Section 1
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Screening for Cervical Carcinoma
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Section 1
(50 cards)
Screening for Cervical Carcinoma
Pap Smear = secondary prevention: catch dysplasia before it develops into carcinoma by scraping cells and analyzing under microscope *most successful screening test (reduced incidence in US) *does NOT screen for adenocarcinoma Schiller test (iodine/potassium iodide): dysplastic epithelium does not stain because of lack of glycogen
Dysgerminoma
Malignant GERM CELL (most common malignant) tumor from OOCYTE characterized by clear cytoplasm w/ central nuclei *Often before age 30 *Male equivalent is seminoma Tumor markers: LDH, hCG
Endometrial Hyperplasia
Hyperplasia of GLANDS RELATIVE TO STROMA from unopposed estrogen Presentation: bleeding Risk factors: - postmenopausal woman - obesity (higher aromatase) - anovulation (no progresterone) - nulliparity - HRT - PCOS - granulosa cell tumor Histology: - CELLULAR ATYPIA (biggest risk factor for development of carcinoma) - simple vs. complex (not that important risk factor)
Lichen Sclerosis vs. Lichen Simplex Chronicus
Sclerosis: thinning ("parchment-like") of epidermis and fibrosis of dermis w/ leukoplakia - post-menopausal women - INCREASED risk of carcinoma (non-HPV) Simplex Chronicus (squamous hyperplasia): thick ("leathery") vulvar skin due to hyperplasia from chronic irritation w/ leukoplakia - NO INCREASED risk of carcinoma
Acute Pancreatitis
Autodigestion of pancreas by pancreatic enzymes (trypsin is first enzyme activated --> activation of other enzymes) --> inflammation, hemorrhage, necrosis (liquefactive and fat necrosis of peripancreatic fat) Causes (I GET SMASHED) - Idiopathic - Gallstones (obstruct pancreatic drainage) - Ethanol (spasm in sphincter of oddi) - Trauma - Scorpion sting - Mumps - Autoimmune - Steroids - HyperCa (activate trypsin) or HyperTG - Endoscopic Retrograde CholangioPancreatography (ERCP) - Drugs (sulfa, PIs, NRTIs etc.) Clinical: - epigastric pain that radiates to back - N/V - periumbilical (cullen) and flank (grey-turner) hemorrhage - enzyme elevation (lipase-later/longer/specific, and amylase) - hypocalcemia (used up in fat necrosis saponification) = poor prognosis - Ranson's criteria determine prognosis Complications - shock (from hemorrhage) - renal failure (from shock) - pseudocyst (fibrous granulation tissue that walls off the necrosis, not epithelium hence pseudo) - abscess (E Coli) - DIC (activated coag factors) - ARDS (enzymes damage alveolar-capillary interface)
Clear Cell Adenocarcinoma
Malignant proliferation of glands, characterized by clear cytoplasm Rare complication of DES-associated adenosis (persistence of columnar epithelium in upper 2/3 of vaginal canal)
Cervical Transformation Zone
Exocervix (vaginal side): stratified squamous Endocervix (uterus side): simple columnar This junction is where cervical pathology occurs
Gynecologic Tumor Epidemiology
Incidence (US) endometrial>ovarian>cervical Incidence (worldwide) cervical>endometrial>ovarian (HPV screen/vaccine not as common) Prognosis ovarian>endometrial>cervical (deeper is worse since less symptoms)
Preeclampsia
Triad (arises in 3rd trimester): HTN (pregnancy-onset), proteinuria, edema Due to abnormality of maternal/fetal vascular (spiral arteries) interface --> endothelial damage, vasoconstriction, ischemia Eclampsia = preeclampsia + seizures HELLP = preeclampsia + thrombotic microangiopathy of liver - Hemolysis (w/ schistocytes) - Elevated Liver enzymes - Low Platelets
Condyloma
Warty neoplasm on vulva Causes: - HPV 6/11 --> condyloma acuminatum (koilocytic change but low risk progression to carcinoma) - 2ndary syphillis --> condyloma latum
Complications of DES
DES Mom (user): - breast carcinoma DES Daughter (in utero): - Adenosis --> Clear Cell Carcinoma - SM tubal proliferation --> ectopic pregnancy or infertility
Granulosa-Theca Cell Tumor
Malignant STROMAL tumor of granulosa and theca cells that produces estrogen --> signs of excess estrogen: - precocious puberty (young) - menorrhagia/metrorrhagia (reproductive) - endometrial hyperplasia/bleeding (post-menopausal) *Call-Exner bodies
Endometrial Carcinoma
Malignant proliferation of endometrial glands (most common INVASIVE carcinoma) Presentation: postmenopausal bleeding Hyperplastic pathway (75%) - estrogen exposure --> hyperplasia --> invasive carcinoma - histology: endometrioid (normal) - ptEn tumor suppressor gene - 60 yr old woman Sporadic pathway (25%) - no precursor, but atrophic endometrium - histology: serous (papillary w/ pSammoma bodies) - p53 mutation --> aggressive - 70 yr old woman
Bartholin Cyst
Dilation of Bartholin gland (posterolateral vulva) due to obstruction --> inflammation --> potential abscess Presentation: - unilateral, painful, cystic lesion - woman of reproductive age
Extramammary Paget Disease
Malignant epithelial cells in epidermis (carcinoma in situ w/ no underlying carcinoma) Presentation: - erythematous - itchy - ulcerated Stains: - PAS+ (P for Paget) - Keratin+ (epithelial) - S100- (melanoma is S100+ve)
Gallstones
Precipitation of cholesterol or bilirubin in bile --> stones in gallbladder caused by: - increased cholesterol/bilirubin - decreased bile acid - stasis Cholesterol (90%) - yellow, radiolucent - fat, fertile (female, estrogen), forty, fibrates...also Crohns/cirrhosis, native american Bilirubin (10%) - black, radio-opaque - extravascular hemolysis (increase heme breakdown) - biliary tract infection (ascaris, clonorchis) Complications: - biliary colic (contraction against lodged stone by meal-induced CCK) - cholecystitis (inflammation) - ascending cholangitis (infection due to obstruction caused by enteric gram -ve...jaundice, fever, RUQ pain) - gallstone ileus (block small bowel after GB>SI fistula) - gallbladder cancer (gallstones --> inflammation --> porcelain --> cancer)
Childhood Infections
Measles (Rubeola) - paramyxovirus (-ssRNA w/ envelope) - 4Cs (cough, coryza, Koplik-spots, conjunctivitis) - rash (starts on head and goes down) - SSPE (immunocompromised) - Warthin-Finkeldey giant cell Rubella (German 3-day measles) - togavirus (+ssRNA w/ envelope) - milder measles (rash/myalgias) - toRches (PDA, pulmonary artery hypoplasia, MR, deafness, glaucoma/cataracts) Mumps - paramyxovirus (-ssRNA w/ envelope) - parotid, testis, pancreas - aseptic meningitis VZV chickenpox - herpes (dsDNA w/ envelope) - rash trunk to extremities --> macule --> vesicle --> rupture --> crust - recurrence = shingles Fifth/B19 (erythema infectiosum) - parvo (dsDNA naked) - slapped cheek rash - hydrops fetalis HHV-6 (Sixth, roseola) - high febrile seizures - later rash (trunk to extremities) Whooping cough (bordetella pertussis) - gram negative coccobaccilus - catarrhal (rhinorrhea, conjunctivitis, fever) - paroxysmal (inspiratory whoop) Diptheria (corynebacterium) - gram +ve bacilli - pseudomembrane pharyngitis - cervical lymphadenopathy (bulls neck) - myocarditis RSV - paramyxovirus (-ssRNA w/ envelope) - winter - bronchiolitis <2 yr olds Epiglottitis (haemophilus) Otitis media - middle ear fluid - <3 yrs - strep pneumo, haemophilus, moraxella
Choriocarcinoma
Malignant GERM CELL tumor from PLACENTA characterized by cytotrophoblasts/synctiotrophoblast (but absent villi) *Hemorrhagic spread (exception to carcinoma - trophoblasts try to find blood) *Poor response to chemo Tumor markers: beta-HCG
Biliary Colic
Waxing and waning RUQ pain due to contraction (CCK-mediated after meal) against a lodged gallstone...pressure relived when stone passed
Endometriosis
Endometrial GLANDS AND STROMA that are found outside of the endometrial cavity (appear as "brown specks") Presentation: - dysmenorrhea (pain w/ menses) - infertility (esp if tubal) - pain w/ defecation (sometimes) - dyspareunia Cause: - retrograde menstruation and implantation - metaplasia - transportation of endometrial tissue via lymphatics Common sites: - ovary (chocolate cysts) - uterine ligaments (pelvic pain) - pouch of douglas (pain w/ defecation) - fallopian tubes (infertility) - myometrium (adenomyosis - due to hyperplasia of basal layer of endometrium)
Asherman Syndrome
Secondary amenorrhea (lack of menses) due to loss of basalis (the regenerative layer) --> scarring Cause: aggressive dilation and curettage (D&C)
Chronic Pancreatitis
From continued bouts of acute pancreatitis --> inflammation, fibrosis, atrophy, and pseudocyst formation Most common causes (not stones): - alcohol (adults) - cystic fibrosis (children) Clinical: - epigastric pain that radiates to back - PANCREATIC INSUFFICIENCY --> malabsorption (steatorrhea, DAKE deficiency) + DM type 1 (destruction of islets) - amylase/lipase are NOT good markers - dystrophic calcifications ("chain of lakes") - increased risk for pancreatic carcinoma
Ovarian Tumor Overview
Surface epithelium (coelomic) - 70% (most common) - Types: serous/mucus cystadenoma/adenocarcinoma; endometrioid (from ovarian endometriosis); brenner (bladder-like) - Symptoms: vague pain, urinary compression - Can cause omental caking - CA-125 tumor-marker Germ Cell Tumors (from the egg) - 15% (2nd most common) - Mimics tissue subtype - Types: fetal (cystic teratoma, embryonal carcinoma); oocytes (dysgerminoma); yolk sac (endodermal sinus); placenta (choricocarcinoma) Sex-Cord Stroma (from CT - fibroblasts, granulosa, theca) - Types: granulosa-theca, sertoli-leydig, fibroma Metastasis - Kruckenberg (bilateral mucinous, signet ring cells, from GI/gastric) - Pseudomyxoma peritonei (mucus in peritoneum, due to appendix or ovary tumor)
HPV
Human Papilloma Virus (HPV) is a sexually transmitted virus that infects the lower genital tract (vulva, vagina, and especially cervix at the transformation zone) Risk factors: multiple sex partners, smoking, early intercourse, HIV Types: - low-risk: 6/11 - high-risk: 16/18 and 31/33 Mechanism: - Infection --> dysplasia (CIN) --> invasive carcinoma - high risk HPV creates gene products that destroy tumor suppressors and increase the risk for dysplasia (E6 destroys p53, E7 destroys Rb)
Vulvar Carcinoma
Malignant, arising from SQUAMOUS epithelium...very RARE Presentation: leukoplakia (must be distinguished from lichen) HPV type - HPV 16/18 - arises from vulvular intraepithelial neoplasia (VIN) = dysplasia (high N:C, hyper chromatic, pleomorphic, mitotic) - often reproductive age Non-HPV type - arising from lichen sclerosis - elderly women
Cholecystitis
Inflammation/THICKENING of the gallbladder wall caused by gallstones (GB distention --> vessel compression --> ischemia) or infection (primary or secondary to stones), or primary ischemia (systemic problem) Acute: - RUQ pain that radiates to right scapula (w/ murphys sign) - N/V - fever w/ elevated WBC - elevated alkaline phosphatase Chronic: long-standing cholelithiasis (always) - vague RUQ pain - rokitanksy-aschoff sinuses (invagination of mucosa) - complication: porcelain GB (shrunken, hard, calcified)
Cervical Intraepithelial Neoplasia (CIN)
Dysplastic growth at the cervical transformation zone caused by high-risk HPV that destroy tumors suppressors (p53/Rb) Characteristics: - koilocytic change - nuclear atypia - increased mitosis Grading (higher grade is less likely to reverse): - CIN 1 (mild - 1/3 of epithelium) - CIN 2 (moderate - 2/3 of epithelium) - CIN 3 (severe - most of epithelium) *all of the above are REVERSIBLE - Carcinoma in situ (all of epithelium) *NON-REVERSIBLE
HPV Vaccine
Quadrivalent: 6/11 (condylomas) and 16/18 (CIN/carcinoma) - Protection only lasts for 5 years - Pap smear still necessary (doesn't work against 31/33)
Vaginal Structure
Embryology: - lower 1/3 derived from urogenital sinus (normally non-keratinized stratified squamous epithelium) - upper 2/3 derived from mullerian duct (normally columnar epithelium) Lower 1/3 (non-keratinized stratified squamous) usually replaces upper 2/3 so that they whole vagina is same epithelial type *Adenosis = PERSISTENCE of columnar epithelium in upper 2/3 of vaginal canal (often due to DES exposure in utero)
Vaginal Carcinoma
Malignant carcinoma from SQUAMOUS epithelium, related to high-risk (16/18) HPV (precursor is VAIN) Often secondary to cervical squamous cell carcinoma Spread: - lower 1/3 --> inguinal nodes - upper 2/3 --> iliac nodes
Hydatidiform Moles
Abnormal conception characterized by swollen/edematous villi w/ proliferation of trophoblast (its all DADS FAULT) Findings: - absent heart sounds - "snowstorm" appearance on ultrasound - larger than normal uterus - higher b-hCG than expected - passage of "grape-like" masses in 2nd trimester (if no prenatal care) Associations: - early preeclampsia - theca-lutein cysts - hyperemesis gravidarum - hyperthyroidism - later choriocarcinoma Complete - completely dad (2 sperm + empty ovum = 46) - complete mole (no fetal tissue) - completely edematous (all villi are edematous) - complete proliferation (diffuse proliferation) - HIGHER (b-hCG and risk for choriocarcinoma) Partial - part dad/part mum (2 sperm + 1 egg = 69) - part fetal (fetal tissue present) - part edematous (some villi) - part proliferation (focal) - LOWER (b-hCG and low risk for choriocarcinoma) Treatment: - dilation and curettage (complete removal) - methotrexate
Hormonal Effects on Endometrium
Estrogen: hyperplasia --> carcinoma Progesterone: atrophy (protective against carcinoma)
Mature Cystic Teratoma (Dermoid Cyst)
Benign GERM CELL (most common benign) cystic tumor from MATURE FETAL tissue of 2 or 3 embryologic layers (ex. hair, skin/sebum, teeth) *Struma ovarii = thyroid tissue (can cause hyperthyroid) *If immature (often neuroectoderm) can be malignant
Endometrial Polyp
Hyperplastic, well-circumscribed protrusion of endometrium Presentation: - abnormal bleeding - painless *Can be caused by tamoxifen (SERM that is agonist at uterus)
Pancreatic Carcinoma
Adenocarcinoma arising from pancreatic ducts that has a late presentation (poor prognosis) Risk factors: - elderly - SMOKING - chronic pancreatitis Clinical - epigastric pain - weight loss (cachexia) - head (tumor mass effect): obstructive jaundice w/ palpable gallbladder (courvesiers) - tail: mets, type 1 DM (islet knockout) - migratory thrombophelbitis (swelling/tender/erythema in extremities - trousseau) Tumor marker: CA 19-9 Prognosis: BAD (<6 months average)
Endodermal Sinus (Yolk Sac) Tumor
Malignant GERM CELL (most common in KIDS) tumor from YOLK SAC *Schiller-Duval bodies (glomerular-like) Tumor markers: AFP
Cervical Carcinoma
Invasive carcinoma that arises from CIN-dysplasia Presentation: - middle aged woman - vaginal bleeding (esp post-coital) Risk factors: - high-risk HPV - smoking - immunodeficiency (cannot destroy virus) Complication: lateral invasion to ureters or anterior invasion to bladder --> hydronephrosis and post-renal failure --> death
Sertoli-Leydig Cell Tumor
Sertoli cells (form tubules) and Leydig cells (Reinke crystals) --> androgen (hirsutism and virilization)
Fibroma
Benign STROMAL tumor of ovary characterized by proliferation of spindle-shaped fibroblasts *Meigs syndrome: pleural effusion and ascites DUE to fibroma (stops after removal)
Leiomyoma (Uterine Fibroid)
Benign proliferations (often multiple) of myometrial smooth muscle, related to estrogen exposure (enlarge during pregnancy, premenopausal, decrease in menopause) *does not progress to sarcoma *very common (20-30% of women) Characteristics: - MULTIPLE - well-defined - WHITE wholly mass Presentation: - usually asymptomatic - can causes bleeding/infertility *Leiomyosarcoma: - de novo (not from leiomyoma) - single - necrotic/hemorrhagic - postmenopausal
Serous/Mucinous Surface Epithelial Ovarian Tumors
Serous (watery, 80%) vs. mucinous (mucus, 20%) based on what fills the cyst Benign (cystadenoma): single cysts, flat lining, premenopausal vs. Malignant (cystadenocarcinoma): complex, thick/shaggy lining, postmenopausal vs. Borderline: between benign/malignant *BRCA1 mutation --> risk of serous carcinoma of the ovary and fallopian tubes
Sepsis
A constellation of clinical/lab findings that lead to suspicion of a serious infection Manifestations: - septic splenitis: enlarged, soft, neutrophils - bacteremia (or fungi, virus, parasite) - fever/hypothermia - WBCs - hypotension --> septic shock - DIC (coagulation AND fibrinolysis activated by cytokines --> bleeding and ischemia) - end organ damage (ARDS, ARF, liver, HF) Causes: - UTI (Ecoli, Pseudomona, Klebsiella, Enterobacter, Proteus) - Pneumonia (strep pneumo, haemophilus, staph-super, klebsiella, legionella, mycoplasma, chlamydia) - Meningitis (group B strep, Ecoli, listeria, neisseria, haemophilus, strep pneumo) - Cellulitis (pyogenes) - Peritonitis (after ascites, GI, GU infections)
Exotic Infections
Treponema (not sexually transmitted) - Yaws: papillomatous nodules followed by gummas (necrotic lesions on bones/nasopharynx) - Pinta: pruritic papules that change color and eventually lose color - Bejel: endemic syphillis (no tertiary cardio) Borrelia (Lyme disease) - Ixodes tick (attached for 24 hours) - NE/midwest - 1 (local): erythema migrants (bullseye) - 2 (systemic): facial nerve palsy, arthritis, cardiac block RMSF (rickettsia ricketsii) - Dermacentor tick - SE states - initial: fever, myalgia, headache - later: rash (starts on wrist/ankles, includes palms/soles) Q fever (coxiella) - blood/tissues/placentas of infected farm animals...aerosolized spores - NO rash...pneumonia, culture -ve endocarditis, hepatitis Typhus (rickettsia prowazekii) - epidemic/louse-borne (passed in feces after blood meal) - rash (trunk to extremities) - myalgia/pneumonia/encephalitis Plaque (yersinia pestis) - rat flea vector - bipolar gram-ve coccobaccili - bubonic, septicemic, pneumonic
Uterine Anatomy
Endometrium - mucosal lining - hormone-sensitive - grows/proliferative (estrogen), prepares/secretory (progesterone), shedding/menses Myometrium - smooth muscle
Endometritis
Bacterial infection of endometrium Acute: - caused by retained product of conception - symptoms: fever, pain, bleeding Chronic: - lymphocytes, PLASMA cells - causes: retained product of conception, PID, IUD, TB - symptoms: pain, bleeding, INFERTILITY
Embryonal Rhabdomyosarcoma
Malignant mesenchymal proliferation of immature skeletal muscle (rhabdomyoBLAST w/ cross-striations = desmin/myogenin +ve) Presentation: - child (<5 yrs) - "grape-like" mass (sarcoma botryoides) that bleeds and protrudes from vagina/penis
Placental Anomalies
Previa (preview of placenta) - overlies cervical os - 3rd trimester bleeding - may require C-section Abruption - separation of placenta prior to delivery - risk factors: trauma, smoking/cocaine, HTN/preeclampsia - common cause of still birth - presentation: 3rd trimester bleeding, fetal insufficiency, possible DIC/shock for mother Accreta/increta/percreta - implantation in myometrium with 3 types distinguishable by depth (Accreta=Attaches; INcreta=INvades; PERcreta=PERforates) - difficult delivery - postpartum bleeding
Ectopic Pregnancy
Implantation of fertilized ovum at a site other than uterine wall (most common is fallopian tube) often due to scarring (ex. endometriosis, PID) Presentation: - lower quadrant abdominal pain (must rule out) - can rupture --> hemorrhage
PolyCystic Ovarian Syndrome (PCOS)
Syndrome of multiple ovarian cysts from degenerated follicles --> bilateral enlarged cystic ovaries Increased LH (LH:FSH = 2:1) --> increased androgens (hirsutism) --> increased estrogens --> increased estrogen (estrone) --> follicular degeneration AND decreased FSH (feedback) Presentation: - obesity (high adipose aromatase --> peripheral androgen conversion to estrogens) - hirsutism (increased androgens) - infertility (anovulation) - insulin resistance --> Type 2 DM in 10-15 years - increased risk for endometrial carcinoma (high unopposed estrogen) Treatment: - weight reduction - OCP - clomiphene (ovulation) - ketoconazole, spironolactone
Misc Ovarian Cysts
Common cysts that can cause pain and enlarged ovaries Luteal Cyst: hemorrhage into corpus luteum Follicular Cyst: degeneration of a follicle prior to rupture/ovulation
Section 2
(50 cards)
Esophagitis
Inflammation of the esophagus that can be caused by a number of things: - GERD (#1) - eosinophillic esophagitis (eosinophil infiltration due to atopy) - HSV ("punched-out" ulcers) - CMV (immunosuppressed, linear) - candida (immunosuppressed, white plaque) - ingestion of toxic substances
Celiac Disease
Immune-mediated damage of small bowel due to gluten (gliadin) exposure Pathogenesis - gliadin is deaminated by tTG (tissue transglutaminase) - deaminated gliadin is presented on MHC II on APC cells - TH mediate damage Risk factors: - DQ2/8 Findings: - chronic diarrhea, bloating, (failure to thrive in children) - associations: dermatitis herpetiformis (IgA deposition in dermal papillae) - duodenal biopsy shows villi flattening, crypt hyperplasia, and lymphocytes in epithelium Labs: - IgA Ab vs. endomysium, tTg, gliadin - some can be IgA deficient (use IgG instead) *increased risk of malignancy (small bowel carcinoma, T-cell lymphoma)
Chronic Gastritis
Chronic INFLAMMATION of stomach mucosal from 2 etiologies: autoimmune vs. H. pylori Both associated with intestinal metaplasia (mucus cells that aren't normally in stomach) and increased risk for gastric cancer H. pylori (most common - 90%) - ureases/proteases weaken the mucosal defenses - most often ANTRAL (2nd - body) - increased risk for ulceration, gastric adenocarcinoma, and MALT lymphoma Autoimmune - T-cell mediated damage (Type 4 HS) --> Ab (side-effect of damage) - Ab vs. parietal cells (achlorhydria) in body/fundus - G-cell hyperplasia in response to low acid - Ab vs. IF (megaloblastic/pernicious anemia due to low B12 absorption - most common cause of deficiency)
Mumps
Bilateral inflamed parotitis Also: orchitis, pancreatitis, aseptic meningitis *Elevated serum AMYLASE (either pancreas or salivary glands) *Elevated serum LIPASE (just pancreas)
Mucoepidermoid Carcinoma
Malignant (most common malignant) tumor of MUCINOUS and SQUAMOUS cells that is usually in the parotid and can involve the facial nerve --> palsy/pain
Duodenal Atresia
Failure of the duodenum to canalize --> - polyhydramnios (failure to swallow fully) - billious vomiting (after bile enters) - distention of stomach and duodenum --> "double-bouble" *Associated with Downs
Ulcerative Colitis
- ULCER (just mucosa/submucosa) - COLON (starts in rectum and works it way up CONTINUOUSLY through colon to cecum) --> LLQ pain with BLOODY diarrhea - Microscopic: crypt abscess (neutrophils) - Gross: pseudo polyps (the part that isn't eroded appears raised) and loss of haustra (flat pipe) - Complications: toxic megaCOLON, carcinoma - Associations: p-ANCA, primary sclerosing cholangitis - Smoking PROTECTS
Ménétrier Disease
Hyperplastic gastric folds (rugae) that look like brain gyri --> excess mucus production and decreased acid production
Aphthous Ulcer (Canker Sore)
