pathology III: intestinal disorders I

this pathology lecture covered diarrhea and enterocolitis.

questions
developmental abnormalities...
1. what is a gastroschisis?
2. what is an omphalocele?
3. what is "heterotopia"?
4. what is meckel's diverticulum?
5. what is the "rule of 2's" in regards to meckel's diverticulum?
6. what is hirschsprung disease?

diarrhea...
7. how is diarrhea defined?
8. what is secretory diarrhea and what are the common triggers? what is the effect of fasting?
9. what is osmotic diarrhea and what are the common triggers? what is the effect of fasting?
10. what is exudative diarrhea? what is the effect of fasting?
11. what are some causes of "deranged motility" diarrhea?

celiac disease...
12. what are the genetic markers related to celiac disease?
13. gliadin is deaminated by...
14. what are some histomorphological features of celiac disease?
15. which sites are the best sites to biopsy in celiac?
16. what are some of the main symptoms of celiac?
17. what are some secondary manifestations of celiac?
18. what are the sequelae for celiac?
19. celiac might be associated with a lower risk for...
20. what are the tests used to diagnose celiacs?

other forms of enterocolitis...
21. tropical sprue may be associated with which microorganisms?
22. what is "whipple disease"?
23. what are some clinical features of whipple disease?
24. what type of diarrhea occurs in lactase deficiency?
25. what causes malabsorption in bacterial overgrowth syndrome?
26. how is bacterial overgrowth syndrome diagnosed?
27. what are the clinical features of bacterial overgrowth syndrome?
28. what is the etiology of enterocolitis due to pancreatic insufficiency?
29. what is the clinical presentation of enterocolitis due to pancreatic insufficiency?

infectious enterocolitis...
30. what is the most common cause of infectious enterocolitis in the world?
31. what is the morphology of the intestinal mucosa in infectious enterocolitis?
32. what are the three mechanisms for pathogenesis of infectious enterocolitis?
33. what is the most common caused of infectious enterocolitis caused by parasites?
34. pseudomembranous enterocolitis is mainly due to which microorganism?
35. what is the morphology of pseudomembranous enterocolitis in the colon?
36. what does the "pseudomembrane" refer to in pseudomembranous enterocolitis?

answers
1. failure of formation of some portion of the intestinal wall.
2. herniation of the abdominal viscera which results from failure of formation of a portion of the abdominal musculature.
3. 1-2 cm nodules of gastric or pancreatic mucosa.
4. a solitary diverticulum up to 6cm in diameter near the IC valve that results from failed involution of the vitelline duct.
5. 2% of the population affected
within 2 feet of IC valve
2 inches long
2 times as common in males
symptomatic by age 2
6. bowel obstruction from a congenital lack of enteric innervation of a portion of the distal intestine which can lead to megacolon.

7. more than 250g of stool/day composed of 70-95% water.
8. secretion of isotonic fluid and over 500g stool/day, commonly caused by v. cholera. can also be triggered by castor oil and other substances. persists with fasting.
9. output of fluid in the intestine due to increased osmotic pressure in the lumen. abated by fasting.
10. diarrhea with purulent, bloody stools; persists with fasting. can be caused by IBD, shigella, salmonella, etc.
11. diabetes
thyrotoxicosis
bacterial overgrowth
irritable bowel disease.

12. HLA DQ2 and DQ8.
13. TTG: tissue trans glutaminase.
14. villous atrophy
leukocytic infiltrates
crypt hyperplasia
15. duodenum, proximal jejunum.
16. diarrhea, flatulence, weight loss, fatigue, constipation.
17. ataxia
B12 deficiency
chronic anemia
dermatitis herpetiformis
osteoporosis
18. increased risk for GI cancers, bone fractures.
19. breast and lung cancer.
20. TTG, AGA, EMA.

21. e. coli, hemophilus.
22. a rare condition that involves tropheryma whippelii found in macrophages in the lamina propria of the SI, with no inflammation.
23. LA
hyperpigmentation
malabsorption
polyarthritis
CNS problems
24. osmotic.
25. bile deconjugation, mucosal damage by bacteria, and increased competition for nutrients.
26. by testing H2 and methane levels in breath.
27. diarrhea, abdominal pain, malabsorption, weight loss
28. cystic fibrosis
chronic pancreatitis
pancreatic adenocarcinoma
29. steatorrhea, gas, bloating, nutrient deficiency.

