316

SEC TION III

Endocrine
endocrinePhysiology

Prolactin
SOURCE

Secreted mainly by anterior pituitary.

FUNCTION

Stimulates milk production in breast; inhibits

ovulation in females and spermatogenesis
in males by inhibiting GnRH synthesis and
release.

Excessive amounts of prolactin associated with

libido.

REGULATION

Prolactin secretion from anterior pituitary

is tonically inhibited by dopamine from
hypothalamus. Prolactin in turn inhibits
its own secretion by dopamine synthesis
and secretion from hypothalamus. TRH
prolactin secretion (e.g., in 1 or 2
hypothyroidism).

Dopamine agonists (e.g., bromocriptine)

inhibit prolactin secretion and can be used in
treatment of prolactinoma.
Dopamine antagonists (e.g., most antipsychotics)
and estrogens (e.g., OCPs, pregnancy)
stimulate prolactin secretion.

Higher cortical
centers

Hypothalamus

Dopamine

1 hypothyroidism

TRH

Posterior
pituitary

Anterior
pituitary

Estrogen

FSH

Prolactin

GnRH
LH

Breast

FAS1_2015_10-Endocrine-JB_311-340_NTC.indd 316

Pregnancy

Ovulation
Spermatogenesis

Milk production

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Endocrine
endocrinePhysiology

SEC TION III

317

Growth hormone (somatotropin)

SOURCE

Secreted by anterior pituitary.

FUNCTION

Stimulates linear growth and muscle mass

through IGF-1 (somatomedin C) secretion.
insulin resistance (diabetogenic).

REGULATION

Released in pulses in response to growth

hormonereleasing hormone (GHRH).
Secretion during exercise and sleep.
Secretion inhibited by glucose and
somatostatin release via negative feedback by
somatomedin.

Excess secretion of GH (e.g., pituitary adenoma)

may cause acromegaly (adults) or gigantism
(children).

Ghrelin

Stimulates hunger (orexigenic effect) and GH

release (via GH secretagog receptor). Produced
by stomach. with sleep loss and Prader-Willi
syndrome.

Ghrelin make you hunghre.

Leptin

Satiety hormone. Produced by adipose tissue.

during starvation. Mutation of leptin gene
congenital obesity. Sleep deprivation
leptin production.

Leptin keeps you thin.

Endocannabinoids

Stimulate cortical reward centers desire for

high-fat foods.

The munchies.

Appetite regulation

Antidiuretic hormone
SOURCE

Synthesized in hypothalamus (supraoptic

nuclei), released by posterior pituitary.

FUNCTION

Regulates serum osmolarity (V2-receptors)

and blood pressure (V1-receptors). Primary
function is serum osmolarity regulation (ADH
serum osmolarity, urine osmolarity) via
regulation of aquaporin channel insertion in
principal cells of renal collecting duct.

REGULATION

Osmoreceptors in hypothalamus (1);

hypovolemia (2).

FAS1_2015_10-Endocrine-JB_311-340_NTC.indd 317

ADH level is in central diabetes insipidus(DI),

normal or in nephrogenic DI.
Nephrogenic DI can be caused by mutation in
V2-receptor.
Desmopressin acetate (ADH analog) is a
treatment for central DI.

11/6/14 12:55 PM

Pathology
PATHOLOGYNeoplasia

SEC TION II

235

Disease conditions associated with neoplasms

Gastrointestinal
Acanthosis nigricans

Rare paraneoplastic indicator of visceral malignancy (more commonly associated with insulin
resistance)

Barrett esophagus

Precursor to esophageal adenocarcinoma

Chronic atrophic
gastritis, postsurgical
gastric remnants

Predispose to gastric adenocarcinoma

Cirrhosis

Predisposes to hepatocellular carcinoma

Ulcerative colitis

Predisposes to colon adenocarcinoma

Musculoskeletal and skin

Actinic keratosis

Precursor to squamous cell carcinoma of the skin

Dermato- and
polymyositis

Predispose to visceral malignancies, particularly genitourinary

Dysplastic nevus

Precursor to malignant melanoma

Multiple seborrheic
keratoses

GI, breast, lung, and lymphoid malignancies

Paget disease of bone

Predisposes to 2 osteosarcoma and fibrosarcoma

Plummer-Vinson
syndrome

Predisposes to squamous cell carcinoma of the esophagus

Tuberous sclerosis

Often manifests with multiple hamartomatous (benign) tumors including giant cell astrocytomas,
renal angiomyolipomas, cardiac rhabdomyomas; tumors may become malignant