Painful, superficial ulcer on oral mucosa...grayish base with erythema *often in relation to stress, and recur Behcet Syndrome (immune complex vasculitis): recurrent aphthous ulcers, genital ulcer, uveitis
Sialadenitis
Inflammation of salivary gland, often due to an obstructing stone (sialolisthiasis) Causes: - stone - bacterial (S aureus) - viral (mumps) - autoimmune (Sjogrens)
Hemochromatosis
Disorder of excess body iron that deposits in tissues (liver, pancreas, heart, joins) and causes damage via free radicals Pathogenesis: - Primary: AR defect (HFE gene, C282Y) in iron regulation in enterocyte --> all iron that is absorbed goes into blood - Secondary: chronic transfusions Clinical (late adulthood) - micronodular cirrhosis (liver) - secondary DM (pancreas) - bronze skin (skin) - cardiac arrhythmia and dilated cardiomyopathy (heart) - arthropathy (joints) - gonadal atrophy (pituitary) - increased risk of HCC Labs: - increased ferritin (storage), increase serum iron, increase transferrin saturation, decreased TIBC - Prussian blue stain Treatment: - phlebotomy - iron chelators (...ferox)
Hepatocellular Carcinoma
Malignant tumor of hepatocytes Risk factors: - chronic hepatitis (B/C) - cirrhosis (alcoholic, hemochromatosis, wilsons) - aspergillus aflatoxins (grains) Complications: - Budd-Chiari (hepatic vein obstruction --> blood backup w/ hepatomegaly and ascites) Tumor marker: AFP
Carcinoid Tumor
Low-grade neuroendocrine (chromogrannin +ve) malignancy that normally occurs in the small bowel...it is asymptomatic (liver detoxifies 5-HT to 5-HIAA) until it metastasizes and doesn't dump into liver via portal system Pathology: small, well-demarcated polyps Presentation (after mets): - bronchospasm/wheezing - flushing - diarrhea - TIPS (tricuspid insufficiency, pulmonic stenosis) *no LH lesions due to MOA that metabolizes it
Alcoholic Liver Disease
3 patterns of injury: Fatty liver: - accumulation of fat - heavy, greasy liver - reversible Alcoholic hepatitis: - long-term (5 years) - acetaldehyde damages hepatocytes (inflammation and necrosis) - mallory body (damaged keratin filaments) - AST>ALT - painful hepatomegaly Alcoholic cirrhosis: - complication of chronic alcohol-induced liver damage - most common cause of cirrhosis in West
Squamous Cell Carcinoma
Malignant neoplasm of squamous cells in oral mucosa (often in floor of mouth and detected late)...95% of oral cavity cancer Risk factors: tobacco, alcohol Precursors (squamous cell dysplasia): - leukoplakia (white plaque that cannot be scraped away) - erythoplakia (red plaque = vascularized leukoplakia) <more likely to be malignant
Peptic Ulcer Disease
SOLITARY ULCER in proximal duodenum (90%) or distal stomach (10%) Duodenal: - H pylori (95%) or ZES (5%) - DECREASED pain w/ meals --> weight gain (eat to feel better) - hypertrophy of mucus-producing brunners glands - complications include posterior perforation --> pancreatitis or gastroduodenal artery bleeding - NO RISK of carcinoma Gastric: - H pylori (70%) or NSAIDS - GREATER pain w/ meals --> weight loss (feel better to starve) - complications include hemorrhage of left gastric artery (most often on lesser curvature) - increased risk of carcinoma (biopsy to check if irregular and malignant)
Lactose Intolerance
Decreased lactose metabolism due to lactase enzyme decreased function 1) Congenital (rare, young child) 2) Acquired (brush-border loss, older child) 3) Infection (temporary) Presentation: - abdominal distention - diarrhea
Acute Gastritis
Simple ACIDIC damage to stomach mucosa (either increased production or decreased protection/defenses) Some defenses that can fail: - mucin layer - bicarb secretion - blood supply (take acid away) Mechanisms of injury: - shock (ICU patient) --> decreased blood flow --> mucosal ischemia --> stress ulcers - severe burn (curling ulcer) --> hypovolemia --> mucosal ischemia (reduced blood supply) - NSAIDS (decreased PG --> increased acid and decreased mucus/bicarb/bloodflow) - alcohol (damage mucosa making it susceptible to acid damage) - chemo (knock out mucosal stem cells) - increased ICP (cushing ulcer) --> vagal stimulation --> ACh-induced acid Results - superficial inflammation - erosion (epithelial layer) - ulcer (mucosal layer)
Meckel Diverticulum
TRUE diverticulum (all three layers out pouch) due to persistence of VITELLINE (omphalomesenteric) DUCT Rules of 2s - 2% of people (most common GI tract anomaly) - 2 inches long - 2 feet from IC valve - first 2 years of life - 2 tissue types (gastric/pancreatic) Presentation: bleeding, volvulus (twisting on mesentery --> ischemia), intussusception (telescoping due to traction/inflammation that causes "dragging") - mimics appendicitis with RLQ pain
Mucocele
A dome shaped mucosal swelling due to: - escape of saliva in CT from trauma to gland (extravasation) - obstruction and subsequent dilation and back up of ducts (retention) *Most common non-neoplastic lesion of salivary glands
Tracheoesophageal Fistula
Congenital defect of an abnormal connection between trachea and esophagus...most common is proximal atresia with distal fistula Presentation: - vomiting - polyhydramnios (can't swallow as much fluid) - aspiration (food from stomach back into trachea --> lungs) - abdominal distention (air into intestines)
Warthin Tumor
Benign cystic tumor with ABUNDANT LYMPHOCYTES AND GERMINAL CENTERS (cystic lymph tissue)...2nd most common tumor of salivary glands (usually in parotid)
Achalasia
Disordered relaxation/motility of LES (lower sphincter) --> constant closure --> food-buildup ("bird-beak" on barium swallow) Pathogenesis: damaged ganglion cells in myenteric/auerbach (between muscle layers in muscularis) plexus --> disordered relaxation/motility Causes: - idiopathic (most common) - 2ndary to Chagas disease (megaesophagus) Clinical - dysphagia (SOLIDS AND LIQUIDS) - putrid breath (rotting food) - LES pressure high on manometry (can't relax) - increased risk for squamous cell carcinoma
Oral Thrush
Superficial white deposit (cheese-like) on the oral mucosa/tongue that CAN be scraped off...in immunocompromised patients by candida
HBV Serology
Concepts: - Surface Ag is the key marker of INFECTION (acute if <6 months, chronic if >6 months) - IgM vs. core is the definition of ACUTE - Sign of victory is IgG vs. surface Components: - HBsAg: SURFACE antigen (indicates current infection, whether acute or chronic) - Anti-HBsAg: indicates immunity, whether recovered or immunized - HBcAg: CORE antigen (not used) - Anti-HBcAg: IgM indicates acute or recent (window); IgG indicates chronic or recovered - HBeAg: ENVELOPE antigen that is secretes w/ DNA (indicates replication and transmissibility, acute of infective chronic) - Anti-HBeAg: indicates low transmissibility, but has or had infection Acute: - sAg (current infection) - eAg (transmissible) - IgM to core (acute) Immunized: IgG to surface only Recovered: IgG to surface, core, and envelope Chronic: - sAg (current infection) - eAg (transmissible) OR Anti-HBe (non-transmissible) depending on infectivity - IgG to core (chronic) Window: ONLY IgM to core (recent) but no IgG to surface yet
Appendicitis
Acute inflammation of the appendix, often due to fecalith (adults) or lymphoid hyperplasia (children) Presentation: - diffuse pain --> mcburneys point pain Complications: - rupture --> peritonitis - abscess DDX: diverticulitis, ectopic pregnancy, meckels diverticulum
Reye Syndrome
Fulminant liver failure and encephalopathy in children who take aspirin (only indicated in kawasaki) with a viral illness...aspirin metabolites decreased beta-ox of FA by inhibiting mitochondrial enzymes Presentation: - fatty liver - hypoglycemia --> coma - elevated liver enzymes - N/V - hepatomegaly
Esophageal Motility Disorders
Achalasia: incomplete relaxation of LES --> high resting tone Diffuse esophageal spasm: uncoordinated, spastic SM contraction --> "corkscrew" Scleroderma: sclerosis and atrophy of SM --> decreased LES tone
Gastroesophageal Reflux Disease (GERD)
LES not as tight as it should be --> acid reflux from stomach into esophagus --> stress-induced metaplasia (non-keratinizing squamous --> non-ciliated columnar w/ goblet = Barretts esophagus) Risk factors: - alcohol - tobacoo - obesity - high fats - caffeine - hiatal hernia Clinical - "heartburn" (mimics MI chest pain) - asthma (adult-onset) due to irritated airway - damage to teeth enamel - ulceration/stricture/barretts esophagus *barretts esophagus has an increased risk for adenocarcinoma
Liver Tumors
Hepatic Adenoma: - benign - exogenous hormones: OCP/anabolic steroids, regresses after cessation - increases during pregnancy - risk of rupture and hemorrhage Focal Nodular Hyperplasia: - localized hyperplastic nodule - central stellate scar Angiosarcoma: - malignant - endothelial - carcinogens: arsenic, vinyl chloride (PVC) Cavernous hemangioma: benign Mets: - colon, pancreas (portal) - breast, lung (common) - "bumps" (multiple nodules) on free edge
Wilson Disease
AR defect in ATP-mediated copper transport system (ATP7B gene, chr 13) resulting in low copper into ceruloplasmin (transporter) and low excretion in bile --> build up in hepatocytes and build up in tissues --> free radical (OH) damage Clinical - cirrhosis (liver) - neurologic/psychiatric (brain) - kayser-fleisher rings (cornea - deschemets) LabsL - increased urinary copper - decreased ceruloplasmin Treatment: chelation with penicillamine
Zenker Diverticulum
A false diverticulum from outpouching of mucosa through a defect in muscular wall, normally ABOVE UES (junction of esophagus and pharynx) Presentation: - dysphagia - halitosis (bad breath - due to rotting food)
Pleomorphic Adenoma
Benign tumor of MULTIPLE (pleomorphic - biphasic) tissues: stroma (ex. cartilage) and epithelial (ex. glands)...most common tumor of salivary gland (usually in parotid) Presentation: - mobile - painless - no invasion (facial nerve near parotid is fine) - well-circumscribed BUT irregular margins (hard to excise well --> recurrence) *Can progress to carcinoma - 10% (would invade facial nerve --> palsy)
Whipple Disease
Systemic tissue damage due to Tropheryma whippelii infection Pathogenesis: macrophages cannot digest bacteria and become foamy (PAS+) --> compression of lacteals in lamina propria --> malabsorption of chylomicrons and steatorrhea Symptoms (CAN): - cardiac valves - arthritis - neurologic
Gallbladder Carcinoma
Adenocarcinoma from the glandular epithelium of the gallbladder Risk factors: - gallstones - porcelain GB Cholecystitis in elderly woman Poor prognosis
Hepatitis Viruses
A (RNA picorna) - fecal-oral - only acute - travelers - mild symptoms - IgM = active - IgG = past infection or immunization (for travel) E (RNA hepe) - fecal-oral - only acute - waterborne - mild symptoms, but fulminant (massive necrosis) in pregnant women - IgM = active - IgG = past (no immunization) B (DNA hepadna) - birth, sex, blood (IVD) - 20% are chronic - risk of HCC D (RNA delta) - defective (depends on HBV) - superinfection worse (after) - coinfection not bad (same time) C (RNA flavi) - sex, blood (IVD) - 80% are chronic - risk of HCC - HCV-RNA test
Cirrhosis
End-stage liver damage characterized by fibrotic bands (mediated by TGF-beta from stellate cells that are beneath the endothelial cells of sinusoids) and regenerative nodules Clinical - Portal HTN --> ascites, splenomegaly (w/ low platelets due to sequestration), portosystemic shunts (varices, hemorrhoids, caput medusa), hepatorenal syndrome - Decreased detox function of ammonia --> mental status change (encephalopathy), asterixis, coma - Decreased estrogen removal --> gynecomastia, spider angioma, palmar erythema - Decreased bilirubin conjugation --> jaundice - Decreased protein synthesis --> hypoalbuminemia (edema) and hypoclotting-factors (coagulopathy) - increased risk of HCC Caused by: - alcoholic liver disease - micronodular (60-70%) - chronic viral hepatitis (post-necrotic - various nodule sizes) (B/C - 10%) - hematochromatosis - micronodular (5%) - biliary disease - mono lobular micro nodular (5%)
Biliary Disease
Primary Biliary Cirrhosis - autoimmune granulomatous destruction of INTRAhepatic bile ducts - lymphocytes - anti-MITOCHONDRIAL Ab - high ALP - women, 40 yrs old, w/ other autoimmune disease Secondary Biliary Cirrhosis - extrahepatic obstruction --> bile backup and damage of duct - high ALP w/ -ve AMA Primary Sclerosing Cholangitis - inflammation and fibrosis (onion-skin) of INTRA and EXTRAhepatic bile ducts - "chain of pearls" as some regions appear dilated between fibrosed areas - associated with UC and p-ANCA (man w/ IBD) - increased risk of cholangiocarcinoma Presentation of biliary disease: - pruritus (bile), jaundice (bilirubin) dark urine (CB), light-colored stool (no bile in gut), hepatosplenomegaly (back-up) - both can lead to later cirrhosis - labs: increased CB, ALP
Tropical Sprue
Similar to celiac, but: - responds to abx - arises after infectious diarrhea - damage is more in jejunum/ileum vs. duodenum --> nutritional deficiency - after people visit tropical place
Esophageal Varices
Dilated submucosal vein in lower esophagus, secondary to portal HTN (portosystemic shunt backup --> left gastric vein backup --> dilated esophageal veins) Complication - normally asymptomatic - PAINLESS (vs. Mallory-Weiss) hematemesis *common in cirrhosis (seen in alcoholic liver disease)...most common cause of cirrhotic death
Mesenteric Ischemia
Lack of blood supply to the small intestine via arteries that run along a mesentery Transmural = thrombosis (A-fib, DVT w/ patent FO) or mesenteric venous thrombosis Mucosal: hypotension, atherosclerosis (angina-like)
Hepatitis
Inflammation of liver parenchyma due to hepatitis viruses, other viruses (EBV/CMV), alcohol (alcoholic hepatitis), toxins (amanita phalloides, CCl4), and drugs (acetaminophen, INH, halothane) Acute (<6 months) presentation: - mixed jaundice - dark urine (CB is water soluble) - fever, malaise, nausea - ALT>AST Chronic (>6 months) presentation: - same symptoms with continued inflammation - risk of progression to cirrhosis and hepatocellular carcinoma Pathology - patchy necrosis (more in zone 3) - lobular disarray - lymphocytes (viral)
Salivary Gland Basics
3 major glands: parotid, submandibular, sublingual Many minor glands - Parotid = serous --> Stensen duct (maxillary 2nd molar) - Submandibular = mixed --> Wharton duct (floor of mouth) - Sublingual = mucus --> many ducts
Jaundice
Abnormal yellowing of skin/sclera due to excess bilirubin deposition that is normally due to increased production or decreased excretion Increased UNCONJUGATED (UGT capacity): - hemolysis (overwhelm UGT capacity) - physiologic newborn (deceased UGT capacity) - Gilbert (low UGT-mild) and Crigler-Najjar (absent UGT-fatal) Increased CONJUGATED (transport/obstruction after UGT): - Dubin-Johnson (transport out of liver, black liver) - Rotor (transport out of liver, normal liver) - Obstructive (gallstones, cancer, parasites, biliary tract disease) --> other findings from damage (ALP) and bile is blood Increased MIXED: Hepatitis - unconjugated: destroy hepatocytes (less UGT capacity) - conjugated: destroy bile ductules (CB leaks out)
Esophageal Web
Protrusion of the mucosa (most superficial layer) into the lumen of the esophagus (upper) --> dysphagia (obstruction of big solids) Association - increased risk for squamous cell carcinoma - Plummer-Vinson syndrome: esophageal web, iron deficiency anemia, beefy-red tongue (atrophic glossitis - you can see the underlying blood vessels)
Gastric Carcinoma
Malignant adenocarcinoma of surface epithelial cells sub classified as intestinal or diffuse Intestinal - large, irregular ulcer - lesser curvature - risk factors: intestinal metaplasia (chronic gastritis, nitrosamines (smoked foods), smoking Diffuse - signet rings cells that infiltrate stomach wall --> desmoplasia (thickening/leathery = linitis plastica) - NO risk factor associations Presentation: - presents late --> poor prognosis - weight loss - abdominal pain - anemia - early satiety Early spread (lymph nodes) or liver (portal) - virchow: left supraclavicular - krukenberg: bilateral ovaries, mucin-secreting signet ring cells (diffuse-type) - sister mary joseph: subQ periumbilical
Normal Heme Metabolism
1) RBC consumed by RES macrophages --> hemoglobin --> heme + globin 2) Heme --> Fe + protoporphyrin 3) Protoporphyrin --> UCB 4) Albumin carries UCB to liver 5) Liver conjugates (UCB --> CB) by uridine glucuronyl transferase (UGT) in hepatocytes 6) CB is transferred to bile and released 7) Intestinal flora convert CB --> urobillinogen --> stercobilin (brown stool) and urobilin (yellow urine after being reabsorbed and secreted)
Esophageal Carcinoma
Malignant carcinoma of the esophagus that is separated into adeno (lower 1/3) vs. squamous (upper 2/3) Adenocarcinoma (glands) - most common in west - lower 1/3 - related to GERD, barrett metaplasia, obesity, smoking Squamous cell carcinoma - most common worldwide - upper 2/3 (often middle) - risk factors (irritants): alcohol, tobacco, hot liquids, achalasia (food buildup), esophageal web (food buildup), toxic ingestion (ex. lye), esophagitis Clinical - late presentation --> poor prognosis - progressive dysphagia - weight loss, pain, hematemesis - may invade laryngeal nerve --> hoarseness/cough Lymph spread - upper 1/3: cervical - middle 1/3: mediastinal - lower 1/3: celiac
Oral Hairy Leukoplakia
White "fluffy" patches on the LATERAL tongue that CANNOT be scraped off...look similar to oral thrush (candidiasis) but due to EBV infection (EBV-induced hyperplasia) in HIV patients
Mallory-Weiss Syndrome
Longitudinal lacerations at GEJ (gastro-esophageal) caused by severe vomiting (acid toxic to epithelium) Presentation: - common in alcoholic, bulimics --> PAINFUL hematemesis Complication: Boerhaave syndrome (boer through esophagus --> air in mediastinum and subcutaneous air-bubbles/emphysema)
Section 3
(50 cards)
Changes in Blood Circulation at Birth
Prior to birth there are 3 shunts: - Ductus venosus: blood from placenta enters via umbilical vein and skips the liver into IVC - Foramen ovale: the high O2 blood from placenta --> umbilical vein --> ductus venosus --> IVC --> heart is shunted from R>L heart and into systemic circulation - Ductus arteriosus: the low O2 from the SVC --> RA --> RV --> pulmonary artery --> PDA (due to high pulmonary resistance) --> systemic circulation At birth: - pulmonary resistance decreases (lose thick medial layer) - shunts close - LV hypertrophies
Right-to-Left Shunts
Right to Left Shunts (all begin with T) are the causes for early/newborn cyanosis (requires surgery or PDA maintaining) 1: Truncus arteriosus (1 vessel) - single artery from PA/Aorta (lack of aorticopulmonary septum formation) - accompanied by VSD (both ventricles feed into this artery) 2: TGA (2 vessels) - aorta from RV, pulmonary artery from LV (separate systems) - not compatible w/ life w/o a shunt 3: Tricuspid atresia (3 = tri) - absence of tricuspid --> ASD (and VSD to get some blood to lungs) - RA hypoplastic 4: Tetralogy of fallot (4 = tetra) - PROV: Pulmonic stenosis, Rvh, Overriding aorta, Vsd 5: TAPVR (5 letters) - pulmonary veins drain back to RH (separate circulations) - must have ASD or PDA
Oligohydramnios
Causes (not enough urine): renal agenesis, ARPKD, obstructive uropathy (posterior urethral valves below bladder) Effects: - pulmonary hypoplasia (also caused by diaphragmatic hernia compressing UNILATERAL lung) - Potter sequence (hitting walls) --> low-set ears, small jaw, flattened nose, limb defects - amnion nodosum (vernix caseosa from fetal skin rubbing on amniotic membrane)
Ductal Carcinoma In Situ (DCIS or Intraductal Carcinoma)
Malignant proliferation of cells in ducts that does not invade into BM (no mass) Pathogenesis: center of mass dies (necrotic) and becomes calcified (detectable on mammography) Camedo-type: necrosis and calcification in center Paget: DCIS that extends up to the nipple up to the skin --> eczematous changes (underlying carcinoma)
Hereditary Non-Polyposis Colorectal Cancer (HNPCC - Lynch)
AD mutation of DNA mismatch repair genes (MSH2/MLH?) --> microsatellite (non-coding region that still gets copied) instability - increased risk for CRC (most often appears on RIGHT SIDE) - also increased risk for ovarian and endometrial cancer
Fibroadenoma
Tumor of fibrous tissue and glands...the most common benign tumor of the breast...most common in premenopausal Presentation: - well-circumscribed, mobile (not stuck), marble-like - estrogen-sensitive (pregnancy, prior to menstruation) *benign, no increased risk for cancer
Neuroblastoma
Most common tumor of kids <1y/o that is often seen in the retoperitoneum (adrenal, sympathetic chain)...originates from neural crest Histology: - small round blue cells - Homer-Wright rosettes Presentation: - abdominal mass/pain - endocrine symptoms (proptosis, diarrhea, cushings) - respiratory symptoms - "opsoclonus-myoclonus" (dancing eyes and feet) - blueberry muffin rash Unfavorable Prognosis: - Older age - 1p deletion - Diploid - N-myc amplification - High mitosis - Poorly differentiated *Ganglioneuroblastoma (50:50) and Ganglioneuroma (0:100) other variations
Glycogen Storage Disorders
*Very Poor Carbohydrate Metabolism 1 (Von gierkes) 2 (Pompes) 3 (Coris) 5 (Mcardles) Von-Gierke (1) - Glucose-6-phosphatase (making glucose that can leave the cell after glycogenolysis) - Symptoms (severe): increased glycogen (G6P inhibits glycogenolysis) --> hepatomegaly, severe hypoglycemia, increased lactate (and uric acid due to competition for excretion) Pompes (2) - Lysosomal alpha-1,4--glucosidase - Symptoms: heart (cardiomegaly, hypertrophic cardiomyopathy), tongue, liver Coris (3) - Debranching enzyme (alpha-1,6-glucosidase) --> inability to liberate the final glucose (so not as sever) - Symptoms: mild hypoglycemia (no lactate increase), hepatomegaly, limit-dextran (can't debranch) accumulation Mcardles (5) - Muscle glycogen phosphorylase --> cannot break it down - Symptoms: muscle pain/cramps, myoglobinuria (red urine) Treatment: - hepatic/hypoglycemic (von-gierke/cori) --> eat cornstarch (slow release glucose) or frequency glucose - muscle (mcardles): sugar prior to exercise, avoid exercise
CHD Associations
Rubella (PDA, PS) Turners (coarctation, bicuspid aortic) DiGeorge (Truncus arteriosus, T4 fallot) Marfan (MVP, TAA, AR, dissection) Downs (ASD-primum, VSD, cushions-mitral)
Malformation Associations
Downs: single palmar crease, epicanthal folds, CHD, hirschsprungs, duodenal atresia Turner: cystic hygroma, shield chest, edema of hands/feet, short, coarctation Edwards: small jaw, rocker feet, clenched fists Patau: holoprosencephaly, polydactyl, cleft Thalidomide: limbs, ears, brain DES: vaginal malformations, clear cell adenocarcinoma
NRDS
Sufactant deficiency --> increased surface tension of alveoli and alveolar collapse --> cyanosis and dyspnea Dx: - L/S ratio (>2 is good, <1.5 is bad) - CXR white out Risk factors: - prematurity (low surfactant) - maternal DM (insulin downregulates surfactant) - C-section (less stress --> less steroid --> less surfactant) Complications (from supplemental O2): - ROP (proliferation of retinal vessels --> retinal detachment) - intraventricular hemorrhage - Old BPD (necrosis of respiratory epithelium --> fibrosis)