30. rotavirus.
31. increased mitosis, neutrophilic infiltrate, villi blunting, loss of microvilli.
32. preformed toxin, toxigenic (toxin formed in gut), enteroinvasive.
33. giardia.
34. c. difficile.
35. yellow, plaque like adhesions, looks like bad acne.
36. damaged crypts that have been filled with mucopurulent exudate. 37.

pathology III: esophageal and gastric disorders quiz review

here are some study questions for the quiz on esophageal and gastric disorders.

questions
esophageal disorders...
1. what is the etiology of achalasia?
2. what is the morphology of achalasia?
3. what are the possible sequelae of achalasia?
4. what is DES?
5. what is the morphology of DES?
6. what are the clinical manifestations of DES?
7. what is nutcracker esophagus?
8. what are the clinical manifestations of nutcracker esophagus?
9. what is the etiology of diverticula?
10. what are diverticula called in the proximal vs. distal portion of the esophagus?
11. what are the two types of hiatal hernia? which is most common?
12. what are some complications of hiatal hernias?
13. what is the etiology of mallory weiss syndrome?
14. what is the morphology of mallory weiss?
15. what are the sequelae of mallory weiss?
16. what is the etiology of esophageal varices?
17. what layer of the esophageal wall are esophageal varices?
18. what is a complication of esophageal varices?
19. what is the clinical presentation of esophageal varices?

esophagitis...
20. what are the etiologies for esophagitis that involve external irritation?
21. what are the etiologies for esophagitis that involve decreased LES tone?
22. what are some other etiologies of esophagitis?
23. what are the histomorphological characteristics of esophagitis?
24. what is the morphology of candida esophagitis?

barrett's esophagus, adenocarcinoma...
25. what is the most common etiology of barrett's esophagus?
26. what is the gross morphology of barrett's esophagus?
27. patches that are bigger than what size are at greater risk for developing adenocarcinoma?
28. what is the histomorphology of barrett's esophagus?
29. what is the etiology of esophageal adenocarcinoma?
30. risk of adenocarcinoma might be decreased by...
31. what is the morphology of esophageal adenocarcinoma? where in the esophagus does it affect?

squamous cell carcinoma vs. adenocarcinoma...
32. what is the difference in epidemiological factors in SCC vs. adenocarcinoma?
33. what is the etiology of SCC?
34. what is the difference in location for SCC vs. AC?
35. what is the morphology of SCC?
36. what is the 5 year prognosis for SCC?
37. what is the prognosis for AC?

h. pylori...
38. h. pylori is present in what percentage of chronic gastritis?
39. what are the characteristics of h. pylori that allow it to flourish in the GI system?
40. what are two outcomes of h. pylori infections?
41. what is the morphology of a stomach infected with h. pylori?
42. what are the techniques used to diagnose h. pylori infection?

figure 17-11, robbins 8th ed...
43. what are some "defensive forces" present in normal gastric mucosa?
44. what are injurious forces that can damage gastric mucosa?
45. what are the layers in a gastric ulcer from the lumen to the serosa?

acute gastritis...
46. what are the most common etiologies of acute gastritis?
47. what is the gross morphology of acute gastritis?
48. what kind of exudate is associated with acute gastritis?
49. what are the clinical manifestations of acute gastritis?

chronic gastritis...
50. chronic gastritis is characterized by...
51. what is the incidence of chronic gastritis in the US?
52. what are the etiological mechanisms for chronic gastritis?
53. what are some examples of autoimmune conditions that could result in chronic gastritis?
54. what is the gross morphology of chronic gastritis?
55. what are the clinical manifestations of chronic gastritis?
56. diagnosis of chronic gastritis is made by...
57. what are the complications of chronic gastritis?
58. what is a MALToma?

gastric cancer...
59. which countries does gastric cancer have a particularly high incidence in?
60. which blood type has a high incidence for gastric cancer?
61. which races are particularly affected by gastric cancer?
62. what are some diet related risk factors for gastric cancer?
63. what is the gross morphological difference between a gastric ulcer and gastric cancer?
64. what locations are gastric cancer and a gastric ulcer most prone to affect?
65. what is the histomorphological features of the intestinal and diffuse variants of gastric cancer?
66. both the intestinal and diffuse variants of gastric cancer spread to...
67. describe the stages of pathological progression in gastric cancer.

virchow's node and sister mary joseph nodule...
68. what does virchow's node refer to?
68. what does the sister mary joseph nodule refer to?

answers
1. nerve degeneration causes increased LES tone, decreased LES relaxation, and aperistalsis.
2. progressive dilation, variable wall thickness, loss of myenteric plexus.
3. from increased pressure: SCC, candida esophagitis, diverticula.
4. failure of functional peristalsis: entire esophagus contracts simultaneously.
5. twisted corkscrew shaped esophagus.
6. dysphagia, odynophagia.
7. functional peristalsis but with high amplitude contractions.
8. odynophagia.
9. abnormal motility / spasm.
10. proximal: Zenker. distal: traction.
11. 95% are sliding. 5% paraesophageal.
12. ulceration, hemorrhage, perforation, strangulation, obstruction. [hi. strangle and tear the ham which is perfectly obstructing you]
13. severe alcoholism.
14. longitudinal lacerations, mm to cm in length.
15. inflammatory ulcers, mediastinitis, chronic blood loss.
16. increase in portal hypertension. can be from alcoholic cirrhosis, non-alcoholic cirrhosis, portal vein thrombosis.
17. submucosa.
18. rupture and hemorrhage into into lumen and esophageal wall.
19. asymptomatic until rupture.

