease or deplete peripheral levels of
inhibitors  Benserazide  ↑ bioavailability of serotonin, dopamine, norepinephrine, epinephrine
peripheral L-DOPA
 Always administered with
L-DOPA

 Direct stimulation of  GI side effects (eg, nausea, vomiting)

striatal dopamine  Orthostatic hypotension
Dopamine  Ropinirole
receptors  Drowsiness
agonists  Pramipexole
 Used predominantly for  Impulse control disorders
bradykinesia  Neuropsychiatric effects (eg, hallucinations)

 L-DOPA can freely cross

BBB  GI side effects (eg, nausea, vomiting)
 Converted to dopamine  Neuropsychiatric effects (eg, hallucinations)
Dopamine
 L-DOPA via DOPA decarboxylase  Hypokinesia
precursors
 Direct dopaminergic  Dyskinesia
effect at central  Akinetic crisis
D2 receptors

Monoamine  Stops breakdown of  Headache

 Selegiline
oxidase B dopamine to metabolite  Dyskinesia
 Rasagiline
inhibitors DOPAC  Neuropsychiatric effects (eg, hallucinations)

 Inhibition of NMDA
receptor
 Livedo reticularis
NMDA  ↑ dopamine release
 Amantadine  Ataxia
antagonists  ↓ dopamine reuptake
 Peripheral edema
 Drug of choice for
akinetic crisis

3-OMD = 3-O-methyldopa; BBB = blood brain barrier; CNS = central nervous system;. COMT = catechol-O-methyltransferase; DOPAC = 3,4-
dihydroxyphenylacetic acid; GI = gastrointestinal; L-DOPA = levodopa; NMDA = N-methyl-D-aspartate.
Summary of Diuretics

Mechanism of
Class/Drug Use Adverse Events
Action

Carbonic Anhydrase  Block

 Drowsiness
Inhibitors carbonic
 Glaucoma  Hypokalemia
 Topical: anhydrase in
 Acute mountain  Metabolic
dorzolamide, proximal
sickness acidosis
brinzolamide tubule
 Urine  Paresthesia
 Intravenous,  Decrease
alkalinization  Hypersensitivi
oral: bicarbonate
ty
acetazolamide absorption

Loop Diuretics  Inhibit Na-K-  CHF  Low

 Furosemide 2Cl cotranspo  Pulmonary potassium,
 Torsemide rter in loop of edema magnesium,
 Ethacrynic acid Henle  Acute renal calcium
failure  Elevated uric
 Hypercalcemia acid
 Hypertension  Ototoxicity
 Hypersensitivi
ty
  Metabolic
alkalosis

 Acute
 Osmotic  Cerebral edema hypovolemia
diuretic;  Acute  Pulmonary
Mannitol increases glaucoma edema and
water  Clears renal CHF
excretion toxins (contraindicati
ons)

 Offset
 Inhibit
Sodium Channel hypokalemia of
sodium
Blockers other diuretics  Acidosis
channels in
 Amiloride  Hyperaldostero  Hyperkalemia
collecting
 Triamterene nism
duct
 Lithium toxicity

 Hypokalemia
 Metabolic
 Hypertension
Thiazide Diuretics  Inhibit Na-Cl alkalosis
 CHF
 Chlorthalidone cotransporter  Hypercalcemia
 Renal stones
 Hydrochlorothia in distal  Hyperuricemia
 Nephrogenic
zide convoluted  Hypersensitivi
diabetes
 Indapamide tubule ty
insipidus
 Hyperglycemi
a

CHF = congestive heart failure.

Tetralogy of Fallot includes pulmonic valve stenosis, right ventricular hypertrophy, overriding aorta, and a ventricular septal defect.
Explanation: This infant likely has tetralogy of Fallot (ToF) as evidenced by the boot-shaped heart on chest x-ray, left upper sternal border
harsh systolic murmur, and cyanotic episodes. Of the choices, only right ventricular hypertrophy is seen in ToF.

ToF is the most common cyanotic congenital heart disease (CHD), accounting for up to 5% of all CHD. Important clinical findings include:

 Presentation: Many patients with ToF are diagnosed prenatally. After birth, most patients present around 4 to 6 months of
age. Clinical presentation at this age can be either cyanotic episodes (tet spells) or symptoms of heart failure (failure to thrive,
dyspnea, and fatigue).
 Examination: In ToF, patients classically develop a harsh systolic ejection murmur, heard best at the left upper sternal border. A single
P2 may be appreciated.
 Diagnosis: Chest x-ray may reveal a "boot-shaped heart." ECG can demonstrate signs of right ventricular
hypertrophy. Echocardiography and cardiac catheterization are the gold standards in diagnosis.

In ToF, there is significant right outflow tract obstruction secondary to anterior malalignment of the interventricular septum, which results in a
ventricular septal defect. There is also an overriding aorta as well as pulmonary stenosis/obstruction, narrowing secondary to septal deviation.
The outflow tract obstruction ultimately results in right ventricular hypertrophy. These findings are seen in the image below.
The below image is a chest x-ray that shows a boot-shaped heart (outlined in brown) due to right ventricular hypertrophy and a concave
pulmonary arterial segment seen in patients with tetralogy of Fallot.
Physical examination findings consistent with pancreatic cancer may include the Courvoisier sign, which is indicated by an enlarged and
palpable gallbladder that is classically painless, resulting from the gallbladder having become dilated because of blockage of the common bile
duct by a mass in the head of the pancreas.
ExplanationThis patient likely has pancreatic cancer, as evidenced by a presentation that is consistent with the most common symptoms of this
disease, including epigastric pain, weight loss, fatigue, and anorexia. Pancreatic adenocarcinoma affects the head of the pancreas in 75% of the
cases, leading to obstructive jaundice. Additionally, painless palpation of the distended obstructed gallbladder may be appreciated, which is
known as the Courvoisier sign.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Smoking is the most significant risk factor. Pancreatic
cancer has a poor prognosis, often due to an advanced stage of disease at the time of diagnosis. Surgical resection is the only potentially
curative treatment. Because of the frequently advanced presentation at the time of diagnosis, however, < 15% of patients are surgical
candidates.

Physical examination findings consistent with the diagnosis of pancreatic cancer are described by several eponymous terms, including:

 Courvoisier sign: an enlarged and palpable gallbladder, which is classically painless, resulting from chronic obstruction of the common
bile duct (eg, due to a mass in the head of the pancreas) that, over time, distends the gallbladder without significant inflammation
 Trousseau syndrome: migratory and recurrent superficial thrombophlebitis (inflammation and thrombosis of the superficial veins)
 Virchow node: left supraclavicular adenopathy suggesting an abdominal malignancy, such as pancreatic cancer
By contrast, acute inflammation of the gallbladder due to an obstructing stone (eg, in the case of acute cholecystitis) presents without
distention, often causing a positive Murphy sign.

Common Diagnostic Eponyms and Associated Conditions

Eponym Description Disease Processes

Courvoisier sign Palpable gallbladder with concomitant painless jaundice Biliary obstruction, usually pancreatic cancer

Trousseau syndrome Migratory, recurrent superficial thrombophlebitis Malignancy, commonly pancreatic

Virchow node Left supraclavicular adenopathy Abdominal malignancy, commonly pancreatic

Fever
Charcot triad Right upper quadrant pain Ascending cholangitis
Jaundice

Reynold pentad Charcot triad with altered mental status and hypotension Ascending cholangitis

Murphy sign Pain with inspiration on palpation of the gallbladder Acute cholecystitis

Kehr sign Pain in the left shoulder due to irritation of the diaphragm Ruptured spleen

Pain palpation LRQ abdomen 1/3rd from R ASIS to umbilicus =

McBurney point Acute appendicitis
appendix base

Rovsing sign Pain in RLQ w/ palpation of L side of abdomen Acute appendicitis

Blumberg sign Rebound tenderness Peritonitis

Grey-Turner sign Ecchymosis of flank d/t retroperitoneal bleeding Hemorrhagic pancreatitis

Hemorrhagic pancreatitis
Cullen sign Periumbilical ecchymosis w/ edema of subcutaneous tissue
Ruptured ovarian cyst

Fox sign Ecchymosis over inguinal ligament d/t retroperitoneal bleeding Hemorrhagic pancreatitis

Battle sign Ecchymosis at base of skull Basilar skull fracture

Homan sign Calf pain w/ dorsiflexion of foot Deep vein thrombosis

Alpha2 receptors occur primarily on presynaptic nerve terminals, where they inhibit the release of norepinephrine and acetylcholine. Some
alpha2 receptors cause vasoconstriction, but alpha1 is the dominant receptor maintaining vasoconstriction. Thus, lack of stimulation of
alpha2 receptors is unlikely to cause this patient’s symptoms.
Beta1 receptors are found in the heart, where they increase the rate and force of the contraction, and the juxtaglomerular apparatus in the
kidney, where they increase the release of renin. The inability of this patient’s heart rate to increase when he stands up is due to a lack of
stimulation of beta1 receptors by norepinephrine in the heart. It is not, however, the cause of his postural hypotension, which results from lack
of alpha1 stimulation.
Beta2 receptors are found in the heart, blood vessels supplying skeletal muscle, the lung, and the liver. They respond to circulating epinephrine
but not norepinephrine. They increase heart rate and force of contraction, relax smooth muscle in blood vessels and bronchioles, and increase
gluconeogenesis and glycogenolysis in the liver. Since the deficit causing the patient to have low blood pressure is a lack of norepinephrine, this
would have no effect on beta2 receptors, since they respond only to epinephrine.
Dopamine D1 receptors in the periphery are located on renal vascular beds, where they cause vasodilation. Thus, loss of stimulation of
D1 receptors would not cause a decrease in blood pressure, as is seen in this patient.

Paroxysmal nocturnal hemoglobinuria presents with episodic hemoglobinuria. Its symptoms are caused by the inability to inhibit complement-
mediated cell lysis.
Explanation: This patient's presentation is consistent with paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by
complement-mediated hemolysis. PNH is caused by an acquired mutation in the PIGA gene that results in decreased synthesis of the
glycosylphosphatidylinositol (GPI) anchor protein. In the absence of the GPI anchor protein, cell surface proteins that would normally
inactivate complement (eg, CD55 decay accelerating factor and CD59 membrane attack complex inhibitory protein) are unable to attach to the
cell surface. The absence of these protective proteins results in complement-mediated hemolysis of red blood cells.

Patients with PNH will sometimes present with dark urine secondary to hemoglobinuria. Dark urine is most commonly seen upon
awakening due to increased binding of complement to red blood cells overnight. This occurs because sleeping is associated with a mild
respiratory acidosis due to a decreased respiratory rate and complement more readily binds to red blood cells in acidotic states.

On the COMLEX, patients with PNH will often present with a classical triad of Coombs test–negative hemolytic anemia, large vein thrombosis,
and pancytopenia. Thrombosis is believed to occur secondary to the release of prothrombotic factors from lysed red blood cells and is often
seen in the hepatic vein. As a result, patients may present with acute right upper quadrant pain, hepatosplenomegaly, and evidence of liver
dysfunction. Additional sites of thrombosis can include the portal, mesenteric, and cerebral veins. Pancytopenia is believed to occur secondary
to stem cell injury.

For patients with suspected PNH, diagnosis is made via flow cytometry that will show an absence of CD55/59 on red blood cells. Treatment is
with eculizumab, a monoclonal antibody that inhibits terminal complement protein C5.

Paroxysmal Nocturnal Hemoglobinuria

Acquired mutn PIGA gene  impaired synthesis of glycosylphosphatidylinositol anchor protein  impaired
Pathophysiology
attachment of protective proteins  complement-mediated hemolysis

Classical triad:
 Hemolytic anemia
 Pancytopenia
Clinical features  Large vein thrombosis
Other features:
 Hemoglobinuria (dark urine), often seen upon awakening
 Renal dysfunction secondary to hemosiderosis

 Hemolytic anemia
  lactate dehydrogenase
  indirect bilirubin
Laboratory findings
  reticulocytes
  haptoglobin
 Negative Coombs testing

Diagnosis Flow cytometry is negative for CD55/59

Management Eculizumab (targets terminal complement protein C5)

Shigella dysenteriae is a virulent, Gram-negative rod that does not ferment lactose and does not produce hydrogen sulfide. S. dysenteriae is
transmitted through ingestion of contaminated food and presents as fever, mucoid/bloody diarrhea, and abdominal pain.
Explanation: This patient likely has an infection with Shigella dysenteriae, as suggested by her fever, mucoid/bloody diarrhea, and abdominal
pain that began after eating what was likely a contaminated salad, as well as her stool culture that is positive for a Gram-negative
rod that does not ferment lactose or produce hydrogen sulfide (H2S).

Shigella species cause a specific type of infectious diarrhea called bacillary dysentery, which presents as blood and mucus in the stools
(dysentery) and is characterized by severe inflammation of the intestinal mucosa. Shigella dysenteriae is a Gram-negative rod that does not
ferment lactose and does not produce hydrogen sulfide. It is also acid-stable and, thus, a very low burden of pathogens (10–100 organisms) can
cause disease in patients. The abdominal tenderness in the right and left lower quadrants observed during this patient's physical examination is
consistent with the inflammation and irritation of the intestines seen in shigellosis. Moreover, this patient's history of exposure to a common
salad buffet at a wedding suggests a potential foodborne transmission, as Shigella can be transmitted via contaminated food or water.

Management includes mainly supportive care, but for individuals with severe disease and patients at risk for complications (eg, those who are
immunocompromised), treatment with either ciprofloxacin, trimethoprim-sulfamethoxazole, or azithromycin can be considered. Antibiotic
therapy should be tailored based on local antibiograms, as resistance to each of these agents has been documented in certain regions.

The following image shows Shigella. Note the pink (Gram-negative) rods, as seen on light microscopy.

The below algorithm presents the characteristic identifying features of Shigella dysenteriae and other Gram-negative bacteria. Note
that Shigella does not ferment lactose or produce H2S.
Answer A: Clostridium difficile is a Gram-positive, anaerobic rod that causes diarrhea and colitis with symptoms of mucoid, occasionally bloody
diarrhea, fever, and systemic symptoms. C. difficile infection is a common cause of healthcare-associated diarrhea, especially in patients who
have recently received antibiotics. This patient, who has no history of prior hospitalization or antibiotic use and has a negative Gram stain, is
unlikely to have C. difficile infection.
Answer B: Escherichia coli is a Gram-negative, facultative anaerobic bacterium that can cause a variety of diarrheal diseases, depending on the
pathogenic strain. Enterotoxigenic E. coli produces heat-labile and heat-stable toxins, leading to a watery, traveler's diarrhea-like illness.
Enterohemorrhagic E. coli, notably strain O157:H7, causes bloody diarrhea and is associated with hemolytic uremic syndrome, particularly in
children. E. coli typically ferments lactose, making it unlikely to be the causative organism of this patient's condition.
Answer C: Salmonella typhi is a Gram-negative and lactose-negative bacterium that causes typhoid fever. S. typhi is motile due to the presence
of flagella. S. typhi is unique in its ability to invade the intestinal mucosa and cause systemic illness. Infected patients can present with
bacteremia, constipation, or diarrhea, and 20% of patients may have rose spots on the trunk. Salmonella bacteria produce H2S, making it
unlikely to be the causative organism of this patient's condition.
Answer E: Yersinia enterocolitica is a Gram-negative, facultative, intracellular bacterium that is often implicated in zoonotic yersiniosis, which
presents as diarrhea, fever, and occasionally, pseudoappendicitis (isolated right-lower quadrant tenderness). This patient's pathogen was
acquired by ingestion of a contaminated salad (not from raw or undercooked pork/animal contact), and cases of bloody diarrhea related
to Shigella are much more common than those related to Yersinia infections.
Insight: The etiology of diarrhea may be clued in with key features. It's important to notice them when they appear on the COMLEX.