Hirschsprung Disease
Failure of ganglion (myenteric and submucosa) to descend from neural crest --> inability to contract/relax and do peristalsis Clinical - failure to pass meconium (like CF) - bilious vomiting - empty rectal vault - dilation (megacolon) of bowel proximal to obstruction - rectal suction biopsy (takes deeper layers) --> absent ganglion cells Associations: - Downs - RET mutation Treatment: resect and pull-through
Priapism
Painful, sustained erection --> 4 hours Associations (ischemic): - sickle cell (sickled RBC get trapped) - meds (sildenafil, trazoBONE) Treat IMMEDIATELY
Cryptorchidism
Failure of the testicle to descend into scrotal sac...the most common male genital abnormality - 3% @ birth, 1% @ 1yr *most resolve spontaneously (after age 2 should be done by surgeon) *more common in prematurity, low birth weight Physiology: - 1st phase: transabdominal (controlled by AMH) - 2nd phase: inguinoscrotal (controlled by androgens) Complications: - impaired spermatogenesis (too warm >37) - testicular atrophy w/ infertility - increased risk of seminoma
Periductal Mastitis
Smoking --> relative Vit A deficiency --> inability to maintain epithelium of lactiferous duct --> squamous metaplasia --> inflammation Presentation: - subareolar mass - nipple retraction (non-cancerous cause)
Left-to-Right Shunts
Left to Right Shunts (all 3 letters) --> Late (L for Left and Late) cyanosis (2ndary to Eisenmengers syndrome...they are also the most common (VSD being the most) VSD - cause of death is CHF - faster to eisenmengers ASD - septum primum (low)...also associated w/ AV endocardial cushion defect (ex. mitral) - septum secundum (high)...isolated - paradoxical embolism in PFO - fixed, split S2 (more blood in pulmonary) - slow to eisenmengers PDA - normally closes at 2 weeks - continuous machine-like murmur - PGE kEEp open; INDomethacin INDs
Misc. Metabolic Disorders
Morquio Syndrome - N-acetylgalactosamine-6-sulfatase (keratan sulfate) - severe growth limitation, coarse face, cloudy cornea, skeletal abnormalities (ribs/chest --> resp/cardio complications) Fabry (XR) - alpha-galactosidase A (ceramide trihexoside) - early: peripheral neuropathy, angiokeratomas, hypohidrosis (low sweat) - late: renal failure, CVD Metachromatic Leukodystrophy (AR) - arylsulfatase A (cerebroside sulfate) - demyelination --> dementia/ataxia Krabbe Disease (AR) - galactocerebrosidase (galactocerebroside/psychosine) - peripheral neuropathy (low tone), developmental delay, "krabby" - irritable Gaucher Disease (AR) - glucocerebrosidase (glucocerebroside) - MOST COMMON - hepatosplenomegaly, pancytopenia, aseptic necrosis of femur, lipid-laden macrophages ("crumpled paper") Niemann-Pick Disease (AR) - sphingomyelinase (sphingomyelin) - progressive neurodegeneration, foam cells (lipid-laden macrophage), "cherry red spot" - ashkenazi jews
Phyllodes tumor
Similar to fibroadenoma, due to overgrowth of fibrous tissue Presentation: - "leaf-like" lobulations - older women (5th decade) *can be malignant
Intraductal Papilloma
Small papillary (finger-like) projection into a large duct, near the nipple, lined by 2 cells (epithelial and myoepithelial) Presentation: - nipple discharge (bloody or serous) - premenopausal - must be distinguished from papillary carcinoma (no double cell layer)...common in postmenopausal *slight increased risk for cancer
Invasive Lobular Carcinoma
Invasive carcinoma of cells that lack E-cadhedrin (don't stay together) --> "single-file" pattern
Colonic Polyps
Hyperplastic (most common) - hyperplasia of glands - "serrated" - usually in left (rectosigmoid) - benign, no malignant potential Adenomatous (2nd) - neoplastic proliferation of glands - benign, but premaligant (adenoma-carcinoma sequence) Hamartomatous - non-neoplastic distortion of normal architecture - no malignant potential - associated with juvenile-polyposis and peutz-jeghers
Bronchopulmonary Dysplasia
Old: associated with oxygen therapy for premature babies --> necrosis of respiratory epithelium and fibrosis New (considering better treatment for premature babies) - reduced alveolar development --> lower surface area for gas exchange --> lung damage
Lung Development
Stages (EPCSA - Evangelical Presbyterian Church of South America) Embryonic (3-6): Segmental airways from trachea to tertiary bronchi Pseudoglandular (6-16): Continued bronchiolar development to terminal bronchioles Canalicular (16-24): terminal bronchioles become respiratory bronchioles Saccular (24-birth): epithelium thins and alveoli (terminal sacs) begin to develop Alveolar (birth-8 yrs): adult alveoli (continued septation) *Respiration is capable around week 25 (surfactant and first terminal sacs)
Phimosis/Paraphimosis
Phimosis: cannot retract foreskin --> infections Paraphimosis: non-reducible foreskin after a forced contraction --> urinary restriction and pain
Disorders of Galactose Metabolism
How does galactose enter glycolysis? - Galactose --> Galactose-1-P (galactokinase) - Galactose-1-P --> Glucose-1-P (uridyltransferase w/ UDP-glucose cofactor) Galactokinase Deficiency (galactokinase) - MILD - galacticol accumulates --> cataracts - galactose in blood/urine (but not much damage done) Classic Galactosemia (uridyltransferase) - BAD - Gal-1-P uridyltransferase deficiency, --> Gal-1-P accumulations --> P depletion - Symptoms: failure to thrive, jaundice, hepatomegaly, cataracts (galacticol), retardation, E coli sepsis - Treatment: avoid galactose and lactose
Kidney Morphogenesis
Kidneys: - occurs "inside out" - nephrogenic zone is the outer, primitive layer that persists until 37 weeks
Breast Cancer Overview
Most common, but 2nd most death (after lung) Risk factors: - age (post-menopause) - early menarche/late menopause (increased estrogen exposure) - obesity (higher aromatase) - atypical hyperplasia - FH - BRCA1/2 - AA (increased triple -ve) Types: - Terminal duct - Ductal CIS - Pagets (DCIS to nipple) - Invasive Ductal Carcinoma - Lobule - Lobular CIS - Invasive Lobular Carcinoma Prognosis (TNM) - Mets is most important - Spread to axillary lymph nodes is most useful (use sentinel lymph node biopsy - inject die to see how far it spreads) Predictive factors (Predict response to treatment) - ER/PR +ve (tamoxifen) - nuclear - HER2/Neu/c-erbB2 (trastuzumab) - cell surface receptor - triple -ve...often AA...poor prognosis
Squamous cell carcinoma of the penis
Malignant proliferation of squamous cells on penile skin Risk factors: - high risk HPV (16/18/31/33) - foreskin (no circumcision) --> inflammation - phimosis - lichen sclerosis Presentation: - ulcerated or fun gating mass - pain, discharge, difficulty voiding Precursors (in situ carcinomas): - Bowen: leukoplakia on shaft - Bowenoid papules: reddish papules - Erythroplasia of Queyrat: erythroplakia of glans
Colorectal Carcinoma
3rd most common incidence and cause of death (after prostate/breast and lung), most common in elderly (>60-70) Risk factors: - red meat - low fiber - smoking - IBD 2 pathways: - adenoma-carcinoma sequence (APC-->K-ras-->p53/COX)...FAP - microsatellite instability pathway (DNA mismatch repair enzyme defect)...HNPCC Presentation: - left --> "napkin ring" w/ decreased stool size and bloody stool - right --> "raised" lesion with iron-deficiency anemia (due to occult bleeding) and vague pain Tumor Marker: CEA
Twinning
Dizygotic (fraternal) twins are ALWAYS from 2 fertilized eggs (2 eggs + 2 sperm) --> Dichorionic Diamniotic membranes *Fraternal = DiDi Monozygotic (identical) twins are from 1 fertilized egg (1 egg + 1 sperm) that separates early in pregnancy...the TIMING of the separation determines the number of membranes - early = DiDi (25%) - mid = MonoChorion Diamnion (75%) - late = MonoMono (rare) - very late = MonoMono conjoined (very rare) *Identical = DiDi, MonoDi, MonoMono Twin-twin transfusion syndrome can lead to disproportionate blood supply whenever twins share a CHORION and a SINGLE PLACENTA --> high M&M
Balanitis
Inflammation of the glans penis, most common if uncircumscribed
Mammary Duct Ectasia
Inflammation of the wall of subareolar duct --> dilation Presentation: - multiparous, postmenopausal - green-brown nipple discharge - plasma cells on biopsy
Peyronie disease
Abnormal penis curvature (not fracture) due to fibrous plaque w/in tunica albuginea --> ED, pain, anxiety
Hamartomatous Polyp Disorders
Juvenile Polyposis (AD) - multiple juvenile (hamartomatous) polyps in the colon and stomach - increased risk for carcinoma (since large number) Peutz-Jegher Syndrome (AD) - hamartomatous polyps through GI tract - mucocutaneous hyperpigmentation on lips, oral mucosa, genitals - increased risk fro colorectal, breast, GYN cancer
Invasive Ductal Carcinoma
Invasive carcinoma that forms "duct-like" structures...most common 85% Presentation: - rock hard mass that doesn't move - may result in dimpling/retraction at nipple Types: - tubular: well differentiated tubules with no myoepithelial cells - mucinous: abundant extracellular mucus (tumor cells in mucus pool) - medullary: lymphocytes, plasma cells - inflammatory: dermal lymphatic invasion --> inflammation/swelling w/ peau d'orange (can be mistaken for mastitis)
Disorders of Fructose Metabolism
How does fructose enter glycolysis? - Fructose --> Fructose-1-P (fructokinase) - Fructose-1-P --> DHAP/GAD (aldolase B) Essential Fructosuria (fructokinase) - MILD/NO SYMPTOMS - fructokinase deficiency --> fructose buildup - fructose appears in blood/urine Fructose Intolerance (aldolase B) - BAD - aldolase B deficiency --> F-1-P accumulation --> depletion of P - Symptoms: hypoglycemia, vomiting, poor feeding, jaundice, cirrhosis - Treatment: avoid fructose and sucrose
Familial Adenomatous Polyposis (FAP)
AD loss of the APC tumor suppression gene on chr 5 --> greater risk of K-ras mutations and 100-1000s of polyps --> 100% chance of carcinoma by age 40 Treatment: prophylactic removal of colon Gardner syndrome: FAP with fibromatosis (fibroblast proliferation) and osteoma (benign tumor in skull) Turcot syndrome: FAP with malignant CNS tumors (medulloblastoma, glial tumors)
Wilms Tumor
Most common renal tumor of early childhood, characterized by blastema (undifferentiated mesenchyme) Presentation: - abdominal mass - hematuria - flank pain - HTN (renin secretion) Associations (syndromes): - WAGR (WT1 on chr 11): Wilms, aniridia, Gu malformations, Retardation - Beckwith-Weidemann (WT2 on chr 11): Wilms, organomegaly (including tongue), hemihypertrophy
Hypospadias/Epispadias
Abnormal urethral opening Hypospadias - opening on inferior (ventral when erect) surface of penis - due to failure of urethral folds to close - associated with inguinal hernia and cryptorchidism Epispadias - rare - opening on superior (dorsal when erect) surface of penis - abnormal positioning of genital tubercle - associated with bladder exstrophy
Fibrocystic Change
Fibrosis and cysts in the breast. Most common change in premenopausal breast, due to hormones --> - "lumpy breast" - vague irregularities - blue dome cysts - apocrine metaplasia Benign, with no risk for carcinoma The following DO have an increased risk for carcinoma: - ductal hyperplasia with sclerosing adenosis (2x risk) - atypical hyperplasia (5x risk)
Adenoma-Carcinoma Sequence
The molecular progression from normal colonic mucosa --> adenomatous polyp --> carcinoma *AK-53 COX 1) APC (Adenomatous Polyposis Coli gene) mutation (normally binds b-catenin so it cannot move to nucleus) --> risk of polyp 2) Kras mutation --> actual polyp 3) p53 mutation/increased COX (aspirin protects) --> progression of polyp to carcinoma *Both copies of APC on chr5 need to be knocked out for most people (sporadic), unless you have FAP
Diverticula
Outputting of mucosa and submucosa through muscularis propria (false) in relation to wall stress: - constipation/straining - low fiber diet - arise where vasa recta cross = weak point Diverticulosis = many diverticula Diverticulisis = inflammed diverticula -> LLQ "appendicitis" (fever, WBC, pain) --> risk of fistula (bladder), obstruction, or perforation --> rectal bleeding (hematochezia)
TORCHeS
Toxoplasmosis: chorioretinitis, hydrocephalus, intracranial calcification Other: listeria/agalactiae/ecoli--> neonatal menigitis; parvovirus --> hydrops fetalis Rubella: cataracts, PDA, deafness CMV: hearing loss, seizures, petechial rash, periventricular calcifications Herpes: VZV, HSV2 (encephalitis, herpetic lesions) Syphillis: saddle nose, notched teeth, short maxilla, saber shins, deafness
Other CHD
Ebstein's anomaly - lithium exposure in utero - downward displacement of the tricuspid valve into RV --> "atrialization" (make smaller) of the RV --> RHF Coarctation of the aorta - turners (XO), and bicuspid aorta association - nearing near insertion of ductus arteriosus - HTN in upper extremities and weak/delayed pulse in lower (brachial femoral delay) - intercostal arteries enlarge to give collateral circulation --> "notched" ribs
Mastitis
Bacterial infection of breast that often occurs during breastfeeding (easier for bacteria to get in) and is due to staph aureus Presentation: warm, erythematous breast with purulent discharge Treatment: abx, but continue feeding
Prematurity
Def: <37 weeks gestation and <2500g Effects: - CNS: cerebral palsy, epilepsy, MR - Metabolic: hyperbilirubin --> kernicterus - NRDS - intraventricular hemorrhage (blood vessel rupture --> bleeding into ventricles) - NEC (decreased perfusion --> mucosa necrosis and chance for rupture) Causes: - maj idiopathic - PROM - placental abruption
Congenital Malformations
Occurs in 1-2% of infants Causes: - Unknown (65%!!!) - Hereditary: 20% - Teratogen: 10% (lethal in first few weeks) - Chromosomal: 5% (common cause of lethality pre-birth)
Crohn Disease
Think about NOT UC - TRANSMURAL - ALL INTESTINE (small and big) with SKIP LESIONS --> RLQ pain with NON-BLOODY diarrhea - Microscopic: lymphoid aggregates w/ granulomas - Gross: cobblestone, stricture (thinning - "string sign"), creeping fat (pulled with stricture) Complications: malabsorption (SMALL BOWEL), calcium oxalate kidney stones, fistulas, carcinoma (if colon involvement) Associations: arthritis, uveitis, ankylosing spondylitis/sacroiliitis, erythema nodusum - Smoking HURTS
Infants of Diabetic Mothers
- Increased size - Increased fat - Increased malformations (heart, CNS, renal) - Hypoglycemia (high fetal insulin to down regulate mothers high sugar)
Eisenmengers Syndrome
The L>R shunts (VSD/ASD/PDA) cause an increase in pulmonary blood flow --> pulmonary vasculature remodeling --> pulmonary HTN --> R to L shunt (w/ compensatory RVH) --> LATE CYANOSIS and CLUBBING
Section 4
(50 cards)
CNS cell responses to injury
Neurons: - central chromatolysis: nucleus to periphery in response to axonal transaction - intraneuronal deposits - atrophy: neuronal loss that is accompanied by astrogliosis Glia (oligo, ependyma, astro, microglia): - astrogliosis: "scar tissue" of CNS, produce GFAP - rosenthal fibers: eosinophillic tubular structures in astrocyte processess...pilocytic astrocytoma - corpora amylacea: "brain sand", round concentrically lamented bodies of glycogen
Choriocarcinoma (men)
Malignant germ-cell tumor of trophoblasts (both) = placenta-like TM: b-hCG (characteristic) --> hyperthyroid or gynecomastia (similar alpha subunit as TSH, FSH/LH) Spreads early via blood (like placenta)
Testicular Torsion
Twisting on spermatic cord --> thin-walled veins (easily closed) is blocked --> inability to drain --> hemorrhagic infarction Cause: failure of testes to attach to inner lining of scrotum (via gubernaculum) Dx: - sudden testicular pain - absent cremasteric reflex (nerves in cord)
Seminoma
Malignant germ cell tumor of oocytes...similar to dysgerminoma Histology: - large cells with clear cytoplasm and central nuclei (fried egg) - HOMOGENOUS mass with no hemorrhage/necrosis *Good prognosis TM: b-hCG (maybe)
Multiple Endocrine Neoplasia (MEN)
MEN 1 (3P = PIT, PAN, PARA) - AD mutation of MEN 1 gene on chr 11 that codes for Menin (tumor suppressor) - PITuitary hyperplasia/adenoma (prolactin or GH) - PANcreatic neuroendocrine tumore (VIP, ZES, insulin, glucagon) - PARAthyroid hyperplasia/adenoma (1ry hyperPTH) MEN 2A (2P = PARA, PHEO) - AD mutation of RET proto-oncogene on chr 10 that codes for a tyrosine kinase receptor - PARAthyroid hyperplasia/adenoma (1ry hyperPTH) - PHEOchromocytoma (secretes catecholamines) - Medullary thyroid carcinoma MEN 2B (1P = PHEO) - AD mutation of RET proto-oncogene on chr 10 that codes for a tyrosine kinase receptor - PHEOchromocytoma (secretes catecholamines) - Medullary thyroid carcinoma *Mucosal neuromas (oral/intestinal) *Marfanoid habitus
Prostatitis
Acute: bacterial - chlamydia/gonorrhea (young - STD) - ecoli/pseudomonas (old - UTI) - presentation: dysuria w/ FEVER/CHILLS - DRE: tender/boggy - labs: WBCs and bacteria Chronic - dysuria with LOW BACK PAIN - labs: WBCs, but no bacteria
Congenital Adrenal Hyperplasia
CONGENITAL enzyme deficiencies --> low CORTISOL --> high ACTH (feedback) --> BILATERAL ADRENAL HYPERPLASIA *depending on the enzyme that is missing effects the levels of aldosterone and sex hormones and the presentation 21-hydroxylase (most common - top vertical) - cannot produce cortisol OR aldosterone - shunting to sex steroids - low aldo, cortisol, increased sex - presentation (volume): hypoNa/hyperK, hypovolemia w/ hypotension --> increased renin - presentation (sex): virilization, precocious puberty 11-beta-hydroxylase (bottom vertical) - cannot produce cortisol or aldosterone, but CAN make weak mineralocorticoids (DOC) = apparent mineralocorticoid excess - shunting to sex steroids - low aldo, cortisol, increased sex, DOC - presentation (volume): opposite of 21 - hyperNa/hypoK, hypervolemia w/ HTN --> decreased renin - presentation (sex): same as 21 - virilization, precocious puberty 17-alpha-hydroxylase (horizontal) - cannot produce cortisol or sex - shunting to aldosterone - high aldo, low cortisol, sex - presentation (volume): hyperNa/hypoK w/ hypervolemia --> HTN w/ decreased renin - presentation (sex): deficiency --> ambiguous and lacking 2ndary characteristics
Secondary Hyperparathyroidism
Excess PTH due to cause that is extrinsic of parathyroid gland Causes: - renal failure --> renal insufficiency --> decreased phopshate excretion --> increased P --> decreased Ca) - renal failure --> low VitD --> decreased Ca Labs: - increased P, decreased Ca - increased PTH (response) - increased alkaline phosphatase *low Ca effects ALL FOUR GLANDS
Orchitis/Epididymitis
Inflammation of the testicle and epididymis Causes: - chlamydia/neisseria (STD - young men) - E coli/pseudomonas (after UTI - older men) - mumps (meninges, parotid, pancreas - school age) - autoimmune orchitis (granulomatous) - TB
Medullary Carcinoma
Malignant proliferation of C cells (calcitonin) --> high levels of calcitonin --> hypocalcemia Histology: sheets of malignant cells in an amyloid stroma (congo red stain) *Can be familial (MEN2A/B) associated with RET mutations --> prophylactic thyroidectomy
Hypoparathyroidism
LowPTH --> low Ca and high P Causes: - autoimmune damage - surgical excision (during thyroidectomy) - DiGeorge (failure of 3/4th pouches) Symptoms: - spasms, tetany - numbness, tingling - Trousseau sign: occlusion of brachial artery with BP cuff --> carpal spasm - CHvostek sign: tapping on facial nerve (CHeek) --> contraction of facial muscles
Hyperaldosteronism
High aldosterone --> increased Na/water and decreased K/H+ Symptoms: - hypernatremia w/ volume expansion --> HTN - hypokalemia - metabolic alkalosis Primary: - adrenal adenoma = Conn syndrome (or less commonly hyperplasia/carcinoma) - high Aldo - low Renin (due to high blood flow) - treat with aldo receptor antagonist (spironolactone, eplerenone) Secondary: - activation of RAAS (low BP, atherosclerosis, fibromuscular dysplasia) - high Renin --> high Aldo
Primary Hyperparathyroidism
Excess PTH due to parathyroid itself (hyperplasia, adenoma, carcinoma) *adenoma is most common, involving ONE GLAND *hyperplasia (enlarged of FOUR GLANDS) Symptoms (hyperCa): - muscle weakness and constipation (groans) - nephrolithiasis (stones) - depression (psychiatric overtones) - metastatic calcification (esp in kidney tubules) - Acute pancreatic (enzyme activation) - Osteitis fibrosa cystica (bone resorption due to hyperPTH --> fibrosis with cystic spaces) Lab: - high PTH --> high Ca, low P (phosphate trashing) - increase urinary cAMP (since PTH receptor is Gs) - increase alkaline phosphatase (sign of osteoblastic activity which PTH triggers)
Reidels Fibrosing Thyroiditis
Chronic inflammation with extensive fibrosis of thyroid Presentation: - hypothyroidism in 1/3 - HARD AS WOOD, NON-TENDER thyroid - fibrosis can spread to airways/esophagus *mimics anaplastic carcinoma due to extension
Teratoma (men)
MALIGNANT (benign in females) germ cell tumor of mature fetal tissue from 2-3 embryonic layers
Testicular Tumors
2 types: germ-cell and sex-cord stromal (no epithelial) Presentation: - firm, painless mass - DOES NOT illuminate Treatment: - do NOT biopsy (can see scrotum and most are malignant) - radical orchiectomy Germ Cell Tumors (95% - malignant) - Risk factors: UDT, XXY - Occur in 15-40 years olds - Fetal: teratoma, embryonal carcinoma - Oocytes: seminoma (good prognosis) - Placenta: choriocarcinoma - Yolk Sac: yolk sac/endodermal sinus - Mixed (60% of germ cell) Sex-Cord Stromal (5% - benign) - Sertoli: usually silent - Leydig: produces androgen/estrogen, Reinke crystals, precocious puberty/gynecomastia Lymphoma: - most common cause of testicular mass in males >60 - usually large B-cell type
Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Too much ADH --> concentrated urine and EUVOLEMIC (compensatory response) hyponatremia --> mental status changes, seizures, neuronal/cerebral edema (osmotic pull inwards) Causes: - ectopic (small cell lung carcinoma) - CNS trauma - pulmonary infection - drugs (cyclophosphamide) Treatment: - water restriction - hypertonic saline or salt tablets - demeoclocycline (ADH receptor V2 antagonist) or vaptans *correct hyponatremia slowly to prevent central pontine myelinolysis
Parathyroid Disorders
HyperPTH - Primary: hyperPTH --> increased Ca/decreased P - Secondary: increased P --> decreased Ca --> hyperPTH Hypoparathyroidism: parathyroid damage/absence --> low PTH --> low Ca/high P Pseudohypoparathyroidism: PTH resistance --> low Ca despite high PTH Mimics PTH disorder - hypercalcemia of maligancy (PTHrp --> hyperCa) - familial hypercalcemic hypocalciuria: CaSR insensitivity --> hyperCa required to decrease PTH --> hyperCa and hypoCa in urine
Hydrocele
Fluid collection within tunica vaginalis due to incomplete closure of processus vaginalis (infants) or blockage of lymphatic drainage (adults) Presentation: - scrotal swelling - DOES illuminate with U/S (water vs. blood)