20. reflux, radiation, gastric intubation, alcohol, hot fluids, hiatal hernia.
21. hypothryoidism, scleroderma, smoking, obesity, pregnancy.
22. infection / immunosuppression, chemical toxicity, skin disease.
23. eosinophils in the epithelium, basal zone hyperplasia, extended lamina propria papillae.
24. grey/white pseudomembrane loaded with fungal hyphae.

25. long standing GERD.
26. red and velvety patches.
27. 3cm.
28. esophageal epithelium turns into columnar intestinal epithelium with goblet cells.
29. generally occurs in areas of barrett esophagus in patients over 40 years old.
30. h pylori overgrowth.
31. distal esophagus, flat or raised patches that progress to nodular masses that may ulcerate.

32. SCC: older than 50, male, black, iran/china/HK/south africa/PR/eastern europe. AC: older than 40, male, white, US/canada/UK/australia/brazil/netherlands.
33. toxic influences, HPV
34. SCC in mid esophagus, AC in distal esophagus.
35. plaque-like thickenings, tumors that encircle the lumen.
36. superficial: 75%. nodal: 9%.
37. 80%, unless advanced stage: 25%.

38. 90%.
39. motility, urease, protease, adhesion molecules, toxins.
40. antral gastritis / atrophic gastritis, abnormal acid production.
41. intra-epithelial neutrophils, lymphoid aggregates, sub-epithelial plasma cells, hyperplastic / inflammatory polyps.
42. antibody tests, urea breath tests, stool tests, rapid urea test, bacterial culture tests, DNA detection.

43. bicarbonate, mucosal blood supply, mucous secretion, epithelial regeneration.
44. h. pylori
NSAIDs
aspirin
cigarettes
alcohol
hyperacidity
45. necrotic debris
acute inflammation
granulation tissue
scarring (fibrosis)

46. GI irritants, systemic toxins, stress.
47. neutrophils above basement membrane
superficial epithelium erosion
infiltrate and exudate in the lumen
48. fibrin purulent exudate.
49. ulcer like pain
nausea, vomiting
hematemesis

50. chronic mucosal inflammation without erosions that lead to mucosal atrophy and epithelial metaplasia.
51. over 50% in the later decades of life.
52. autoimmune
chronic infection
toxic
mechanical
53. hashimoto, addison's, IDDM.
54. attenuated / flat / reddened mucosa
lymphocytes and plasma cells in lamina propria
metaplasia with intestinal epithelial cells
55. hunger pains
pain at night and with gastric emptying
pain that refers to chest, thoracic spine, left shoulder
56. endoscopy or barium swallow xray.
57. anemia
obstruction
penetration into neighboring organs
perforation
carcinoma in an ulcer [A O P P C] [an outstanding pathologist prevents catastrophe]
58. low grade gastric lymphoma of the MALT tissue.

59. japan and china.
60. type A.
61. african americans, native americans, native hawaiians.
62. food preserved with nitrates
lack of refrigeration
lack of fresh fruits and vegetables
charred foods / polycyclic hydrocarbons
63. gastric ulcer: level margins, smooth base, red/edematous surrounding mucosa.
gastric cancer: raised margins, shaggy/necrotic base, neoplastic tissue extends into surrounding mucosa.
64. GC: lesser curvature, antrum, pylorus. GU: lesser curvature, duodenum.
65. intestinal: broad, cohesive growths, bulky tumors of glandular structures. diffuse variant: signet ring cells, gastric type cells.
66. regional and distant lymph nodes, especially the sentinel node.
67. normal
acute gastritis
chronic gastritis
chronic atrophic gastritis
intestinal metaplasia
dysplasia
gastric adenocarcinoma

68. the sentinel lymph node, the lymph node to which gastric carcinoma often metastasizes.
68. a nodule in the periumbilical region that can be an indicator of metastasis of gastric carcinoma.

pathology III: uterine pathologies part II

this lecture was the 2nd half of the uterine pathology series and focused on uterine neoplasms. the first and most common type are leiomyomas, also known as uterine fibroids. leiomyomas are the most common neoplasms in women and can have multiple manifestations within the uterine wall and yet still be benign and asymptomatic. they are almost always found within the myometrium, appear round, discrete, gray white with smooth muscle "whorling" patterns. histologically, muscle cells appear uniform and have oval nuclei, and there are no mitotic figures present. leiomyomas have a few rare variants, such as benign metastasizing leiomyoma (metastasis via the vascular system, commonly to the lung) and disseminated peritoneal leiomyomatosis (multiple nodules in the peritoneal cavity). clinically, it can present as abnormal bleeding, sudden pain, frequent urination, and decreased fertility.