Diarrhea

Organism Notes

Bloody Diarrhea

Comma- or S-shaped organisms

Campylobacter
Growth at 42°C
 Protozoan
Entamoeba histolytica Amebic dysentery
Liver abscess

O157:H7
Enterohemorrhagic Escherichia coli Can cause hemolytic uremic syndrome
Makes Shiga-like toxin

Enteroinvasive Escherichia coli Invades colonic mucosa

Lactose negative
Salmonella (non-typhoidal) Flagellar motility
Has animal reservoir, especially poultry, and eggs

Lactose negative
Very low ID50
Shigella Produces Shiga toxin
Human reservoir only
Bacillary dysentery

Daycare outbreaks
Yersinia enterocolitica
Pseudoappendicitis

Watery Diarrhea

Pseudomembranous colitis
Clostridium difficile Associated with antibiotics and PPIs
Occasionally bloody diarrhea

Clostridium perfringens Also causes gas gangrene

Traveler's diarrhea
Enterotoxigenic Escherichia coli
Produces heat-labile and heat-stable toxins

Giardia
Protozoa
Cryptosporidium

Comma-shaped organisms
Vibrio cholerae Rice-water diarrhea
Often from infected seafood

Rotavirus
Viruses Norovirus
Enteric adenovirus

PPIs = proton-pump inhibitors.

Mumps virus and its complications, such as meningitis, can be prevented or lessened with the administration of the MMR (measles, mumps,
and rubella virus) vaccine.
Explanation: This patient likely has meningitis as a complication of mumps virus infection. The swelling on the right side of the face is indicative
of parotitis due to dissemination of the mumps virus to the salivary glands. The virus has further spread to the meninges of the central nervous
system, producing symptoms of meningitis, including severe headache, fever, nausea, and vomiting. This is supported by the inability of the
patient to move his head back without pain (neck stiffness).

The patient demonstrated elevated white blood cell numbers with a predominance of lymphocytes, normal glucose levels, increased opening
pressure, and slightly elevated protein in the cerebrospinal fluid, supporting the diagnosis of viral meningitis. A lack of Gram staining of the
cerebrospinal fluid confirms aseptic meningitis. Together with the unilateral painful swelling of the face, the patient likely has mumps and viral
meningitis.

The vaccine most effective at preventing or lessening the severity of mumps infection is the live-attenuated MMR (measles, mumps, and
rubella) vaccine. The vaccine status of the patient was not provided because this could be an unvaccinated patient or a breakthrough case in a
fully vaccinated patient.
 Cerebrospinal Fluid Analysis of Bacterial vs. Viral Infections

Reference Range Bacterial Viral

White blood cells 0–10/mm3 10–2,000/mm3 100–1,000/mm3

Predominant cell type None – few cells (any type) Neutrophils Lymphocytes

Glucose 40–70 mg/dL < 40 mg/dL 40–70 mg/dL

Pressure 70–180 mmH2O 200–500 mmH2O < 250 mmH2O

Protein 8–32 mg/dL > 32 mg/dL 8–32 mg/dL or > 32 mg/dL

Answer A: The Hib vaccine is administered to prevent infection by Haemophilus influenzae type b bacteria, which can disseminate from the
nasopharynx to the meninges. This infection can occur throughout life but is more likely during early childhood. This patient's cerebrospinal
fluid analysis, however, was not consistent with bacterial meningitis, given the predominance of lymphocytes, normal glucose levels, and lack
of bacterial staining. Therefore, this vaccine would not be the most effective at preventing his disease.
Answer B: IIV, or inactivated influenza virus tetravalent vaccine, is given seasonally to prevent influenza. While rare, the influenza virus may
produce aseptic meningitis similar to that seen in this patient. However, this patient’s painful facial swelling is more indicative of the mumps
virus. Head and neck swelling from the influenza virus is rare and usually restricted to the cervical lymph nodes. Therefore, the IIV vaccine
would not be the most effective at preventing his disease.
Answer C: The MenACWY vaccine is administered to school-aged children to prevent infection and subsequent meningitis caused by Neisseria
meningitidis or meningococcus. If this patient had meningococcal meningitis, there would likely be a rash characteristic of meningococcal
dissemination. Additionally, the patient's cerebrospinal fluid did not reveal Gram-negative bacteria upon staining, making N.
meningitidis meningitis unlikely. Therefore, this vaccine would not be the most effective at preventing his disease.
Answer E: The PCV-13 and new PCV-15 vaccines are designed to prevent Streptococcus pneumoniae or pneumococcus infection. While
pneumococcus is a major cause of upper respiratory infections and meningitis, this patient did not have cerebrospinal fluid analysis consistent
with a bacterial infection (ie, neutrophil-dominant leukocytes and decreased glucose). In addition, streptococcus would stain as Gram-positive,
which was not seen. Therefore, the PCV-13 vaccine would not be the most effective at preventing his disease.

Vitamin Coenzyme Typical Reaction Type Consequences of Deficiency

Thiamine (B1) Thiamine pyrophosphate Aldehyde transfer Beri beri (neurologic and cardiac dysfunction)

Flavin mononucleotide and flavin

Riboflavin (B2) Oxidation reduction Dermatitis, cheilosis
adenine nucleotide

Niacin (B3) NAD+, NADP+ Oxidation reduction Pellagra (dermatitis, dementia, diarrhea, death)

One-carbon transfers; thymine

Folic acid (B9) Tetrahydrofolate Macrocytic anemia, neural tube defects
synthesis

Cobalamin 5'-deoxyadenosylcobalamin and

Methyl group transfer Macrocytic anemia, methylmalonic acidosis
(B12) methylcobalamin

Biotin (B7) Biotin-lysine adducts Carboxylation Rare: dermatitis, hair loss

Group transfer to or from amino

Pyridoxine (B6) Pyridoxal phosphate Rare: confusion, skin rashes
acids

Pantothenic
Coenzyme A Acyl group transfer Rare: numbness, irritability
acid (B5)

Sensory Receptors and Functions

Receptor Location(s) Stimuli Function

Free nerve Dermis Pain Detect pain, hot and cold temperatures, and
ending Cornea Temperature touch pressure
Tongue Mechanical deformation
 Joint capsules

Epidermis
Detect low-frequency vibrations in skin and
Merkel disc Dermis Vibration
mucosa
Mucosal membranes

Ruffini Dermis
Stretch of joints Monitor stretch level of joints
corpuscle Joint capsules

Meissner Papillary dermis Touch

Detect light touch of skin
corpuscle (fingertips and lips) Vibration

Deep dermis
Pacinian Deep pressure Detect pressure and vibrations associated with
Subcutaneous tissue
corpuscle High-frequency vibration movement around joints
Joint capsule

Hair follicle Wrapped around hair

Movement of hair Detect movement of hair at the skin surface
plexus follicles in dermis

Muscle spindle Skeletal muscle fibers Stretch of muscle Monitor stretch levels of muscles

Golgi tendon
Tendons Stretch of tendon Monitor stretch levels of tendons
organ

Congenital syphilis can present with profuse rhinitis ("snuffles"), hepatomegaly, jaundice, rash, generalized lymphadenopathy, and skeletal
abnormalities. Testing for congenital syphilis should include the venereal disease research laboratory (VDRL) test and/or the rapid plasma
reagin (RPR) test, which should then be confirmed with a more specific treponemal test.
Explanation: The premature infant described in this vignette has significant rhinitis (“snuffles”), hemolytic anemia, thrombocytopenia, a skin
rash involving the palms and soles, and hepatomegaly. Of the answer choices provided, he is most likely to have a positive serum venereal
disease research laboratory (VDRL) test due to congenital syphilis. Infants with congenital syphilis are treated with intravenous penicillin G.

Congenital syphilis is caused by the spirochete Treponema pallidum and may present with a wide spectrum of symptoms, ranging from stillbirth
or premature delivery to rhinitis (snuffles), hepatomegaly (+/– splenomegaly), maculopapular or vesicular rash with desquamation (can be
anywhere but is prominent on the back, buttocks, thighs, and soles), generalized lymphadenopathy, and skeletal abnormalities (sabre shins,
metaphyseal serration). Other manifestations, which are caused by the rapid dissemination of T pallidum, include the saddle nose deformity,
central nervous system invasion, myocarditis, pneumonia, condylomata lata, and hemolytic anemia.

The diagnosis of syphilis involves starting with a nontreponemal screening test, which is sensitive but not specific. Nontreponemal tests include
the VDRL test and the rapid plasma reagin (RPR) test. These tests must then be confirmed with a specific treponemal test such as the
fluorescent treponemal antibody absorption and the T pallidum particle agglutination test. Maternal VDRL or RPR titers should also be
obtained.

Dextromethorphan (DXM) is found in over-the-counter cough syrups and has multiple mechanisms of action, including NMDA receptor
antagonism and serotonin and norepinephrine reuptake inhibition. Symptoms of DXM abuse include confusion, sedation, hallucinations, fever,
tachycardia, and blurred vision.
Explanation: This patient's history of over-the-counter cough syrup use and his current symptoms are suggestive of dextromethorphan abuse.
Dextromethorphan (DXM) is most commonly found in over-the-counter cough syrups and belongs to the morphinan class of medications; as
such, it has sedative, dissociative, and stimulant properties. DXM has multiple mechanisms of action, including the following:
 Noncompetitive antagonist of NMDA receptors
 Serotonin and norepinephrine reuptake inhibitor
 α1-receptor agonist
 Negative modulator of nicotinic acetylcholine receptors
 Slight agonist activity at mu (μ) opioid receptors

Common side effects of DXM include drowsiness and sedation. However, when taken in high doses, patients can present with hallucinations,
dissociation, diaphoresis, fever, hypertension, tachycardia, blurred vision, dilated pupils, and urinary retention (amongst others). Antagonism
of NMDA receptors is what causes hallucinations and dissociation; as such, these symptoms are also seen with other NMDA antagonists such as
ketamine.

In most cases, treatment of DXM abuse and overdose is largely supportive. However, given that DXM does have mild agonist effects at μ opioid
receptors, naloxone can be given for overdose.

Asbestos is one of several pneumoconioses and is commonly linked to occupational exposures in old naval shipyards, roofing material, ceiling
tiles, and the demolition of old buildings. Patients most commonly present with dyspnea on exertion and dry cough which can progress to
hemoptysis. Additionally, pulmonary function testing in these patients often reveals a restrictive pattern with a decreased FEV1, decreased
FVC, and a normal FEV1/FVC ratio. Asbestos is a family of crystalline hydrated silicates that exists in two different geometric forms, serpentine
and amphibole fibers. Asbestos bodies are golden-brown, fusiform or beaded rods that consist of these asbestos fibers which are coated with
an iron-containing proteinaceous material.

Lateral strain patterns occur when there is rotation of the sphenoid and occiput in the same direction along 2 parallel vertical axes, producing a
shearing force at the sphenobasilar synchondrosis. These strains are named according to the direction of the basisphenoid shift, which is
opposite the direction that the greater wings of the sphenoid move (ie, rightward movement of the greater wings is indicative of the left lateral
strain).
Explanation: This patient's finding on osteopathic structural examination of a rightward translation of the greater wings of the sphenoid in
relation to the occiput is consistent with the diagnosis of a left lateral strain pattern.

Cranial strain patterns of the sphenobasilar synchondrosis (SBS) are appreciated from the vault hold. These strain patterns can be classified by
the implicated axes of motion and their effects on the primary respiratory mechanism. Physiologic strain patterns are typically well
compensated and do not negatively impact physiologic function, whereas pathologic (non-physiologic) strains result in impaired function of
primary respiration.

This patient is noted to have a rightward translation of the greater wings of the sphenoid in relation to the occiput, which is consistent with a
left lateral strain pattern. Lateral strains occur due to a shearing force at the SBS in either the right or left direction. This type of dysfunction
occurs along 2 parallel vertical axes that rotate in the same direction, resulting in the movement of the basisphenoid and basiocciput in
opposite directions.

Understanding the nomenclature of strains is necessary to identify the patient's strain pattern. For example, due to the rotation of the
sphenoid along its vertical axis, the greater wings of the sphenoid shift in the opposite direction of the base of the sphenoid. Because lateral
strains are named according to the direction of basisphenoid shift, this patient's rightward shift of the greater wings is associated with a left
lateral strain.

The following table demonstrates the various cranial strain patterns, including their involved axes and effects on physiologic function.

Cranial Strains: Naming and Axes of Motion

Strain Phys/Path Named For Axis of Motion

Flexion/expansion Physiologic Superior SBS 2 parallel transverse

Extension/contraction Physiologic Inferior SBS 2 parallel transverse

Torsion Physiologic Superior/cephalad greater wing of the sphenoid AP

Sidebending rotation Physiologic Convexity/wide finger side (left or right) 3 total: AP (sidebend), 2 parallel vertical (rotation)

Superior vertical strain Pathologic Superior sphenoid base 2 parallel transverse

 Inferior vertical strain Pathologic Inferior sphenoid base 2 parallel transverse

Lateral strain Pathologic Direction sphenoid base points (left or right) 2 parallel vertical

AP = anterior-posterior; SBS = sphenobasilar symphysis/synchondrosis (ie, joint at which the sphenoid and occiput bases meet).

This image depicts the 2 parallel vertical axes and rotation observed in a left lateral strain.

Answer B: A sidebending rotation strain would occur around 1 AP axis and 2 parallel vertical axes. A sidebending rotation strain is considered a
physiologic motion at the SBS joint. Unlike lateral and vertical strains, which are named for the motion at the sphenoid base, sidebending
rotations are named for the side of convexity/widening. For example, in a left sidebending rotation, the sphenoid and occiput first rotate in
opposite directions (sphenoid right/clockwise and occiput left/counterclockwise) around 2 parallel vertical axes. Then, the sphenoid and
occiput sidebend left in the same direction around a single anterior-posterior (AP) axis (because the left side is the wide/convex side). In the
vault hold, the physician’s palpatory sensation feels as if the fingers widen and move inferiorly on the side of the sidebending (left in this case).
On the other side (right), the fingers will narrow and move superiorly.

To summarize left sidebending rotations: left fingers separate/widen and move inferiorly on the side of convexity (the side that the sphenoid
and occiput sidebend move toward), and the right fingers narrow/approximate and move superiorly on the side of concavity (the side that the
sphenoid and occiput rotate toward). The sidebending precedes the rotation in sidebending rotation cranial strains. Because sidebending
rotations are named for the side of convexity, that finger motion describes a left sidebending rotation around an AP and 2 parallel vertical axes.

Answer C: Torsions are considered a physiologic motion at the SBS joint. Unlike lateral and vertical strains, which are named for the motion at
the sphenoid base, torsions are named for the superior/cephalad motion of the greater wing of the sphenoid. For example, in a left torsion, the
left greater wing of the sphenoid would be superior/cephalad, whereas the left squamous portion of the occiput would be inferior/caudad. This
motion occurs around a single AP axis.

