first aid 2015 pages added

EndocrinE ` endocrine—PhysiologyEndocrinE ` endocrine—PhysiologyS E c T i o n iii316

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.

1° hypothyroidism

Estrogen

Milk productionBreast

Pregnancy

OvulationSpermatogenesis

GnRH

FSH

LH

Higher corticalcenters

Anteriorpituitary

Posteriorpituitary

–

–

–

Hypothalamus

Prolactin

Dopamine TRH

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End oc r inE ` endocrine—PhysiologyEnd oc r inE ` endocrine—Physiology SEc T ion 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 hormone–releasing 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).

Appetite regulation

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.

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.

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.

regUlAtion Osmoreceptors in hypothalamus (1°); hypovolemia (2°).

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Patholog y ` PATHOLOGY—nEOPLASIAPatholog y ` PATHOLOGY—nEOPLASIA SEC t IoN 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

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Pathology ` PATHOLOGY—nEOPLASIAPathology ` PATHOLOGY—nEOPLASIASE C t I oN II232

` PAT H O LO G Y — n E O P L A S I A

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

Epithelialcell layer

Basementmembrane

Blood or lymphatic

vessel

Metastaticfocus

A Normal cells with basal ( A , red arrow) � apical ( A , blue arrow) differentiation.

HyperplasiaEpithelialcell layer

Basementmembrane

Blood or lymphatic

vessel

Metastaticfocus

B Hyperplasia—cells � in number B .Dysplasia—abnormal proliferation of cells with

loss of size, shape, and orientation.

Carcinoma in situ/preinvasive


Basementmembrane

Blood or lymphatic

vessel

Metastaticfocus

C Neoplastic cells have not invaded intact basement membrane C .� nuclear/cytoplasmic (N/C) ratio and clumped

chromatin.Neoplastic cells encompass entire thickness.

Invasive carcinoma


Basementmembrane

Blood or lymphatic

vessel

Metastaticfocus

D Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases) D .

Cell-cell contacts lost by inactivation of E-cadherin.

Metastasis


Basementmembrane

Blood or lymphatic

vessel

Metastaticfocus

E Metastasis—spread 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 first-encountered capillary bed (e.g., liver, lungs, bone, brain, etc.)


Pathology ` PATHOLOGY—InfLAmmATIOnPathology ` PATHOLOGY—InfLAmmATIOnSE C t I oN II226

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, Mönckeberg 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.

A Dystrophic calcification. Note dystrophic calcification (yellow star), small bony tissue (yellow arrows), and thick fibrotic wall (red arrows).

B Metastatic calcification. Note metastatic calcifications of alveolar walls in acute pneumonitis (blue arrows).


Patholog y ` PATHOLOGY—InfLAmmATIOnPatholog y ` PATHOLOGY—InfLAmmATIOn SEC t IoN II 223

Necrosis 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 macrophagesLate: 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

C

D F

A B

E


Mic r obiolog y ` microbiology—VirologyMic r obiolog y ` microbiology—Virology SEc T ioN ii 165

Mumps virus

A

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).

Mumps makes your parotid glands and testes as big as POM-poms.

Rabies virus

A

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.

B Negri body. Characteristic cytoplasmic inclusions (arrows) in neurons infected by rabies virus.

Ebola virus

A

A filovirus A that targets endothelial cells, phagocytes, hepatocytes. Presents with abrupt 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.

Transmission requires direct contact with bodily fluids or fomites (including dead bodies); high incidence of nosocomial infection.

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Mic r obiolog y ` microbiology—ParasitologyMic r obiolog y ` microbiology—Parasitology SEc T ioN ii 153

Nematodes (roundworms)orgaNism traNsmissioN Disease treatmeNt

Intestinal

Enterobius vermicularis (pinworm)

Fecal-oral Intestinal infection causing anal pruritus (diagnosed by seeing egg A via the tape test)

Bendazoles (because worms are bendy)

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.

Trichinosis—fever, vomiting, nausea, periorbital edema, myalgia

Bendazoles

Tissue

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 Elephantiasis—worms block lymphatic vessels C , takes 9 mo–1 yr after bite to become symptomatic

Diethylcarbamazine

Toxocara canis Fecal-oral Visceral larva migrans Bendazoles

CA B


Microbiology ` microbiology—ParasitologyMicrobiolog y ` microbiology—ParasitologySE c T i oN ii154

Nematode routes of infection

Ingested—Enterobius, Ascaris, Toxocara, Trichinella

Cutaneous—Strongyloides, Ancylostoma, Necator

Bites—Loa loa, Onchocerca volvulus, Wuchereria bancrofti

You’ll 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

A B C D E


Microbiolog y ` microbiology—cliNical bac teriologyMic r obiolog y ` microbiology—cliNical bac teriology SEc T ioN ii 141

Syphilis 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 “prostitute’s 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 B C D

E G HF

VDRL false positives VDRL detects nonspecific antibody that reacts with beef cardiolipin. Inexpensive, widely available test for syphilis, quantitative, sensitive but not specific.

False-positive results on VDRL with:Viral infection (mono, hepatitis)DrugsRheumatic fever Lupus and leprosy

Jarisch-Herxheimer reaction

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


Microbiology ` microbiology—cliNical bac teriologyMicrobiolog y ` microbiology—cliNical bac teriologySE c T i oN ii128

α-hemolytic bacteria

A

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)

β-hemolytic bacteria

A

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

Staphylococcus aureus

A

Gram-positive cocci in clusters A . Protein A (virulence factor) binds Fc-IgG, inhibiting complement activation and phagocytosis. Commonly colonizes the nares.

Causes: � Inflammatory disease—skin infections, organ abscesses, pneumonia (often after influenza virus infection), endocarditis, septic arthritis, and osteomyelitis.

� Toxin-mediated disease—toxic shock syndrome (TSST-1), scalded skin syndrome (exfoliative toxin), rapid-onset food poisoning (enterotoxins).

� MRSA (methicillin-resistant S. aureus) infection—important cause of serious nosocomial and community-acquired infections; resistant to methicillin and nafcillin because of altered penicillin-binding 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 (2–6 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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