Xeroderma
pigmentosum,
albinism

Predispose to squamous cell carcinoma, basal cell carcinoma, melanoma

Hematologic
AIDS

Predisposes to aggressive lymphoma (non-Hodgkin) and Kaposi sarcoma

Autoimmune diseases
(e.g., Hashimoto
thyroiditis, SLE)

Predispose to lymphoma

Down syndrome

Predisposes to acute lymphocytic leukemia

Immunodeficiency

Predisposes to lymphoma, melanoma, renal cell carcinoma

Li-Fraumeni syndrome

p53 mutation predisposes to various cancer types at a young age (e.g., sarcoma, breast, leukemia,
adrenal gland)

Radiation exposure

High risk of developing leukemia, sarcoma, papillary thyroid cancer, breast cancer

FAS1_2015_07-Pathol-JB_221-240_NTC.indd 235

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232

SEC TION II

Pathology
PATHOLOGYNeoplasia

``
PATHOLOGYNEOPLASIA
Neoplastic progression

Hallmarks of cancer: evasion of apoptosis, growth signal self-sufficiency, anti-growth signal

insensitivity, sustained angiogenesis, limitless replicative potential, tissue invasion, and metastasis.

Normal cells

Normal cells with basal ( A , red arrow) apical

( A , blue arrow) differentiation.

Hyperplasiacells in number B .
Dysplasiaabnormal proliferation of cells with
loss of size, shape, and orientation.

Neoplastic cells have not invaded intact basement

membrane C .
nuclear/cytoplasmic (N/C) ratio and clumped
chromatin.
Neoplastic cells encompass entire thickness.

Cells have invaded basement membrane

using collagenases and hydrolases
(metalloproteinases) D .
Cell-cell contacts lost by inactivation of
E-cadherin.

Metastasisspread to distant organ, e.g.,

metastatic cells ( E , blue arrow) in liver
parenchyma ( E , red arrow).
Seed and soil theory of metastasis:
Seed = tumor embolus
Soil = target organ is often the firstencountered capillary bed (e.g., liver, lungs,
bone, brain, etc.)

Epithelial
cell layer
Basement
membrane

Hyperplasia

Epithelial
cell layer
Basement
membrane

Epithelial
cell layer
Basement
membrane
Epithelial
cell layer
Basement
membrane

Carcinoma in situ/
preinvasive

Epithelial
cell layer
Basement
membrane

Metastatic
focus

Blood or

lymphatic
Invasive carcinoma
vessel

Metastatic
focus

Blood or
lymphatic
vessel
Metastatic
focus

Metastasis

Metastatic
focus

Metastatic
focus

Blood or
lymphatic
vessel

Blood or
lymphatic
vessel

Blood or
lymphatic
vessel

FAS1_2015_07-Pathol-JB_221-240_NTC.indd 232

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226

SEC TION II

Pathology
PATHOLOGYInflammation

Types of calcification
Dystrophic
calcification

Ca2+ deposition in abnormal tissues A 2 to injury or necrosis.

Tends to be localized (e.g., calcific aortic stenosis).
Seen in TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, fat necrosis,
infarcts, thrombi, schistosomiasis, Mnckeberg arteriolosclerosis, congenital CMV
+ toxoplasmosis, psammoma bodies.
Is not directly associated with serum Ca2+ levels (patients are usually normocalcemic).