In the vault hold, the physician’s palpatory sensation feels as if the left index finger moves superiorly, the right index finger moves inferiorly,
the left fifth finger moves inferiorly, and the right fifth finger moves superiorly. This patient is presenting with findings of a lateral translation
and impaired primary respiratory mechanism that are more consistent with a left lateral strain.

To summarize left torsions: left index finger moves superiorly/cephalad (greater wing of the sphenoid is superior) while the left fifth finger
moves inferiorly/caudad (squamous portion of occiput inferior). Because torsions are named for whichever greater wing of the sphenoid is
superior, that finger motion describes a left torsion around an AP axis.
AP = anterior-posterior.
Answer D: Lateral strain patterns result from a lateral shearing force at the SBS. There is movement of the sphenoid and occiput in the same
direction across 2 parallel vertical axes. This dysfunction is named according to the direction of the basisphenoid shift. Because this patient is
noted to have a rightward translation of the greater wings of the sphenoid in relation to the occiput, it can be inferred that the base of the
sphenoid shifted to the left (ie, left lateral strain).

Answer E: In sidebending rotation strains, the sphenoid and occiput rotate in the same direction around an AP axis and in opposite directions
about 2 vertical axes passing through the foramen magnum and the center of the sphenoid. Because these strains are named after the area of
convexity, a right sidebending rotation represents a convexity on the right. The motion during the cranial rhythmic impulse is described as a
fullness on the side for which the dysfunction is named. This convexity would be noted during the vault hold. This patient is presenting with
findings of a lateral translation and impaired primary respiratory mechanism that are more consistent with a left lateral strain.

AP = anteroposterior.
Answer F: Right torsions are physiologic strain patterns and do not influence the primary respiratory mechanism. These dysfunctions occur due
to the movement of the sphenoid and occiput in opposite directions around an AP axis. A right torsion would be expected when the right
greater wing of the sphenoid is superior in comparison to the left side. This patient is presenting with findings of a lateral translation and
impaired primary respiratory mechanism, which are more consistent with a left lateral strain.
AP = anterior-posterior.
Insight: The vault hold is a commonly used position for osteopathic cranial diagnosis and treatment as the patient is lying supine on the table.
In the vault hold, the physician’s palpatory sensation feels as if the left index finger moves superiorly and the right index finger moves inferiorly
because the index finger is giving information about the positioning of the greater wing of the sphenoid. The positioning of the vault hold
includes:
 Thumbs: together but hovering over the frontal bone without contact
 2nd digit: greater wing of the sphenoid bone
 3rd digit: anterior to external auditory meatus on temporal bone
 4th digit: posterior to external auditory meatus on the temporal bone, superior to the mastoid process
 5th digit: squamous portion of the occipital bone

Haemophilus influenzae type b or non-type b species are etiologic agents of epiglottitis in children.
ExplanationThis child is presenting with a sore throat, high fever, drooling (inability to tolerate own secretions), and tripoding (leaning
forward), concerning for epiglottitis. Epiglottitis is defined as the inflammation of the epiglottis and its surrounding structures. Haemophilus
influenzae type b (Hib) was the most common infectious agent of epiglottitis in children until the introduction of the Hib vaccine. However, it
can still occur in non-immunized, as well as immunized, children with non-type b strains of H. influenzae, which is a gram-negative,
pleomorphic coccobacillus. Dysphagia, drooling, and distress (3 Ds) are hallmarks of epiglottitis in children. Cough is typically absent.

The airway of a patient with epiglottitis is of main concern, as disease progression can cause obstruction, compromising the patient's ability to
breathe. Patients preferably should have their airway secured with endotracheal intubation in the operating room, when feasible, if the patient
is decompensating.

Important clinical characteristics of Haemophilus influenzae type b (Hib) are as follows.

 A gram-negative pleomorphic coccobacillus

 The most virulent among all other strains
 Spread via aerosol or direct contact with respiratory secretions
 Decreased incidence as a result of the Hib vaccine
 Non-life threatening conditions, such as sinusitis and otitis media, treated with beta-lactams such as amoxicillin-clavulanic acid
 Life-threatening diseases (e.g., meningitis, epiglottitis) treated with ceftriaxone
 Rifampin prophylaxis for close contacts
The images depict an endoscopic view of epiglottitis (left) and a classic "Thumbprint sign" on a lateral soft tissue neck radiograph (right).

Epiglottitis

Soft Tissue Neck X-ray

Epiglottis (with abscess)
(Thumbprint sign)
Answer A: Legionella pneumophila is a gram-negative bacillus that is well-known for causing Legionnaires' disease. It is characterized by severe
pneumonia, fever, diarrhea, and CNS symptoms. It is transmitted via aerosol from water sources, such as air conditioning systems, and can be
detected by urine antigen. This patient has no reported water-related environmental exposure. Furthermore, this patient does not have
symptoms such as a cough or diarrhea consistent with Legionnaire's disease.
Answer C: Neisseria species are gram-negative diplococci that can cause a variety of diseases. Gonorrhea, for example, is a sexually transmitted
disease caused by N. gonorrhoeae. It can also result in septic arthritis, neonatal conjunctivitis, pelvic inflammatory disease, and Fitz-Hugh-Curtis
Syndrome. Treatment is with ceftriaxone (+ azithromycin or doxycycline to cover chlamydia). On the other hand, infection with N.
meningitidis leads to meningitis, meningococcemia along with petechial hemorrhages, and Waterhouse-Friderichsen syndrome. This patient
presents with a fever and sore throat. He is also drooling and tripoding, concerning more for epiglottitis than meningitis or other Neisseria-
related illnesses.
Answer D: Corynebacterium diphtheriae is a gram-positive bacillus that causes diphtheria. It is characterized by pharyngitis with a gray-white
membrane at the oropharynx, also known as pseudomembranous pharyngitis, as well as lymphadenopathy. It is transmitted through
respiratory droplets. There is also a cutaneous form of diphtheria that causes chronic non-healing sores and ulcers coated with a gray-white
membrane. Although a sore throat is a typical symptom of diphtheria, this patient has no pseudomembranous finding on his oropharyngeal
exam. Furthermore, he has a classic presentation of epiglottitis - fever, sore throat, tripoding, and drooling.
Answer E: Streptococcus pyogenes is a gram-positive cocci in chains that can cause a wide array of diseases. Pyogenic diseases include
pharyngitis, peritonsillar abscess, cellulitis, and impetigo. Toxigenic causes include scarlet fever, toxic shock-like syndrome, and necrotizing
fasciitis. This patient's clinical presentation is concerning for epiglottitis, which is classically associated with H. influenzae. S. pyogenes can
cause epiglottitis but does so to a lesser extent. There are also no other physical findings pointing towards an oral, skin, or systemic
manifestation of S. pyogenes infection.

Sickle cell crises usually present with joint pain, acute chest syndrome, and splenomegaly. Acute chest syndrome can present as pneumonia
with fever, chest pain, and pulmonary infiltrates. Hemoglobin electrophoresis is used to diagnose sickle cell disease.
ExplanationThis patient with fever, tachypnea, joint tenderness, splenomegaly, dehydration, and suspected pain is most likely experiencing
a sickle cell crisis. His underlying sickle cell disease (SCD) would be best diagnosed using hemoglobin electrophoresis. In the United States, SCD
is also included in the newborn screening panel. SCD is most commonly found in African American patients.

During a sickle cell crisis, sickled red blood cells (RBCs) adhere to vascular endothelial cells causing increased inflammation and activation of
hemostatic mechanisms. These changes cause vascular obstruction and vaso-occlusion, leading to pain and other consequences described
below. They are often brought on by infection, dehydration, or hypoxia.

Characteristic presentations of this condition are discussed below.

 Pain (vaso-occlusive) crisis: This is the most common type of vaso-occlusive event in SCD. Pain episodes can begin as early as 6
months of age. The first pain crisis in young children is often dactylitis (acute pain/swelling in hands and feet). Later on, sites of pain
can include the back, chest, extremities, and abdomen.
 Acute chest syndrome: This refers to a syndrome of fever, chest pain, hypoxemia, or respiratory distress in the setting of a new
pulmonary infiltrate. The cause is often multifactorial (infection, vaso-occlusion, hypoventilation, atelectasis, or fat embolism from
bone marrow).
 Splenic sequestration: This is a potentially life-threatening complication of SCD that mostly occurs in young children with SCD whose
spleens have not yet become fibrotic due to repeated splenic infarction. Patient presentation includes a massively enlarging spleen,
decrease in hemoglobin, and thrombocytopenia.
The image below shows the physiology behind a normal RBC compared with a patient with SCD in regard to vaso-occlusive crisis.

Normal Red Blood Cell Versus Sickle Cell Red Blood Cell

The Thomas test is a useful tool in the evaluation of psoas syndrome.

ExplanationThis patient presents with history and physical findings of psoas syndrome or psoas tendonitis. The special test used to aid in the
diagnosis of this condition is the Thomas test. This test is performed by the patient lying supine, flexing the contralateral knee to the chest
while the affected leg is extended to the exam table. If the affected knee remains involuntarily flexed, the test is positive.

Osteopathic pearl: A positive psoas tender point is a common finding in psoas syndrome, as shown in the exhibit.

Psoas syndrome is typical in athletes performing repeated hip flexion, such as runners, dancers, and gymnasts. Psoas syndrome commonly
presents as pain and stiffness in the hip and thigh region. A snapping feeling is also frequently reported, which is caused by the iliopsoas tendon
catching on the pelvis when the hip is flexed. Typical physical examination and osteopathic examination findings are as follows.

 Tender point medial to the ipsilateral anterior superior iliac spine

 Positive pelvic shift test to the contralateral side
 Sacral dysfunction on an oblique axis
 L1 type 2 somatic dysfunction with flexion, side bending, and rotation to the ipsilateral side
 Spasm of the contralateral piriformis muscle
The Thomas test is positive when the posterior thigh does not touch the table when the contralateral (unaffected) thigh and knee are flexed to
the chest. In a positive test, the knee also flexes less than 80°. These findings occur due to the abnormal length of the hip flexors. The image
below shows positive findings in a patient with a left psoas syndrome (A) compared to normal (B).

Answer A: A patient that is lateral, while extending and adducting the left leg toward the exam table describes the Ober test. This test assesses
for iliotibial (IT) band syndrome, which presents with lateral thigh tenderness affecting anywhere from the pelvis to the tibia. This patient's hip
snapping sensation and the exhibit showing a psoas tender point is most consistent with psoas syndrome, which is diagnosed with the Thomas
test.
Answer B: A patient that is lateral, while extending and adducting the right leg toward the exam table is a provocative maneuver describing the
Ober test, which is used to assess for iliotibial band syndrome. As the thigh is allowed to adduct passively, if the thigh remains suspended off
the table, this indicates a shortened IT band. This patient presents with signs and symptoms of left psoas syndrome. The Thomas test would be
more useful in aiding in the diagnosis of psoas syndrome.
Answer C: Hip flexion and external rotation followed by internal rotation and extension is a provocative maneuver used to test for internal
snapping hip syndrome. While this test would be useful to aid in the diagnosis of psoas syndrome, this patient presents with signs and
symptoms of left psoas syndrome. Therefore, the left hip should be assessed on physical examination, not the right.
Answer D: A patient that is supine while flexing the left knee to the chest and extending the right leg to the exam table is describing the
technique to perform the Thomas test on the right hip. This patient presents with signs and symptoms of left psoas syndrome. Therefore, the
right knee should be flexed to the chest and the left leg extended to properly test for psoas syndrome in this patient.

In subclavian steal syndrome, the basilar artery allows for communication between the left and right sides of the body, resulting in the steal
phenomenon. When there is a critical level of stenosis involving the subclavian artery proximal to the ipsilateral vertebral artery, retrograde
blood occurs through the vertebral arteries when the ipsilateral extremity becomes ischemic. If this collateral blood flow is insufficient to
maintain the metabolic needs of the affected extremity, further blood is "stolen" from the brain, resulting in cerebral ischemia.
Explanation: This question describes the clinical phenomenon known as subclavian steal syndrome. The left subclavian artery has several
branches that include the costocervical trunk, thyrocervical trunk, and vertebral artery. In the case of proximal subclavian artery stenosis, blood
flow through the subclavian artery to the ipsilateral upper limb is diminished; however, perfusion to the affected extremity is maintained
through the ipsilateral vertebral artery. This occurs via retrograde blood flow to the affected extremity. The basilar artery allows for
communication between the left and right vertebral arteries, thus, allowing for collateral blood flow to reach the affected extremity.

When the above patient uses her left arm, her left upper extremity becomes ischemic resulting in vasodilation stealing blood from the brain if
collateral circulation through the contralateral vertebral is insufficient. This results in cerebral ischemia and, in this case, dizziness. Of note,
some collateral flow may occur through the Circle of Willis; however, these vessels are much smaller than the basilar artery and do not
generally contribute a large amount of blood to the ischemic extremity.

Lactase (disaccharidase) deficiency most often develops in its acquired form after childhood, because of downregulation of the lactase gene,
resulting in the defective breakdown of the lactose disaccharide and osmotic diarrhea.
ExplanationThis patient has lactase (disaccharidase) deficiency. She has the acquired type, which is caused by the downregulation of the
lactase gene. It is most common in Native Americans, African Americans, and Asian people. When patients do not have the lactase enzyme
they are unable to digest lactose. These sugars (disaccharides) are unable to be absorbed through the intestinal wall and create a hyperosmotic
intraluminal gradient that draws water into the intestinal lumen causing watery stool. They also are fermented by colonic bacteria, which
results in gas production, causing the symptoms noted by this patient. Her symptoms likely improved when she was treated with antibiotics for
her urinary tract infection because they decreased the colonic bacteria, preventing the fermentation of the lactose that causes the symptoms.

In the question, this patient notes that her symptoms begin after eating a bowl of cereal and drinking a glass of milk. This can also point to a
diagnosis of celiac disease, in which patients have an intolerance to the gluten within the cereal. This patient had a negative tissue
transglutaminase antibody, making celiac disease an unlikely diagnosis; therefore, her symptoms are most likely due to her inability to digest
the lactose in the glass of milk.

Confirmatory diagnosis for lactose intolerance could be done with the lactose hydrogen breath test, which would show an increased hydrogen
content. Additionally, if a stool sample were to be taken from the patient it would demonstrate a decreased pH level, suggestive of lactase
deficiency. A biopsy of her intestine would show normal mucosa. Treatment is based on the avoidance of dairy or supplementation of the
lactase enzyme.