leiomyosarcomas are a rare malignant type of uterine tumor that generally occurs in the myometrium or the endometrial layer undergoing smooth muscle differentiation. they have two common morphologies: a bulky fleshy mass that invades the uterine wall, or a polypoid mass that projects into the uterine lumen. histologically, they can be distinguished from leiomyomas by the mitotic index and degree of necrosis and atypia.

endometrial carcinoma accounts for 7% of all invasive cancer in women and can manifest either as polypoid masses or diffuse tumors over the entire surface of the endometrium. there are two relatively distinct etiological pathways, the first which has a more favorable prognosis and is associated with prolonged estrogen stimulation and endometrial hyperplasia. it is also characterized by well differentiated cells that mimic normal endometrial glands. the second pathway has much less differentiated cells, a greater capacity to invade neighboring structures, and a poorer prognosis.

adenocarcinoma is another type of endometrial tumor that presents with vaginal bleeding with leukorrhea, enlarged uterus, and abnormal cells on pap smear. 80% of cases are stage 1, meaning confined to the corpus of the uterus. a rare variant is the papillary serous / clear cell adenocarcinoma. if adenocarcinoma also involves malignant differentiation of the stromal layer, it is categorized as carcinosarcoma. malignant stromal differentiation also occurs in adenosarcoma, producing large polypoid masses that are managed with oophorectomy.

questions
leiomyomas...
1. what is another name for leiomyomas and how common are they?
2. what is the average number of tumors that a woman with leiomyomas would have?
3. leiomyomas are almost always found...
4. what is the gross morphological appearance of leiomyomas?
5. what is the histological morphology of leiomyomas?
6. what is "benign metastasizing leiomyoma"?
7. what is "disseminated peritoneal leiomyomatosis"?
8. what is the clinical presentation of a patient with leiomyoma?
9. how common is malignancy of leiomyomas?

leiomyosarcomas...
10. leiomyosarcomas arise from...
11. when do leiomyosarcomas commonly occur?
12. what are the two patterns of morphology seen in leiomyosarcomas?
13. how is a leiomyosarcoma differentiated from a leiomyoma histologically?

carcinoma...
14. what percentage of invasive cancers for women does endometrial carcinoma account for?
15. what are some risk factors for endometrial carcinoma?
16. what is the "first type" of pathogenesis of endometrial carcinoma associated with?
17. describe the characteristics of the first pathogenesis type.
18. describe the level of differentiation and prognosis of the second type.
19. what is the gross morphology of endometrial carcinoma?

classification systems...
20. what is FIGO?
21. what are the characteristics of grade 1 FIGO?
22. what are the characteristics of grade 2 FIGO?
23. what are the characteristics of grade 3 FIGO?
24. which structures are involved in stage 1 endometrial adenocarcinoma?
25. which structures are involved in stage 2 endometrial adenocarcinoma?
26. which structures are involved in stage 3 endometrial adenocarcinoma?

endometrial adenocarcinoma...
27. how does endometrial adenocarcinoma present clinically?
29. diagnosis of endometrial adenocarcinoma is made by...
30. what stage is most endometrial adenocarcinoma in the US?
31. what are some rare variants of endometrial adenocarcinoma?

stromal differentiation tumors...
32. what are carcinosarcomas?
33. what does the stroma differentiate into in carcinosarcomas?
34. what type of differentiation has the worse prognosis in carcinosarcomas?
35. what is the prognosis for carcinosarcomas?
36. what are adenosarcomas?
37. when do adenosarcomas typically occur?
38. how are adenosarcomas typically managed and why?

answers
1. uterine fibroids, the most common neoplasms in women.
2. 6.5.
3. in the myometrium of the corpus of the uterus.
4. discrete, round, gray-white with whorled pattern of smooth muscle bundles.
5. uniform muscle cell size with oval nuclei, no mitotic figures.
6. a rare variant of leiomyoma which involves metastasis of tumor, most commonly to lung.
7. a rare variant of leiomyoma which involves multiple small nodules on the peritoneum.
8. abnormal bleeding
urinary frequency
sudden pain
impaired fertility
[leo bleeding urine sudden fertility] [leo's fertility suddenly stopped when he bled urine]
9. very rare.

10. myometrium or endometrial stroma undergoing smooth muscle differentiation.
11. 40-60yo.
12. bulky fleshy masses that invade the uterine wall and polypoid masses that project into lumen. [fleshy walls and polypy lumen]
13. by mitotic index, necrosis, and degree of atypia.

14. 7%.
15. obesity, hypertension, diabetes, infertility, tamoxifen. [ohdit] [ditoh]
16. prolonged estrogen stimulation and endometrial hyperplasia.
17. tend to be well differentiated, mimics normal endometrial glands, and has a more favorable prognosis.
18. poorly differentiated and poor prognosis.
19. either a polypoid tumor or diffuse tumor that involves entire surface of endometrium.