Metastatic
calcification

Widespread (i.e., diffuse, metastatic) deposition of Ca2+ in normal tissue B 2 to hypercalcemia

(e.g., 1 hyperparathyroidism, sarcoidosis, hypervitaminosis D) or high calcium-phosphate product
levels (e.g., chronic renal failure with 2 hyperparathyroidism, long-term dialysis, calciphylaxis,
warfarin).
Ca2+ deposits predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues
lose acid quickly; pH favors deposition).
Patients are usually not normocalcemic.

FAS1_2015_07-Pathol-JB_221-240_NTC.indd 226

Dystrophic calcification. Note dystrophic calcification (yellow

star), small bony tissue (yellow arrows), and thick fibrotic wall
(red arrows).

Metastatic calcification. Note metastatic calcifications of

alveolar walls in acute pneumonitis (blue arrows).

11/6/14 12:22 PM

Pathology
PATHOLOGYInflammation

Necrosis

SEC TION II

223

Enzymatic degradation and protein denaturation of cell due to exogenous injury intracellular
components leak. Inflammatory process (unlike apoptosis).

TYPE

SEEN IN

DUE TO

HISTOLOGY

Coagulative

Ischemia/infarcts in
most tissues (except
brain)

Ischemia or infarction;
proteins denature,
then enzymatic
degradation

Cell outlines preserved; cytoplasmic binding

of acidophilic dyes A

Liquefactive

Bacterial abscesses,
brain infarcts (due to
fat content)

Neutrophils releasing
lysosomal enzymes
that digest the
tissue B ; enzymatic
degradation first,
then proteins
denature

Early: cellular debris and macrophages

Late: cystic spaces and cavitation (brain)
Neutrophils and cell debris seen with bacterial
infection

Caseous

TB, systemic fungi

(e.g., Histoplasma
capsulatum),
Nocardia

Macrophages wall
off the infecting
microorganism
granular debris C

Fragmented cells and debris surrounded by

lymphocytes and macrophages

Fat

Enzymatic: acute
pancreatitis
(saponification)
Nonenzymatic: breast
trauma

Damaged cells release

lipase, which breaks
down fatty acids in
cell membranes

Outlines of dead fat cells without peripheral

nuclei; saponification of fat (combined with
Ca2+) appears dark blue on H&E stain D

Fibrinoid

Immune reactions in
vessels

Immune complexes
combine with fibrin
vessel wall damage

Vessel walls are thick and pink E

Gangrenous

Distal extremity, after

chronic ischemia

Dry: ischemia F

Coagulative

Wet: superinfection

Liquefactive

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Microbiology
microbiologyVirology

Mumps virus
A

Rabies virus
A

Ebola virus
A

FAS1_2015_05-Microbiology-JB_117-196_NTC.indd 165

A paramyxovirus that causes mumps,

uncommon due to effectiveness of MMR
vaccine.
Symptoms: Parotitis A , Orchitis (inflammation
of testes), and aseptic Meningitis. Can cause
sterility (especially after puberty).

Bullet-shaped virus A . Negri bodies B

commonly found in Purkinje cells of
cerebellum and in hippocampal neurons.
Rabies has long incubation period (weeks to
months) before symptom onset. Postexposure
prophylaxis is wound cleaning plus
immunization with killed vaccine and rabies
immunoglobulin. Example of passive-active
immunity.
Travels to the CNS by migrating in a retrograde
fashion up nerve axons after binding to ACh
receptors.
Progression of disease: fever, malaise
agitation, photophobia, hydrophobia,
hypersalivation paralysis, coma death.
More commonly from bat, raccoon, and skunk
bites than from dog bites in the United States.

SEC TION II

165

Mumps makes your parotid glands and testes as

big as POM-poms.

Negri body. Characteristic cytoplasmic inclusions (arrows) in

neurons infected by rabies virus.

Transmission requires direct contact with bodily

A filovirus A that targets endothelial cells,
fluids or fomites (including dead bodies); high
phagocytes, hepatocytes. Presents with abrupt
incidence of nosocomial infection.
onset of flu-like symptoms, diarrhea/vomiting,
high fever, myalgia. Can progress to DIC,
diffuse hemorrhage, shock. High mortality
rate, no definitive treatment. Supportive care.
Strict isolation of infected individuals and
barrier practices for health care workers are
key to preventing transmission.