Lactase Deficiency

 Insufficient lactase enzyme

o Digest lactose on the intestinal brush border
 Into glucose and galactose
o Osmotic gradient forms from undigested sugars
 Primary
o Absence of lactase-persistent allele
o Childhood presentation
o Patient population
Biochemistry
 Asian
 African
 Native American
 Secondary
o Loss of intestinal brush border
 Autoimmune disease
 Gastrointestinal inflammation
 Rotavirus

 Bloating
 Cramping
Clinical presentation  Dietary lactose intolerance
 Flatulence
 Osmotic diarrhea

 Intestinal biopsy
o Normal mucosa
 Lactose hydrogen breath test
Diagnosis
o ↑ hydrogen content
 Stool
o ↓ pH

 Avoid dairy
Treatment  Lactase pill supplement
 Lactose-free milk
Answer B: Defective lymphatic transport is the mechanism for diarrhea in Whipple disease. Whipple disease is a rare bacterial infection of the
small intestine, most common in middle-aged white men. This is not likely in this patient since her symptoms are precipitated by dairy intake
and are not constant.
Answer C: Defective peristalsis could cause constipation or diarrhea. In patients with decreased peristalsis, they would most likely have risk
factors associated with decreased motility (longstanding diabetes, opioid use, etc). Patients with increased peristalsis leading to diarrhea most
commonly will have extraintestinal features consistent with the underlying disease (hyperthyroidism, carcinoid syndrome, etc). This patient
does not have symptoms of hyperthyroidism or carcinoid syndrome and has specific triggers of her diarrhea, which is more consistent with
lactase deficiency.
Answer D: Defective transepithelial transport is one of the causes of diarrhea in celiac disease, tropical sprue, primary bile acid malabsorption,
carcinoid syndrome, autoimmune enteropathy, abetalipoproteinemia, gastroenteritis, and inflammatory bowel disease. These are not likely to
be present in this patient since her symptoms are precipitated by dairy intake and are not constant.
Answer E: Defective intraluminal digestion is a mechanism for diarrhea in chronic pancreatitis, cystic fibrosis, primary bile acid malabsorption,
and inflammatory bowel disease. These are not likely to be present in the patient since her symptoms are precipitated by dairy intake and are
not constant.
Insight
Types of Diarrhea

Inflammatory Motility Osmotic Secretory

Carbohydrates
Excess secretion of electrolytes and
Cause/ Inflammation of Hyperosmotic
Hypermotility water
clinical lumen gradient
Osmotic gap < 50
Osmotic gap > 100

Bacterial dysentery
Chemotherapy Carcinoid Drugs
Bile acid salts
Example Irritable bowel syndrome Lactose intolerance
Vibrio cholerae
disease Hyperthyroidism Lactulose
Radiation
Albendazole is the drug of choice for treating hookworm, an infection caused by Ancylostoma duodenale or Necator americanus. This drug
binds to tubulin to decrease microtubule polymerization and reduce glucose uptake by the organism.
ExplanationHookworm occurs in tropical areas with poor sanitation. It is transmitted by direct skin contact with human-fecal contaminated
soil. The scenario patient has symptoms consistent with hookworm infection. She has pruritis of the skin, gastrointestinal symptoms, and
elevated eosinophils (on complete blood count with differential). In severe cases, patients may have blood loss in the stool, which can cause an
iron-deficiency anemia. Albendazole is the drug of choice for hookworm, which works by inhibiting microtubule polymerization by binding
tubulin.

Albendazole is a benzimidazole that also includes mebendazole and prevents microtubule-dependent uptake of glucose by the worms. This
leads to decreased adenosine-triphosphate production, which causes energy depletion, immobilization/paralysis, and death of the organism.

When used for a short duration (1-3 days) to treat most hookworm infections, albendazole has minimal adverse effects. Mild and transient
epigastric distress, diarrhea, headache, nausea, dizziness, and insomnia can occur. These symptoms can be confused for hookworm infection.

Medications used to treat helminth infections are summarized in the table below.

Summary of Drugs Used in Helminthic Infections

Helminth Drug and Mechanism of Action

Nematodes
 Albendazole (or mebendazole): binds tubulin to decrease microtubule
 Hookwor
polymerization. Reduces glucose uptake.
m
 Pyrantel pamoate: is a depolarizing neuromuscular agent and causes tetany.
 Pinworm
 Ivermectin: binds to chloride channels to cause hyperpolarization and
 Ascaris
paralysis.
 Filaria

Cestodes
 Tapeworm  Praziquantel: increases calcium influx into the cell and causes spastic
Trematodes paralysis of the organism.
 Flukes

The femoral nerve arises from the L2–L4 nerve roots and is found within the femoral triangle immediately inferior to the inguinal ligament and
lateral to the femoral artery. It provides sensation for the anteromedial thigh, femur, and knee. Femoral nerve blocks can be used to provide
anesthesia for patients with pain in the setting of surgical procedures that involve the hip, knee, or quadriceps muscles/tendons.
Explanation: A femoral nerve block can be used for anesthesia for postoperative pain in patients undergoing surgical procedures involving the
hip (eg, total hip arthroplasty) or knee. To perform this procedure, an anesthetic, such as lidocaine, is injected immediately inferior to the
inguinal ligament and lateral to the femoral artery.

The femoral nerve originates from the L2–L4 nerve roots and has both motor and sensory functions:
 Motor: the femoral nerve innervates the quadriceps muscles and, therefore, is involved in leg extension at the knee and flexion at the
hip
 Sensory: the femoral nerve provides sensation for the anteromedial thigh, femur, knee, shin, and arch of the foot
In addition, it is a component of the patellar reflex.

The femoral nerve can be found within the femoral triangle. Specifically, it emerges between the psoas and iliacus muscles and then passes
under the inguinal ligament lateral to the femoral artery. After this, it branches within the femoral triangle into an anterior division and a
posterior division. With this in mind, femoral nerve blocks are placed immediately below the inguinal ligament at the lateral border of the
femoral artery. Doing this will provide adequate anesthesia to the thigh, femur, and knee. In addition, the block will anesthetize structures that
are supplied by the saphenous nerve, which decreases sensation in the medial leg below the knee.

Note that, in some cases, a femoral nerve block may be performed in conjunction with an obturator nerve block, especially for the
management of chronic hip pain.

Femoral Nerve

Origin  Nerve roots: L2–L4

Anatomy  Found within the femoral triangle

  Inferior to the inguinal ligament and lateral to the femoral artery

 Sensory: anterior thigh, medial leg

Function  Motor: quadriceps, iliacus, pectineus, sartorius
 Functions: knee extension, hip flexion, patellar reflex

 Can be injured with pelvic fractures

Injury
 Injury → ↓ leg extension, diminished patellar reflex

Clinical  Femoral nerve blocks can be used for pain management after surgical
significance procedures involving the hip or knee

The following image depicts the anatomy of the femoral triangle.

The midline posterior cervical (PC3) tender point is located on the tip of the spinous process of C2, while the lateral PC3 tender point is located
on the posterolateral aspect of the articular process of C3.
Explanation: Cervical injury can result in a wide variety of somatic dysfunction throughout the cervical spine, including strain-counterstrain
dysfunction, as seen in this case example. It is important for clinical and examination purposes to know the location of the counterstrain points
as well as the classic description of the treatment position for each.

The posterior cervical (PC) counterstrain points can be somewhat confusing given that the numbering does not correlate with the vertebrae
involved. The location of the midline tender points of PC3-PC8 are all on the spinous process of the segment above. The lateral tender points
for PC3-PC8 are located on the posterolateral aspect of the articular process at the level of the given segment.

Please refer to the table below for location and treatment positions for the posterior cervical tender points. Also, please refer to the exhibit
below for a visual representation of the location of PC1-PC8.

Tender Point Location Treatment Position

Flexion of occipitoatlantal (OA), minor side

PC1 inion Inferior nuchal line lateral to inion
bending toward, rotation away

Inferior nuchal line midway between inion and mastoid on splenius Extension of OA, mild compression of head, slight
PC1 occiput
capitis side bending, and rotation away

Extension of OA, mild compression of head, slight

PC2 occiput Inferior nuchal line within semispinalis capitis muscle
side bending, and rotation away

PC2 midline Extension of OA, mild compression of head, slight

Superior or superior lateral tip of C2 spinous process
spinous process side bending, and rotation away

PC3 midline
Inferior or inferolateral tip of C2 spinous process Flexion, side bending away, rotation away
spinous process

PC4-PC8 midline Inferior or inferolateral tip of spinous process above segment Extension, slight side bending, and rotation away
 spinous process

PC3-PC7 lateral Posterolateral tip of articular process on dysfunctional segment Extension, slight side bending, and rotation away

Posterior cervical tender points. Illustration © TrueLearn, LLC

Answer A: AC2 is located bilaterally on the anterior lateral tip of the C2 transverse process.
Answer B: AC3 is located bilaterally on the anterior aspect of the transverse process of C3.
Answer C: PC2 is located on the inferior nuchal line in the semispinalis capitis muscle or on the superior/superior lateral tip of the C2 spinous
process.
Answer E: PC4 is located bilaterally on the lateral aspect of the spinous process of C3 or on the posterolateral aspect of the articular process of
C4.
Insight: Remember to review counterstrain points (location and treatment positions) as you will see them on COMLEX.

Duchenne muscular dystrophy is an X-linked recessive disease caused by a complete absence of the dystrophin gene. Patients will have
proximal muscle weakness, pseudohypertrophy of the calves, and a positive Gower’s sign.
Explanation: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by a complete absence of the dystrophin gene. Note
that the question stem hints at the x-linked nature of the disease by stating that cognitive impairment has been displayed in males (presumably
siblings and/or relatives as the father cannot donate a faulty X chromosome to a male son).

DMD initially presents between 2 to 3-years-old with proximal lower extremity muscle weakness, which leads to muscle degeneration replaced
by fibro-fatty tissue. Patients will have a positive Gower’s sign in which the child uses his hands to walk up the legs from a seated position. The
affected child, therefore, has difficulty running, jumping, and walking up steps. An unusual waddling gait and lumbar lordosis are usually
observed. Cognitive impairment is associated with DMD and supported in the literature, although a direct neurological component has yet to
be established. Physical examination will reveal pseudohypertrophy of the calf, lumbar lordosis, and hyporeflexia.

Osteopathic Pearl: Know the most likely impacted structures associated with any disease process that features a unique gait; COMLEX likes to
ask follow-up anatomy questions to check your understanding of the mechanics of disease process. Here, that would include the gluteus
muscles, Achilles, and hip extensors (see explanation D).

Carbamazepine is used as a first-line treatment for focal tonic–clonic seizures. Carbamazepine may cause blood dyscrasias such as leukopenia,
which would necessitate discontinuing the drug.
Explanation: This patient who presented with localized motor and sensory findings along with altered consciousness most likely suffered a
focal seizure. The first-line treatment for focal seizures is with carbamazepine, which acts by blocking voltage-gated sodium channels in a
voltage-dependent fashion and has a known severe adverse event of agranulocytosis.

Focal seizures can be caused by genetic abnormalities, structural abnormalities in the brain, electrolyte imbalances, infections, and drugs.
Compared with generalized seizures, focal seizures are restricted to single regions of the brain and, therefore, will generally have more
localized motor and sensory symptoms. However, focal seizures can still present with generalized changes to awareness or consciousness as
observed in this patient.

Clinically, focal seizures can be recognized by a unilateral motor (twitching, shaking, atony) and sensory (numbness, tingling, gustatory and
auditory changes), as well as automatism (lip-smacking), emotional lability (sudden onset of laughter or crying), and cognitive changes
(dysphasia, aphasia, amnesia). Following the seizures, classic postictal changes can be observed, such as paralysis and paresthesias as well as
confusion and transient neurologic deficits.

Although a focal seizure is occurring, treatment involves supportive care of the patients (placing them in the recovery position; monitoring
airway, breathing, and circulation; ensuring the environment is safe). If a seizure has lasted longer than 5 minutes, antiseizure medications
should be given. Following the resolution of the seizure, a prophylactic antiseizure medication can be started. For focal seizures, carbamazepine
is a frequent first-line treatment. It acts by inhibiting voltage-gated sodium channels, thereby reducing neuronal excitability. Carbamazepine
has multiple severe adverse events, including Steven-Johnson syndrome, DRESS (drug reaction with eosinophilia and systemic
symptoms) syndrome, and agranulocytosis. This patient with no symptoms but a profoundly decreased leukocyte count may be experiencing
agranulocytosis and should be switched to an alternate antiseizure agent immediately.

Focal Seizures

 Genetic
 Morphologic or structural abnormalities
Etiology  Electrolyte imbalances
 Infections
 Drug intake

 Facial twitching/numbness
 Speech arrest
 Involvement of one side of the body
Clinical features  Generalization is possible
 Aura
 Impaired awareness
 Automatisms

 History and physical

Diagnostics  Assess for trauma during episodes
 Electroencephalography for epileptiform changes

 Acute resuscitation (airway, breathing, and circulation)

 Abortive therapy
Treatment/prognosis
 Long-term antiepileptic drugs needed for epilepsy
 Surgical intervention if resistant to pharmacotherapy

Relative risk is the best statistic for determining the risk of disease after a particular exposure in cohort studies. Cohort studies are prospective
in nature, and subjects are grouped by exposure at the beginning of the study.

The alveolar-arterial (A-a) gradient is normally between 4 and 15 mmHg. Measuring the A-a gradient can be useful when evaluating a patient
with hypoxemia, as a normal A-a gradient suggests that gas exchange and perfusion are not impaired. Hypoxemia with a normal A-a gradient is
typically caused by alveolar hypoventilation (eg, sedative overdose, obesity) or a low partial pressure of inspired oxygen (eg, high altitude).
ExplanationUnder normal circumstances, the partial pressure of oxygen (PAO2) is normally ~ 104 mmHg and, because of a high rate of
O2 diffusion across the alveolar-capillary membrane, the O2 level in the alveolar-capillary blood will rapidly equilibrate with the PAO2. However,
even in the absence of lung pathology, the partial pressure of oxygen in the arterial blood (PaO2) is normally around 100 mmHg. This
discrepancy between the PAO2 and PaO2 is normal and exists because of the addition of deoxygenated blood from the bronchial circulation.
This difference between the PAO2 and the PaO2 is referred to as the alveolar-arterial (A-a) gradient, and studies have shown that a normal A-a
gradient is typically between 4 and 15 mmHg. As this patient has a normal A-a gradient (65 - 58 = 7 mmHg), his hypoxemia is due to
either alveolar hypoventilation or a low fraction of inspired oxygen (FiO2).

Calculating the A-a gradient can be used to help narrow the differential diagnosis of a patient who has hypoxemia. A normal A-a gradient
suggests that perfusion and gas exchange are not impaired. With this in mind, hypoxemia in the setting of a normal A-a gradient suggests
either:

 Alveolar hypoventilation, which is seen when the central respiratory drive is suppressed (eg, sedative overdose, opioid overdose) or
with conditions that decrease the inspiratory capacity (eg, obesity hypoventilation syndrome, neuromuscular disease)
 Low FiO2 (eg, high altitude)
In contrast, an increased A-a gradient will be seen with most lung pathologies, including conditions that involve impaired diffusion capacity (eg,
pulmonary fibrosis) or a ventilation/perfusion (V/Q) mismatch (eg, pulmonary embolism, intrapulmonary shunting).