20. a 3 step grading system for endometroid tumors.
21. moderate differentiation, easily identified glandular patterns.
22. poorly differentiated, well formed glands mixed with malignant cells.
23. solid sheets of malignant cells, barely identifiable glands, increased atypia and mitotic activity.
24. confined to corpus uteri.
25. involves corpus and cervix.
26. outside uterus but not involving pelvis.
27. extends beyond pelvis, or bladder / rectum.

28. vaginal bleeding with leukorrhea, uterine enlargement, abnormal cells on pap.
29. curettage (EMB) and histological exam.
30. 80% stage 1.
31. papillary serous and clear cell with positive or negative peritoneal and adnexal histology.

32. adenocarcinomas with malignant stromal differentiation.
33. mesoderm components- muscle, cartilage, osteoid.
34. serous differentiation.
35. highly malignant, 5 year survival is less than 30%.
36. large polypoid malignancies of the endometrial stroma.
37. 4th or 5th decade.
38. oopherectomy, because they are estrogen sensitive.

pathology III: uterine pathologies part I

lecture 1 / 2 of the pathology of the uterus.

questions
overview...
1. the uterus is composed mostly of...
2. what are menorrhagia and metrorrhagia?
3. what are anovulatory cycles generally caused by?
4. what can anovulatory cycles also be caused by?
5. when do anovulatory cycles most commonly occur?
6. what is an "inadequate luteal phase"
7. what are some symptoms that often accompany an inadequate luteal phase?
8. what is the test used to diagnose inadequate luteal phase? what does it show? when is it performed?

endometritis...
9. acute endometritis is associated with...
10. what are the etiologies of chronic endometritis?
11. what is seen in endometrial tissue in acute and chronic endometritis?

endometriosis and adenomyosis...
12. what is endometriosis?
13. what age does endometriosis generally occur?
14. where in the body does endometriosis commonly affect?
15. what is adenomyosis?
16. what are the histological characteristics of adenomyosis?
17. how common is adenomyosis?
18. what are the clinical symptoms of adenomysosis?
19. what are the signs/symptoms of endometriosis?
20. what is "retrograde/implantation" etiology theory for endometriosis?
21. what is the "metaplastic" theory for endometriosis?
22. what is the "vascular or lymphatic" theory for endometriosis?
23. the vascular/lymphatic theory could explain...
24. what are three "non standard" theories of etiology for endometriosis?
25. what is the morphology of endometriosis implants?
26. what is a "chocolate cyst"?

endometrial polyps...
27. what is an endometrial polyp?
28. how big are endometrial polyps?
29. what are the two histological types of polyps? which one does not respond to progesterone?
30. what is a serious potential complication of endometrial polyps?

endometrial hyperplasia...
31. endometrial hyperplasia is related to...
32. what is the general cause of endometrial hyperplasia?
33. what are estrogen producing factors implicated in the pathogenesis of endometrial hyperplasia?
34. what is "PTEN" and how is it related to endometrial hyperplasia?
35. describe the morphology of simple hyperplasia.
36. simple hyperplasia of the endometrium reflects...
37. what percentage of simple hyperplastic endometrium progresses to adenocarcinoma?
38. what is the morphology of complex hyperplasia of the endometrium.
39. complex hyperplasia is usually associated with...

PID...
40. PID is associated with...
41. statistically, what are the causes of PID in younger vs. older women?
42. what are the clinical manifestations of PID?
43. in PID, where does gonococcal inflammation begin?
44. what other areas are involved in gonococcal inflammation?
45. how else might infection travel to the tubes and ovaries?
46. what are the morphological characteristics of gonococcal derived PID 2-7 after infection?

answers
1. smooth muscle (myometrium)
2. excess bleeding during menses, and between menstrual cycles.
3. excess estrogenic stimulation, lack of progesterone, no corpus luteum development.
4. endocrine disorders, metabolic disorders, ovarian tumors.
5. puberty and perimenopause.
6. inadequate luteal function and low progesterone output with an irregular ovulatory cycle.
7. infertility, increased bleeding, or amenorrhea.
8. endometrial biopsy performed at postovulatory time shows immature secretory endometrium.

9. bacterial infection or incomplete miscarriage.
10. chronic PID
retained gestational tissues
IUD's
TB
[CE PID IUD TB RGT] [iCPTR] [I, COMPUTER]
11. acute: PMN. chronic: plasma cells, macrophages, lymphocytes.