Pituitary Adenoma
Benign tumor anterior pituitary Non-functional (no hormone) - mass effect --> bitemporal hemianopsia - hypopituitarism (compression) - headache Functional (hormone-producing) - prolactinoma: galactorrhea/amenorrhea (females), decreased libido/headache (men)...treat w/ DA agonist (bromocriptine) - GH: gigantism (children), acromegaly (adults), 2ndary DM (glucagon-like)...treat w/ ocreotide - ACTH: cushing disease (with hyper pigmentation) - TSH/LH/FSH (rare)
Hypopituitarism
Insufficient hormone production due to loss of pituitary parenchyma loss (>75% --> symptoms) Causes: - non-functional pituitary adenoma, craniopharyngioma - Sheehan syndrome (birthing-related blood loss causes infarction of pituitary that is more susceptible due to increased demand of pregnancy; symptoms: poor lactation, loss of pubic hair) - empty sella (trauma or congenital-arachnoid herniation) Treatment: HRT
Hydrocephalus
Communicating (decreased CSF absorption by arachnoid granulations) - post-meningitis scarring - Arnold-Chiaria malformation - choroid-plexus tumor overproducing CSF Non-communicating (obstructive) - foramen of monro (lateral --> 3rd) - cerebral aqueduct (3rd --> 4th) Normal pressure hydrocephalus - increased CSF and dilated ventricles BUT normal pressure - wet (incontinence), wacky (dementia), wobbly (ataxia) Hydrocephalus ex vacuo - atrophy of brain tissue leads to compensatory increase in CSF (alzheimer's, HIV, Pick)
Varicocele
Dilation of the spermatic vein (in pampiniform plexus) due to impaired drainage - most common in left side (left gonadal vein drains into left renal vein - can be invaded by RCC) Presentation: - scrotal swelling with "bag of worms" - increased temperature --> infertility - does NOT illuminate with U/S
Hyperthyroid
Increase TH --> - increased BMR (increases synthesis of Na/K ATPase) - increase sympathetic (increased b1 receptors) Symptoms - weight loss with increased appetite - heat intolerance/sweating (heat production) - tachycardia w/ arrhthymias - tremor, anxiety, insomnia - diarrhea - oligomenorrhea - bone resorption - hypocholesterolemia - hyperglycemia (glucagon-like) - hyperreflexia - warm, moist skin Labs: - increase T3/4 - decreased TSH Causes - Graves - Toxic multinodular goiter - Thyroid storm (massive elevation of catecholamines and TH after acute stress)
Multinodular Goiter
Enlarged thyroid gland with multiple goiters due to relative iodine deficiency that is normally euthyroid Can become TOXIC (TSH-INDEPENDENT) --> hyperthyroid
BPH
Age-related hyperplasia of stroma and glands related to DHT...test-->DHT via 5-alpha-reductase (more sensitive as age) *no increased risk of malignancy Incidence: - 50% @ 50 - 75% @ 80 Presentation: - obstructive (transition/periurethral zone - lateral/middle lobes) --> start/stop, dribbling, impaired emptying - SM bladder hypertrophy (pushing against obstruction) - backup --> hydronephrosis, UTI - irritative (frequency, urgency, nocturia) Labs: - PSA is "slightly" elevated (4-10)...cancer is normally >10...normal is <4 Treatment: - alpha 1 anatagonist (terazosin, tamsulosin) --> relax SM - 5-alpha reductase inhibitor (finasteride)
Adrenal Insufficiency
Lack of adrenal hormones --> - hypotension (cortisol) - hypoNa/hyperK and hypoVolemia (Aldo) - metabolic acidosis (Aldo) - hyperPigmentation (increased ACTH w/ MSH/POMC - only in Primary) - vomiting and diarrhea Acute (rapid hypotension and shock): - Waterhouse-Friderichsen syndrome (neisseria meningiditis --> hemorrhage) - abrupt withdrawal of glucorticoids Chronic (Addisons): - autoimmune - TB - AIDS - metastatic carcinoma (esp lung cancer)
Papillary Carcinoma
Most common malignant thyroid carcinoma...good prognosis Histology: - papillary (finger-like) projections - Orphan Annie-eyed nuclei (white clearing in center of nucleus) w/ nuclear grooves - psammoma bodies Risk factors - ionizing radiation Spread: cervical nodes
Anaplastic Carcinoma
Undifferentiated malignant tumor of the thyroid that invades local structures --> dysphagia (esophagus) or respiratory compromise (larynx) *similar to Ridels fibrosing thyroiditis except older patients Histology: undifferentiated
Thyroid Neoplasia
Distinct, solitary nodules that are more likely to be benign Dx: - radioactive uptake (increased in nodular goiter and Graves; decreased-cold in neoplasia) - FNA to biospy (too bloody to resect) Types: - follicular adenoma (benign) - Papillary (80% of malignant) - Follicular - Medullary - Anaplastic Treatment: thyroidectomy --> complications of hoarseness (laryngeal nerves) and hypocalcemia (removal of PTH)
Thyroglossal Duct Cyst
Thyroid develops at the base of the tongue and travels along the thyroglossal duct to anterior neck Cyst (persistent duct) presents as an anterior neck mass that moves with swallow
Hypothyroid
Decrease TH --> - weight gain with decreased appetite - cold intolerance (minimal heat production) - bradycardia and SOB - hypoactivity w/ weakness - constipation - hypercholesterolemia - hypoglycemia - oligomenorrhia - hyporreflexia - cool, dry skin - myxedema (accumulations of GAGs in skin/soft tissue --> deep voice, large tongue, edema-like) Labs: - decrease T3/4 - increased TSH Causes: - cretinism (congenital) - Hashimoto thyroiditis - Subacute granulomatous thyroiditis - Riedel thyroiditis - Iodine deficiency or excess - Goitrogens (amiodarone, lithium) - radioiodine ablation tx for hyperTH
Cretinism
Congenital hypothyroidism Symptoms: - mental retardation (TH is required for brain development) - short stature - coarse facial features - umbilical hernia - enlarged tongue Causes: - maternal hypothyroidism - thyroid agenesis - dyshormonogenetic goiter (deficiency of TPO) - iodine deficiency
Hashimoto Thyroiditis
Most common cause of iodine-sufficient hypothyroidism....autoimmune destruction of thyroid gland (CD4/8, cytokines, Ab) Associations: - HLA-DR5 - increased risk of B-cell lymphoma Presentation - initial hyperthyroidism (leakage of already synthesized) followed by gradual hypothyroidism - anti-TG and anti-TPO Ab often present - smooth goiter (increased TSH due to low feedback) Histology - chronic inflammation with germinal centers - hurthle cells (eosinophillic metaplasia of cells lining the follicles)
Posterior Fossa anomalies
Arnold-Chiara Type 2: cerebellar tonsillar + vermis herniation, aqueductal stenosis/hydrocephalus, meningomyelocele Dandy Walker: enlarged/cystic posterior fossa (4th ventricle), agenesis of cerebellar vermis
Graves Disease
Hyperthyroidism (most common cause) due to an IgG autoAb that stimulates TSH receptor (HS 2) Clinical - goiter (stimulation from Ab) - hyperthyroidism - exopthalmos (fibroblast on lids) - pretibial myxedema (fibroblast in dermal shin --> glycosaminoglycan) Histology: - irregular follicles - "scalloped colloid" Labs: - increase TH - decreased TSH - TSI - hyperglycemia Treatment: - beta-blockers (symptomatic) - thioamides (PTU, methimazole) - radioiodine ablation
Pseudohypoparathyroidism (Albright hereditary osteodystrophy)
High PTH with end-organ resistance to PTH --> apparent hypoparathyroidism (low Ca, high P) Genetics: AD inheritance of defect Gs alpha subunit on PTH receptor Symptoms: - hypocalcemia with high PTH - shortened 4/5 digits - short stature
Yolk Sac Tumor
Malignant germ cell tumor that resembles yolk sac...most common in CHILDREN (<3 yrs) Histology: - yellow, mucinous - Schiller-Duval (glomerulus-like) TM: AFP (characteristic)
Diabetes Insipidus
Inability of action of ADH that is either central or peripheral Clinical - polyuria/dipsia - hypernatremia and high osmolality - hyperosmotic volume contraction - dilute urine (inability to concentrate) Dx: water deprivation (should lead to urine concentration) doesn't change urine osmolality Central/Neurogenic: ADH deficiency (hypothalamic or post pit pathology) - decreased ADH - trauma, tumor, infection - treatment: desmopression (ADH/vasopressin analog), hydration Peripheral/Nephrogenic: ADH insensitivity (renal) - normal or increased ADH - caused by meds (lithium, demeoclocycline) or inherited - no response to desmopressin - treatment: thiazides, hydration
Pheochromocytoma
BROWN tumor of chromaffin cells in adrenal medulla (from neural crest) --> increased catecholamines Symptoms: - episodic HTN - headaches - palpitations, tachycardia - sweating Dx: - increased serum metanephrines (meta/normeta) - increased 24-hr metanephrines/VMA Treatment: - resection w/ phenoxybenzamine and beta-blocker (pan-alpha blockers to block before tumor removed so that NE/E that escapes doesn't work) Rule of 10s - 10% bilateral - 10% familial (MEN 2A/B, VHL, NF1) - 10% malignant - 10% outside adrenal medulla (bladder wall) - 10% in kids - 10% calcify
Prostatic Adenocarcinoma
Malignant proliferation of prostatic glands...most common cancer in men (2nd death, after lung) Occurs in posterior/peripheral prostate --> asymptomatic until late in course Risk factors: - age - race (AA) - diet in high sat fats Screening (age 5) - DRE (best since it palpates the posterior lobe) - PSA (>10 is worrisome at any age, but esp. young) Dx: - REQUIRES biopsy (needle core) - nuclei contain dark nucleoli - Gleason grading system (multiple regions/2 is based on architecture) - Tumor markers, PAP, PSA Complications: - spread to lumbar spine (osteoblastic mets) --> low back pain w/ increased alkaline phosphatase Treatment: - prostatectomy - continuous (instead of pulsatile) GnRH analog (leuprolide) --> decreased FSH/LH - flutamide (androgen receptor inhibitor)
Neural Tube Defects
Failure of closure of the neural tube. Associated with decreased folate prior to conception/during pregnancy. Can diagnosis in utero (AFP) Anencephaly (anterior): absence of brain/calvarium, "frog-like", polyhydramnios due to low swallowing Spina bifida occulta: bony defect in vertebral column w/ no neural protrusion...can show a tuft of hair Meningocele: protrusion of meninges through bony defect Meningomyelocele: protrusion of meninges and spinal cord through bony defect --> severe dysfunction
Follicular Carcinoma
Malignant proliferation of follicles that is surrounded by a fibrous capsule with INVASION through the capsule (unlike follicular adenoma) *FNA cannot distinguish (invasion is the only difference) *Mets occur hematogenously
Cushings Syndrome
Excess of cortisol --> - muscle weakness with thin extremities (protein breakdown to provide aa for gluconeogenesis) - moon facies, buffalo hump, truncal obesity - hyperglycemia - abdominal red-purple striae (cortisol impairs collagen synthesis) - HTN (upregulates alpha-1 receptors) - osteoporosis - amenorrhea - immunosuppression (inhibits PLA2 --> less AA metabolites-PG/LT/TX; inhibits IL-2; inhibits histamine) ACTH-secreting pituitary adenoma - DISEASE (most common endogenous) - increased ACTH - BILATERAL enlargement - high-dose dexamethasone suppresses cortisol Exogenous paraneoplastic ACTH - most common - increased ACTH - BILATERAL enlargement - high-dose dexamethasone does NOT suppress (it is a cancer) Exogenous corticosteroids - decreased ACTH (feedback) - BILATERAL adrenal atrophy Primary adrenal adenoma/hyperplasia/carcinoma - decreased ACTH (feedback) - UNILATERAL atrophy (opposite adrenal) - UNILATERAL enlargement Dx: - increased 24 urine cortisol (ALL 4) - ACTH (up in 2, down in 2) - high-dose dexamethasone (distinguish between source of ACTH - ectopic vs. pituitary)
Subacute granulomatous thyroiditis (de Quervain)
Granulomatous thyroiditis that follows a viral infection, flu-like illness Presentation: - TENDER (de QuerPAIN), soft thyroid - increased ESR (inflammation) - transient hyperthyroidism that can progress (not always) to hypothyroid - self-limited course
Cerebral edema
Vasogenic: increased vascular permeability (destroy cell tight junctions) and plasma filtrate in white matter...infection, lesion, infarction Cytotoxic: swelling of cells in gray matter from water/Na influx w/o permeability alteration...hypoxia, hypoosmolality Interstitial: transudation of CSF from ventricles in severe hydrocephalus
Embryonal Carcinoma
Malignant germ cell tumor of immature (vs. teratoma) fetal tissue Histology: hemorrhagic mass w/ necrosis Aggressive with early hematogenous spread TM: AFP, b-hCG (maybe)
Intracranial Pressure (ICP)
CPP = MAP - ICP
Forebrain anomalies
Polymicrogyria: too many convulsions Lissencephaly (agyria): smooth brain (no convulsion) Megal/microencephaly: big/small brain volume Holoprosencephaly: failure of hemispheric separation --> cyclopia (worst), midline facial anomalies Agenesis of corpus callosum: "batwing" ventricles
Follicular Adenoma
Benign proliferation of follicles surrounded by a FIBROUS CAPSULE that is usually non-functional
Section 5
(50 cards)
Coup vs. contrecoup
Coup = blow to stationary head Contrecoup = blow to a decelerating head ex. injury to occipital brain --> anterior rebound Shaken-baby syndrome: multiple coup/contrecoup contusions due to ample subdural space with immature brain --> cerebral edema, subdural hematoma, retinal hemorrhage --> 20% fatality but the rest are handicapped
Meningitis CSF Findings
Bacterial: neutrophils, low glucose, increased protein Viral: lymphocytes, normal glucose (they are dead), increased protein Fungal: lymphocytes, low glucose
Meningitis Etiologies
Neonates: GBS (agalactiae), E. Coli, Listeria Nonvaccinated kids: H. influenzae Children/Teens: N. meningiditis (nasopharynx) Adults/Eldery: Strep pneumo, Listeria Viral: Coxsackie, Echo, Polio
Motor Unit
Neuron or CN + muscle fibers that it innervates
Epidural hematoma
Bleeding outside of dura due to skull fracture leading to rupture of middle meningeal artery Lens-shaped lesion (separation of dura from skull) since dura sticks to skull at some points Clinical: "talk and die", lucid interval followed by neurologic signs --> herniation
Pilocytic Astrocytoma
BENIGN tumor in POSTERIOR FOSSA (ex. cerebellum) in CHILDREN Histology: well-circumscribed with cystic and nodular appearance, biphasic (some dense, some loose regions) Rosenthal fibers (eosinophilic corkscrew fibers) GFAP +ve Prognosis: good if resected early
Wallerian Degeneration
Following traumatic transection of axon the portion of axon distal to injury begins to break down...myelin is catabolized by Schwann cell and engulfed --> myelin ovoids
Cerebral Ischemia
Damage to brain (>5 mins) due to lack of glucose/oxygen to neurons Causes: low perfusion (athersclerosis, shock), hypoxia (anemia) Susceptible areas: watershed (between major arteries), pyramidal neurons of hippocampus (CA1 Sommers), purkinje layer of cerebellum, cerebral cortex (layers 3/5/6) Susceptible cells: neurons>oligo>astro
Metastases to Brain
Lung, Breast, Kidney, Lymphoma
Schwannoma
BENIGN tumor of SCHWANN cells in ADULTS Involves cranial nerves (most commonly CN8 at cerebellopontine angle --> DEAFNESS/TINNITUS) Stain S-100 +ve, "ice cream cone" sign into internal acoustic meatus Can be bilateral in NF-2
Craniopharyngioma
BENIGN SUPRATENTORIAL tumor derived from EPITHELIAL remnants of RATHKE'S POUCH (precursor to anterior pituitary) --> bitemporal hemianopsia (ddx in child vs. pituitary adenoma) Calcification is common (tooth enamel), "motor-oil" cysts
Leukodystrophies
All are due to lack of enzyme and subsequent de/dysmyelination (less production or maintenance of myelin) Krabbe Disease: AR, galactocerebroside beta-galactosidase deficiency, accumulation of galactocerebroside metabolite called sphingosine/psychosine in macrophages --> toxic to myelin sheath --> exaggerated startle and hyper irritable infants (krabby), optic atrophy, globoid cells Metachromatic Leukodystrophy: AR, arylsulfatase deficiency, cerebroside sulfate (and other sulfatides) accumulates...sulfatides bind dyes and change color, spares subcortical Adrenoleukodystrophy: XL, disruptive metabolism of VLCFA...can't add CoA --> buildup in CNS/adrenal/testes
Myelin
Myelin Protein Zero (50%) and Myelin Basic Protein (2nd most abundant) One oligo myelinates MANY in CNS (loss = plaque) One schwann myelinates ONE in PERIPHERAL (loss = segmental)
Diffuse Axonal Injury
Injury to white matter caused by angular head acceleration (ex. MVA, falls) Microscopic axonal injury with axonal retraction, swelling and distal degeneration
Herniation
1) Subfalcine/cingulate: cingulate gyrus under the falx cerebri --> ACA compression 2/3) Transtentorial/uncal: medial temporal lobe over tentorium cerebelli --> compression of contra cerebral peduncle (ipsi hemiparesis) + PCA (contra homo hemi) + CN3 ("down/out/dilated") 4) Cerebellar tonsillar: tonsils into foramen magnum --> compression of brain stem and coma/death from CP arrest
Hemangioblastoma
BENIGN tumor of CEREBELLUM (infratentorial) in ADULTS Assoc. with VHL syndrome with concurrent retinal angiomas Histology: thin-walled capillaries w/ foamy, vacuolated cells (not oligo) Gross: can be hemorrhagic
Spinal cord infarction
L4 and T1 are most vulnerable
Lyme Disease
Caused by borrelia burgdorferi from ixodes tick --> meningitis, facial nerve palsy, encephalopathy
Brain abscess
Localized suppurative (bacterial) infection with central necrosis and inflammatory cells surround by reactive gliosis. Caused by strep/staph Can rupture into dura/ventricles
Intracerebral hemorrhage
Bleeding into brain parenchyma --> hemorrhagic stroke Caused by rupture of Charcot-Bouchard micro aneurysms of lenticulostriate vessels in basal ganglia/internal capsule (secondary to HTN/amyloid)
Chronic Traumatic Encephalopathy
Concussions from sports-related brain injuries --> similar changes to alzheimer's (atrophy, tau accumulation, neuronal loss) Clinical: mood, behavioral, memory disorders
Werdnig-Hoffman Disease (Spinal Muscular Atrophy)
Inherited degeneration of anterior motor horn (AR) --> "floppy baby" (no tone or reflexes) and death a few years after birth
Oligodendroglioma
MALIGNANT tumor of OLIGODENDROCYTES in ADULTS most often in WHITE MATTER of FRONTAL LOBE --> seizures Histology: "fried egg" clear cytoplasm and "chicken wire" capillary pattern (like a branching tree), often calcified 1p, 19q deletion Prognosis: slow growing, 2-10 yrs
Stroke epidemiology
Athersclerotic/embolic (ischemic): high incidence, low mortality Hemorrhagic (ICH/SAH): low incidence, high mortality
Perinatal cerebrovascular disease
Germinal matrix hemorrhage graded 1-4 1: blood DOES NOT EXTEND into ventricles 2: blood DOES extend into ventricles 3: blood DOES extend into ventricles and forms a CAST 4: blood extends into WHITE MATTER
Waterhouse-Friderichsen
Neisseria meningiditis infection leading to adrenal hemorrhage and insufficiency Clinical: purpura, DIC, coma
Ischemic Stroke
Thrombotic: atherosclerotic plaque rupture and thrombus formation --> pale infarction Embolic: embolus travels from another region (ex. DVT with patent FO, A-fib) --> hemorrhagic infarct (due to embolus lyse) Lacunar: secondary to hyaline arteriolosclerosis (HTN/DM) in lenticulostriate vessels --> cystic (lacunar/lake) regions of in basal ganglia/thalamus
Multiple Sclerosis
Autoimmune (T-cell and humoral) destruction of CNS myelin and oligodendrocytes --> gray periventricular plaques (oligo loss and reactive gliosis) in white matter Epi: white women in 20-30s, HLA-DR2, regions away from equator Clinical (relapsing and remitting) - blurred vision in one eye (optic neuritis) - vertigo, nystagmus, intention tremor, scanning speech (brainstem/cerebellum) - INO (MLF) - hemiparesis or hemisensory (subcortical white matter) - bladder/bowel incontinence (ANS) CSF: increased lymphocytes, increased IgG (oligoclonal bands), myelin basic protein Treatment: steroids (acute) and beta-interferon (chronic) Variants: acute (fatal over months) and optical (bilateral optic neuritis)
Poliomyelitis
Damage to anterior motor horn due to polio virus --> LMN signs
Types of Injury in PNS
- Segmental dymyelination (loss of schwann cells) - Axonal degeneration (injury to axon) w/ subsequent muscular atrophy - Reinnervation (from another nerve --> muscle changes to nerve fiber type) - Myopathy (muscle damage without nerve damage)
Meningitis
Infection/inflammation of leptomeninges (pia/arachnoid) Presentation (triad): headache, neck stiffness, fever WITH photophobia, vomiting, altered mental status Treatment: CSF sample (L4-L5) from subarachnoid space Complications (bacterial): death, hydrocephalus, hearing loss, seizures
Treatment of increased ICP
- Osmotic agents (mannitol) and diuresis (acetazolamide) - Head elevation - Hyperventilation (decrease CO2 --> vasoconstriction response) - CSF drainage (shunt, LP) - Burr hole/craniectomy
Progressive histopathology of cerebral ischemia
Liquefactive necrosis 12-48 hours: red (eosinophillic) neurons 1-3 days: neutrophils 3-5 days: macrophages (microglia) 1-2 weeks: reactive gliosis (granulation tissue) >2 weeks: glial scar surrounding a cystic space
Misc associations with brain infections
HSV 1: children/adults, temporal and orbital, hemorrhagic, cowdry A HSV 2: neonates after birth CMV: immunosuppressed, owls eye Candida: immunosuppressed, pseudohyphae Mucor: nonseptate, nasal sinus Aspergillus: branching septate, from lung Cryptococcus: mucoid capsule, pigeon Toxoplasmosis: HIV, ring-enhancing, cats Cysercercosis: taenia solium, pork, calcified cysts Naegleria fowleri: amoeba, infested fresh water
Neurosyphillis
Caused by treponema pallidum (tertiary) and can be seen with warthin-starry stain. Clinical: meningovascular neurosyphillis, subacute encephalitis (mental deterioration and mood alterations), tabes dorsalis (degeneration of dorsal columns), argyll-robertson pupils
Axonal regeneration and remyelination
Regeneration: Happens after peripheral axonal injury but is a very slow process (limited by rate of neurofilament transport)...done by growth cones (regenerating cluster) at stump that use schwann cells left behind Remyelination: stripped axon provides stimulus...cells in endoneurium can replace schwann cells --> "onion bulb" appearance of concentric layers
Pituitary Adenoma
Most commonly prolactinoma, leads to bitemporal hemianopia from pressure on optic chiasm
Friedreich's Ataxia
Degenerative disorder of spinocerebellar (limb/trunk ataxia), dorsal columns (loss of vibration/proprioception), pyramidal (muscle weakness) tracts and loss of DTRs Cause: AR, GAA repeat in frataxin on chr9 (iron binding protein that normally transports iron out of mitochondria) --> iron buildup with free radical damage via Fenton rxn Assoc. with hypertrophic cardiomyopathy, DM, and kyphoscoliosis
Glioblastoma Multiforme (Grade IV astrocytoma)
Most common MALIGNANT tumor in ADULTS Found in CEREBRAL HEMISPHERES, might cross-over ("butterfly"), ring-enhancing (due to microvascular hyperplasia) Histology: poorly circumscribed, "pseudopalasading" with central necrosis Stain GFAP +ve Median survival = 1 yr
Meningioma
BENIGN tumor in ADULTS of ARACHNOID cells in meninges, more frequent in WOMEN May have dural attachment (w/ "tail"), parasagittal Histology: "whorled" pattern and psammoma bodies (laminated calcifications) Symptoms: compresses, but does not invade brain --> seizures