Alveolar-arterial Gradient

Description  A-a gradient = PAO2 – PaO2

 The PaO2 is slightly lower because of the addition of deoxygenated
blood from the bronchial circulation
 Normal gradient: 4–15 mmHg
  A-a gradient increases with age because of age-related decline in O2-
diffusing capacity

 Useful for narrowing the differential diagnosis of hypoxemia

Utility
 A normal A-a gradient suggests that O2 diffusing capacity is intact

Causes of hypoxemia  Alveolar hypoventilation (eg, opioid/sedative overdose, obesity

with a normal A-a hypoventilation syndrome, myasthenia gravis)
gradient  Low FiO2 (eg, high altitude)

Causes of hypoxemia  Dead space ventilation (eg, pulmonary embolism)

with  Diffusion limitation (eg, pulmonary fibrosis, emphysema)
an increased A-a  Intrapulmonary shunt (eg, pneumonia, pulmonary edema)
gradient  Right-to-left shunt

A-a = alveolar-arterial; PAO2 = partial pressure of oxygen in the alveoli; PaO2 = partial pressure of oxygen
in the arterial blood; FiO2 = partial pressure of inspired oxygen; V/Q = ventilation/perfusion.
Answer B: Dead space ventilation is seen when the alveoli are adequately ventilated but there is no alveolar perfusion (eg, pulmonary
embolism) and, as such, the O2 present in the alveoli does not get taken up into the blood. In this scenario, the A-a gradient would be increased
(not normal, as seen in this patient).
Answer C: Diffusion impairment is seen when pathology disrupts the alveolar-capillary membrane and prevents normal oxygen diffusion. This
can be seen in several forms of lung pathology, including chronic obstructive pulmonary disease and pulmonary fibrosis. Because O 2 uptake is
impaired, the A-a gradient would be increased (not normal, as seen in this patient).
Answer D: Intrapulmonary shunting occurs when blood perfuses alveoli that are not ventilated. This results in a V/Q mismatch and will thus
increase the A-a gradient, making an intrapulmonary shunt unlikely in this patient with a normal A-a gradient. Conditions that are associated
with intrapulmonary shunting include pulmonary edema and pneumonia.
Answer E: Eisenmenger syndrome is seen when an uncorrected left-to-right shunt (eg, ventricular septal defect) progresses to a right-to-left
shunt. When this occurs, deoxygenated blood on the right side of the heart bypasses the pulmonary circulation and enters the left side of the
heart and the systemic circulation. In this scenario, the PaO2 will be decreased and, as such, the A-a gradient will be increased (not normal, as
seen in this patient).
Insight: Note that the normal A-a gradient will increase with age because of age-related decline in O2-diffusing capacity.

In children and young adults, the differential diagnosis for cardiogenic syncope and/or sudden cardiac death should include hypertrophic
cardiomyopathy, congenital long QT syndromes (resulting in torsades de pointes), Brugada syndrome, and Wolff-Parkinson-White syndrome.

Hypertrophic cardiomyopathy is most commonly caused by autosomal dominant mutations involving cardiac sarcomere proteins, such as beta-
myosin heavy chain. Patients often present with presyncope/syncope, a systolic ejection murmur heard best at the left sternal border, and a
family history of sudden cardiac death. An echocardiogram showing significant interventricular septal hypertrophy confirms the diagnosis.
ExplanationThis patient likely has hypertrophic cardiomyopathy, as suggested by his young age, syncope in the setting of athletic activity,
characteristic heart murmur, family history of sudden death at a young age during athletic activity, and significant hypertrophy of the
interventricular septum on echocardiography.

Hypertrophic cardiomyopathy is an autosomal dominant disorder. It is most commonly caused by missense mutations in genes encoding
cardiac sarcomere proteins. Among the answer options, the only cardiac sarcomere protein is beta-myosin heavy chain. Hypertrophic
cardiomyopathy may also be caused by mutations in genes encoding several other cardiac sarcomere proteins, including cardiac myosin
binding protein-C (most commonly), cardiac troponin T, cardiac troponin I, myosin regulatory light chain, myosin essential light chain, alpha-
cardiac actin, and tropomyosin 1.

In hypertrophic cardiomyopathy, hypertrophy of the interventricular septum can lead to left ventricular outflow tract obstruction, resulting in
symptoms such as dyspnea on exertion and presyncope/syncope. Patients also have an increased risk of sudden cardiac death secondary to
ventricular arrhythmias. The characteristic murmur in hypertrophic cardiomyopathy is a systolic ejection murmur, which is heard best along the
left sternal border and increases in intensity with maneuvers that decrease venous return to the heart (eg, Valsalva maneuver, rising from a
sitting to standing position).

Hypertrophic Cardiomyopathy

 Autosomal dominant mutations in genes encoding cardiac sarcomere

proteins (eg, cardiac beta-myosin heavy chain)
Pathophysiology
 Asymmetric hypertrophy of the interventricular septum → left ventricular
outflow tract obstruction (hypertrophic obstructive cardiomyopathy)
  Frequently asymptomatic
 Palpitations, dyspnea, presyncope/syncope, chest pain (anginal or atypical),
fatigue
 Systolic ejection murmur
Clinical features
o Maximal along the left sternal border
o Intensity increases as left ventricular volume decreases (eg,
hypovolemia, Valsalva maneuver, moving from sitting to standing,
tachycardia)

 Electrocardiogram:
o Left ventricular hypertrophy, deep narrow Q waves in
inferior/lateral leads
Diagnosis
 Echocardiography:
o Systolic anterior motion of the mitral valve, asymmetric thickening
of the interventricular septum and left ventricular wall

 Sudden cardiac death (especially with intense physical activity)

Complications
 Heart failure

The latissimus dorsi works to adduct, extend, and internally rotate the humerus. Myofascial release to the latissimus dorsi is done with the
patient in a lateral recumbent position and the physician's caudad hand below the patient's arm and the cephalad hand over the patient's
shoulder, grasping the affected tissues and applying traction by leaning backward.
ExplanationThis patient presents with posterior shoulder pain as a result of pitching in baseball. The mechanism of injury and the location
places the likely source at the latissimus dorsi, which is the widest muscle in the human body. The origins are the spinous processes of T7-T12,
9th to 12th ribs, lumbar and sacral vertebrae, iliac crest, and the inferior angle of the scapula. The insertion of the latissimus dorsi is at the
medial lip of the bicipital groove of the humerus. It adducts, extends, and internally rotates the humerus.

Many sports activities such as tennis, gymnastics, and baseball can cause latissimus dorsi pain, and patients commonly feel pain inferior to the
shoulder blade. Myofascial release is a passive, direct or indirect technique. This technique is unique in that it can be modified to treat directly
and aggressively or indirectly and very gently. By being passive, the patient does not participate or contract muscles, and the physician does all
of the work. Myofascial release to this muscle can be done with the patient in a lateral recumbent position with the affected side up. The
physician reaches his/her caudad hand under the patient's arm and places his/her cephalad hand over the patient's shoulder. For treatment of
the lower parascapular muscles, the patient's arm is draped over the physician's cephalad arm. Traction is applied to the affected tissues by
leaning away from the patient with the physician's elbows locked in extension.

Latissimus dorsi highlighted in red.

Answer A: The deltoid muscle is responsible for shoulder abduction, flexion, and extension. Myofascial release to the deltoid muscle is done
with direct pressure over the deltoid muscle.
Answer B: The erector spinae muscle group comprises the iliocostalis muscle, longissimus muscle, and spinalis muscle. As a group, these
muscles straighten and rotate the back. Myofascial release to this group of muscles can be done with the patient in a prone position with the
physician applying pressure directly over the muscles.
Answer D: The pectoralis major muscle is responsible for adducting and medially rotating the humerus. Myofascial release to the pectoral
muscle is typically done with the patient in a supine position and the physician at the head of the table. The physician grasps the anterior
axillary folds and distal aspects of the pectoralis muscles and, with the arms in extension, leans back, away from the table.
Answer E: The serratus posterior inferior muscle suppresses the lower ribs and aids in expiration. This muscle is located deep to the inferior
portion of the latissimus dorsi muscle. Myofascial release treatment to this muscle group can be done with pressure over the lower portion of
the latissimus dorsi, the muscle that lies superior to serratus posterior inferior muscle.
InsightVideos on COMLEX, such as the one in this question, can run a minute or longer. This can be disconcerting when 80 seconds is the
average allotment for each item on the exam. Don't feel that you need to view the entire video; when you are confident that you know the
answer, complete the question, and move on.

Mixed cryoglobulinemia is a small vessel vasculitis. It is important to be able to identify different vasculitis syndromes rapidly on COMLEX.
Recall these key differences among commonly tested small vessel vasculitides.

Small Vessel Vasculitis

Behçet syndrome  Aphthous ulcers

 Erythema nodosum
 Genital ulcerations
  HLA-B51 associated
 Herpes simplex virus and parvovirus
 Immune complex
 Middle Eastern descent

 Immune complex-mediated leukocytoclastic

 7-10 days after medication/infection
o Allopurinol
o Cephalosporins
Cutaneous small vessel vasculitis o HCV
o HIV
o Penicillin
o Phenytoin
 Palpable purpura

 Asthma
 Eosinophils
 IgE levels ↑
Eosinophilic granulomatosis with
 Necrotizing vasculitis
polyangiitis
 Pauci-immune glomerulonephritis
(previously known as Churg-Strauss
 Peripheral neuropathy
syndrome)
 Purpura
 Sinusitis
 Skin nodules

 Chronic sinusitis
 Hematuria
Granulomatosis with polyangiitis  Hemoptysis
(previously known as Wegener  Mastoiditis
granulomatosis)  Necrotizing granulomas/glomerulonephritis
 Otitis media
 Perforation of nasal septum

 Abdominal pain
o Intussusception
 Arthralgia
Immunoglobulin A vasculitis  Childhood systemic vasculitis, following upper
respiratory infection
 IgA immune complexes
 Palpable purpura on buttock/legs

 Necrotizing vasculitis
 No nasopharyngeal involvement
Microscopic polyangiitis
 Palpable purpura
 Pauci-immune glomerulonephritis

 Arthralgia
 Cryoglobulin
 Hepatitis C virus
Mixed cryoglobulinemia  Palpable purpura
 Peripheral neuropathy
 Renal disease
 Weakness

Mixed cryoglobulinemia is a small vessel vasculitis characterized by palpable purpura, arthritis, peripheral neuropathy, and glomerulonephritis
resulting from precipitation of temperature-sensitive immune complexes. It is most strongly associated with hepatitis C virus infection but can
also be observed in patients with mycoplasma pneumonia, multiple myeloma, and lupus.
ExplanationThis patient is presenting with palpable purpura, arthralgia, weakness, and nonspecific systemic symptoms and has an elevated
cryoglobulin. This combination immediately raises the suspicion for mixed cryoglobulinemia syndrome (MCS). The social history of illicit drug
use raises suspicion of hepatitis C virus (HCV) infection, which is the most common cause MCS. MCS refers to the presence of either type II or
type III cryoglobulins circulating in the serum, which manifest as a systemic vasculitis that causes purpura, arthralgia, and weakness and can
advance to more severe forms that include neurologic and kidney involvement.

The pathogenesis of the syndrome is mediated by the deposition of antigen–antibody complexes within the capillaries and small arterioles. This
mechanism leads to positive antinuclear antibodies and rheumatoid factor on routine labs, given the autoimmune nature of the syndrome. In
addition, low serum C4 is frequently seen as part of the syndrome as the complement immune process is depleted. In this patient, rheumatoid
factor is positive, further supporting the diagnosis of MCS. Diagnosis of MCS does not follow a strict diagnostic protocol but is based on clinical
findings and an elevated cryoglobulin > 5 mg/dL. Cryoglobulins are IgM immune globulins that precipitate at temperatures below 37.0°C
(98.6°F).

Cryoglobulinemia is associated with a number of conditions, including infections by HCV, hepatitis B virus (HBV), HIV, and Mycoplasma
pneumoniae; plasma cell dyscrasias (multiple myeloma, Waldenström macroglobulinemia); and systemic lupus erythematosus. The most
common cause is an association with HCV, seen in 80%-90% of patients with MCS. Given this patient's illicit drug use history and high clinical
suspicion for MCS, HCV infection is the most likely underlying cause of her presentation.

Mixed Cryoglobulinemia

 Arthralgia
 Kidney failure
 Microscopic hematuria
 Nonspecific systemic
Clinical course o Hypocomplementemia
o Neuropathy
o Weakness
 Palpable purpura
 Skin ulcers

 Antinuclear antibody variable

 Cryoglobulin > 5 mg/dL
 Hypocomplementemia
o Low C4 serum levels
Lab evaluation Hepatitis C virus RNA reflex test
o Antibody presence
 Rheumatoid factor positive
 Temperature-dependent increase in apparent leukocytes
o When tested at < 30°C (86°F)

 Illicit drug use

 Hepatitis B virus
 Hepatitis C virus
o Most common cause
Risk factors
o 80%-90% of cases
 HIV
 Mycoplasma pneumoniae
 Systemic lupus erythematosus

 Deposition of antigen–antibody complexes

Pathogenesis
o Capillaries and small arterioles

Following infection with Neisseria meningitidis, colonization of the nasopharynx can occur in those who have been in recent close contact with
the patient. Thus, chemoprophylaxis with rifampin, ciprofloxacin, and ceftriaxone is indicated to eradicate the organism from the nasopharynx.
ExplanationThe most common cause of meningitis in patients aged 6 to 60-years old is Streptococcus pneumoniae, although Neisseria
meningitidis is the most common cause in teenagers and college aged children. N. meningitidis is transmitted through respiratory and oral
secretions. A lumbar puncture will typically reveal an increased opening pressure, increase in polymorphonuclear leukocytes, increased
protein, and a decrease glucose concentration. Empiric treatment is initiated with ceftriaxone and vancomycin, and once N. meningitidis is
confirmed ceftriaxone is continued. Meningococcal meningitis is treated with penicillin once the isolate is proven to be penicillin-susceptible.
Family members or those who have had recent close contact to a patient with meningitis must undergo chemoprophylactic antibiotic
treatment due to the high incidence of nasopharyngeal colonization of the organism. The agent most commonly used in this situation is
rifampin. Rifampin blocks mRNA synthesis by inhibiting DNA-dependent RNA polymerase. It is used for meningococcal meningitis prophylaxis
and chemoprophylaxis in close contacts to children with Haemophilus influenzae type B. Side effects include increased risk of drug interactions
due to up-regulation of the liver microsomal P-450 system, along with the secretion of reddish-orange body fluids. Other regimens for
antibiotic prophylaxis can include ceftriaxone and ciprofloxacin, although rifampin is the first-line agent used in these situations.
Answer A: Ampicillin blocks bacterial cell wall synthesis by binding to penicillin-binding proteins and blocking the transpeptidase cross-linking
of peptidoglycans. It is bactericidal and used in the treatment of gram-positive causative organisms such as S. pneumoniae, Streptococcus
pyogenes, and Actinomyces israelii. It is penicillinase-sensitive, so bacteria that have the presence of beta-lactamase are resistant due to the
ability to cleave the beta-lactam ring. The further addition of clavulanic acid to the regimen will protect against beta-lactamase cleavage. Side
effects include hypersensitivity reactions, a maculopapular sandpaper-like rash, and pseudomembranous colitis.
Answer B: Azithromycin is a bacteriostatic macrolide that blocks protein synthesis at the 50S ribosomal subunit by inhibiting translocation.
Macrolides bind to the 23S rRNA of the 50S ribosomal subunit to prevent translocation. It is used in the treatment of atypical pneumonia
caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae, (and C. psittaci), and Legionella pneumophila. It can also be used in the
treatment of the sexually transmitted infections caused by Chlamydia trachomatis. Side effects include GI disturbance, acute cholestatic
hepatitis, and skin rashes. Other macrolides include erythromycin and clarithromycin.
Answer C: Gentamicin is an aminoglycoside that binds to the 30S ribosomal subunit to inhibit bacterial protein synthesis. This is done due to
interference of the proofreading process, which results in premature termination. Aminoglycosides also inhibit ribosomal translocation in
which the peptidyl-tRNA moves from the A-site to the P-site. Gentamicin is used primarily for the treatment of aerobic, gram-negative bacteria.
Side effects include nephrotoxicity, ototoxicity, and tinnitus. Other aminoglycosides include tobramycin, and streptomycin, and amikacin.
Answer E: Vancomycin blocks bacterial cell wall formation by binding to the D-ala D-ala portion of cell wall precursors and thus inhibiting
peptidoglycan synthesis. Vancomycin is used in the treatment of gram-positive organisms, especially drug resistant organism such as
Staphylococcus aureus, Enterococci, and Clostridium difficile. Side effects include nephrotoxicity, ototoxicity, and “red man syndrome” with
diffuse flushing when infused at a rapid pace.

