GI

** 5-HT3 receptor antagonists are useful for the treatment of visceral nausea due to
gastrointestinal insults, such as gastroenteritis, chemotherapy, and general anesthesia.
Antihistamines and anticholinergics are recommended for vestibular nausea. Dopamine
antagonists are useful for nausea associated with migraine.

** Nutmeg gross liver in congestive hepatopathy

** Cholangiocarcinoma: Adenocarcinoma with cuboidal or columnar cells with prominent

nucleoli arranged in glandular structures, + Mucin production, + desmoplasmic response

** Well-differentiated neuroendocrine tumors (ie, carcinoid tumors) arise from neuroendocrine

cells and are composed of uniform tumor cells with round nuclei, salt and pepper chromatin, and
eosinophilic cytoplasm. Although most are found incidentally (ie, asymptomatic), some may
obstruct the lumen, causing acute appendicitis.
** Treatments for hepatic encephalopathy include lactulose (increases conversion of ammonia
to ammonium) and rifaximin (decreases intraluminal ammonia production).
** Liver histology in alpha-1 antitrypsin deficiency shows hepatocellular globules that are
positive for periodic acid–Schiff staining and resistant to diastase digestion. Although neonatal
cholestasis can occur with this condition, transaminases are typically elevated, and the
gallbladder would be normal.

** γ-glutamyl transpeptidase is an enzyme predominantly present in hepatocytes and biliary

epithelia. While it too can be found in various extrahepatic tissues (organs such as kidney,
spleen, pancreas, heart, lung, and brain), GGTP is not present to a significant extent in bone. It
is therefore particularly useful in determining whether an elevated alkaline phosphatase is of
hepatic or bony origin.

**Biliary atresia is a progressive, complete or partial obstruction of extrahepatic bile ducts. The
biliary tree is normal at birth and subsequently undergoes destruction that is thought to be
immune-related or viral-induced. Infants may appear healthy at birth, but then present with
jaundice within the first 2 months of life, along with dark urine and acholic (pale or clay-colored)
stools due to excessive renal excretion of bilirubin and lack of intestinal bile, respectively.
Physical examination may also reveal firm hepatomegaly due to inflammation. Laboratory
findings, including elevated direct bilirubin and gamma-glutamyl transferase, are consistent with
cholestasis.
** Malabsorption is a syndrome of impaired intestinal digestion and absorption. Fats are
typically the most severely affected macronutrient in generalized malabsorption, and testing the
stool for fat (eg, with Sudan III stain) is the most sensitive strategy for screening for
malabsorptive disorders.
** Dyssynergic defecation occurs when the puborectalis muscle or the internal or external anal
sphincter fails to relax during defecation, leading to chronic constipation. Dyssynergic
defecation is usually considered a functional disorder and occurs more commonly in the elderly
but may also occur with certain neurologic disorders (eg, Parkinson disease, multiple sclerosis)
or trauma.
** Normal swallowing involves a complex sequence of voluntary and reflexive processes that
move food from the mouth to the esophagus while preventing it from entering the airway (ie,
aspiration). Three main airway-protective movements occur during normal swallowing:

Displacement of the larynx superiorly and anteriorly under the base of tongue, which allows food
to be directed into the more posteriorly located esophagus

Tilting of the epiglottis to block the airway

Closing of the glottis by adduction of the vocal folds

The most important airway-protective movements during swallowing are the anterior/superior
displacement of the larynx, the tilting of the epiglottis to block the airway, and vocal fold
adduction. A chin-tuck maneuver can be helpful in some patients with aspiration by simulating
the airway-protective movement of the larynx.

** Fat vacuoles within hepatocytes (ie, microvesicular steatosis) are seen in Reye syndrome, an
uncommon condition in which young children develop hepatic dysfunction and encephalopathy
after aspirin ingestion during a viral illness (eg, influenza). Bilirubin is typically normal, and
transaminases would be very high.

In normal individuals, migrating motor complexes cause intestinal peristalsis, which clears
bacteria and reduces the reflux of colonic organisms into the small bowel. Patients with
impaired gut motility (eg, long-standing diabetes mellitus with autonomic neuropathy) are at
increased risk for SIBO, as are patients with anatomic (eg, bowel adhesions, intestinal blind
loops from surgery) or fibrotic (eg, scleroderma, prior radiotherapy) disruptions of intestinal flow
Endocrine:

** Cortisol increases the conversion of norepinephrine to epinephrine in the adrenal medulla by

increasing the expression of phenylethanolamine-N-methyltransferase.

** The alpha-2-mediated inhibitory effect is generally predominant, causing sympathetic

stimulation to lead to overall inhibition of insulin secretion.
** Glucagon increases serum glucose by increasing hepatic glucose production via
glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose from
noncarbohydrate sources). Glucagon-induced glycogenolysis is the predominant initial means
of rapidly increasing blood glucose levels during hypoglycemia.