12. presence of endometrial glands and stroma in ectopic locations.
13. 3rd and 4th decades.
14. endometrial tissues found in:
ovaries
uterine ligaments
rectovaginal septum
pelvic peritoneum
laparotomy scars
[oh... your butt has a poo poo scar]
15. presence of endometrial tissue in uterine wall.
16. irregular nests of endometrial stroma within myometrium.
17. in up to 20% of uteri.
18. menorrhagia, colicky dysmenorrhea, dyspareunia, pelvic pain
[add men dys dys pelvic] [the ADD man: "this- this pelvic pain!!!!"]
19. infertility
dysmenorrhea
pelvic pain
deep dyspareunia
pain with BM, urine
[endo infertility dys pelvic deep BM] [end this infertility with this deep pelvic shit]
20. retrograde menses through the fallopian tubes spreads endometrial tissue in the peritoneal cavity.
21. coelemic epithelium produces endometrial tissue directly.
22. dissemination of endometrial tissue through veins or lymph nodes.
23. lesions in lungs / lymph nodes.
24. GI dysbiosis (candida in particular), hereditary influences, aromatase cytochrome P450, dioxin / PCB exposure.
25. nodules with red-blue to yellow-brown appearance on or below serosal surfaces, sometimes with fibrous adhesions.
26. endometrial tissue on the ovaries.

27. a sessile mass projecting into the endometrial cavity.
28. 0.5-3cm.
29. functional and hyperplastic (doesn't respond to progesterone).
30. adenocarcinoma.
31. carcinoma.
32. prolonged estrogen stimulation of endometrium by anovulation or increased estrogen production.
33. menopause, PCOS, ovarian tumors, ERT.
[hyper men hurt because of tumors]
34. a tumor suppressor gene that, when inactivated, can contribute to endometrial hyperplasia by increasing endometrial sensitivity to estrogen.
35. irregular gland shape, similar to proliferative endometrium without mitotic figures.
36. persistent estrogen stimulation.
37. 1-8%.
38. increased number and size of endometrial glands with irregular shape
scalloped or tufted surface on epithelial lining
mitotic figures
39. altered PTEN gene expression.

40. STI's, endogenous vaginal flora.
41. younger: STI. older: endogenous flora.
42. pelvic pain
adnexal tenderness
fever
vaginal discharge and bleeding
nausea / vomiting
back pain
CMT
dysuria
deep dyspareunia
43. Bartholin glands and periurethral glands.
44. cervix, uterus, uterine tubes, ovarian region.
45. through procedures such as abortion, D+C.
46. inflamed glands
acute suppurative inflammation of superficial mucosa
spared endometrial tissue
lumen filled with purulent exudate
tubo-ovarian abscesses
hydrosalpinx
[PID glands superficial spared lumen tubo salpinx] [stuPID glands: spared the superficial tubs of lemons instead of the minx]

pathology III: pathology of female genitalia

this lecture covered the pathology of various conditions of female genitalia. in general most of the dermatological conditions we learned about in CPD I have the same effect in the vaginal region, although may be named differently (inflammatory dermatitis = vulvitis). psoriasis, lichen simplex chronicus, lichen planus all affect the vulva and have unique histological features: psoriasis has hyperkeratosis / loss of granular cell layer / acanthosis / rete peg elongation / vascular dilation. LSC has thickened epidermis and leukocytic infiltrate. lichen planus has sawtooth rete pegs / basal cell layer degeneration / thickened granular layer / inflammatory infiltrate.

lichen sclerosus is a white thickening of the vulvar or perianal skin and associated with an increased risk for vulvular cancer. it might present with intense pruritis that may cause the patient to itch herself to the point of ulceration. LS is characterized microscopically by edematous degeneration of the basal cell layer, loss of rete pegs, dense collagen/fibrous replacement of dermis, and band like leukocytic infiltrate.

bartholin's cyst results from a blocked bartholin duct generally resulting from a previous infection and is relatively common, affecting all ages. they are 3-5 cm and the larger cysts are generally more painful. the cysts are generally lined by transitional epithelium, squamous metaplasia, or normal duct cells.

genital herpes can present in the vulvar or anal region and are generally from HSV infection. the characteristic histomorphological finding for HSV infection is the multinucleated giant cell. genital warts, otherwise known as condyloma acumata, are generally from HPV infection-- HPV strains 6 and 11 cause 90% of cases. HPV is also an STD spread by skin to skin contact. the histomorphology of genital warts are acanthosis, hyperkeratosis, and cytoplasmic vacuoles. condylomas can also be caused via syphilus, in which case it can be accompanied by vaginal discharge.

vaginosis refers to an imbalance in the bacterial flora that results in dominance of one or two species; in low pH, trichomonas may dominate and in high pH candida may dominate. histologically, one may see clue cells, which is an epithelial cell that is covered with bacteria.

vulvar intraepithelial neoplasm results in hyperpigmented skin plaques that can appear red, white, yellow, or multipigmented. although VIN is associated with a primary squamous neoplasm and high risk HPV strains (16, 18, 31, 45), it can often regress spontaneously in young women. risk for progressing to invasive cancer increases with age over 40 or so.

vulvar carcinoma makes up 3% of female genital cancers and is mostly squamous cell carcinoma (85%) and adenocarcinoma (15%). they are classified further by HPV involvement: on a histological level, poorly differentiated cells are positive for HPV, while well differentiated, keratinizing cells are negative for HPV. potential for metastasis depends on size and depth of tumor as well as lymphatic involvement-- if VC does metastasize, it might involve the iliac, inguinal, peri-aortic, pelvic lymph nodes and go to the lungs or liver.