11/6/14 1:11 PM

Microbiology
microbiologyParasitology

SEC TION II

153

Nematodes (roundworms)
ORGANISM

TRANSMISSION

DISEASE

TREATMENT

Intestinal
Enterobius vermicularis Fecal-oral
(pinworm)

Bendazoles (because worms

Intestinal infection causing
are bendy)
anal pruritus (diagnosed by
seeing egg A via the tape test)

Ascaris lumbricoides
(giant roundworm)

Fecal-oral; eggs visible in feces

under microscope B

Intestinal infection with

possible obstruction at
ileocecal valve

Bendazoles

Strongyloides
stercoralis

Larvae in soil penetrate the

skin

Intestinal infection causing

vomiting, diarrhea, epigastric
pain (may feel like peptic
ulcer)

Ivermectin or bendazoles

Ancylostoma
duodenale, Necator
americanus
(hookworms)

Larvae penetrate skin

Intestinal infection causing

anemia by sucking blood
from intestinal walls

Bendazoles or pyrantel
pamoate

Trichinella spiralis

Fecal-oral; undercooked meat

(esp. pork)

Intestinal infection; larvae

enter bloodstream and encyst
in striated muscle cells
inflammation of muscle.
Trichinosisfever, vomiting,
nausea, periorbital edema,
myalgia

Bendazoles

Onchocerca volvulus

Female blackfly bite

Hyperpigmented skin and

river blindness (black flies,
black skin nodules, black
sight); allergic reaction to
microfilaria possible

Ivermectin (ivermectin for river

blindness)

Loa loa

Deer fly, horse fly, mango fly

Swelling in skin, worm in

conjunctiva

Diethylcarbamazine

Wuchereria bancrofti

Female mosquito

Elephantiasisworms block
lymphatic vessels C , takes
9mo1yr after bite to
become symptomatic

Diethylcarbamazine

Toxocara canis

Fecal-oral

Visceral larva migrans

Bendazoles

Tissue

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154

SEC TION II

Microbiology
microbiologyParasitology

Nematode routes of
infection

IngestedEnterobius, Ascaris, Toxocara,

Trichinella
CutaneousStrongyloides, Ancylostoma,
Necator
BitesLoa loa, Onchocerca volvulus,
Wuchereria bancrofti

Youll get sick if you EATT these!

These get into your feet from the SANd.
Lay LOW to avoid getting bitten.

Cestodes (tapeworms)
ORGANISM

TRANSMISSION

DISEASE

TREATMENT

Taenia solium A

Ingestion of larvae encysted in

undercooked pork

Intestinal infection

Praziquantel

Ingestion of eggs

Cysticercosis,
neurocysticercosis B

Praziquantel; albendazole for

neurocysticercosis

Diphyllobothrium
latum

Ingestion of larvae from raw

freshwater fish

Vitamin B12 deficiency

(tapeworm competes for B12
in intestine) megaloblastic
anemia

Praziquantel

Echinococcus
granulosus C

Ingestion of eggs from dog

feces
Sheep are an intermediate host

Hydatid cysts D in liver E ,

causing anaphylaxis if
antigens released (hydatid
cyst injected with ethanol
or hypertonic saline to
kill daughter cysts before
removal)

Albendazole

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Microbiology
microbiologyClinical Bacteriology

Syphilis

SEC TION II

141

Caused by spirochete Treponema pallidum.

1 syphilis

Localized disease presenting with painless chancre A . If available, use dark-field microscopy to
visualize treponemes in fluid from chancre B . VDRL in ~ 80%.

2 syphilis

Disseminated disease with constitutional symptoms, maculopapular rash C (including palms and
soles D ), condylomata lata E (smooth, moist, painless, wart-like white lesions on genitals); also
confirmable with dark-field microscopy.
Serologic testing: VDRL/RPR (nonspecific), confirm diagnosis with specific test (e.g., FTA-ABS).
Secondary syphilis = Systemic. Latent syphilis ( serology without symptoms) follows.