Syringomyelia
Cystic degeneration of anterior white commissure in spinal cord from C8-T1 --> bilateral loss of pain/temp sensation in a "cape-like" pattern Associated with Type 1 Chiari Can spread to anterior horn (motor weakness) or lateral horn (sympathetic-horners)
Prion Disease
PrPc (chr 20) is normal and in alpha-helix PrPsc is abnormal and in beta-sheet - resistant to degradation - resistant to sterilization - makes others change - no immune response --> "spongy" vacuolization from damage to neurons/glial cells Can be sporadic (happens randomly), inherited (familial fatal insomnia), transmitted (vCJD-BSE, iatrogenic CJD, Kuru) Creutzfeldt-Jacob: - mostly sporadic, but can be transmitted (corneal transplant or human growth hormone) - dementia/ataxia/startle myoclonus - rapid progression with death <1yr - period "spike-waves" on EEG VariantCJD (mad cow-BSE, younger/slower, +behavioral changes) Kuru: acquired from cannibalism Fatal Familial Insomnia: sleep disturbances, ataxia, autonomia, coma
Sub-arachnoid hemorrhage (SAH)
Bleeding into SA space due to rupture of berry aneurysm (circle of willis) --> bleed on bottom of brain Berry aneurysms are associated with ADPKD, marfans, and ehlers-danlos. Clinical symptoms: "worst headache of life", xanthrochomia (yellow hue of CSF in LP due to bilirubin)
CNS Tumor Summary
Adults (70% supratentorial)...Good MOSH PIT - Glioblastoma multiforme (grade IV astrocystoma) - Meningioma - Oligodendroglioma - Schwannoma (infratentorial) - Hemangioblastoma (cerebellar) - Pituitary Adenoma Children (70% infratentorial)...PMEC - Pilocytic astrocytoma - Medulloblastoma - Ependymoma - Craniopharyngioma (supratentorial)
Amyotrophic Lateral Sclerosis
AKA Lou Gehrig's...Degenerative MOTOR (no sensory) disorder with UMN (lateral corticospinal tract) and LMN (anterior motor horn) signs Initial signs: atrophy and weakness of hands (fine finger movement) --> lower limbs, tongue/pharynx/larynx with sparing of eyes and sphincters Cause: sporadic (normally), rare familial (zinc-copper SOD mutation --> free radical injury in neurons)
Skull fractures
Diastatic: cross sutures Comminuted: highly fragmented Depressed: sunken in Orbit/ethmoid --> "raccoon eyes" Basilar --> "battle sign" of swollen mastoid Ring --> fall on butt and "ring" around foramen magnum
Subdural hematoma
Bleeding beneath the dura due to rupture of bridging veins (trauma, elderly, alcoholics) Crescent-shaped lesion on CT and progressive neurologic signs --> herniation
Stroke symptoms
- Weakness/numbness of one side of the body - Aphasias - Loss of vision one eye - Dizziness or loss of balance - Severe headache
Ependymoma
MALIGNANT tumor of EPENDYMAL cells lining the 4th ventricle (--> can cause hydrocephalus) in CHILDREN Histology: perivascular pseudorosettes
Medulloblastoma
MALIGNANT tumor of CEREBELLAR GRANULAR cells (NEUROECTODERMAL origin) in CHILDREN Can compress 4th ventricle and cause hydrocephalus. Can send "drop metastases" to spinal cord. Histology: Homer-Wright rosettes, small round blue cells
Section 6
(50 cards)
Sarcoidosis
Systemic disease of noncaseating granulomas (CD4 T-cell response)...classically seen in AA females, but young non-smokers Lung: - hilar lymph nodes - stellate inclusions ("asteroid bodies") within giant cells in UPPER AND MIDDLE LOBES Systemic: - uveitis - skin (erythema nodosum) - salivary/lacrimal glands (like sjogrens) Clinical: - SOB and cough - elevated ACE - hypercalcemia (epithelioid histiocytes produce 1-alpha hydroxylase --> increased Vit D --> hypercalcemia) - negative TST due to anergy Treatment: steroids
Pulmonary Hypertension
PPa>25 (normal = 10) Primary: idiopathic, BMPR2 mutation --> proliferation of vascular SM Secondary: - hypoxemia (obstructive/restrictive) --> hypoxic vasoconstriction - CHD and left>right shunt --> volume overload in right heart (eisenmengers) - recurrent PEs - left heart failure leading to back pressure Histology: pulmonary artery arthersclerosis, SM hypertrophy, intimal fibrosis, plexiform lesion Clinical --> RVH - seen as exertional SOB and RHF
Microscopic features of MS
Active plaques: inflammatory cells (T) surround, preservation of axons with destruction of oligo Inactive plaques: less infiltrate, gliosis Shadow plaques: border between affected and unaffected, thinned-myelin
Vitamin Deficiencies
Thiamine (B1) - TPP is a cofactor for dehydrogenase (pyruvate and alpha-ketoglutarate) + transketolase rxns responsible for breaking down glucose --> less glucose --> heart/brain injuries - Wernicke's encephalopathy (acute, mammillary bodies): triad of ataxia, confusion, ophthalmoplegia - Korsakoff's psychosis (chronic, medial dorsal thalamus): confabulation and retrograde amnesia - Dry (polyneuritis and muscle wasting) and Wet (dilated cardiomyopathy and edema) Ber1 Ber1 B12 (cobalamin) - cofactor for homocysteine --> methionine and methylmalonyl-CoA --> succinyl-CoA in breakdown of odd/branched FA - abnormal myelin production results --> subacute (slow) combined (ascending and descending) degeneration of dorsal, lateral corticospinal, and spinocerebellar tracts --> ataxia, numbness, weakness Folate (B9-not so benign) - NTD if deficient during conception and early gestation Niacin (NAD/B3) - Three D's of pellagra: diarrhea, dementia, dermatitis
Vascular Dementia
2nd most common cause of dementia HTN, atherosclerosis and vasculitis --> recurrent multifocal infarction
Central Pontine Myelinolysis
Focal demyelination of central pons (anterior brain stem) by macrophages due to rapid IV correction of hyponatremia --> disrupted consciousness/delirum + bilateral paralysis ("locked in") Occurs in malnourished patients (ex. alcoholics, liver disease)
Pleural effusion
Fluid between pleural layers Transudate (bilateral, <1.015)): CHF, nephrotic, cirrhosis of liver Exudate (unilateral, >1.015): infection, cancer Chylothorax: milky lymphatic fluid Hemothroax: blood due to ruptured AA
Alzheimer's Disease
Degenerative disease of the cortex leading to dementia (most common cause) Pathophysiology: breakdown of amyloid precursor protein (normally APP>A-alpha, but APP>A-beta is pathological) Clinical: slow-onset memory loss (recent to distant) and progressive loss of cognitive function (motor/language skills, behavior/personality) with no focal neurologic deficits (paralysis/sensory loss) Sporadic (late, predisposed by ApoE4, decreased by ApoE2) vs. Early (familial presinilin 1 (chr2), presinilin 2 (chr 14) and Downs (chr21)) Histologic features - cerebral atrophy with hydrocephalus ex vacuo - extracellular A-beta neuritic plaques w/ trapped neuritic processes esp around vessels (cerebral amyloid angiopathy --> hemorrhage) - intracellular neurofibrillary tangles of paired helical filaments (PHF) from hyperphosphorylated tau (MT organizing protein) - loss of neurons in the nucleus basalis of Meynert
Chronic bronchitis
CLINICAL definition: productive (mucus) cough of 3 months over a minimum of 2 years...related to SMOKING (irritants) Pathology: hypertrophy of bronchial mucous glands (due to smoking) such that "Reid Index" (gland thickness vs. wall thickness) > 50% Clinical: - productive cough - "blue bloaters" from cyanosis due to CO2 trapping (PaCO2 up and PaO2 down) --> cor pulmonale (hypoxic vasoconstriction --> PHTN/RVH/RHF) - increased risk of infection (behind "tube" blockage) - wheezing, crackles, dyspnea
Pulmonary edema
Transudate (hemodynamic pressure causes) - CHF (LHF leading to back-pressure) - decreased oncotic pressure (nephrotic syndrome, liver cirrhosis) - lymphatic blockage (tumor) Exudate - infections - ARDS Histology: - fluid in alveolar spaces - hemosiderin (iron) laden macrophages (heart failure cells) - chronic passive congestion Clinical - SOB, hypoxic - crackles (wet)
Asthma
REVERSIBLE airway bronchoconstriction and SM hypertrophy, most often type 1 hypersensitivity allergy (associated with allergic rhinitis, eczema)...can also be exercise, viral, aspirin (+nasal polyps) Initial exposure: TH2 cells induced by allergen to secrete IL-4 (IgE), IL-5 (eosinophils), and IL-10 (TH2) Reexposure: IgE cross-link on mast cells - preformed mediators (histamine-vasodilation/permeability) - generation of LTC4/D4/E4 (bronchoconstriction) - later inflammation (MBP from eosinophils) Clinical: SOB, wheezing, productive cough Histology of sputum: - curschmann spirals (spiral-shaped mucus plugs) - charcot-leyden crystals (MBP aggregates from eosinophils)
Charcot Marie Tooth (Hereditary Motor and Sensory Neuropathy)
AD progressive disorder --> sensorimotor issues including distal muscle weakness, scoliosis, muscular atrophy of calf, pes cavus (high arch)
Pneumothorax
Air in pleural space (between visceral and parietal) Clinical: decreased expansion, fremitus, and breath sounds on affected side w/ hyper resonance Spontaneous: rupture of emphysematous bleb, young/tall/males, "collapse", trachea shifts to injured side Tension: penetrating injury, air enters (but can't leave) and pushes trachea to other side Open (air goes in and out) vs. Closed (air stays in and just needs to be drained) vs. Tension (air keeps going in but doesn't come out)
Lewy Body Dementia
Related to Parkinson's except: - cortical (instead of basal ganglia) Lewy Bodies - hallucinations and dementia come earlier - Parkinsonian (TRAPS) features come later
Restrictive Lung Disease
Characterized by restricted filling of the lung (decreased TLC) due to: - interstitial lung disease (MANY causes) - mechanical/structural problem with chest wall (polio, myasthenia gravis, scoliosis, morbid obesity) Spirometry: FVC DOWN, FEV1 down, FEV1/FVC is increased (>80%) Due to fibrotic interstitium, DLCO (diffusion ) is also impaired Clinical: SOB, hypoxia, "dry" crackles
Hypersensitivity Pneumonitis
Granulomatous rxn (type III/IV) to inhaled organic antigen: - farmers lung (microployspora faeni in moldy hay) - malt workers lung due to aspergillum - pigeon breeders lung due to pigeon droppings Acute: fever, cough, SOB, resolves with removal Chronic: interstitial fibrosis
Emphysema
Destruction of alveolar air sacs by proteases/elastase --> loss of elastic recoil, increased compliance, dilated air sacs, and decreased DLCO (less surface area to diffuse) Why obstructive (air trapping)? - loss of elastic recoil --> lower ability of "balloons" to "ping" air out - collapse of bronchiole walls (pressure dysfunction) Clinical: - "pink puffer" (pursed lips and prolonged expiration to prevent airway collapse) - CXR shows dilated "barrel chest" and hyper inflated lungs (decreased elastic recoil leads to chest wall winning "tug of war" and increased FRC) - SOB and non-productive cough - later cor pulmonale (PHTN/RVH/RHF) - weight loss (due to effort/exercise of breathing) Pathophysiology (imbalance of proteases and antiproteases): - smoking: smoke up regulates proteases, centroacinar, upper lobes - alpha-1-antitrypsin deficiency: A1AT misfolding in ER of hepatocytes (pink/PAS positive globules), proteases win, panacinar, lower lobes
Goodpasture's syndrome
Ab vs alpha-3 chain of type IV collagen --> - acute renal failure from RPGN (hematuria) - pulmonary hemorrhage (hemoptysis) Clinical: linear IgG immunofluorescence along glomerular and alveolar BM
Atelectasis
AKA lung collapse leading to perfusion without ventilation (V/Q mismatch) Causes: - resorption (airway obstruction not allowing air through so not inflating portion of lung) - compression: pleural effusion or pneumothorax - contraction: due to fibrosis
Duchenne Muscular Dystrophy
X-linked disorder w/ deleted dystrophin (like a tendon - helps anchor muscle fibers to ECM) Clinical: - normal at birth but can't keep up - initial proximal weakness (begins at pelvic girdle) - calf pseudo hypertrophy (actually replaced by fibrous/fat) - serum CK is raised - Gower's sign (using upper extremities to help them get up)
Mesothelioma
Malignant tumor of mesothelial (pleural) cells that "encases" the lung Associated with occupational exposure to asbestos (construction, plumbing, shipbuilding)...10% risk if exposed by 35 year latency Clinical: - pleural effusions (fluid make by mesothelium), SOB, pleuritic chest pain - CXR shows diffuse bilateral "shadows" - 50% mortality <1 yr
Anatomy of respiratory system
Trachea: cartilage, pseudostratified ciliated Bronchi: pseudo stratified ciliated, cartilage, mucus glands Bronchiole: Clara cells, no glands, smooth muscle Respiratory bronchioles --> alveolar ducts --> alveolar sacs Capillary-alveolar space: each has its own epithelium and BM w/ interstitium between Pneumocytes: 1: flat, 95% of surface 2: small, surfactant, regenerative, induce fibrosis
Gun Shot Wounds
Distance: - Contact: muzzle imprint (discoloration) - Close (6-8 inches): bullet + gunpowder stippling + soot - Intermediate (1-3 feet): bullet + gunpowder stippling - Distant (3+ feet): bullet only Entrance wounds (circular) vs. exit wounds (stellate, irregular)
Pneumoconioses
Small particles engulfed by alveolar macrophage (dust cell) --> IL1/TNF --> fibrosis...most often occupational exposure: Coal worker (carbon dust): "black lung", assoc. with RA (Caplan syndrome), UPPER lobes Carbon pollution (mild exposure): benign, anthracosis, carbon-laden macrophages in lung and hilar lymph nodes Silicosis: sandblasters (cleaning brick buildings), silica miners, silica impairs phagolysosomal fusion, silicotic nodules (concentric collage fibers) increased risk for TB and lung cancer, UPPER lobe (like TB) Berylliosis: miners, aerospace workers, noncaseating granulomas in lung, hilar nodes, and other organs (like sarcoid), increases risk for lung cancer, upper lobes Asbestosis: construction/plumbers/ships, fibrosis of lung and pleura, asbestos bodies (long, golden brown, "ferruginous" body), mesothelioma, lung cancer (more), laryngeal cancer, LOWER lobes
Guillian-Barre Syndrome
Life-threatening autoimmune peripheral demyelination associated with previous infections (campylobacter jejuni, CMV/EBV) and subsequent cell-mediated immune response a few weeks later --> segmental dymyelination and ascending paralysis Clinical: ascending motor paralysis that can progress to respiration (support w/ ventilator) Treatment: plasmapheresis, IVIG helps
Frontotemporal Dementia (Pick's)
Degenerative disease that PICKS the frontal (behavioral) and temporal (language) cortices eventually progressing to dementia...little memory loss initially Occurs earlier than Alzheimer's (40-60 years) Histology: - ROUND, silver-staining aggregates of tau protein in neurons - posterior 2/3 of super temporal gyrus is spared
Myotonic Dystrophy
AD w/ anticipation due to CTG repeats in DMPK gene --> sustained involuntary contractions (myotonia) with difficulty releasing Clinical: myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia (My Tonia, My Testicles, My Toupee, My Ticker)
Metabolic Disturbances on Neurologic System
Hypoglycemia - loss of neurons in hippocampus and cortical 3, 5, 6 Hyperglycemia - hyperosmolar coma and diabetic ketoacidosis --> confusion/stupor/coma Hepatic encephalopathy - complications of liver failure/cirrhosis - blood is shunted around liver and NH3 (ammonia) is not metabolized...also other toxic chemicals --> seizures, asterixis, coma
Types of guns
Handguns (one bullet and short barrel) - Revolvers: user must manually "revolve" to rotate new bullet into barrel - Automatic: force from fired cartridge helps to reload (bullet has rotating marks on it) Shotguns (multiple pellets and long barrel)
COPD (obstructive lung diseases)
Characterized by obstruction of air flow resulting in air trapping during expiration Types: bronchitis, emphysema, asthma, bronchiectasis Spirometry: - FVC down, FEV1 DOWN --> decreased FEV1/FVC ratio (<70%) - TLC and RV increased (due to air trapping)
Progressive Multifocal Leukoencephalopathy (PML)
JC polyoma virus infection of oligodendrocytes --> demyelination of CNS Immunosuppression (AIDS, leukemia) leads to reactivation of latent virus Rapid neurologic signs --> death
Natural causes of sudden death
>90% are cardiovascular (80% of those are due to atherosclerosis) - CAD (most common, >60% luminal narrowing...death may result from ischemia or ischemia-induced arrhythmia) - PE (saddle embolus) - Myocarditis (viral, Coxsackie B) - Valvular (bicuspid aortic, rheumatic mitral, MVP) - Berry aneurysms --> SAH - ICH from HTN or amyloid - Perforated peptic ulcer - Intense anaphylaxis (type I HS) - HOCM (young athletes w/ enlarged heart and septal thickening)
ARDS (acute respiratory distress syndrome)
Damage to alveolar-capillary interface --> protein leakage/edema (non-cardiogenic), necrotic epithelial cells, and hyaline membrane (fibrin-rich fluid and necrotic debris) Clinical: - hypoxemia/cyanosis (thicker diffusion barrier) - lung collapse (atelectasis due to increased surface tension) - CXR shows diffuse "white-out" - interstitial fibrosis (restrictive-like) Causes: sepsis, infection, shock, trauma, aspiration, pancreatitis, DIC, hypersensitivity, drugs...neutrophils secrete proteases (imbalance) and free radicals --> damage to pneumocytes (I and II) Treatment: - underlying cause - PEEP (keep lungs open)
Alzheimer's Treatment
AChEI (mild to moderate for slowing the progression): Tacrine, Donezipil, Rivastigmine, Galantamine NMDA antagonist (moderate to severe): Memantine
Pneumonia Overview
Infection of the lung parenchyma...normally occurs with impaired defenses (ex. cough reflex, mucus plugging, ciliary stasis, viral pneumonia superinfection) Clinical: - fever and chills - cough with sputum (pus and/or blood) - tachypnea - pleuritic chest pain (maybe pleural rub) - bronchial breath sounds w/ dullness to percussion and increased fremitus - elevated WBC (infection) Complications: - empyema (pus in pleural space) - bacteremia: spread in blood - lung abscess: walled off infection Diagnosis: - CXR (lobar vs. broncho vs. interstitial) - sputum stain - blood work
Bronchiectasis
Dilation of airways leading to lost ability of air to exit (ex. air slower through big pipe, circles around)...secondary to necrotizing inflammation to airway walls Causes: - cystic fibrosis - kartagener syndrome (defective dyne arm of cilia --> sinusitis, situs inversus, infertility, lung infection-can't clear) - infections - bronchial obstruction - allergic bronchopulmonary aspergillosis (asthmatics and cystic fibrosis have hypersensitivity to aspergillus) Clinical: cough, SOB, copious foul-smelling sputum (rotting in lung) - later hypoxemia and cor pulmonale - amyloidosis (due to chronic inflammation)
Parkinson's Disease
Degenerative disease with loss of dopaminergic neurons in substantia nigra pars compact --> striatum in basal ganglia (nigrastriatal pathway) Etiology: aging, maybe MPTP (illicit drug) Clinical (TRAPS, which can progress to dementia): - Tremor (pill rolling at rest) - Rigidity (cogwheel) - Akinesia/bradykinesia (w/ expressionless face) - Postural instability - Shuffling gate Histology: - loss of pigmented neurons in substantia nigra - round, eosinophilic inclusions of alpha-synuclein (Lewy bodies)
Huntington Disease
Degeneration of GABA neurons in caudate nucleus of basal ganglia --> less inhibition of cortex --> unwanted movement (chorea) Genetics: AD, chr4, CAG repeats of hungtintin gene w/ anticipation through males (expansion occurs during spermatogenesis) Symptoms: chorea + athetosis ("snake-like") that can lead to dementia/depression (high suicide rate) Histology: atrophy of caudate (larger lateral ventricle since caudate borders ventricle) *HUNT 4 DANCING SNAKE and GrAB her and put into a CAGe
Parkinson Treatment
Levodopa (DA replacement) DBS on subthalamic nucleus
Blunt vs. Sharp force trauma
Blunt force --> Lacerations (skin tearing) Abrasions (scrape/friction) Contusions (bruise w/ bleeding) Sharp force --> Stab (depth bigger than length) Incised (depth less than length) Puncture (pointed object) Chop
Cause vs. Mechanism vs. Manner
Cause: disease/injury responsible for initiating the lethal sequence of events Mechanism: physiological derangement produced by the cause that results in death itself Ex. GSW led to exsanguination (Cause = GSW, mechanism = exsanguination) Ex. Cardiovascular disease led to myocardial infarction (Cause = CVD, mechanism = MI) The cause and mechanism can be vice versa Manner: how the cause arose (natural vs. accident vs. suicide vs. homicide vs. undetermined)
Inflammatory Myopathies
Polymyositis: symmetrical proximal muscle weakness (problems with stair, chairs, hair) --> distal later...also heart/lung/vessel manifestations Dermatomyositis: polymyositis + rashes (periorbital heliotrope and knuckles/elbows gottrons papules)
Postmortem changes
Rigor mortis: stiffening, disappearance of ATP, 3-36 hours, starts in small (jaw) and spreads to large muscles, can be mechanically broken by stretching Livor mortis: accumulation of blood with pale areas where resting on surface, 2-6 hours = in vessels and can be blanched, 10+ hours = in interstitium and cannot be blanched (tardieu spots = petechiae) Desiccation: drying of tissues/mucous membranes (lips/eyes/scrotum) --> red/black Ocular: open eyes --> red/black with drying (tache noire) in 3 hours, closed eyes --> cloudy corneal in 24 hours Decomposition: - green discoloration of abdomen (24-36 hours) - marbling (hemolysis of blood vessels) - epidermis becomes detached - sulfhydryl groups give bad odor - gassy distension of cavities Adipocere: adipose becomes waxy and acts as preservative, only in wet places)
Subacute Sclerosing Panencephalitis (SSPE)
Progressive, debilitating sequelae of measles virus from infancy --> death Viral inclusions in neurons (gray) and oligodendrocytes (white)
Cases reportable to a medical examiner
Natural deaths (where cause may still be unknown) and non-natural deaths (homicide, suicide, accident) Homicide: volitional act by another (but no "criminal" intent - leave it to the legal system) Suicide: intentional, self-inflicted Accident: no evidence of intent (ex. MVA, fall, OD, drowning) Natural death w/ no need for internal autopsy: - 50-60 history of cardiac disease - <50 with terminal cancer, AIDS - >60 with no suggestion of anything except natural death
Neurotoxicities
CO: - hypoxic damage (cortex, hippocampus, cerebellar) - cherry red skin - globus pallidus necrosis Methanol: - metabolized to formic acid - toxic to retinal ganglion cells --> metabolic acidosis, blindness Ethanol (long term): - cerebellar degeneration (ataxia, wobbly gait, nystagmus) - peripheral neuropathy - rhabdomyolysis - FAS (retardation, smooth philtrum, epicanthal folds) Radiation: - increased ICP (HA, N/V, papilledema) - coagulative necrosis and vasogenic edema - tumors: meningiomas, sarcomas, gliomas Lead: - children: CNS, mental development + encephalopathy - adults: peripheral neuropathy (demyelination --> wrist/foot drop)
Idiopathic Pulmonary Fibrosis (Usual Interstitial Pneumonia)