** Ghrelin stimulates appetite and promotes weight gain. Leptin and insulin act in the CNS to
decrease appetite. Caloric restriction leads to increased ghrelin levels along with decreased
insulin and leptin levels, causing an increase in appetite that can make it difficult to maintain
weight loss.

**

** This patient's increased levels of thyroxine (T4), triiodothyronine (T3), and TSH are
concerning for thyroid hormone resistance. Most cases are due to an inherited mutation
affecting thyroid hormone receptor beta, which results in decreased thyroid hormone sensitivity
in the hypothalamic-pituitary-thyroid axis and peripheral tissues. Increased levels of T3 and T4
normally provide negative feedback to the pituitary to decrease TSH production. However,
because pituitary cells are also resistant to thyroid hormone in this condition, TSH rises, driving
further production of T3 and T4.

** Methimazole and propylthiouracil are thioamide drugs used for treating hyperthyroidism.
They inhibit thyroid peroxidase, the enzyme responsible for both iodine organification and
coupling of iodotyrosines. Propylthiouracil also decreases the peripheral conversion of T4 to the
active hormone T3, although methimazole does not have this effect.

** 5-alpha-reductase inhibitors (eg, finasteride) reduce conversion of testosterone to

dihydrotestosterone. In men with benign prostatic hyperplasia, these agents reduce prostate
volume and alleviate obstruction of urinary flow. However, they are associated with androgen-
deficiency effects, including decreased libido, erectile dysfunction, and decreased ejaculate
volume.

** The surface receptor for insulin is a transmembrane protein with intrinsic tyrosine kinase
activity in its cytoplasmic domain. Insulin binding activates tyrosine kinase, leading to
phosphorylation of insulin receptor substrate 1 (IRS-1). IRS-1 then activates several
intracellular pathways that induce the physiologic effects of insulin. Activation of the MAP
kinase pathway promotes mitogenic functions such as DNA synthesis and cell growth. In
contrast, activation of phosphatidylinositol-3-kinase (PI3K) stimulates metabolic functions such
as translocation of GLUT-4 to the cell membrane, glycogen synthesis, and fat synthesis. PI3K
promotes glycogen synthesis by activating protein phosphatase, an enzyme that
dephosphorylates glycogen synthase, leading to its activation

** Coadministration with various foods (eg, soy products) or drugs (eg, iron, calcium, antacids)
can lead to poor intestinal absorption of levothyroxine. In this case, iron binding to levothyroxine
in the gastrointestinal tract caused circulating levothyroxine levels to decrease, resulting in
symptoms of hypothyroidism (eg, constipation, poor linear growth) and increased TSH
production. Because this patient's thyroid function tests at age 4 months were normal, iron
supplementation was likely started in the past 2 months to treat the physiologic waning of iron
stores that occurs at this age.

Psych

**
PULM
** Cystic fibrosis is an autosomal recessive disease caused by mutations in the CF
transmembrane conductance regulator (CFTR) [Link] CFTR protein is a transmembrane
ATP-gated chloride channel.

MICRO

** Alcohol-based disinfectants kill enveloped viruses (eg, influenza) by dissolving their outer lipid
envelope. Nonenveloped viruses are less susceptible to some alcohol-based disinfectants
because they have no lipid envelope to target.

**Norovirus is the most common cause of viral gastroenteritis. Symptoms include diarrhea,
vomiting, fever, malaise, and headache. The diarrhea is typically watery without blood or mucus
due to lack of small bowel inflammation.
** HBV has several additional mechanisms that promote HCC, including the following:
Integration into the host genome – Nearly 90% of patients with chronic HBV who develop HCC
have evidence of HBV DNA in the chromosomes of tumor cells. Production of oncogenic viral
proteins

Hematology
**

** Both HbC and HbS result from missense mutations, a type of mutation in which a single base
substitution results in a codon that codes for a different amino acid.
** Pure red cell aplasia is a rare form of bone marrow failure characterized by severe anemia
with reticulocytopenia and morphologically normal platelets and leukocytes. It is most common
with thymoma, lymphocytic leukemia, and parvovirus B19 infection.

**

** The most common masses in the anterior mediastinum are the 4 Ts: thymoma, teratoma (and
other germ cell tumors), "terrible" lymphoma, and thyroid neoplasm. An anterior mediastinal
mass with elevated serum levels of alpha fetoprotein and β-hCG is classic for a
nonseminomatous germ cell tumor.

** Tumors can acquire resistance to multiple chemotherapeutic agents by increasing expression

of P-glycoprotein, a transmembrane ATP-dependent efflux pump that has broad specificity.