Primary hyperaldosteronism is a type of secondary hypertension. In this condition, unregulated excess production of the mineralocorticoid,
aldosterone, leads to sodium retention, hydrogen and potassium urinary excretion, and renin level suppression. This leads to the classic triad of
hypertension, unexplained hypokalemia, and metabolic alkalosis.
ExplanationPrimary hyperaldosteronism has a classic triad of hypertension, unexplained hypokalemia (despite being on lisinopril which
normally increases potassium), and metabolic alkalosis (increased bicarbonate) as seen in this patient. Aldosterone, the principal
mineralocorticoid produced in the adrenal cortex, is part of the renin-angiotensin-aldosterone system, which is important in regulating blood
pressure. In primary hyperaldosteronism, unregulated excess aldosterone leads to sodium retention and loss of hydrogen and
potassium. Adrenal hyperplasia and adrenal adenomas are the main causes of this condition.

Aldosterone acts on receptors in the principal cells of the distal tubule and the collecting duct of the nephrons to conserve sodium and secrete
potassium. It also works on sympathetic receptors in the peripheral vasculature to cause vasoconstriction. Both mechanisms lead to
hypertension. Because renin is responsive to elevated blood pressure and sodium, it is appropriately suppressed in the setting of excess
aldosterone production. This causes an elevated aldosterone to renin ratio, a characteristic laboratory finding.

Approximately 95% of hypertension cases are due to essential hypertension, meaning there is no identifiable cause for the elevated blood
pressure. It is neither practical nor cost-effective to perform a thorough workup on everyone with hypertension in an attempt to look for rare
secondary causes. However, certain clinical scenarios should increase your suspicion and warrant further evaluation:

 Resistant hypertension: Defined as blood pressure not being at goal despite being on 3 blood pressure medications, one of which is a
diuretic
 Age: People < age 30 years with no other identifiable risk factors
 End-organ damage: Patients with severe hypertension leading to end-organ damage (e.g., renal injury)
 Laboratory findings: Hypertension with hypokalemia and metabolic alkalosis
Common causes of secondary hypertension and their corresponding characteristics (see table below).

Common Causes of Secondary Hypertension

Disease Characteristics

Primary kidney disease Elevated serum creatinine and/or abnormal urinalysis

Renal artery stenosis:

Younger females, "string of beads" appearance on imaging
fibromuscular dysplasia

If bilateral, an increase in creatinine > 50% after starting an angiotensin converting enzyme inhibitor
Renal artery stenosis:
Older adult with other cardiovascular disease
atherosclerosis
Recurrent flash pulmonary edema

Primary aldosteronism Hypokalemia with metabolic alkalosis

 Obstructive sleep apnea Obese individuals who snore loudly and have apnea

Medication induced Oral contraceptives, androgens, steroids, and non-steroidal anti-inflammatory drugs

Pheochromocytoma Paroxysmal elevated blood pressure, headaches, palpitations, and sweating.

Cushing syndrome Cushingoid facies, central obesity, proximal muscle weakness, stria (> 1 cm)

Coarctation of the aorta Hypertension in upper extremities, decreased pulses in lower extremities
Answer B: Adrenal insufficiency can occur in the setting of adrenal hemorrhage (most commonly if patients are on blood thinners), adrenal
tuberculosis (most common cause in developing countries), and autoimmune adrenal adenitis — called Addison disease (most common cause
in developed countries). Patients have hypotension, hyponatremia, hyperkalemia, and hypoglycemia. These examination findings are the exact
opposite of this patient.
Answer C: Cushing syndrome or disease occurs as a result of excess glucocorticoid. It can be caused by a pituitary tumor secreting excess
adrenocorticotropic hormone (ACTH) in Cushing disease, ectopic ACTH production in Cushing syndrome, or iatrogenic exogenous steroid use.
Classic physical findings on examination are wide abdominal stria, a buffalo hump, truncal obesity, moon facies, proximal muscle weakness, and
hypertension. This patient has a normal physical exam and body mass index.
Answer D: Essential (or primary) hypertension describes elevated blood pressure of unknown cause. It is the most common type of
hypertension. Risk factors include African American race, family history of hypertension, obesity, consuming excessive amounts of salt or
alcohol, smoking, and diabetes. This patient has no identifiable risk factors increasing the probability of a secondary cause of hypertension,
such as primary hyperaldosteronism.
Answer E: Pheochromocytoma is the most common tumor of the adrenal medulla, secreting epinephrine, norepinephrine, and dopamine. It
causes episodic symptoms that can be remembered by the “5 Ps": pressure (elevated blood pressure associated with sweating and anxiety),
pain (headache), perspiration (drenching), palpitations, and pallor. This patient has none of these symptoms, and her laboratory findings of
hypernatremia and hypokalemia are characteristic of primary hyperaldosteronism.
Insight Know the common causes of secondary hypertension and their differentiating features.

Lithium is the drug of choice for acute mania in bipolar patients. It commonly causes an action tremor that is exacerbated by caffeine.
ExplanationThis patient likely has bipolar disorder, given her symptoms of mania, which include a decreased need for sleep and an increase in
activities that may be considered "high risk-taking." The first-line drug of choice for acute mania is lithium, which acts as a mood stabilizer. The
patient describes frequent caffeine consumption via coffee and having trouble keeping her tray still as a waitress. This history points to a very
common side effect of lithium, an action tremor.

A tremor that occurs due to lithium occurs in nearly 25% of patients. Although the tremor can occur at any time, it is most commonly noted at
initiation or up-titration of the medication. Factors that increase the risk of tremor include higher lithium doses and serum concentrations,
anxiety, caffeine, medications (eg, antiarrhythmics, beta-adrenergic agents, carbamazepine, and valproate), emotional and physical stress,
fatigue, and older age.

Adverse Effects of Mood Stabilizers

Mood Stabilizer Adverse Effects

 Aplastic anemia
Carbamazepine  Stevens-Johnson syndrome and toxic epidermal necrolysis
 SIADH and hyponatremia

 Agranulocytosis
 Myocarditis
Clozapine
 Metabolic syndrome
 Seizures

 Mild skin rash

Lamotrigine
 Stevens-Johnson syndrome

 Action tremor
 Hypothyroidism
Lithium
 Nephrogenic diabetes insipidus
 Ebstein anomaly (teratogenic)

Valproate  Alopecia
 Liver toxicity
  Neural tube defects (teratogenic)
 Pancreatitis

SIADH = syndrome of inappropriate antidiuretic hormone secretion.

Nocardia species are Gram-positive, weakly acid-fast bacilli with a filamentous appearance in tissues and culture. They cause pulmonary
infections in immunocompromised patients, which are treated with trimethoprim-sulfamethoxazole.
ExplanationThis immunosuppressed patient likely has a pulmonary infection caused by Nocardia asteroides, a Gram-positive bacterium found
ubiquitously in the soil. Nocardia species are strict aerobic rods that appear as branched filaments in tissues and culture, as shown in the
exhibit. They stain weakly acid-fast because of the medium-chain mycolic acids in their cell wall. Nocardia causes pulmonary disease
(bronchitis, pneumonia, lung abscesses) in immunocompromised patients, especially those with T-cell deficiency (eg, leukemia, HIV/AIDS,
immunosuppressive therapy).

Patients infected with HIV have a specific decline in CD4+ helper T cells, resulting in inversion of the normal CD4/CD8 T-cell ratio and
dysregulation of B-cell antibody production. This leads to impaired immune responses to certain antigens, with failure to adequately respond
to opportunistic infections and normally harmless commensal organisms. The type of opportunistic infection depends on the CD4 count. The
median CD4 count of HIV-positive patients who develop nocardiosis is ~ 50 cells/mm3.

The lungs are the primary site of nocardial infection in most patients. If Nocardia infection remains localized to the lungs, it can usually be
treated effectively with sulfa drugs, most commonly oral trimethoprim-sulfamethoxazole (TMP-SMX). However, the bacterium has a high
predilection for hematogenous spread to the central nervous system or skin. This can lead to necrotizing cutaneous infections and brain
abscesses. Disseminated nocardiosis requires prolonged treatment with a combination of antibiotics, including TMP-SMX, amikacin, and/or
imipenem.

The below image is an acid-fast stain of Nocardia, which appears as branched filaments (arrow).

Answer A: Amphotericin B is an antifungal agent used to treat serious, systemic mycoses caused
by Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, and Mucor. Aspergillus causes pulmonary infections in
immunocompromised patients and has a branched formation in culture. However, it does not stain acid-fast and is, therefore, not the likely
pathogen in this patient.
Answer B: Azithromycin is a macrolide used to treat atypical pneumonia caused by Mycoplasma, Chlamydia, or Legionella. It is also used for
prophylactic treatment against Mycobacterium avium-intracellular complex (MAC) in immunocompromised patients. While HIV/AIDS patients
are at increased risk for MAC infections, these mycobacteria do not have a branched appearance on acid-fast staining.
Answer C: Caspofungin is an antifungal agent used in combination therapy to treat invasive aspergillosis. Aspergillus is not the likely causative
agent in this patient because it does not stain acid-fast.
Answer D: Isoniazid is used for prophylaxis and treatment of Mycobacterium tuberculosis infection. Immunocompromised patients are at
higher risk of developing active pulmonary tuberculosis. Although M. tuberculosis is an acid-fast bacillus, it does not have a branching
formation when cultured.

Joint Aspiration Fluid Analysis

WBC Count
Condition Examples Color (cells/mm³ Notes
)

Normal N/A Clear < 200 N/A

Noninflammatory • Osteoarthritis Clear 200-2000 Unremarkable appearance

• Avascular necrosis
 • Meniscal tear

• Low glucose in RA
• Crystal-induced • Gout crystals: negative
arthritis ≥2000 but birefringent
Inflammatory Cloudy
• Spondyloarthritis < 50,000 • Calcium pyrophosphate
• Rheumatoid dihydrate crystal/pseudogout
crystals: positive birefringence

• Gram stain and cultures assist in

• Bacteria
diagnosis
Septic • Mycobacteria Turbid/gray ≥50,000
• Low glucose in bacterial septic
• Fungal
joint

• Hemophilia
• Scurvy • Predominantly red blood cells
Hemorrhagic Red Variable
• Trauma • Cytology if malignant
• Tumor/neoplasm

RA = rheumatoid arthritis.
Answer A: Direct joint inoculation is a possible mechanism of infection in septic arthritis, but it is not as common as hematogenous spread.
However, clinical context is important; if the patient had recently had knee surgery, trauma, or injections, this mechanism of infection becomes
more likely. In this patient scenario, direct joint inoculation is an incorrect answer.
Answer C: Inflammatory response to bacterial presence in the joint contributes to pathology due to leukocytes releasing inflammatory
mediators, which lead to tissue damage. However, this is not the most common mechanism of infection in septic arthritis, making
inflammatory mediators an incorrect answer choice.
Answer D: Sexual transmission is a possible initial mechanism of infection that can lead specifically to gonococcal septic arthritis, which is
caused by Neisseria gonorrhoeae. However, while the organism is typically contracted via sexual transmission, gonococcal septic arthritis still
typically occurs from hematogenous spread of the bacteria to the joint membrane, which makes sexual transmission an incorrect answer.
Answer E: Spread of existing infection to the joint from adjacent tissues is another possible mechanism behind septic arthritis. Infection in the
skin, soft tissue, or bones can migrate into joint capsules. Ruptured diverticulitis has also been cited as a source of posterior hip septic arthritis
due to retroperitoneal penetration of bacteria. However, this is the least common mechanism of septic arthritis infection, making spread from
adjacent tissue an incorrect answer.
Insight: Septic arthritis can be a presenting manifestation of infective endocarditis, especially in intravenous drug users. Keep a high index of
suspicion for IE in these patients.

Septic arthritis is most commonly caused by bacterial seeding of the synovial membrane via hematogenous spread. Less common mechanisms
of infection in septic arthritis include direct inoculation of bacteria into the joint and extension of preexisting skin/soft tissue/bone infection
into the joint.
Explanation: This patient's presentation is suggestive of septic arthritis, which typically occurs in a single joint with signs/symptoms including
severe pain, limited range of motion, erythema, and edema, as seen in this patient. The knee is the most common joint affected by septic
arthritis, it being the site of infection in >50% of cases. The most common mechanism of infection is by hematogenous spread of bacteria to
the synovial membrane. The current patient has several predisposing factors for septic arthritis, including advanced age, preexisting joint
disease (rheumatoid arthritis), and immunosuppression (patient has diabetes and is on methotrexate).

While hematogenous spread is the most common mechanism for seeding bacteria into the joint, other mechanisms of infection for septic
arthritis include the following:

 Direct inoculation of bacteria into the joint—can be from bites, trauma, joint injections, or joint surgery
 Extension of infection from adjacent tissues—cellulitis, fasciitis, osteomyelitis, "dirty" central line attempts (subclavian and femoral)
Diagnosis of septic arthritis hinges on synovial fluid analysis (see table below) and positive growth on culture. Additional findings may include
elevated C-reactive protein and erythrocyte sedimentation rate and leukocytosis on complete blood count. Imaging of the affected joint should
be obtained to evaluate the extent of bone and joint disease, and to establish a baseline to compare with as treatment progresses. Blood
cultures should also be obtained in the initial workup.

Blunt thoracic trauma can result in a pulmonary contusion, and patients will typically develop tachypnea, dyspnea, and hypoxemia within 24
hours of the initial injury. Hemodynamic studies will show a normal central venous pressure and pulmonary capillary wedge pressure.
ExplanationBlunt chest trauma can result in many complications and as such, you must work through a broad differential diagnosis. Here, the
patient's presentation— progressively worsening tachypnea, hypoxemia, and unilateral, irregular infiltrates on chest x-ray (CXR)—is most
concerning for a pulmonary contusion.
Pulmonary contusion is characterized by parenchymal bruising of the lung and results in alveolar hemorrhage and edema. It is most commonly
seen following blunt thoracic trauma and may be seen with or without rib fractures. Patients are often asymptomatic at the time of
presentation (especially on the COMLEX) and will initially have a normal CXR; however, symptoms will typically develop within 24 hours and
include tachypnea, tachycardia, and hypoxemia. When symptoms develop, physical examination will show decreased breath sounds or rales in
the affected area and CXR typically shows patchy, irregular alveolar infiltrates. Hemodynamic studies can help differentiate from other
potential complications of blunt thoracic trauma and will include a normal central venous pressure (CVP) and pulmonary capillary wedge
pressure (PCWP).