cervical cancer is the 5th most common cancer of women in the world and the 8th most common cancer of american women. it is caused by HPV infection and has increased likelihood in women who have risky sexual activity at a young age or have the high risk HPV strains (16, 18, 31, 45). oral contraceptives and tobacco are also associated as risk factors for cervical cancer. the extent of spread of cervical cancer is classified in four stages: stage I is confined to the cervix, stage II can extend to the upper 2/3 of the vagina, stage III to the pelvis, and stage IV beyond the pelvis and metastasis to other areas.

questions
various conditions...
1. what is inflammatory dermatitis of the vulva called?
2. vulvitis might be seen with patients with what skin conditions?
3. what are the histomorphological features of vulvar psoriasis? ††
4. what is lichen simplex chronicus?
5. what are the histological features of LSC?
6. what is widespread LSC called? what might it be a complication of? √√
7. what is lichen planus?
8. what age group of women does vulvular/vaginal lichen planus usually affect?
9. what are the histological features of lichen planus? †√

lichen sclerosus...
10. what is lichen sclerosus?
11. LS is associated with an increased risk for...
12. what are some other clinical features of LS?
13. what are the histological features of LS? √√

bartholin's cyst...
14. how common is a bartholin's cyst and what age does it affect? √
15. what is the etiology of a bartholin's cyst? √
16. what is the general size of the bartholin's cysts? √
17. larger bartholin's cysts are... √
18. bartholin's cysts are lined by what types of cells? √√

genital herpes and warts...
19. which regions may genital herpes present in? √
20. primary infections present with... X
21. what characteristic histologic feature is shown with HSV infection? √
22. what is the scientific name for genital warts? †
23. what is the etiology of genital warts? √
24. HPV strains 6 and 11 cause... †
25. HPV strains 16 and 18 cause... †
26. how is HPV spread? √
27. what are the histological features of genital warts? †
28. what is condyloma latum of syphilus and what is it caused by?
29. what might CLS be accompanied by?

vaginosis...
30. what is bacterial vaginosis?
31. what are clue cells in the context of bacterial vaginosis?
32. what are two microorganisms commonly associated with bacterial vaginosis?
33. how does vaginal pH correspond to the type of microorganism that dominates the vaginal flora?

vulvar intraepithelial neoplasia...
34. what is the appearance of a vulvar intraepithelial neoplasia?
35. 10-30% of VIN cases are associated with...
36. VIN affects mostly women of what age?
37. what is found in 90% of VIN cases?
38. describe the prognosis of VIN in younger women.

vulvar carcinoma...
39. what are the different types of vulvar carcinoma and what are their relative percentages?
40. what are two general categories of vulvar carcinomas?
41. how does HPV involvement change the histomorphology of vulvar carcinoma?
42. what factors is the metastasis of VC due to?
43. which lymph nodes does metastasis of VC involve?
44. distant metastasis of VC usually involves...

vaginal carcinoma...
45. how common are vaginal carcinomas?
46. what type of vaginal carcinoma is associated with women whose mothers were treated with DES during pregnancy?
47. male offspring of mothers with vaginal carcinoma are at an increased risk for...

cervical cancer...
48. how prevalent is cervical cancer in the US and world?
49. what is the causative factor in nearly all cases of cervical cancer?
50. which strains of HPV are involved in cervical cancer?
51. what is the possible genetic component involved in the pathogenesis of cervical cancer?
52. what are some risk factors for cervical cancer?
53. what is the current classification system for cervical carcinoma?

koilocytosis...
54. what are the cellular changes involved in koilocytotic atypia?
55. koilocytosis atypia are made up of which cells?
56. what is a ASC-US?
57. what are the hallmarks of CIN1?
58. what are the hallmarks of CIN2?
59. what about CIN3?
60. what are the four stages of cervical cancer and what are they characterized by?

answers
1. vulvitis.
2. psoriasis, eczema, allergic dermatitis.
3. hyperkeratosis/parakeratosis
loss of granular layer
epidermal acanthosis
elongated rete pegs
vascular dilation. [hyper loss of cans makes your veins longer] [ker gran can rete vasc] [
4. a generalized skin condition characterized by lichenification due to chronic itching.
5. thickened epidermis, leukocytic infiltrate.
6. neurodermatitis, complication of atopic dermatitis.
7. a common skin condition (PPPP- purple polygonal pruritic papules) causing inflammation and maybe ulceration.
8. women of childbearing age.
9. sawtooth rete pegs, basal cell layer degeneration, thickened granular cell layer, inflammatory infiltrate. [i plainly saw the generation of inflamed grandmas]

10. white thickening of vulvar and perianal skin.
11. vulvular cancer.
12. itchiness; patient might create ulcerations. intravaginal area not affected.
13. edematous degeneration of basal cell layer, rete pegs disappear, dense collagenous fibrous tissue replaces dermis, band like lymphocytic infiltrate. [edema, disappear, dense, band] [in LS, eddie disappeared in a thick band]

14. fairly common, all ages.
15. blockage of bartholin duct usually due to preceding infection.
16. 3-5 cm.
17. more painful.
18. transitional epithelium, normal duct tissue, or squamous metaplasia.