Fibrosis of lung interstitium...unknown etiology but possibly cyclical injury (temporal heterogeneity with some cysts and some fibrosis) where TGF-beta from injured type 2 pneumocytes causes collagen deposition Must exclude fibrosis by drugs (amiodarone and bleomycin) and radiation Clinical: - progressive SOB and cough - fibrosis on CT ("honeycomb") often in LOWER lobes - poor outcome (<3 yr survival) Treatment: lung transplant
Leprosy
Lepromatous: infected schwann cells --> demyelination and remyelination with fibrosis at site of injury --> symmetric loss of pain fibers (unaware of injuries) Tuberculoid: cell-mediate --> granulomas and more localized
NRDS (neonatal respiratory distress syndrome)
Respiratory to distress in neonate due to inadequate surfactant --> increased surface tension --> alveolar collapse (hard to inflate again) Clinical: - tachypnea - high respiratory effort w/ accessory muscles - hypoxemia w/ cyanosis Caused by: - prematurity: surfactant starts at 28, adequate at 34, Lecithin:sphingomyelin ratio (lecithin/PDC increase) >2 is adequate - C-section: lack of stress-steroids (steroids increase surfactant production) - maternal diabetes: insulin decreases surfactant Complications: - PDA (hypoxemia-caused since oxygen closes the DA) - necrotizing entercolitis (hypoxemia) - free-radicals from oxygen therapy --> ROP (blindness) and bronchopulmonary dysplasia Treatment: - maternal steroids before birth - artificial surfactant after birth
Pulmonary embolism
Consequence of DVT from legs...most are clinically silent (collateral blood supply) Significance and outcome depends on size: - small: silent, or increase PHTN - medium: wedge-shaped infarct - big (saddle): death from acute right heart failure Risk factors: cancer, stasis, hyper coagulable, OCP, pregnancy Clinical: - chest pain, SOB, hemoptysis - pleural rub
Section 7
(50 cards)
Bronchopneumonia
Scattered patchy consolidation around bronchioles Microbes (bacterial): - staph aureus (superinfection, IVD, nosocomial) - hemophillus (COPD) - pseudomonas (CF) - moraxella (COPD)
Hematuria
Gross (visible by eye) vs. microscopic (>3 RBCs/hpf) Urine dipstick normally detects microscopic (FP w/ myoglobin, antiseptic solutions, bleach) Isomorphic: anywhere in GU system Dysmorphic: glomerular origin RBC casts: glomerular Main causes: - UTIs (women) - bladder cancer (men) - kidney disease (men)
Quick Pulmonary Associations
Hemoptysis: cancer, pneumonia, infarction, TB, bronchiectasis Clubbing: cancer, abscess, empyema, UIP Cavitation: abscess, squamous cell carcinoma, TB, fungus Upper zone: coal workers pneumoconiosis, silicosis, TB, sarcoid Lower zone: asbestosis, UIP
Interstitial (Atypical) Pneumonia
Diffuse interstitial infiltrates w/ mild symptoms (minimal sputum/cough and low fever) Microbes (virus and weird bacteria): - mycoplasma (young adults, cold agglutinin) - chlamydia (young adults) - coxiella (high Q fever, farmer/vets, spores from cattle placentas) - RSV (infants) - CMV (transplant, AIDS, owls eye) - HSV - influenza (elderly/immunocompromised, can be super infected) - adenovirus (mild, "smudge cells")
Essential Mixed Cryoglobulinemia
Resembles MPGN except presence of "PAS-positive capillary loop thrombi" IgG-IgM deposits (linked together) that aggregate when cooled Associated with Hep C
IgA Nephropathy (Berger)
Nephritic syndrome due to IgA immune complex deposition in mesangium (most common nephropathy) that presents in childhood as EPISODIC HEMATURIA often following an MUCOSAL INFECTION (ex. respiratory, GI)...since IgA defends mucosal lining...defective glycosylation of IgA1 could be important LM: mesangial proliferation EM: mesangial deposits IF: IgA deposits Associations: Henoch-Schonlein purpura
Misc. pneumonia
Nosocomial: ill patients, immunocompromised, abx, ventilator (pseudomonas, staph) Lipoid: aspiration of oily substance (ex. mineral oil) engulfed by macrophages --> foamy cytoplasm
Bronchioalveolar carcinoma
Adenocarcinoma in situ (so peripheral) characterized by "thickened" alveolar walls from columnar Clara cells CXR: pneumonia-like consolidation Treatment: resection, good prognosis
Goodpasture Syndrome
A cause of RPGN with linear IF due to anti-BM Ab...these Ab are against collagen IV alpha 3 in BM of alveoli and glomeruli --> hemoptysis and hematuria
Rapidly Progressive Glomerulonephritis (RPGN/Crescentic)
Nephritic syndrome that progresses to renal failure in weeks-months...characterized by "crescents" composed of fibrin, macrophages, C3b Many causes (use IF): - linear (Goodpasture syndrome due to Ab vs. BM) - granular (PSGN or DPGN) - negative...pauci-immune (vasculitis - perform ANCA)
Complications of Lung Cancer
PSHH Pleural involvement (esp. adeno) that could lead to effusions SVC syndrome (obstruction) leading to distended neck veins and edema of face/UE Hoarseness from compression of the superior recurrent laryngeal nerve Horner's syndrome (Pancoast-apical tumor) from compression of sympathetic chain
Pneumocystis jiroveci
Remains latent and reactivated in immunocompromised (AIDS <200) Histology: - foamy, pink exudate ("cotton candy") - mononuclear infiltrate - silver stain (GMS)
Glomerulus Anatomy
Mesangial: between (mes) vessels (angial) Endothelium, BM, and Epithelium make up the filtration barrier which is negatively charged due to heparin sulfate proteoglycans
Minimal Change Disease
Most common NEPHROTIC syndrome in CHILDREN Pathogenesis: loss of podocyte foot processes (effacement) due to cytokines...selective proteinuria (lose albumin but not Ig) LM: normal EM: effacement (flattening) of foot processes IF: negative Assoc: mostly idiopathic, but seen w/ Hodgkin lymphoma (overproduction of cytokines), respiratory infections (25%), immunizations (10%), and drugs (NSAIDs) Treatment: excellent response to steroids (adults not as good as children) but can progress to FSGS
Microalbuminuria
Definition: 30-300g albumin/day Associated with DM (20%) and HTN (30%)
Diabetic glomerulonephropathy
High glucose --> NEG of VASCULAR BM --> protein leaking in and hyaline arteriolosclerosis of efferent-2nd arteriole --> hyper filtration (increased GFR) --> sclerosis of mesangium Initial: microalbuminuria Later: nephrotic syndrome LM: Kimmelstiel-Wilson nodules (mesangial sclerosis/expansion) + membrane thickening
Adenocarcinoma
Most common lung cancer in nonsmokers and females and people with previous lung scars Peripheral location (can spread to pleura) Histology: mucin+ with glandular pattern Treatment: resection, good prognosis
Nephritic Syndrome
Glomerular disorders characterized by glomerular inflammation (neutrophils) Pathogenesis: immune-complex deposition activates complement --> C5a --> neutrophils --> hypercellular/inflamed glomeruli Also seen: - hematuria (with RBC casts and dysmorphic RBCs) - HTN (due to salt retention) - periorbital edema (loose CT) - oliguria - azotemia (increased BUN and creatinine) - proteinuria (<3.5g/day) Types: - PSGN - RPGN - DPGN/MPGN (nephritic-nephrotic) - Alport Syndrome - IgA Nephropathy (Berger)
Polycystic Kidney Disease (PKD)
INHERITED, BILATERAL defect of ENLARGED kidneys with cysts in CORTEX and MEDULLA ARPKD (infants) - worsening renal failure and HTN (increased renin) - born with Potter sequence (facies, pulmonary hypoplasia) - hepatic cysts and fibrosis w/ PHTN ADPKD (ADults) - mutation at birth (APKD1/2), but cysts develop over time - flank pain, hematuria, HTN (increased renin), progressive renal failure - associated with berry aneurysms (cyst in brain), hepatic cysts, and mitral valve prolapse
Drugs that cause ischemic ATN
NSAIDs (inhibit PG at afferent arteriole) and ACE-I/ARBs (inhibit ATII at efferent arteriole) --> potential decrease in blood flow to kidney and possibility for pre-renal azotemia and ischemic ATN
Pauci-immune causes for RPGN
Weg(c)ener's granulomatosis: c-ANCA, nasopharynx/sinuses/lung/kidney Churg-Strauss: p-ANCA, necrotizing, granulomatous inflammation, eosinophilia, asthma Microscopic polyangiitis: p-ANCA, lung/kidney/skin w/ pulmonary hemorrhage
Lung abscess
AKA aspiration pneumonia...seen in alcoholics, comatose patients...often in right lower lobe (anatomy of airway) Microbes (anaerobes): - bacteroides, fusobacterium, peptococcus - staph aureus CXR: air-fluid level Treatment: clindamycin
Large Cell Carcinoma
Highly anaplastic, pleomorphic large cells (no glands, mucin, bridges, or pearls) Treatment: resection, poor prognosis
Acute Renal Failure (ARF)
Acute, severe decrease in renal function with marked azotemia (decrease in BUN and Cr) and oliguria...also called Acute Kidney Injury (AKI) Pre-renal: decreased blood flow to kidneys (shock, dehydration) - decrease GFR w/ azotemia, oliguria - BUN:Cr>15 (wants to resorb lots to conserve volume-BUN can, but Cr cannot) - FENa <1% and Uosm>500 (tubular concentrating function remains intact) Intrinsic: due to ATN, ischemia/toxins, interstitial nephritis, and sometimes acute GN (RPGN/HUS) - decrease GFR (debris obstructing tubules) - BUN:Cr<15 (disrupted reabsorbing capacity) - FENa>2% and Uosm<500 (concentrating function disrupted) - brown, granular casts Post-renal: obstruction of the urinary tract - decrease GFR (back-pressure) w/ azotemia, oliguria - early stage: BUN:Cr>15 (increased tubular pressure "forces" BUN out), FENa<1% and Uosm>500 (tubular concentrating function remains intact - late stage: long standing obstruction leads to disrupted tubular function...BUN:Cr<15, FENa>1%, Uosm<500
Diffuse Proliferative Glomerulonephritis (DPGN)
Nephritic syndrome (can present as nephrotic like MPGN) due to immune complex deposition (sub endothelial or intramembranous) LM: wire looping (loopus) IF: granular (IgG, IgA, C3, !C1q!) Associations: - most common cause of death in LUPUS - can also lead to RPGN (crescentic)
Congenital Nephrotic Syndrome (Finnish)
Rare genetic condition due to mutations in nephrin, a protein in the filtration slit diaphragm between podocytes --> nephrotic presentation (massive proteinuria after birth) Seen in neonates (often premature and small)
Focal Segmental Glomerular Sclerosis
Focal: <50% of glomeruli Segmental: only part of each glomeruli LM: focal segmental sclerosis (hyalinosis) EM: effacement (flattening) of foot processes IF: negative (maybe IgM, C3, C1) Etiologies: - primary idiopathic (most common) - secondary: familial/genetic HIV, heroin use, sickle cell disease, Hispanics, African Americans, obesity Treatment: poor response to steroids
Poststreptococcal Glomerulonephritis (PSGN)
Nephritic syndrome 2-3 weeks after group A beta-hemolytic strep (with M protein, increased anti-DNase B titers, ASO) infection of skin/pharynx...usually seen in children Clinical: hematuria (cola-colored), oliguria, HTN, edema (peripheral and periorbital) IM: hypercellular, inflamed (enlarged) glomerulus EM: subepithelial IC humps (but no BM thickening since it is acute) IF: "starry sky" granular appearance (IgG, IgM, C3) C3 levels return to normal in 2 weeks (unlike DPGN and MPGN) Treatment: supportive (normally resolves, but can progress to RPGN)
Nephrotic Syndrome
Glomerular disorders (damage to filtration charge barrier) characterized by >3.5g/day proteinuria and: - hypoalbuminemia (pitting edema) - hypogammaglobulinemia, IgG (infections) - hypercoagulable (preferential loss of antithrombin III) - hyperlipidemia/cholesterolemia (liver makes fat to "thicken" blood since protein was lost) - frothy urine with fatty casts Types: - Minimal Change Disease - FSGS - Membranous Nephropathy - MPGN/DPGN - Diabetic GN - Amyloidosis
Amyloidosis
Kidney is most commonly involved organ in systemic amyloidosis...amyloid deposits in mesangium --> nephrotic syndrome LM: Congo red stain shows apple-green birefringence under polarized light Types: - AL-primary (lamda light chains): associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma - AA-secondary (serum amyloid A): associated with chronic inflammatory states such as RA, AnkSpon, IBD, Crohn's, Ulcerative Colitis
Monoclonal Ig Light Chain Deposition Disease (MIDD)
Associated with plasma cell dyscrasias (multiple myeloma, MGUS) with a nephrotic presentation --> light chain (kappa) deposition in GBM and tubular BM --> nodular mesangial expansion (like diabetic GN)
Lobar Pneumonia
Consolidation of an entire lobe of the lung Microbes (bacterial): - strep pneumo (95%, esp asplenic) - klebsiella (aspiration due to malnourished/debilitated, alcoholics, elderly, diabetics, "currant jelly sputum") - legionella (water source, silver stain) Stages: - congestion: dilation and permeability of vessels --> edema (red and boggy) - red hepatization: spongy lung --> "solid" liver (due to exudate of PMNs, RBCs, and fibrin filling alveolar spaces) - gray hepatization: degradation of red cells within exudate - resolution
Alport Syndrome
X-linked (alpha 5...3 is also lost) (sometimes AR-alpha 3) inherited defect in type IV collagen --> hematuria, sensorineural hearing loss, and eye problems (retinopathy, lens dislocation, cataracts) EM: Thinning and splitting followed by thickened/layered "basket-weave" BM *"Can't see, can't pee, can't hear a buzzing bee"
Membranous Nephropathy
Most common cause of nephrotic syndrome in CAUCASIAN adults characterized by THICK glomerular BM due to SUB EPITHELIAL immune complex deposition IC involves Ab vs. megalin (rats) or phospholipase A2 Assoc: Hep B>C, SLE (most common nephrotic for SLE), tumors, drugs (NSAIDs, penicilamine, gold) LM: GBM thickening EM: "spike and dome" IF: granular Treatment: poor response to steroids and can progress to chronic renal failure
Proteins in Urine
Proteinuria = albuminuria (ish) Albumin = 66.5kD, -ve charge (sticks to +vely charge dipstick) Ig (whole thing) = 150kD, +ve charge Ig kappa/lambda (light) = 22kD, +ve charge (doesn't stick to +vely charge dipstick) Measuring proteinuria: - g of protein/day (measure for 24 hours) - mg of protein/mg of creatinine (one sample) **these are basically the same because the average person excretes 1g of creatinine per day (so 1g and 24 hours are the same) Ranges: - normal: <200 protein, <30 albumin - microalbumin: 30-300 albumin - non-nephrotic: 200-3500 protein, 300-3000 albumin - nephrotic: >3500 protein, >3000 albumin
Squamous Cell Carcinoma
Squamous: Sentral, Smokers, paraneo Syndrome (PTHrp --> hypercalcemia) Histology: keratin pearls and intercellular bridges, cavitation Treatment: resection
Renal Agenesis
Absent kidney formation Unilateral: hypertrophy and hyper filtration of compensating kidney --> renal failure later Bilateral: oligohydramnios (no urine) --> lung hypoplasia (no stretch from urine) and Potter sequence (flat face and low set ears w/ limb deformities)...incompatible with life
Cortical Necrosis
True coagulative necrosis of renal cortex (spares medulla) Causes: placental abruption (obstetric emergency), severe shock, ethylene glycol
Medullary Cystic Kidney Disease
INHERITED, AD defect leading to cysts in MEDULLARY collecting ducts --> parenchymal fibrosis and SHRUNKEN kidneys and worsening renal failure
Acute Tubular Necrosis
Injury and necrosis of tubular epithelial cells...most common cause of ARF (intrinsic azotemia) Necrotic epithelial cells shed and plug tubules --> decreased GFR (back pressure) and muddy brown/granular casts (dead cells) Epithelial damage leads to lower reabsorption ability - BUN:Cr<15 - FENa>2% and Uosm<500 Etiologies: - ischemia (PT and medullary TAL): decreased blood supply that is often preceded by prerenal azotemia - toxins (PT): aminoglycosides, heavy metals (lead/cisplatin), myoglobinuria (crush injury), ethylene glycol, radio contrast dye, urate (tumor lysis - dead cancer cells - use allopurinol during chemo) Histology: - loss of tubular brush border - tubular dilation and "flattening" - granular casts Clinical: - oliguria w/ muddy brown/granular casts - elevated BUN and Cr (BUN:Cr<15) - hyperkalemia and AGMAcidosis (decreased excretion of both) Treatment: requires immediate dialysis, can be reversible since cells can regenerate
Stages of lupus nephritis
1 and 2 = minimal clinical symptoms 3 and 4 = nephritic with low C3 5 = nephrotic 6 = ESRD 1 - Minimal - LM: normal - IF: deposits 2 - Mesangial proliferative - LM: mesangial hypercellularity - IF: deposits 3 - Focal: <50% of glomeruli w/ subendo deposits 4 - Diffuse: >50% of glomeruli w/ subendo deposits 5 - Membranous: subepi on LM and IF 6 - Advanced sclerosis: 90% globally sclerosed
Fungal pneumonias
Dimorphic fungi that cause localized disease in immunocompetent but disseminated disease in immunocompromised (mold in soil, yeast in human): Coccidioides: deserts, spores, spherules Histoplasma: Ohio river valley, bat droppings (caves) Blastomyces: Ohio river valley, broad budding Opportunistic fungi: - candidiasis - cryptococcus: bird dropping, disseminate to meninges, mucoid capsule w/ india ink - mucor: nasal cavity and sinuses, DKA - aspergillosis: 45deg branching, fungus ball in cavity (TB), invasive (blood vessels), allergic BPA --> ashtma/bronchiectasis, hypersensitivity pneumonitis (malt workers)
Horseshoe Kidney
U-shaped conjoined kidney at lower pole...can't ascend all the way because it gets stuck on IMA
Dysplastic Kidney
NONINHERITED, congenital malformation of renal parenchyma w/ cysts and abnormal tissue (DYSPLASIA - ex. cartilage/smooth muscle)...most frequent cause of abdominal mass in newborn Usually unilateral, but can be bilateral (and must be distinguished from PKD)
Bronchial Carcinoid tumor
Well differentiated neuroendocrine cells (chromogranin +ve) that form a polyp-like mass in bronchus (arranged in nests) --> mass effect and possible carcinoid syndrome (5-HT --> flushing, diarrhea, hypotension, wheezing)
Lung Cancer Overview
Most common cause of cancer mortality (2nd most common cancer) - 15% overall survival Risk factors: smoking (polycyclic aromatic hydrocarbons + arsenic, proportional to pack yrs), radon (isotope decay from uranium), asbestos (lung>mesothelioma) Clinical presentation: - symptoms: cough, hemotypsis weight loss - CXR: solitary "coin" nodule (could be benign ex. granuloma, hamartoma) Small cell (15%-chemo-too small to resect) vs. Non-small cell (85%-resective) T: size N: spread to Nodes (hilar and mediastinal) M: adrenal gland
Membranoproliferative Glomerulonephritis (MPGN)
Nephrotic or nephritic syndrome characterized by THICK glomerular BM with "tram-track" appearance due to immune complex deposition...mesangial cells proliferate and "cut" deposit into "tracks" LM: GBM thickening EM: "tram track" IF: granular Types: - I: sub endothelial deposit, associated with Hep C>B, more often "tram tracks", low complement - II: dense deposit - intramembranous deposit of C3, associated with C3 nephritic factor (stabilizes C3 convertase to breakdown C3 --> overactive comp and low C3) Treatment: poor response to steroids and can progress to chronic renal failure
ANCAs
p-ANCA: perinuclear (stains nuclear envelope but not cytoplasm), anti-MPO c-ANCA: cytoplasmic (stains cytoplasm - big hole - but not nucleus), anti-PR3
Small Cell (oat cell) carcinoma
Aggressive, poorly differentiated small (oat) cells (dark blue with scant cytoplasm) of neuroendocrine origin (Chromogranin A +ve) with scant cytoplasm Small: Sentral, Smokers, paraneo Syndrome (Adh, Acth, Antibodies that cause lAmbert-eAton) Treatment: chemo (too small to resect)
Tuberculosis
Inhalation of mycobacterium tuberculosis --> granuloma formation (TH1 releases IFN-alpha leading to macrophage activation) Primary: focal caseating necrosis in LOWER lobe with fibrosis and calcification (Ghon complex) --> asymptomatic (but +ve PPD) Secondary: reactivation (AIDS, aging etc.) --> cavitary caseating necrosis in UPPER lobe --> fevers, night sweats, cough w/ blood, weight loss Systemic spread: - meningitis (basilar) - kidneys (sterile pyuria) - lumbar vertebrae (Pott's) - cervical lymph nodes
Section 8
(50 cards)
Calcineurin Inhibitor Toxicity
Cyclosporine A and Tacrolimus are both Calcineurin inhibitors used in transplants (immunosuppression) but they have significant toxicity. Pathology: isomorphic vacuolization of PT epithelium
Fat necrosis
Fatty acids released when fat dies and binds to calcium (saponification) calcium deposits and "chalky" soap, which appear dark blue on H&E - Trauma to breast Fat necrosis of PERIpancreatic fat
Cellular mechanisms of adaptation
Cell may respond to stress by metaplasia/hyperplasia/dysplasia AND: - sequestering cytoplasmic damaged organelles in phagosomes --> lipofuscin (residual bodies) - induce more/less production of organelles
Mediators of acute inflammation
TLRs: - on innate immune cells - recognize PAMPs (ex. LPS on gram-ve) and DAMPs --> upregulation of NF-kB transcription factor --> release of inflammatory mediators Arachidonic Acid: - released from PL in membrane by PLA2 - AA (acted on by COX) --> PG --> vasodilation/permeability and fever/pain (PGE2) - AA (acted on by 5-lipo) --> LT --> attracts neutrophils (LTB4) and vasoconstriction/bronchospasm and increased permeability Mast cells: - activated by trauma, C3a/5a, IgE cross-linking - immediate: preformed histamine (vasodilation, vascular permeability) - delayed: AA metabolites (LT) Complement: - all pathways lead to C3/C5 convertase and MAC - C3a/C5a (anaphylatoxins) --> mast cell degranulation - C5a = neutrophil chemoattractant - C3b = opsonin for phagocytosis - MAC = lyse microbes Factor XII (Hageman) --> coagulation --> bradykinin (vasodilation, vascular permeability, pain)
NSAIDS and Corticosteroids
NSAIDS (aspirin) --> COX inhibition --> stop PG synthesis Corticosteroid --> PLA2 inhibition --> stop PG AND LT synthesis
Renal Transplant Rejection
Major indications: HTN, DM Hyperacute - minutes to hours - host preformed Ab vs. blood antigens Acute - weeks to months - T-cell or Ab mediated vs. HLA antigens Chronic - months to years - diffuse interstitial fibrosis and arterial sclerosis
Cellular injury
Injury occurs when stress exceeds the cell's ability to adapt (hyper/meta/dysplasia)...the injury can be reversible or irreversible Causes of injury: - inflammation - nutritional excess/deficiency - hypoxia - genetic mutation - trauma
Acute Interstitial Nephritis
Drug-induced hypersensitivity (drugs act as haptens) rxn involving the interstitium (the CT b/w tubules) that results in ARF (intrarenal azotemia) Drugs: NSAIDs, penicillin, diuretics, sulfa, phenytoin Clinical: - oliguria w/ EOSINOPHILS in urine - fever and rash - hematuria Treament: resolves w/ cessation of drug, but can lead to renal papillary necrosis
Carbon tetrachloride
A solvent used in dry-cleaning industry that leads to oxidative free radical injury CCl4 --> CCl3 (by P450 system) --> cellular injury and ribosomal swelling --> loss of protein synthesis --> lower apolipoproteins --> fatty liver
Necrosis vs. Apoptosis
Necrosis: PATHOLOGIC cell (MANY) death that is accompanied by INFLAMMATION Apoptosis: PHYSIOLOGIC (programmed) cell (ONE or FEW) death that is ENERGY-DEPENDENT
Metaplasia
Change in stress --> change in CELL TYPE Often seen in epithelium (ex. Barrett esophagus - with reflux, the esophagus epithelium changes from squamous --> columnar mucin-producing...to handle acid reflux) REVERSIBLE, but can progress --> dysplasia --> cancer (ex. Barrett's esophagus --> adenocarcinoma) Ex. myositis ossificans - ossification of skeletal muscle during trauma (density in muscle on XR)