Management is typically conservative and includes pain control, incentive spirometry, and supplemental oxygen.

Complications of Blunt Thoracic Trauma

Complication Clinical Presentation Diagnostic Findings

 Seen with acceleration-deceleration

injury (eg, MVA)
 Shearing of the aortic isthmus -->
hemorrhage and hypovolemic  CXR → mediastinal
Aortic dissection
shock → often fatal widening
 Chest pain ± radiation to the back
 Aortic regurgitation → diastolic
murmur, wide pulse pressure

 Typically unilateral
Bronchial  CXR → air in the pleural
 Absent breath sounds
rupture space
 Subcutaneous emphysema

 Beck's triad → hypotension, JVD, and  ↑ CVP

Cardiac
muffled (distant) heart sounds  ↑ PCWP
tamponade
 Pulsus paradoxus  ECG → electrical alternans

 Rare
Diaphragmatic  CXR → abdominal contents
 Bowel sounds over the hemithorax
rupture in the hemithorax
 Absent breath sounds

 Subcutaneous emphysema
 CXR → mediastinal
Esophageal  Hematemesis
widening ± pleural effusion
rupture  "Crunching" sound heard during
 ↑ amylase
cardiopulmonary auscultation

 Often seen with rib fractures →  CXR → pleural effusion ±

laceration of intercostal vessels partial opacification of the
Hemothorax  Typically unilateral hemithorax
 Decreased breath sounds  Bloody drainage from chest
 Hypotension tube

 Symptoms may not be present at

 ↑ CVP
admission → develop within 24 hours
 ↑ PCWP
 Symptoms often appear following
Myocardial  ECG may show premature
fluid bolus
contusion ventricular complexes
 Hypotension, palpitations, JVD
 CXR → pulmonary edema
 Pulmonary edema → bilateral
(bilateral infiltrates)
crackles

 Unilateral
 Absent breath sounds
 CXR → area without lung
Pneumothorax  May cause obstructive shock →
markings
hypotension, JVD
 CXR → area without lung markings

Pulmonary  Symptoms may not be present at  CXR → patchy alveolar

 admission → develop within 24 hours
 Typically unilateral
 Tachypnea, tachycardia, and
contusion infiltrates
hypoxemia
 ± hypotension
 Decreased breath sounds

 Pleuritic chest pain

 CXR → fractures
 Tenderness to palpation
 CXR may be normal
Rib fracture  Complications → splenic (left side) or
because rib fractures are
liver laceration (right side),
often difficult to visualize
hemothorax, pulmonary contusion

CVP = central venous pressure; CXR = chest x-ray; JVD = jugular vein distention; MVA = motor vehicle
accident; PCWP = pulmonary capillary wedge pressure.

The below chest x-ray shows a right-sided pulmonary contusion and multiple rib fractures.

Answer A: Blunt thoracic trauma is a common cause of cardiac tamponade; however, patients will typically present with hypotension, jugular
venous distention, and distant (or muffled) heart sounds. Diagnostic findings consistent with cardiac tamponade include mediastinal widening
on CXR and electrical alternans (alternating amplitude of the QRS complexes) on ECG. Additionally, the CVP (and PCWP) will typically be
elevated in patients with cardiac tamponade (whereas it was normal in this patient). Note that for most questions on the COMLEX, cardiac
tamponade secondary to trauma will be present on arrival to the emergency department, not several hours later.
ECG shows electrical alternans in a patient with cardiac tamponade. Electrical alternans is characterized by alternating amplitudes of the QRS
complexes (indicated by the red arrows).
Answer B: Fat embolism is most commonly seen after long bone (eg, femur) or pelvic fractures, not chest wall injuries. In addition to dyspnea
and hypoxemia, patients will typically have a petechial rash, obstructive shock, and neurologic changes (eg, altered mental status).
Answer C: Injury to the lung parenchyma can result in a hemothorax, and patients will present with dyspnea and hypoxemia. Chest imaging will
typically show a unilateral pleural effusion (eg, blunting of the costodiaphragmatic angles) and partial opacification of the hemithorax. This
patient has patchy, irregular alveolar infiltrates on CXR, which is more consistent with a pulmonary contusion.

The arrow points to a hemothorax in the left lung.

Answer D: Blunt thoracic trauma is a common cause of pneumothorax, and patients will typically present with dyspnea and hypoxemia. In
most cases, pneumothorax occurs unilaterally, and patients will have decreased or absent breath sounds in the affected lung field. CXR is
diagnostic and will show an area of the lung without lung markings that is bordered by a visceral pleural line. Here, pneumothorax is unlikely
based on the patient's CXR findings. Additionally, a pneumothorax secondary to trauma would have most likely been present at the time of
admission (whereas symptoms caused by a pulmonary contusion may develop several hours later).

The arrow points to a left-sided pneumothorax.

InsightMake sure that you are able to utilize the CVP and PCWP when working through a question stem. The following table highlights the
conditions that are associated with an increased CVP and/or PCWP.

Central Venous Pressure Pulmonary Capillary Wedge Pressure

(normal = 6-8 mm Hg) (normal = 4-12 mm Hg)

Pathophysiology  Reflects blood pressure in the  Reflects blood pressure in the

vena cava left atrium
 Represents the amount of blood  Left-sided congestion of blood
returning to the heart and the → congestion of blood in
heart's ability to pump blood into pulmonary veins → ↑
the systemic circulation pulmonary capillary wedge
 ↑ central venous pressure is seen pressure
 when blood becomes congested
on the right side of the heart

 Cardiac tamponade
 Cardiogenic shock
 Mechanical ventilation with
positive end-expiratory pressure  Acute mitral regurgitation
 Myocardial contusion  Cardiac tamponade
Causes of
 Pneumothorax  Cardiogenic shock
increase
 Pulmonary artery hypertension  Left heart failure
 Pulmonary embolism  Volume overload
 Right heart failure
 Right ventricle infarction
 Volume overload

 Distributive shock (eg, sepsis,

Causes of  Distributive shock
anaphylaxis)
decrease  Hypovolemia
 Hypovolemia

Eosinophilic granulomatosis with polyangiitis is a small-vessel vasculitis characterized by granulomatous, necrotizing inflammation and
eosinophilia. Patients typically have respiratory and constitutional symptoms in addition to purpuric skin lesions and/or polyneuropathy.
Laboratory studies will show eosinophilia.
ExplanationThis patient likely has eosinophilic granulomatosis with polyangiitis (EGPA), as suggested by his constitutional symptoms,
recurrent sinusitis, asthma, purpura, and eosinophilia. EGPA is a small-vessel vasculitis characterized by granulomatous, necrotizing
inflammation and eosinophilia. Upper respiratory symptoms are the most common initial manifestations, and patients typically have new or
worsening asthma in addition to recurrent sinusitis or allergic rhinitis. Nasal polyps also may be present on examination.

Following the allergic stage, patients may progress to the eosinophilic stage and develop constitutional symptoms, such as fever, weight loss,
night sweats, and cough in addition to demonstrating marked eosinophilia on laboratory studies.

The final stage is the vasculitic stage, which is characterized by purpuric skin lesions (and/or skin nodules) and peripheral neuropathy, often in
the form of wrist drop and/or foot drop. Cardiac involvement is common during the vasculitic stage, and heart disease accounts for
approximately 50% of deaths in patients with this condition.

Diagnostic findings consistent with EGPA include eosinophilia, increased concentrations of IgE, and perinuclear anti-neutrophil cytoplasmic
antibodies (p-ANCA). An arterial biopsy can show necrotizing, granulomatous inflammation. Once diagnosed, treatment typically consists of
glucocorticoids and other immunosuppressive medications (eg, azathioprine and cyclophosphamide).

Eosinophilic Granulomatosis with Polyangiitis

 Granulomatous, necrotizing vasculitis with eosinophilia

Etiology
 Affects small-sized arteries

 Allergic stage: patients initially have upper respiratory symptoms and findings
(allergic stage)
 Progression to the eosinophilic stage: eosinophilia and constitutional
symptoms (eg, fever, weight loss, malaise)
o New or worsening asthma is a common finding
o Recurrent sinusitis
Clinical o Allergic rhinitis
features o Nasal polyps
 Vasculitic stage
o Purpuric skin lesions and skin nodules may be present
o Peripheral neuropathy (wrist drop and foot drop are common)
o Blood clots may occur
o Heart disease is the most common cause of death
o Patients may also experience gastrointestinal and renal involvement

Diagnostic  Laboratory findings

findings o Eosinophilia (eosinophils > 3%)
 o ↑ serum IgE
o Perinuclear anti-neutrophil cytoplasmic antibodies
 Histopathology
o Granulomatous, necrotizing inflammation within small-sized vessels

The below histology image is of an arterial biopsy showing EGPA. Note the necrotizing, granulomatous inflammation.

Answer A: Granulomatosis with polyangiitis (also known as Wegener disease) is a small-vessel vasculitis that also may result in respiratory
symptoms. Patients typically have a combination of chronic sinusitis, otitis media, and/or perforation of the nasal septum in addition to
hemoptysis, cough, and/or dyspnea. Renal involvement is common, and patients can have hematuria and renal dysfunction secondary to
crescentic glomerulonephritis. It typically does not present as skin lesions, polyneuropathy, or eosinophilia, making it unlikely in this patient.
Answer B: Granulomatous inflammation of large arteries is seen with Takayasu arteritis, which typically occurs in Asian women aged < 40
years. Clinical features include constitutional symptoms (eg, fever, night sweats), arthritis, myalgias, weak upper extremity pulses, and skin
nodules. Eosinophilia (as seen in this patient) is not a common laboratory finding.
Answer D: Mixed cryoglobulinemia results in small-vessel vasculitis because of mixed IgG and IgA immune complex deposition. Cryoglobulins
are immunoglobulins that precipitate in cold temperatures and are often seen with viral infections, especially hepatitis C. Patients generally
have a triad of palpable purpura, weakness, and arthralgia; peripheral neuropathy and renal disease may also be seen. Although this patient
has purpuric skin lesions and peripheral neuropathy, his respiratory symptoms and eosinophilia make EGPA a more likely diagnosis.
Answer E: Transmural inflammation of the arterial wall with fibrinoid necrosis would suggest polyarteritis nodosa (PAN). PAN typically occurs in
middle-aged men, and approximately 30% of patients are seropositive for hepatitis B. PAN is a medium-vessel vasculitis that most commonly
affects the renal and visceral vessels. As a result, patients often have abdominal pain, weight loss, melena, and/or hematochezia as well as
renal dysfunction. PAN does not affect the pulmonary arteries, and upper respiratory symptoms are not seen. In addition, eosinophilia is not a
common feature, making PAN unlikely in this patient.
InsightMake sure that you can differentiate between the small-vessel vasculitides that are associated with anti-neutrophil cytoplasmic
antibodies.

Anti-neutrophil Cytoplasmic Antibody–Associated Small-vessel Vasculitis

 Eosinophilic Granulomatosis w/
Granulomatosis w/ Polyangiitis Microscopic Polyangiitis
Polyangiitis

c-ANCA is most common

Type of
p-ANCA p-ANCA may be seen (although not typically p-ANCA
ANCA
on the exam)

 Focal necrotizing vasculitis in

small-sized arteries
Granulomatous, necrotizing Necrotizing vasculitis without
Etiology  Necrotizing granulomas in the
inflammation in small-sized arteries granulomas
lungs and upper airway
 Necrotizing glomerulonephritis

 Respiratory symptoms
o Asthma is very  Upper respiratory tract symptoms
common (especially o Perforation of nasal
on the exam) septum  No nasopharyngeal
o Recurrent sinusitis o Recurrent sinusitis involvement
o Allergic rhinitis o Otitis media  Constitutional symptoms
Clinical o Nasal polyps  Lower respiratory tract symptoms  Palpable purpura
features  Constitutional symptoms: o Hemoptysis  Renal disease → rapidly
fever, weight loss, night sweats o Cough progressive
 Purpuric skin lesions o Dyspnea glomerulonephritis
 Polyneuropathy, often wrist  Renal disease  rapidly o Hematuria
drop or foot drop progressive glomerulonephritis
 Cardiac involvement may occur o Hematuria
 Renal involvement is rare

 No eosinophilia  No eosinophilia
 c-ANCA  p-ANCA
 Eosinophilia  p-ANCA (less common)  Red blood cell casts on
Diagnostic
 p-ANCA  Red blood cell casts on urinalysis urinalysis
findings
  IgE   serum concentrations of urea   serum concentrations of
nitrogen and creatinine urea nitrogen and creatinine
 Nephritic range proteinuria  Nephritic range proteinuria

ANCA = anti-neutrophil cytoplasmic antibodies; c-ANCA = cytoplasmic anti-neutrophil cytoplasmic antibodies; p-ANCA = perinuclear anti-
neutrophil cytoplasmic antibodies.

Pemphigus vulgaris is an autoimmune blistering disease caused by IgG antibodies against desmosomes located on the surface of keratinocytes,
resulting in flaccid bullae and erosions on the skin and oral mucosa. It is associated with the use of certain drugs, including cephalosporins.
Explanation: This patient likely has pemphigus vulgaris, an autoimmune blistering disease caused by IgG antibodies against desmosomes
located on the surface of keratinocytes (desmoglein 1 and 3). Binding of antibodies causes a loss of cell-to-cell adhesion, called acantholysis,
which results in intraepidermal blisters that are fragile and easily broken, manifesting as painful, flaccid bullae and erosions on examination.
This is in contrast to the tense bullae of bullous pemphigoid.

As in this patient, the bullae demonstrate the Nikolsky sign, in which gentle pressure to the bulla causes the epidermis to separate off.
Pemphigus vulgaris involves mucosal surfaces in 50%-70% of patients and has a mortality rate of 5%-15%, depending on extent of disease. The
following triggers of pemphigus vulgaris have been reported: thermal burns, infections, emotional stress, and drugs including penicillamine,
captopril, cephalosporins, and nonsteroidal anti-inflammatory drugs. The mean age of onset is 50-60 years, but of interest, it has been reported
that the average age of onset is younger in Southeast Asian populations and is more common in persons of Jewish descent.

The below image shows a net-like or lacy immunofluorescence staining pattern seen in pemphigus vulgaris.
Answer A: A biopsy with direct immunofluorescence in a linear dermal–epidermal distribution is seen in bullous pemphigoid, another
autoimmune blistering disease caused by antibodies against hemidesmosomes. Patients present with tense bullae on examination.
Answer C: A duodenal biopsy showing mucosal atrophy, loss of villi, and crypt hyperplasia is seen in celiac disease, which is associated with
dermatitis herpetiformis. Skin lesions in dermatitis herpetiformis are highly pruritic papules, vesicles, and plaques located primarily on extensor
surfaces.
Answer D: Chocolate agar is a medium enriched with lysed blood cells (giving it its color), which provides necessary nutrients for the
fastidious Neisseria gonorrhea. Gonorrhea in men is most commonly associated with urethral discomfort, discharge, and dysuria and not the
skin lesions seen here.
Answer E: A positive enzyme-linked immunoabsorbent assay for retrovirus would be seen in HIV infection. Skin manifestations of acute HIV
infection are most commonly in the form of a generalized, pruritic papular eruption. Although this patient should be tested for HIV given his
history of a sexually transmitted disease, his lesions are caused by pemphigus vulgaris.
InsightBe able to distinguish bullous pemphigoid from pemphigus vulgaris. Pemphigus vulgaris more frequently involves oral mucosa, consists
of flaccid blisters and erosions, and is caused by autoantibodies against desmosomes on keratinocytes. Differences between these two bullous
skin disorders are summarized in the table below.