3 syphilis

Gummas F (chronic granulomas), aortitis (vasa vasorum destruction), neurosyphilis (tabes dorsalis,
general paresis), Argyll Robertson pupil (constricts with accommodation but is not reactive to
light; also called prostitutes pupil since it accommodates but does not react).
Signs: broad-based ataxia, Romberg, Charcot joint, stroke without hypertension.
For neurosyphilis: test spinal fluid with VDRL and PCR.

Congenital syphilis

Presents with facial abnormalities such as rhagades (linear scars at angle of mouth, black arrow
in G ), snuffles (nasal discharge, red arrow in G ), saddle nose, notched (Hutchinson) teeth H ,
mulberry molars, and short maxilla; saber shins; CN VIII deafness.
To prevent, treat mother early in pregnancy, as placental transmission typically occurs after first
trimester.
A

VDRL false positives

VDRL detects nonspecific antibody that reacts

with beef cardiolipin. Inexpensive, widely
available test for syphilis, quantitative, sensitive
but not specific.

Jarisch-Herxheimer
reaction

Flu-like syndrome (fever, chills, headache, myalgia) after antibiotics are started; due to killed
bacteria (usually spirochetes) releasing endotoxins.

FAS1_2015_05-Microbiology-JB_117-196_NTC.indd 141

False-positive results on VDRL with:

Viral infection (mono, hepatitis)
Drugs
Rheumatic fever
Lupus and leprosy

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128

SEC TION II

-hemolytic bacteria
A

-hemolytic bacteria
A

Staphylococcus aureus
A

Microbiology
microbiologyClinical Bacteriology

Form green ring around colonies on blood agar A . Include the following organisms:
Streptococcus pneumoniae (catalase and optochin sensitive)
Viridans streptococci (catalase and optochin resistant)

Form clear area of hemolysis on blood agar A . Include the following organisms:
Staphylococcus aureus (catalase and coagulase )
Streptococcus pyogenesgroup A strep (catalase and bacitracin sensitive)
Streptococcus agalactiaegroup B strep (catalase and bacitracin resistant)
Listeria monocytogenes (tumbling motility, meningitis in newborns, unpasteurized milk)

Gram-positive cocci in clusters A . Protein A

(virulence factor) binds Fc-IgG, inhibiting
complement activation and phagocytosis.
Commonly colonizes the nares.
Causes:
Inflammatory diseaseskin infections,
organ abscesses, pneumonia (often after
influenza virus infection), endocarditis,
septic arthritis, and osteomyelitis.
Toxin-mediated diseasetoxic shock
syndrome (TSST-1), scalded skin syndrome
(exfoliative toxin), rapid-onset food
poisoning (enterotoxins).
MRSA (methicillin-resistant S. aureus)
infectionimportant cause of serious
nosocomial and community-acquired
infections; resistant to methicillin and
nafcillin because of altered penicillinbinding protein.

TSST is a superantigen that binds to MHC II

and T-cell receptor, resulting in polyclonal
T-cell activation. Staphylococcal toxic shock
syndrome (TSS) presents as fever, vomiting,
rash, desquamation, shock, end-organ failure.
Associated with prolonged use of vaginal
tampons or nasal packing. Compare with
Streptococcus pyogenes TSS (a toxic shock
like syndrome associated with painful skin
infection).
S. aureus food poisoning due to ingestion of
preformed toxin short incubation period
(26 hr) followed by nonbloody diarrhea
and emesis. Enterotoxin is heat stable not
destroyed by cooking.
Staph make catalase because they have more
staff. Bad staph (aureus) make coagulase and
toxins. Forms fibrin clot around self abscess.

Staphylococcus
epidermidis

Infects prosthetic devices (e.g., hip implant, heart valve) and intravenous catheters by producing
adherent biofilms. Component of normal skin flora; contaminates blood cultures. Novobiocin
sensitive.

Staphylococcus
saprophyticus

Second most common cause of uncomplicated UTI in young women (first is E. coli). Novobiocin
resistant.

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