Sequence of events in cell injury
EM (minutes): membrane swelling, mitochondrial densities, nuclear loss LM (later): swelling, fatty change Gross: necrosis
Affects on low ATP on cells
Low ATP (from OxPhos deficiency in hypoxia) --> Na/K pump dysfunction --> high intracellular Na --> swelling (water follows) --> Ca pump dysfunction --> high intracellular Ca --> activation of BAD enzymes --> anaerobic glycolysis --> lactic acid buildup --> protein/nuclear denaturation
Chronic Renal Failure (CRF)
ESKF that can result from insults to ANY area of kidney (glomerulus, tubules, inflammatory, vascular)...most commonly w/ DM, HTN, glomerular disease --> shrunken/cystic kidneys that don't work Symptoms (MAD HUNGER): - Hyperkalemia and Metabolic Acidosis (cannot excrete H+/K+) - Uremia...increased nitrogenous waste products --> nausea/anorexia, pericarditis, encephalopathy w/ asterixis, urea crystals in skin - Na/H20 retention --> HTN/edema - Anemia (less erythropoietin from renal peritubular interstitial cells) - Hypocalcemia (decreased 1-alpha hydroxylation of vitamin D) - Renal osteodystrophy (hypocalcemia --> increased PTH-secondary hyperparathyroidism --> bone resorption/osteoporosis + osteomalacia/cannot mineralize) Treatment: dialysis or transplant
Gangrenous necrosis
Prolonged ischemia of limbs/GI tract Dry: no infection Wet: superimposed infection liquefaction
UTI basics
Infection of urethra, bladder (cystitis), or kidneys (pyelonephritis) More common in women (shorter urethra due to ascending infection) Risk factors: sexual intercourse, urinary stasis, catheters
Renal oncocytoma
BENIGN epithelial tumor with a gross appearance of "well-circumscribed mass (solid/tan) with central scar" - no "clear" cells unlike RCC. Often resected to exclude malignancy Histology: cells with abundant mitochondria Clinical: flank pain, hematuria, palpable mass
Calcium deposition (calcification)
Dystrophic: deposits of calcium on DEAD tissue in NORMAL serum calcium levels (ex. saponifaction in fat necrosis) Metastatic: deposits of calcium/phosphate on ALL BODY tissue in HIGH serum calcium
Inflammation overview
Inflammatory cells, proteins, and fluid enter interstitial space...divided into acute (neutrophils) and chronic (lymphocytes) 1st: fluid (edema), proteins (complement) 2nd: neutrophils (24 hrs) 3rd: macrophage (2-3 days) Characteristics: - redness/warmth (hyperemia from vasodilation - histamine, PG, bradykinin) - swelling (exudative edema - histamine) - pain (bradykinin, PGE2) - fever (IL-1/6, TNF --> PGE2 --> raise hypothalamic set-point)
Wilm's Tumor (nephroblastoma)
MALIGNANT kidney tumor of immature mesenchyme (blastema) often seen in children (average age 3 years) Clinical: palpable mass, hematuria, HTN (renin secretion) Pathogenesis: loss of function of tumor suppresor WT1/2 on chr 11 Can be part of syndrome: - WAGR (WT1): Wilm's tumor, Aniridia, Genital abnormalities, Retardation - Beckwith-Wiedemann (WOHHM - WT2): Wilm's tumor, Organomegaly, Hypoglycemia, Hemihypertrophy, Macroglossia
Chronic Pyelonephritis
The result of multiple episodes of acute pyelonephritis --> interstitial fibrosis and tubular atrophy...REQUIRES predisposition (vesicoureteral reflux in children, BPH/carcinoma/stone in adults) --> cortical scarring (esp at poles) w/ blunted calyces Histology: "thyroidization" (atrophic tubules w/ eosinophilic proteinaceous material looks like follicles)
Liquefactive necrosis
Tissue becomes liquefied due to enzymatic lysis of cells/protein (enzymes leak out of dead cells) - Brain (microglial cells) - Abscess (neutrophils) Pancreatitis (pancreatic enzymes)
Irreversible cellular injury
Membrane damage (hallmark) - PLASMA membrane (leaking of cytoplasmic contents into serum ex. cardiac troponin, Ca2+ into cell) - MITOCHONDRIAL membrane (loss of OxPhos and cytc leaking apoptosis) LYSOSOMAL membrane (hydrolytic enzymes activated by Ca2+ kill stuff)
Acute inflammation
Characterized by edema and neutrophils - fluid and PMN filtered through vessel wall Response to infection (innate, to eliminate pathogen) and necrosis (clear debris)
Angiomyolipoma
Hamartoma composed of blood vessel (angio), muscle (myo), and fat (lipoma)...common in TSC
Dysplasia
Disordered cellular growth and the proliferation of PRECANCEROUS cells...can arise from hyper/metaplasia REVERSIBLE (remove inciting stress)
Coagulative necrosis
Nucleus disappears BUT cell shape/structure remains intact/firm Often due to ischemia/infarct (except brain) wedge-shaped infarct Two kinds: - Red: due to REPERFUSION of LOOSELY organized tissue due to VENOUS OCCLUSION (artery still supplies) or COLLATERAL CIRCULATION (lung, liver, intestine) White (pale): solid organs with a single blood supply (heart, kidney, spleen)
Cell death
Nuclear loss (hallmark) - Pkynosis: condensation - Karyorrhexis: fragment - Karyolysis: dissolution
Free radicals
Oxygen species with UNPAIRED ELECTRONS in outer shell...the bad ones (3 middle) can be "dealt with" by listed enzyme O2 --> O2' (SOD) --> H202 (CAT) --> OH' (glutathione peroxidase) --> H20
Cystitis
UTI of the BLADDER Clinical (no systemic): dysuria, frequency/urgency, and suprapubic pain Lab findings: - cloudy urine - >10 WBCs/hpf - +ve leukocyte esterase on dipstick (WBC) - nitrites on dipstick (bacteria convert nitrate to nitrite) - 100k CFU in culture Etiology: - E Coli (80%) - Staph saprophyticus: young, sexually active women - Klebsiella pneumoniae - Proteus mirabilis: alkaline/ammonia urine - Enterococcus faecalis Sterile (-ve culture) with pyuria (+ve dipstick and microscopic) --> urethritis caused by Neisseria/Chlamydia
Free radical injury
Can be physiologic (ETC) or pathologic (radiation, inflammation, drugs, metals, reperfusion) Free radicals cause tissue damage by peroxidation of lipids (membrane damage) and oxidation of DNA (mutations) Protective mechanisms: - antioxidants (ACE) - enzymes (catalase, SOD, glutathione peroxidase) - metal carriers (transferrin/ferritin-iron, cerulopaslmin-copper)
Squamous Cell Carcinoma (urinary tract)
Malignant proliferation of squamous cells (doesn't normally have squamous cell epithelium, so must start after squamous metaplasia due to chronic irritation)...worse prognosis than transitional cell Most common in bladder Risk factors: - chronic cystitis - schistosoma hematobium (middle eastern male) - long standing nephrolithiasis - smoking Clinical: painless hematuria
Renal Cell Carcinoma (RCC)
MALIGNANT epithelial (PCT) tumor of kidney tubules Epi: - older men (3M:F) - 70% of renal carcinoma - occur in smokers (sporadic) Gross: well-circumscribed but irregular yellow mass protruding from cortex Histology: "clear cell" filled with lipids/glycogen Clinical: - triad: hematuria, palpable mass, flank pain - fever, weight loss - paraneoplastic syndrome (EPO --> polycythemia, renin --> HTN, PTHrp --> hypercalcemia, ACTH --> Cushings) - can lead to left-sided varicocele after spread to left renal vein (hematogenous spread although epithelial - spreads to lung/bone) - can spread to retroperitoneal lymph nodes Pathogenesis: - loss of VHL (3 letters) tumor suppressor gene on chr 3 in RCC (3 letters) --> IGF (3 letters) --> HIF (3 letters) --> VEGF/PDGF - sporadic: unilateral, upper pole, older males, cigarette smoke - inherited: VHL disease, younger, bilateral, w/ hemangioblastoma of cerebellum Grading: 1- confined to kidney 2 - invades the peri-renal fat 3 - involves the lymph nodes or renal vein 4 - distant metastases Prognosis: 5-yr survival is 70% for grades 1-3
Thrombotic Thrombocytopenic Purpura (TTP)
Inherited defect due to Ab vs. ADAMTS13 (a plasma metalloprotease that cleaves/degrades vWF) --> micro thrombi formation (--> low platelets) and hemolytic anemia (RBCs "shear" over thrombi) Clinical: - thrombocytopenia (formation of thrombi) - purpura - hemolytic anemia (shearing of RBCs) - CNS involvement (unlike HUS, which involves kidney more)
Papillary Renal Carcinoma
10-15% of renal carcinomas (after 70% clear cell) Histology: - psammoma bodies - foamy macrophages - hemorrhage Genetics: - trisomies of chr7/17 - loss of Y chr
Reversible cellular injury
Cellular swelling (hallmark) due to increase intracellular Na+ and following water - Loss of microvilli (like blowing up a latex glove and loss fingers) - Membrane blebbing Dissociation of ribosomes from RER decrease in protein synthesis
Caseous necrosis
Combination of coagulative/liquefactive necrosis...granulomatous inflammation in TB/fungal infections
Autophagy
- Intracellular - Lysosome-mediated - Ovoid inclusion bodies - Ubiquitination
Hemolytic-Uremic Syndrome (HUS)
Consumption of undercooked beef w/ EHEC O157:H7 w/ Shiga toxin --> endothelial damage --> micro thrombi formation (--> low platelets) and hemolytic anemia (RBCs "shear" over thrombi) Clinical: - acute diarrhea (bacterial infection) - thrombocytopenia (formation of thrombi) - hemolytic anemia (shearing of RBCs) - ARF (thrombi and vasoconstriction in glomerular capillaries --> hypoperfusion)
Steatosis (fatty change)
Accumulation of TG Can be due to: - starvation - alcohol (most common) - CCl4 poisoning (dry cleaning)
Atrophy
Decrease in cell SIZE (ubiquitination of cytoskeleton and autophagy of organelles) and NUMBER (apoptosis) due to decrease in stress/hormones/nutrients
Hypoxia
Hypoxia = low oxygen supply to tissue (impair OxPhos leading to low ATP/energy) and causes cellular injury Can be due to: - ischemia (decreased blood to tissue - atherosclerosis, shock, decreased venous drainage) - hypoxemia (PaO2<60 - high altitude, hypoventilation, alveolar diffusion defect, V/Q mismatch) - low O2 binding capacity (anemia=low Hb, CO poisoning=normal Hb but competitive binding, methmoglobinemia=oxidant stress on Fe-->Fe3+ within Hb leads to inability to bind O2)
Transitional (urothelial) Cell Carcinoma
Malignant tumor from urothelial lining (epithelial hyperplasia precedes) of renal pelvis/ureter/bladder/urethra Most common type (90%), most often in bladder, most often w/ older adults most often papillary Risk factors (Pee SAC): - Phenacetin - Smoke (polycyclic aromatic hydrocarbons, naphthylamine) - Azo/Aniline dyes (hairdresser) - Cyclophosphamide Clinical: painless hematuria
Nephrolithiasis (kidney stones)
Precipitation of urinary solute as a stone (from low urine or high solute leading to a high solute concentration) Clinical: - colicky pain - hematuria - unilateral flank tenderness - stone is usually passed (surgery if not) 4 types: - Calcium (80%): most often hypercalcuria w/ normocalcemia (idiopathic), can be ethylene glycol, vitamin C - Ammonium magnesium phosphate (15%): infection w/ urease +ve (Klebsiella, Staph sapro, Proteus), staghorn caliculi - Uric acid (5%): radiolUcent, hot/arid climate, acidic urine w/ low volume, gout or high cell turnover (leukemia) - Cystine (1%): children, AR condition cystinuria
Fibrinoid necrosis
Damage to blood vessel wall due to leaking of proteins into wall bright pink staining - Malignant HTN Vasculitis
Pyelonephritis
UTI of the KIDNEY...usually due to ascending infection (vesicoureteral reflux, catheter, obstruction predisposes) Clinical: fever + leukocytosis (systemic signs) w/ flank pain, WBC casts (intrarenal), and cystitis signs (dysuria, urgency/freq) Etiology: - E Coli (90%) - Enterococcus faecalis - Klebsiella
Oncosis
Cellular swelling
Apoptosis
Energy-dependent (uses ATP) programmed cell death of single/small groups of cells...no inflammation Process/features: - eosinophillic cytoplasm - cell shrinks - nucleus condenses/fragments - apoptotic bodies fall (like leaves from a tree) and are phagocytzed Mediated by caspases (caspase 3 is central) --> proteases (cytoskeleton) and endonucleases (DNA --> specific-sized fragments) Intrinsic (mitochondrial) pathway (caspase 9): bcl-2 (holds cyt c) inactivation --> cyt c leakage --> apoptosome --> apoptosis Extrinsic (receptor-ligand) pathway (caspase 8): FasL binds Fas receptor, TNF and TNF-R CD8 T-cell pathway: perforins (create pores) and granzymes (activate caspases)
Renal Papillary Necrosis
Necrosis of renal papillae that presents with gross hematuria and flank pain...can come from acute interstitial nephritis Causes included (SAAD): - Sickle cell - Analgesics (chronic NSAIDs) - Acute pyelonephritis - DM
Hypertrophy vs. hyperplasia
-trophy: increase in cell size (NOT #) due to increase in stress/work -plasia: increase in cell # due to increase in stress/work Normally occur together, EXCEPT heart/brain/nerve (cannot make new cells, so only undergo hypertrophy) Hyperplasia CAN --> dysplasia --> cancer (ex. endometrium, NOT BPH)
Section 9
(50 cards)
Repair in wound healing
Damaged tissue is replaced with a fibrous scar because it cannot be regenerated (either permanent tissue OR if stem cells are lost) - myocardium (MI) - DEEP skin cuts (stem cells in basal layer are lost)
Neoplasia
Unregulated, irreversible, monoclonal (from one progenitor cell - only one isoform is found) Can be benign (local) or malignant (invasion with potential for metastases)
Cancer screening
Goal of screening is to find dysplastic change before cancer arises OR cancer before symptoms Common screening: - pap smear (find CIN - cervical intraepithelial neoplasia) - mammography (find ductal carcinoma in situ - prior to invasion) - PSA/DRE (grows in posterior, find prostate cancer before spread) - hemoccult/colonoscopy (find benign adenomas/polyps and remove)
Type I HSR Examples (2)
Allergic/atopic (rhinitis, eczema, asthma, hives/urticaria) Anaphylaxis (sytemic)
Mechanism of repair in wound healing
1) Granulation tissue - consist of fibroblast (deposit type III collagen), capillaries (by VEGF, provide nutrients), myofibroblasts (contract wound) 2) Scar formation - collagenase removes type III collagen (requires zinc) - type I collagen replaces
Tumor nomenclature
Epithelial cell lineage: - glands: adenoma vs. adenocarcinoma - branching projection: papilloma vs. papillary carcinoma - polyps (non-branching) - cystic Mesenchymal lineage: - fat: lipoma vs. liposarcoma - bone: osteoma vs. osteosarcoma - vessel/endothelial: hemangioma vs. angiosarcoma - smooth muscle: leiomyoma vs. leiomyosarcoma - skeletal muscle: rhabdomyoma vs. rhabdomyosarcoma - CT: fibroma vs. fibrosarcoma - cartilage: chondroma vs. chondrosarcoma Lymphocyte (only malignant): lymphoma/leukemia Melanocyte: nevus (mole) vs. melanoma Blastoma: tumor of progenitor cells Teratoma: tumor of germ cells
Mixed connective tissue disease
Mixed features of SLE, systemic sclerosis, polymyositis Have an ANA and autoantibody vs. U1 ribonucleoprotein
Type IV HSR Pathogenesis
Delayed or cell-mediated (T-cell response) - NO antibodies - sensitized T-cells encounter antigen and release cytokines leading to macrophage activation - can lead to granuloma formation - cytotoxic T-cells also involved
Tumor markers
NOT used for diagnosis (because lack of sensitivity/specificity), but is used to monitor recurrence and response to treatment. Tissue biopsy is REQUIRED for diagnosis PSA: prostate, BPH Chromogranin: neuroendocrine CA 125: ovarian CEA: colorectal/pancreatic ACTH: small cell of lung AFP (transiently elevated in pregnancy): hepatocellular Monoclonal IgG: multiple myeloma Calcitonin: medullary thyroid
Benign vs. Malignant tumors
Benign: - slow-growing - well circumscribed and distinct - mobile - organized - small, uniform nuclei Malignant: - rapid-growing and invasive - poorly circumscribed - fixed - disorganized - large, dark, polymorphic nuclei
Sjogren's Overview and Pathogenesis
Often seen in older women Autoimmune destruction of lacrimal/salivary glands Lymphocyte-mediated (Type 4 HSR) Often seen along with rheumatoid arthritis (may have RF present, whether coupled with RA or not)
Polymyositis/Dermatomyositis
Autoimmune rxn against skeletal muscles (proximal/shoulders weakness and degeneration) No skin rash = polymyositis, with CD8 T-cells With skin rash (scaling on knuckles/knees, heliotrope periorbital) = dermatomyositis, with CD4 T-cells ANA (specifically anti-Jo1 vs. histidyl tRNA synthetase)
Carcinogenesis (oncogenes)
Proto-oncogenes are necessary for normal cell growth and differentiation: - growth factors (ligands that induce growth, ex. PDGF) - growth factor receptors (ex. HER2) - signal transducer (ex. ras) - cell cycle regulators (ex. cyclin, CDK) Mutations --> oncogenes --> unregulated/abnormal growth
Scleroderma Clinical Features (w/ Ab types)
Limited CREST (anti-centromere Ab): rarely effects organs Calcinosis, anti-Centromere Raynaud's Phenomenon Esophageal dysmotitlity Sclerodactyly (skin of hands tight) Telangiectasias Diffuse (antiScl70 vs. DNA topoisomerase I): earlier visceral involvement - GI tract (esophagus dysmotility) - Lung (pulmonary fibrosis) - Kidney (scleroderma renal crisis) - Heart (myocardial fibrosis)
Type I HSR Pathogenesis
Allergic, Atopic, Anaphylactic Antigen (dander, mold, drug etc.) cross-links IgE on mast cells (on SECOND exposure) leading to: first phase (immediate, minutes): release of preformed vasoactive amines (ex. histamine) from mast cells delayed phase (hours): release of leukotrienes and recruitment of inflammatory cells...can be due to eosinophils
Leukocyte Adhesion Deficiency (LAD)
Clinical characteristics: delayed separation of umbilical cord (dead cells don't get cleared), increased circulating neutrophils (don't get into tissue), recurrent infections with no pus Pathophysiology: lack of CD-18 integrins on neutrophils so that they can't bind ICAM/VCAM on endothelium during acute inflammation
Epidemiology of Cancer
Cancer is 2nd leading cause of death in adults/children Adults: CVD, CANCER, chronic respiratory Children: Accidents, CANCER, congenital Incidence: skin, breast/prostate, lung, colorectal Death: lung, breast/prostate, colorectal Lung has HIGH mortality (no screening mechanism and presents late in course - 15% 5-yr survival)
Xeroderma pigmentosum
UVB damage causes pyrimidine dimers, which is normally repaired by restriction endonucleases In XP, the RE are mutated --> permanent DNA damage
Carcinogens (chemicals)
Aflatoxins (aspergillus - stored grains) --> hepatocellular carcinoma Alcohol --> oropharynx/upper esophagus, pancreatic carcinoma, hepatocellular carcinoma Arsenic (in cig smoke) --> skin, lung, angiosarcoma of liver Asbestos --> lung cancer (most likely), mesothelia Cigarettes (polycylic hydrocarbons) --> oropharynx/esophagus, lung, kidney, bladder Nitrosamines (smoked food, Japan) --> stomach carcinoma Vinyl chloride (PVC workers) --> angiosarcoma of liver
Autoantibodies in Sjogren's (3)
ANA: sensitive More specific (against ribonucleoproteins) Anti-SSA (Ro) - can cross placenta --> neonatal lupus and congenital heart block Anti-SSB (La)
Regeneration in wound celling
Damaged tissue can be replaced if stem cells are available to replace it: Labile tissue - stem cells are continuously dividing (ex. skin, bone marrow, bowel) Stable tissue - stem cells are quiescent (G0) but can reenter division (ex. liver) Permanent tissue - no regeneration possible (ex. brain, heart, nerves)
Two-hit hypothesis
Two copies of a gene must be knocked out before symptomatic evidence/tumor formation. ex. rb - if germline mutation then only 1 more hit is needed --> common-ish bilateral retinoblastoma - if sporadic mutations then 2 unlikely hits are needed on the SAME cell --> rare unilateral retinoblastoma
Chronic Granulomatous Disease (CGD)
Clinical characteristics: increased infections with catalase +ve species (s.aureus, pseudomonas cepacia) Pathophysiology: AR or X-linked, NADPH oxidase defect (O2 --> superoxide) Diagnosis: NBT test...remains colorless when O2 CANNOT be converted to superoxide
Chediak-Higashi Syndrome
Clinical Characteristics (BALING): - Bleeding (defective hemostasis) - Albinism (cannot transport melanin) - Leukopenia (difficulty dividing neutrophils) - Infections (cannot destroy pathogens) - Neuropathy (peripheral) - Granules Pathophysiology: AR MT defect that impairs protein/lysosome trafficking --> cannot destroy pathogens or traffic proteins
Type IV HSR Examples (5)
Contact dermatitis (poision ivy, nickel) TB/PPD Sarcoidosis, Berylosis Type I DM Transplant rejection
Drug-induced SLE (Drugs-3/Ab)
Caused by: Hydralazine, Procainamide, Isoniazid Antihistone-Ab Removal of drugs --> remission
Autoantibodies in SLE (4)
ANA: sensitive Anti-dsDNA OR anti-Smith: specific Anti-phospholipid: leads to antiphospholipid syndrome (hypercoagulable state and thrombosis formation...FP syphillis - anticardiolipin, and elevated PTT - anticoagulant)
Carcinogenesis
Cancer requires initiation (DNA damage by caused by carcinogen) AND promotion (continued proliferation and additional mutations)
Scleroderma Overview and Pathogenesis
Presents in middle-aged females Sclerosis of skin, small blood vessels, and visceral organs (fibroblast activation leads to collagen deposition in tissues)
Systemic Lupus Erythematous (SLE) Overview and Pathogenesis
Most commonly seen in middle-aged women of AA/Hispanic/Asian descent Characterized by flare-ups and remissions Apoptosis of cells (in UV damage/sunlight) --> released DNA --> ANA rxn Ab-Ag complexes deposit systemically (Type 3 HSR) --> complement activation/destruction Complement (C1q/C4/C2 - from early classical) deficiency predisposes...lower ability to opsonize Ag-Ab complexes >90% 5-year survival (with biggest killers being renal failure or infection)
Kinetics of tumor growth
Symptoms normally arise after 30 divisions (2^30 cells = 10^9), which is late in course. Only 10 more divisions, 10^12 cells, are compatible with life Tumor growth is NOT associated with a shortened cell cycle, but rather an imbalance between cell production/loss. Also, more cells might be in the proliferative state. Chemotherapy works BEST on fast growing tumors because it affects cells that are actively proliferating
Chronic inflammation
Compared to acute inflammation, it is delayed but more specific. Characterized by lymphocytes (mononuclear) and plasma cells (eccentric nuclei) in tissues Most often seen in: - persistent infections - viruses/fungi/parasites - autoimmune disease - cancer CD4 T-cells: - 1st signal: recognized extracellular antigen on MHC2 on APCs - 2nd signal: activation by B7 onto CD28 --> TH1 (IL-2, IFN-g - cellular) --> TH2 (IL-4, IL5, IL-10 - humoral) CD8 T-cells: - 1st signal: recognize intracellular antigen on MHC1 on all cells - 2nd signal: IL-2 from TH1 CD4 --> killing (1. perforins and granzymes; and 2. express FasL to Fas-R to activate apoptosis) B-cells: activate in 2 ways... - antigen binds surface IgM/IgD - present extracellular antigen to T-cell and CD40-CD40L activation --> IL4/5 --> class-switching --> plasma cell proliferation
Tumor progression
Although tumor origin is monoclonal, the longer a tumor grows, the more subtypes of cells will be evident --> heterogeneity. Subtypes with survival advantage will live longer.