Autoimmune Bullous Skin Diseases

Characteristic Pemphigus Vulgaris Bullous Pemphigoid

Plane of cleavage Intraepidermal Subepidermal

Autoantibody target Desmoglein 1 and desmoglein 3 (in desmosomes) BP180 and BP230 (in hemidesmosomes)

Bullae Flaccid Tense

Nikolsky sign Positive Negative

Fibular neck fractures predispose to common peroneal nerve injuries, which typically manifest as foot drop. The common peroneal nerve
branches into the deep and superficial peroneal nerves: the deep peroneal nerve innervates the anterior compartment of the lower leg,
whereas the superficial peroneal nerve innervates the lateral compartment. The extensor hallucis longus is a component of the anterior
compartment; thus, a common peroneal nerve injury will result in reduced strength of this muscle.
Explanation: This patient presents with swelling, bruising, and pain following direct trauma to the lateral side of his knee. This is suspicious for
a fibular neck fracture, which is confirmed by the radiograph in the exhibit. With a fibular neck fracture, injury to the common peroneal
nerve is a concern. Injury to this nerve causes inability to dorsiflex the foot, producing foot drop. Of the muscles listed, only the extensor
hallucis longus is innervated by branches of the common peroneal nerve.

The three main nerves of the lower leg are the common peroneal nerve, tibial nerve, and saphenous nerve. The table below describes the
anatomy of these nerves, as well as their sensory and motor innervation.

Nerves of the Lower Leg

Root
Nerve Course Sensory Innervation Motor Innervation
s

Common L4– Arises from the sciatic nerve at the popliteal  Sural cutaneous nerve Short head of the biceps femoris
 (with branches from the
tibial): skin over the lower
fossa and courses along the medial border
posterolateral aspect of
of the biceps femoris. It then continues
the lower leg
peroneal S2 inferiorly and wraps around the neck of the
 Lateral sural cutaneous
fibula, after which it immediately bifurcates
nerve: skin over the upper
into superficial and deep branches.
lateral aspect of the lower
leg

Arises from the common peroneal nerve

 Skin of the anterior aspect
Superficial L4– and courses inferiorly in the superficial Fibularis longus and brevis (foot
of the lower leg and
peroneal S2 aspect of the lateral compartment of the evertors)
dorsum of the foot
lower leg

Anterior compartment of the

Arises from the common peroneal nerve
lower leg: tibialis anterior,
Deep L4– and courses inferiorly along a deep path  Skin between the first and
extensor digitorum longus,
peroneal S2 adjacent to the tibial artery in the anterior second toes
and extensor hallucis longus.
compartment of the lower leg
Also some intrinsic foot muscles.

Arises from the posterior branch of the

femoral nerve and courses through the  Skin of the medial aspect
Saphenous L2–L4 None
adductor canal with the femoral artery and of the lower leg and foot
vein

Posterior compartment of the

Arises from the sciatic nerve at the popliteal lower leg: popliteus, flexor
 Skin of the heel and
L4– fossa and courses inferiorly along the hallucis longus, flexor digitorum
Tibial plantar surface of the
S3 posterior aspect of the tibia. It gives off longus, tibialis posterior,
foot
branches for the sural nerves. plantaris, soleus, and
gastrocnemius

The below image is a radiograph of the lower extremity showing a fibular neck fracture (arrow).

Answer B: The flexor digitorum longus muscle is part of the posterior compartment of the lower leg. Thus, it is innervated by the tibial nerve.
Given the blow to the lateral side of the knee, it is most likely that this patient has a common peroneal nerve injury, not a tibial nerve injury.
The flexor digitorum longus assists with plantarflexion of the foot and toes.
Answer C: The gastrocnemius muscle is part of the posterior compartment of the lower leg. It consists of a medial and lateral head and lies
superficial to the soleus muscle. It is innervated by the tibial nerve, which is not the nerve most likely to be injured by trauma to the lateral side
of the knee. The gastrocnemius is a powerful plantar flexor of the foot.
Answer D: The popliteus is part of the posterior compartment of the lower leg. Located behind the knee, it originates on the anterior part of
the popliteal groove on the lateral surface of the lateral femoral condyle and inserts on the posterior surface of the tibia in a fan-like fashion. It
is innervated by the tibial nerve, which is not the nerve most likely to be injured in this patient, who sustained a blow to the lateral side of his
knee. The popliteus muscle primarily acts by assisting medial rotation and flexion at the knee.
Answer E: The tibialis posterior muscle is part of the posterior compartment of the lower leg. It is innervated by the tibial nerve and would
therefore not be affected by a common peroneal nerve injury, which is the most likely nerve injury with a blow to the lateral aspect of the
knee. The tibialis posterior assists with plantarflexion of the foot.

In polymyositis, the inflammatory cells invade the fascicle of individual muscle fibers. Dermatomyositis is characterized by immune complex
deposition in the perimysium and perifascicular regions.
Explanation: This picture shows the degeneration of muscle fibers caused by the Anti-Jo-1 antibodies in polymyositis. In polymyositis, the
cellular infiltrate is predominantly within the fascicle with inflammatory cells invading individual muscle fibers.

Histopathology shows focal endomysial infiltration by CD8+ T lymphocytes and macrophages, capillary obliteration, endothelial cell damage,
and increased amounts of connective tissue due to muscle fiber necrosis. This is due to T cell-mediated muscle injury from CD8+ T lymphocytes.

Patients with polymyositis present with insidious onset of symmetrical, proximal muscle weakness in the upper and lower extremities, as
evidenced by the inability to comb her hair and walk up and downstairs. Patients with polymyositis may also report muscle pain and
tenderness. All of the muscles of the thighs, trunk, shoulders, hips, and upper arms can become involved. Muscle weakness may fluctuate from
week to week or from month to month. The patient may also report exertional dyspnea, secondary to weakness of the chest wall muscles and
diaphragmatic muscles. The weakness of these aforementioned muscles may result in exhalation dysfunctions of the rib cage, where
inspiration does not result in nearly as much change in anteroposterior diameter as does expiration for these pump handle ribs.

Patients with either dermatomyositis or polymyositis may have "mechanic's hands," a roughening or cracking of the skin of the tips and lateral
aspects of the fingers, resulting in irregular, dirty-appearing lines, but this finding is more common in dermatomyositis.

Laboratory studies reveal an elevated serum concentration of creatine kinase, lactate dehydrogenase, and aldolase. Anti-Jo-1 antibodies can be
measured in the serum. The definitive test for establishing the diagnosis of polymyositis is a muscle biopsy.

Prednisone is the first-line treatment for polymyositis.

The below image is a muscle biopsy in a patient with polymyositis that shows invasion of muscle fibers by lymphocytes (arrow).

Beta-adrenergic receptor overdose can result in mild hypoglycemia, bradycardia, and hypotension. It is important to recognize these
symptoms, as an antidote exists—glucagon. Glucagon increases cAMP and can be used for a beta-adrenergic receptor overdose, as it can
increase cardiac contractility and heart rate by this mechanism. In addition, it would correct the hypoglycemia induced by a beta-adrenergic
receptor antagonist overdose, as it would increase the conversion of glycogen to glucose in the liver.
ExplanationThis pediatric patient is presenting with mild hypoglycemia, bradycardia, and hypotension, most likely as a result
of accidental overdose of a beta-adrenergic receptor antagonist such as nadolol, a nonselective beta1 and beta2 antagonist. When bradycardia
is significant enough to reduce cerebral perfusion, syncope can occur, likely explaining her laceration and hematoma. There are no other signs
indicating excessive bleeding.

Nonselective beta-blockers are medications used to manage anxiety, tachycardia (atrial fibrillation), hypertension, and migraines. Although not
the first-line for hypertension as monotherapy, they may be a good option if the patient has a concurrent condition with an indication for its
use.
An overdose with these agents will present as bradycardia and hypotension (beta1 blockade), while masked hypoglycemia presents from
antagonism of the beta2 receptor. In addition, there is reduced conversion of glycogen to glucose by this blockade, and it can cause mild
hypoglycemia.

Glucagon increases cAMP and can be used for a beta-adrenergic receptor overdose and to increase cardiac contractility and glucose levels. In
addition, this medication is used to treat severe hypoglycemia.
The following table lists different pharmacologic overdoses, including their presentation and antidote.

Summary of Toxicities, Presentation, and Antidotes

Drug Overdose Presentation Antidote

• Tinnitus
• Fever
Aspirin • Respiratory alkalosis (early) Sodium bicarbonate
• Metabolic acidosis (oxidative
phosphorylation, later)

• Right, upper quadrant pain

Acetaminophen N-acetylcysteine
• Centrilobular necrosis of liver

Dabigatran Bleeding (nose, stool, urine) Idarucizumab

Warfarin or • Bleeding (nose, stool, urine) Vitamin k (minor bleed)

rat poison • Elevated PT Fresh frozen plasma or 4-factor prothrombin complex concentrate

• Bradycardia
Beta-adrenergic
• Hypotension
receptor Glucagon
• Hypoglycemia
antagonists
• Fatigue

• Bradycardia
• Hypotension
Calcium channel IV calcium
• Tachycardia (dihydropyridines)
blockers Insulin
• Hyperglycemia
• Dizziness

Cluster headaches are associated with watery eyes, nasal congestion, and Horner syndrome (miosis, ptosis, and anhidrosis). They are treated
with 100% oxygen and triptans.
ExplanationThis patient is most likely experiencing cluster headaches, which are characterized by watery eyes, nasal congestion, periorbital
pain, and Horner syndrome (miosis, ptosis, and anhidrosis). Cluster headaches are usually brief and recurring. Males tend to experience this
type of headache more commonly than females. Alcohol is a common trigger and may have been a factor in this patient who drinks "more than
most." Administering oxygen or sumatriptan and removing the offending agent are effective treatments.

Cluster headaches are characterized by their unilateral autonomic findings, severity, and shorter duration (30 minutes–3 hours). Attacks are
recurrent (up to 8 per day) in a clustered period (typically 6–12 weeks).
Acute therapy is used to abort the headache attack. Potential options for acute treatment include:
 Oxygen: 100% oxygen should be tried initially if available, given its safety profile.
 Triptans: Subcutaneous sumatriptan injections are preferred.
o However, if they are not possible, intranasal triptans can be used.
 They should be given in the nostril contralateral to the headache due to the autonomic findings on the ipsilateral
side.
Preventive options should also be initiated to suppress attacks over the cluster duration. Verapamil is considered first-line therapy, although
glucocorticoids can be used for an individual cluster (but not long-term).

Primary Headache Syndromes

Etiology Cluster Headache Migraine Headache Tension Headache

Localization/  Unilateral  Unilateral  Bilateral

duration  15 minutes–3 hours  4–72 hours  > 30 minutes
  Repetitive, brief,
excruciating pain  Pulsating
with lacrimation pain  Steady pain
and rhinorrhea  Nausea  Band-like features
Description
 May have Horner  Photophobia  No photophobia
syndrome  May have an  No aura
 More common in aura
males

 Pain control:
o Muscle
 100% oxygen  Triptans
Treatment relaxants
 Sumatriptan  NSAIDs
o NSAIDs
o Acetaminophen

Damage to the primary motor cortex leads to dysarthria as well as weakness of the contralateral upper extremity. Since it does not involve an
area of the brain's language centers, an aphasia will not result.
Explanation: This patient presents with dysarthria (difficulty speaking). His speech is slurred because the area of the brain that innervates the
muscles involved in generating speech is damaged, most likely from a middle cerebral artery (MCA) stroke. He can comprehend the situation as
well as speak in complete sentences and repeat language. His language function is intact, and he is not aphasic. In addition, the patient also has
focal upper extremity weakness. These findings support damage to the motor cortex in the MCA distribution. The cortical homunculus is
arranged such that the arm and mouth are close together. Location B represents part of the primary motor cortex.

Key features of the primary motor cortex (location B) are as follows:

 Location: The primary motor cortex is located in the lateral precentral gyrus. It is the most posterior gyrus in the frontal lobe.
 Blood supply: Branches from the MCA supply the majority of the primary motor cortex, namely the lateral portion, where the muscles
of the upper extremity and the face/tongue/pharynx are represented. Branches of the anterior cerebral artery supply the medial
aspect, where the muscles of the lower extremity are represented.
 Function: The primary motor cortex is responsible for conscious initiation of movement, and it is where the upper motor neurons
originate before creating the corticospinal and corticonuclear (corticobulbar) tracts. Symptoms of an MCA stroke include upper
extremity weakness contralateral to the lesion, and dysarthria due to damage to upper motor neurons that innervate speech muscles.
Fluency, repetition, and comprehension are all intact, as lesions of this area do not produce aphasia.
Aphasias can be differentiated by evaluating a patient for fluency, repetition, and comprehension of speech. The following table summarizes
the language aphasia (if any) with damage to each area in this question:

Language Aphasia Affected Based on Location

 Area Aphasia Fluency Repetition Comprehension

Arcuate fasciculus Conduction Intact Impaired Intact

Primary motor cortex None¹ Intact Intact Intact

Broca area Broca Impaired Impaired Intact

Wernicke area Wernicke Intact Impaired Impaired

Visual association cortex None Intact Intact Intact

¹dysarthria will result instead

Answer A: Location A represents the arcuate fasciculus, a dense neural tract that connects the Wernicke area in the superior temporal gyrus
with the Broca area in the inferior frontal gyrus. Damage to this area leads to conduction aphasia. Patients are able to speak correctly and fully
understand speech; however, they are unable to repeat unfamiliar words spoken to them. These patients are fully aware of their difficulties.
The patient in the scenario has dysarthria with motor dysfunction, not conduction aphasia.
Answer C: Location C represents the Broca area, located within Brodmann areas 44 and 45 of the inferior frontal gyrus of the left cerebral
hemisphere. Damage to this area leads to Broca aphasia characterized by impaired fluency. Affected patients can generate speech only with
great effort and have impaired repetition. Patients are able to comprehend speech, and they are aware of their difficulties. The patient in the
scenario has intact language, not consistent with Broca aphasia.
Answer D: Location D represents the Wernicke area located within Brodmann area 22 of the posterior superior temporal gyrus of the left
cerebral hemisphere. Damage to this area leads to Wernicke aphasia, which is characterized by impaired comprehension and repetition.
Patients are able to speak fluently, but they are not aware of their difficulties. They often exhibit paraphasia, the tendency to substitute
incorrect words in speech. The patient in the scenario was able to repeat words and make complete sentences, but had slurred speech
consistent with dysarthria, not aphasia.
Answer E: Location E represents the visual association cortex located in the lateral occipital lobe. Damage to this area can be caused by a
stroke involving the MCA or a coup-contra-coup injury. A coup-contra-coup injury is caused by a direct blow to the frontal skull, transferring
force to the brain, and causing the occipital lobe to impact the occipital bone. Patients with damage in the visual association cortex present
with visual deficits related to the damaged area. For example, they might recognize an object but are unable to identify color, or they might be
unable to determine the speed and direction of moving objects. The patient in the scenario did not exhibit any of these findings but rather had
slurred speech with contralateral arm weakness consistent with a primary motor cortex injury.