Type III HSR Pathogenesis
Immune Complex deposition in tissues - Ag-Ab binding leading to complement activation and inflammation
Clinical Features of SLE (7)
Non-specific: fever, weight loss, fatigue, lymphadenopathy More specific: (CRASHER) CNS (psychosis/seizures) Rashes: "malar" butterfly, "discoid"...both after sunlight Arthritis Serositis (pleuritis/pericarditis) Hematologic: Ab vs. blood cells (type 2 HSR) Endocarditis (Libman-Sacks - vegetations on both sides of mitral valves) Renal damage (nephrotic/nephritic)
Granulomatous inflammation
Characterized by epitheloid histiocytes (macrophage with abundant pink cytoplasm) surrounded by giant cells and rim of lymphocytes Can be caseating (TB/fungi) or noncaseating (sarcoid, beryllium, cat scratch, crohn) Pathophysiology: macrophages present antigen to CD4 T-cells --> macrophage secretes IL-12 --> TH1 upregulation --> TH1 secrete IFN-g --> macrophages go to epitheloid histiocytes/giant cells
Carcinogens (microbes)
EBV --> nasopharyngeal carcinoma (chinese/african), Burkitt's lymphoma, Hodgkin's lyphoma HHV-8 --> Kaposi sarcoma (older eastern european males, AIDS, transplant pts) HBV/HCV --> hepatocellular carcinoma HPV 16/18 --> vulva/vagina/anus/cervix H. pylori --> gastric/duodenal adenocarcinoma HTLV-1 --> T-cell leukemia/lymphoma (Japan) Liver fluke (chonorchis sinensis) --> cholangiocarcinoma Schistoma haematobium --> bladder cancer
Wound healing
Begins when inflammation begins and occurs via regeneration (only in labile/stable tissues with stem/quiescent cells) and/or repair (when stem cells are not/never present)
Tumor suppressors (2)
p53: regulates progression from G1-->S - if damage, calls DNA repair - if damage irreparable --> BAX --> disrupt bcl-2 (normally stabilizes mitochondrial membrane) --> cyt c leakage from mitochondrial membrane --> apoptosis ...Li-Fraumeni = germline p53 mutation Rb: regulates progression from G1-->S - "holds" E2F until it is phosphorylated by CDK4 --> release and normal progression - mutation leads to "free" E2F and uncontrolled growth
Type III HSR Examples (3)
SLE, Arthus rxn, serum sickness
Neutrophil attractants
IL-8, LTB4, C5a, and bacterial products
Type II HSR Pathogenesis (3) and Examples (3, 3, 2)
Cytotoxic (via antibody/complement binding) destruction via: - opsonization (Ab or C3b) --> phagocytosis (hemolytic disease or newborn, transfusion rxns, autoimmune hemolytic anemia) - antibody binding to basement membrane or ECM --> Fc-mediated inflammation (good pastures - antiglomerularBM-ab, vasculitis-ANCA, bullous pemphigoid - blisters between epiderm/derm) - antibody mediated dysfunction (stimulation - graves TSH, inhibition - MG ACh)
Oncogenes (4 types)
Growth factors: PDGFB (astrocytoma) Growth factor receptors: - HER2/neu (breast) - RET (MEN2A/B, medullary thyroid) - KIT (gastrointestinal stromal) Signal transducers: - ras (mutated ras loses GTPase activity leading to excess signal to nucleus, MANY cancers) - ABL (tyrosine kinase in 9:22 philadelphia chr translocation) --> CML Transcription factors: c-myc (burkitts lymphoma) n-myc (neuroblastoma) l-myc (lung, small cell)
Primary vs. secondary intention
Primary: bring wound edges together (ex. suture) Secondary: edges NOT approximated...granulation tissue fills and myofibroblasts contract wound to make it smaller
Reasons for delayed wound healing
- Infection (continues to call in neutrophils) - Vit C (hydroxylation of collagen), copper (lysyl oxidase), or zinc (collagenase) deficiency
Tumor invasion and spread
Invasion: - down regulation of CAM, E-cadherin --> dissociation of cells in epithelium - attach to laminin on BM - destroy BM collagen type IV with collagenase - attach to fibronectin in ECM - enter vasculature (sarcomas - mesenchyme) or lymphatics (carcinomas - epithelial) and SPREAD - hide from immune system by aggregating with platelets
Carcinogens (radiation)
Ionizing...OH free radicals (nuclear reactor, radiotherapy, Chernobyl) --> AML, CML, papillary carcinoma of thyroid Non-ionizing...pyrimidine dimer (sunlight - UVB) --> melanoma
Neutrophils in acute inflammation
Peak @ 24 hours after inflammation begins 1) Margination (move to edge) 2) Rolling - hit the selectin "speed bump" that bind sialyl Lewis X on neutrophils - P-selectin (upregulated by histamine) from Weibel-Palade body - E-selection (upregulated by TNF/IL-1) 3) Adhesion - CAMs on endothelium upregulated by TNF/IL-1 - Integrins (CD18 - deficient in LAD) upregulated on neutrophils by C5a/LTB4 4) Transmigration/Diapedesis - due to chemoattractants IL-8, C5a, LTB4 5) Phagocytosis - consume pathogens/necrotic tissue using pseudopods - enhanced by opsonins (IgG/C3b) 6) Destruction of phagocytosed material - O2-dependent killing via HOCl (bleach) created in oxidative burst - O2-independent killing via lysozyme/MBP (eosinophils) 7) Resolution - neutrophils die by apoptosis --> pus
Sjogren's Clinical Features
Common: dry eyes, dry mouth, inflammatory joint pain Proof of Sjogren's: Lymphocytic sialadenitis (lymphocytic infiltrate in the salivary gland in the lips) Increased risk: dental caries (lack of saliva), B-cell lymphoma (unilateral parotid enlargement)
Macrophages in acute inflammation
Peak @ 2-3 days after inflammation begins 1-4) Margination, Rolling, Adhesion, Diapedesis (same as neutrophil) 5) Phagocytosis - O2-independent killing (lysozyme) 6) MANAGE inflammation (4 options) - resolution and healing (anti-inflammatory cytokines, IL-10 + TGF-b) - continue acute inflammation (IL-8 call new neutrophils) - abscess formation ("wall off" the inflammation by fibrosis) - chronic inflammation (present to CD4 T)
Section 10
(50 cards)
Primary hemostasis
Formation of a weak PLATELET PLUG (aggregation of platelets) after endothelium vessel wall damage 1) Transient vasoconstriction of damaged vessels ("knee-jerk" reflex) - mediated by neural stimulation - endothelin released (and mediates) 2) Platelet adhesion - vWF (from Weibel-Palade body in endothelial cell AND alpha-granules of platelets) binds exposed endothelium - platelets bind vWF using GPIb receptor 3) Platelet degranulation - ADP (induces GPIIb/IIIa receptor on platelets - necessary for aggregation) - TXA2, a COX product (promotes platelet aggregation - chemoattractant) 4) Platelet aggregation - fibrinogen is the linker molecule that binds GPIIb/IIIa receptors - results in a WEAK platelet plug
Buerger Disease
Pathology: necrotizing vasculitis of digits due to SMOKING Clinical features: gangrene of fingers/toes, raynaud phenomenon
Antithrombotic properties of endothelium
The endothelium has antithrombotic effects and releases factors including: Anticoagulant: - Heparin-like molecules (enhance Antithrombin III --> bind and inhibit thrombin) - Thrombomodulin (modulates thrombin --> activates protein C/S --> inactivated clotting factors V/VIII) Antiplatelet: - ADPhosphaTASE (cleaves ADP) - NO (vasodilation) - PGI2 (prostacyclin, inhibits aggregation) Fibrinolytic: - tPA (activates plaminogen --> plasmin)
Consequences of liver failure of secondary hemostasis
- Decreased production of coagulation factors AND - Decreased activation of epoxide reductase (that recycles vitamin K) --> abnormal secondary hemostasis
Type I DM
Clinical features: weight loss, hyperglycemia, polyphagia, polyuria, polydipsia, glycosuria Pathophysiology: insulin deficiency due to autoimmune destruction by T-cells (aberrant MHC II expression by beta cells) with inflammation of islets Typical patient: thin child Genetics: associated with DR3/DR4, 50% concordance Treatment: life-long insulin *risk for diabetic ketoacidosis
Thrombosis
PATHOLOGIC formation of blood clot (thrombus) in artery or vein (DVT most common) that develop when risk factors are present (hyper coagulable, endothelium damage, disrupted flow) Thrombus (vs. postmortem clot) - lines of Zahn (layers of RBC and platelet/fibrin) - attachment to vessel wall - white head (exposed to flow) and red tail
Hemostasis vs. Thrombosis
Hemostasis: physiologic (healthy) arrest of hemorrhage in response to vascular injury Thrombosis: pathologic (unhealthy) formation of a blood clot with healthy vessels
Type II DM (more common - 90%)
Clinical features, polyuria, polydipsia, polyphagia, and hyperglycemia Pathophysiology: insulin resistance due to decreased number of insulin receptors...followed by insulin deficiency (later) as beta cells get exhausted AND amyloid deposition (amylin secreted with insulin) Typical patient: middle-aged, obese adult Genetics: strong concordance (90%) *risk for hyperosmolar non-ketotic coma (high glucose leads to osmotic diuresis leading to dehydration/hypotension/coma)
Non-enzymatic glycosylation as a sequela of DM
- NEG of large/medium vessel basement membrane --> advanced glycosylation end products (AGEs) --> cross-link plasma protein --> artherosclerosis --> CAD --> peripheral vascular disease and amputation NEG of small vessel (arterioles) basement membrane causing hyaline arteriolosclerosis --> glomerulosclerosis (preferential on efferent arteriole --> hyperfiltration) --> retinal hemorrhage NEG of Hb --> HbA1C
Kawasaki disease
Clinical features: rash on palms/soles, MI (preferential to coronary arteries), fever, lymphadenopathy Classic patient: <4yr old asian child Treatment: aspirin (inhibit platelet aggregation)...NOT for virus infection due to worry of Reyes
Hemolytic Uremic Syndrome (HUS)
Pathophysiology: endothelium damage (from infections - EHEC - O157:H7) --> platelet micro thrombi --> microangiopathic hemolytic anemia EHEC from undercooked beef (industrialized countries)...the "verotoxin" damages endothelium Clinical findings: skin/mucosal bleeding (platelets used up), microangiopathic anemia (shearing across micro thrombi), fever, renal insufficiency (uremic - often occurs in small vessels of kidney)
Glanzmann thrombasthenia
Genetic GPIIb/IIIa deficiency (platelet aggregation is impaired) There are THREE As (IIIa) in glAnzmAnn thrombAsthenia
Vitamin K Deficiency
Vitamin K is made by colonic bacteria, activated/recycled in liver by epoxide reductase (inhibited by warfarin/coumadin) and is responsible for the gamma-carboxylation of factors II, VII, IX, X, C/S Vitamin K deficiency (and secondary hemostasis clinical findings) results from: - warfarin/coumadin therapy - newborns (no bacteria in GI tract to make Vit K) - fat malabsorption (since it is a fat soluble vitamin) - antibiotic therapy (disrupts GI bacteria that make it)
Hemophilia A
Genetics: X-linked recessive deficiency in Factor VIII (AAte) Clinical findings: deep tissue and post surgical bleeding Lab findings: increased PTT (intrinsic pathway), normal PT, decreased factor VIII Treatment: synthetic factor VII
Fibrinolysis
tPA (tissue plasminogen activator) activates plasminogen --> plasmin --> plasmin cleaves fibrin/fibrinogen AND destroys coagulation factors alpha-2-antiplasmin (inactivates plasmin) Disorder mostly associated with activation (streptokinase/urokinase activate plasminogen) even when it is not needed (not stable clots to cleave) --> FIBRINOGEN (not fibrin) cleaving --> NO D-dimer...but still raised PT/PTT
Coagulation Factor Inhibitor
Autoantibody against coagulation factors (auto-FVIII is most common) --> similar findings of hemophilia EXCEPT: when treat with plasma/factor infusion, PTT does not correct (inhibitor binds synthetic factor as well)
Weg(C)ener's Granulomatosis
Pathology: small-vessel necrotizing granulomatous vasculitis involving nasopharynx/lung/kidneys (C-shape) Clinical features: sinusitis, nasopharyngeal ulceration, hemoptysis, hematuria, C-ANCA Treatment: Cyclophosphamide
Hyperemia vs. Congestion
Active hyperemia is due to arteriolar dilation (ex. when exercising to increase blood flow to skeletal muscles) Passive hyperemia (congestion) - LHF --> chronic congestion of lung --> pulmonary edema (with "HF cells" laden with hemosiderin) - RHF --> chronic congestion of liver --> "nutmeg liver"
Grading/Staging of Cancer
Grade (less important): degree of differentiation or similarity to host tissue, 1= good, well diff...4 = bad, poor diff (anaplastic) Stage (more important for prognosis): T = Tumor size (or depth) N = spread to Nodes M = Metastasis...most important
Osmotic damage as a sequela of DM
Glucose enters cell --> sorbitol (conversion by aldose reductase) --> osmotic damage (swelling) When glucose enters: - Schwann cells --> neuropathy - pericytes on retinal bv --> aneurysms --> blindness - lens --> cataracts
Systemic Hypertension
BP >140/90 Primary (95%): unknown etiology, risk factors include age, race (AA), obesity, stress, lack of exercise, salt Secondary (5%): identifiable cause - renal artery stenosis (--> increased renin --> RAAS --> increased TPR and fluid retention)...unilateral atrophy of kidney seen Benign: mild/moderate, no clinical signs (although chronic changes) --> hyaline arteriolosclerosis Malignant: BP >180/120 --> end-organ damage (renal failure, headache, papilledema) --> hyperplastic arteriolosclerosis
Churg-Strauss Syndrome
Pathology: Necrotizing granulomatous vasculitis with EOSINOPHILS involving lungs/heart Clinical features: asthma, P-ANCA, IgE increase
Lipoprotein formulas
Total C = VLDL-C + HDL-C + LDL-C HDL-C = measured directly VLDL-C = TG/5 LDL-C = Total C - (HDL-C + VLDL-C)
Arteriolosclerosis
Narrowing of small arterioles Hyaline arteriolosclerosis - proteins leak into walls --> vascular thickening --> pink hyaline - caused by benign HTN (forcing protein into wall) and DM (NEG of BM leading to leaky wall) - leads to end-organ ischemia (classically arterioloNEPHROsclerosis) Hyperplastic arteriolosclerosis - thickening of small blood vessels due to SM hyperplasia ("onion-skin" wall) - caused by MALIGNANT HTN - leads to fibrinoid necrosis (hemorrhage) and "flea-bitten" acute renal failure
Temporal (giant cell) arteritis
Pathology: large-vessel granulomatous (giant-cell) arteritis of branches of carotid artery (often temporal) leading to intimal fibrosis Clinical signs: headache, bulging temporal artery, visual disturbances (ophthalmic artery), jaw claudication, elevated ESR Stereotypical patient: older woman Treatment: corticosteroids (to avoid blindness)
Causes of edema
- Increased capillary/venous hydrostatic pressure (venous occlusion, CHF) - Reduced oncotic pressure of capillaries (liver failure, decreased albumin synthesis) - Lymphatic obstruction (cancer, inflammation, resection, filariasis) - Increased osmotic pressure of ISF (sodium accumulation)
Immune Thrombocytopenic Purpura (ITP)
Pathophysiology: autoimmune IgG against platelet antigens --> eaten by splenic macrophages --> thrombocytopenia (low platelets) Acute (after a viral infection) vs. Chronic (long-term disease that can be associated with other autoimmune disorder ex. SLE) Lab findings: low platelets, normal PT/PTT (coagulation factors not affected), increased megakaryocytes (trying to produce more platelets) Treatment: corticosteroids, splenectomy (eliminates SOURCE of Ab and SITE of DESTRUCTION)
Secondary hemostasis
Stabilization of platelet plug via the COAGULATION CASCADE Coagulation cascade generates thrombin --> thrombin cross-links fibrinogen to fibrin --> stable thrombus
Hemophilia B
Genetics: Factor IX (B after A, 9 after 8) deficiency Same clinic/lab findings and treatment as hemophilia A (except factor IX is low)
Microscopic Polyangitis
Pathology: small-vessel necrotizing vasculitis involving lung/kidneys (NOT nasopharynx) Clinical features: hemoptysis, hematuria, P-ANCA
Diabetic ketoacidosis
Excessive serum ketones (from TG breakdown --> FFA --> ketoacids) Metabolic acidosis (w/ anion gap), hyperglycemia, hyperkalemia Clinical features: hyperventilation (to blow off acid), dehydration, nausea, vomiting, mental status change, fruity breath
Clinical features of cancer
Primary or metastatic tumors can destroy of compress host tissue leading to certain local factors: - obstruction of ducts - irritate surfaces - lead to inflammation - disrupt hormone secretion Systemic (distant) factors called paraneoplastic syndrome, for example: - ectopic hormone production - skin changes - erythropoietin production --> polycythemia - hypercalcemia from bone resorption
Henoch-Schonlein Purpura
Pathology: vasculitis due to IgA immune complex deposition...in children Clinical features: palpable purpura on buttocks and legs, GI bleeding, hematuria children
Disseminated Intravascular Coagulation
PATHOLOGIC activation of the coagulation cascade --> blocking of small vessels (ischemia and infarction) --> consumption of platelets/factors --> bleeding (IV sites, mucosal surfaces, body orifices) Secondary to another disease process: - obstetric complication (amniotic fluid with tissue thromboplastin leak into maternal circulation) - sepsis (EColi and Nmeningiditis) --> endotoxin activation of coagulation - adenocarcinoma (mucus activates) - acute promyelocytic leukemia (primary granules activate) - rattlesnake bite (venom activates) Lab findings: thrombocytopenia, PT/PTT up, decreased fibrinogen (consumed), microangiopathic hemolytic anemia, elevated D-dimer (fibrinolysis products)
Atherosclerosis
Intimal plaque (with necrotic lipid core - cholesterol clefts) on wall of medium/large sized vessels Risk factors: - modifiable: HTN, hypercholesterol, smoking, DM - non-modifiable: age (older), gender (males, post-menopause female), genetics, infection (chlamydia pneumoniae) Pathogenesis: lipid enters intima (from LDL) --> oxidize --> picked up by macrophages/SM cells ("foam cells") --> inflammation and healing (fibromuscular cap) Complications: - stenosis (impaired flow and ischemia - peripheral vascular disease, angina, ischemic bowel) - plaque rupture with thrombosis (MI, stroke) - plaque rupture with embolus - weakening of vessel wall --> aneurysm
Takayasu's arteritis
Pathology: large-vesel granulomatous arteritis typically involving aortic arch branch points Clinical signs: visual/neuro symptoms, weak or absent pulse in upper extremity ("pulseless disease"), elevated ESR Stereotypical patient: young asian female Treatment: corticosteroids
Pulmonary embolus (PE)
Often due to a DVT thromboembolus NORMALLY SILENT, but can result in: - SOB, pleuritic chest pain - V/Q mismatch due to poor perfusion - Wedge-shaped infarct - Sudden death (saddle embolus)
Reteplase/Alteplase
Synthetic tPA used in fibrinolysis
Disorders of primary hemostasis
Major clinical factors: Mucosal (nose bleed, GI bleed, hematuria etc.) and skin (petechiae, purport, ecchymoses, bruising etc.) bleeding Major lab findings: platelet count (low), bleeding time (high), blood smear (to assess number/shape), bone marrow (to assess progenitor megakaryocytes) Separated by quantity of platelets vs. quality of platelets
Genetics of cancer
Inherited (AD): retinoblastoma, familial adenomatous polyposis, MEN, NF1/2, VHL Inherited (AR): Xeroderma pigmentosum (pyrimidine dimers), ataxia-telangiectasia (dsDNA break) Familial: breast, colon, ovarian
Von Willebrand Disease
AD genetic vWF deficiency (impaired platelet adhesion - primary hemostasis) vWF also STABILIZES FACTOR VII (impaired secondary hemostasis) Clinical findings: skin and mucosal bleeding (primary) AND increased PTT (secondary) Lab tests: abnormal ristocetin assay (vWF function)
Virchow's Triad leading to thrombosis
DISRUPTION OF FLOW: stasis (still) and turbulence (non-laminar) due to: - immobilization (bed rest --> stasis) - arrhythmia (ex. A-fib) - aneurysm (turbulence) ENDOTHELIUM DAMAGE (endothelium is normally protective): - exposed SEC --> platelet adhesion - less production of PGI2 (prostacyclin - inhibits platelet aggregation), NO (vasodilation), tPA (breaks clots), and thrombomodulin (modulates thrombin to activate protein C --> inactivation of factors V/VIII) HYPERCOAGULABLE STATE: - upset balance between procoagulants vs. anticoagulants (inherited/acquired disorders) - protein C/S deficiency (normally inactivated V/VII to turn off) - Factor V Leiden (mutated form won't allow inactivation by C/S) - prothrombin 20210A (mutated --> increased expression --> increased thrombin) - antithrombin III deficiency - OCPs (estrogen increases production of coagulation factors)
Bernard-Soulier syndrome
Genetic GPIb deficiency (platelet adhesion is impaired) Blood smear: mild thrombocytopenia, enlarged platelets (Big Suckers - more immature) Bernard starts with ONE B.
Lab neoplasia
Keratin pearls = squamous cell carcinoma Multiple nodules = metastatic OAT cells (elongated, no cytoplasm) = small cell carcinoma Koiliocytes (dense nuclei and halo) = HPV Desmoplasia (transformation to fibrosis in presence of tumor) = breast cancer Tall columnar cells = colonic adenocarcinoma
Coagulation Cascade
A series of enzymatic conversions where each step proteolytically cleaves an inactive proenzyme into an activated enzyme Each step REQUIRES a phospholipid surface (platelet membrane) and Ca2+ INTrinsic pathway (3 letters, left) - activated by SEC and HMWK - 12, 11, 9, 8 - measure PTT - inhibited by HEP EXtrinsic pathway (2 letters, right) - activated by TT (tissue thromboplastin or tissue factor) - 3, 7 - measure PT - inhibited by W/C (warfarin/coumadin) Common pathway (bottom) - 10, 5, 2 (thrombin), 1 (fibrin) - Factor XIIIa (activated by thrombin) cross-links fibrin
Microangiopathic hemolytic anemia
Pathophysiology: pathologic formation of micro thrombi in small vessels --> "shearing" of RBCs when they pass --> hemolytic anemia and schiztocytes
Endocrine pancreas
Composed of islets of Langerhans with: - beta (inner) cells that secrete insulin - alpha (outer) cells that secrete glucagon
Types of embolism
Thromboembolism (most common - 95%): dislodged thrombus breaks off and travels Atherosclerotic embolus: plaque breaks off and travels (prove by cholesterol clefts) Fat embolus: soft tissue/bone trauma Gas embolism: - decompression sickness from diving (nitrogen precipitation in blood) --> "bends" (joint/muscle pain) and "chokes" (respiratory symptoms) - Caisson disease Amniotic fluid embolus: amniotic fluid enters maternal circulation --> DIC (tissue thromboplastin in AF) with keratin-debris in embolus Paradoxical embolus (from R-->L heart by septal defects): to systemic circulation
Polyarteritis nodosa
Pathology: necrotizing vasculitis involving multiple (poly) medium-sized arteries and "nodes" of fibrosis with micro-aneurysms between nodes Clinical signs: HTN (renal artery involvement), abdominal pain (mesenteric artery involvement), neurologic disturbances, skin lesions, NO LUNG affect Associations: Hep B
Thrombotic thrombocytopenic purpura (TTP)
Pathophysiology: deficiency of ADAMSTS13 (autoantibody against) --> no cleaving of vWF into monomers --> abnormal platelet adhesion to vWF --> platelet micro thrombi --> microangiopathic hemolytic anemia Clinical findings: skin/mucosal bleeding (platelets used up), microangiopathic anemia (shearing across micro thrombi), fever, CNS abnormalities (often occurs in small vessels of CNS) Treatment: plasmapheresis, corticosteroids
Section 11
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