19. vulvar or anal.
20. flu like symptoms.
21. multinucleated giant cells.
22. condyloma acuminata.
23. STD from HPV.
24. 90% of genital warts.
25. 70% of cervical cancer.
26. skin/skin contact during sex.
27. acanthosis (diffuse epidermal hyperplasia), hyperkeratosis, cytoplasmic vacuoles.
28. genital wart due to syphilis.
29. vaginal discharge.

30. infection resulting from imbalance of vaginal flora.
31. epithelial cells coated with bacteria.
32. trichomonas vaginalis, candida albicans.
33. low pH generally results in vaginosis from trichomonas, high from candida.

34. hyper-pigmented skin plaques: red, white, yellow, multipigmented.
35. primary squamous neoplasm of vagina or cervix.
36. below 40.
37. high risk HPV strains (16,18, 31, 45).
38. may spontaneously regress.

39. 85% SCC, 15% BCC / melanoma / adenocarcinoma.
40. carcinomas related to HPV or not related to HPV.
41. poorly differentiated cells positive for HPV, well differentiating keratinizing cells negative for HPV.
42. size and depth of tumor, lymphatic involvement.
43. inguinal, iliac, peri-aortic, pelvic.
44. liver or lungs.

45. not common.
46. clear cell adenocarcinoma.
47. peri-anal cancer.

48. 5th most common cancer in the world, 8th in the US.
49. HPV.
50. 16, 18, 31, 45.
51. HLA-B7.
52. early age of sexual activity
multiple sexual partners
high risk HPV strains
oral contraceptives
smoking
genital infections
multiple births [young many risky mouth smoke infect multiple] [many youth risk infecting multiple mouths by smoking]
53. the bethesda system, which groups cervical cancers into high and low grade.

54. enlarged nuclei, halo stain around nucleus.
55. intermediate and superficial squamous cells from vaginal epithelium.
56. atypical squamous cell of undetermined significance.
57. koilocytotic atypia.
58. progressive atypia in all epithelial layers.
59. carcinoma in situ- diffuse atypia, loss of maturation.
60. stage I: confined to cervix.
stage II: upper 2/3 of vagina.
stage III: extends into pelvic wall.
stage IV: beyond pelvis, metastasis.

pathology III: breast pathologies, part II

[this lecture is a continuation of the breast conditions lectures] adenomas are highly glandular benign masses that are the most commonly presented benign tumors of the breast. a fibroadenoma is well encapsulated by fibrous tissue and is generally firm and freely movable. microscopically, they might have hyperplasia of intraductal epithelial cells. fibroadenomas grow and diminish according to hormonal influences, in particular growing during pregnancy and late menses and regressing after menopause.

breast cancer generally presents as a firm, fixed mass associated with skin dimpling, nipple retraction and discharge. some high risk factors include old age, a positive family history, alcoholism, and some hormonal indicators (high IGF-1 levels premenopause and high estrogen levels post menopause). lower risk but still significant factors include smoking, a late first pregnancy, history of other benign lesion. in general, risk for breast cancer increases with lifetime exposure to estrogen, which by virtue of its cell proliferating effect can increase the likelihood of cell mutation that can lead to cancerous cell lines.

there are several types of breast cancer, the most prominent being intraductal or infiltrating ductal carcinoma, which makes up ~80% of breast cancers. this is characterized by a single hard mass with irregular borders that is not easily movable. second most common, 5-10% is lobular carcinoma which is characterized by multiple foci in affected breast and increased risk for bilateral involvement (histological findings might include "signet ring cells"). the least common form is paget's disease of the nipple, which might cause a persistent burning/itching sensation, lead to eczematous changes of the skin, and ultimately to ulcers and destruction of the nipple. inflammatory breast cancer is an uncommon type of ductal carcinoma that involves aggressive inflammation of the affected breast and is notable for sometimes not presenting with a palpable mass during physical examination.

questions
adenomas...
1. what is an adenoma vs. an adenosis?
2. what is the most common benign tumor of the breast?
3. what is the clinical presentation of a fibroadenoma?
4. what are the histological findings of a fibroadenoma?
5. fibroadenomas might increase in size in response to what influences?
6. are fibroadenomas benign or malignant?

intraductal papilloma...
7. how common is an intraductal papilloma?
8. intraductal papilloma is the most common cause of...

breast cancer...
9. what tissue does most breast cancer appear in?
10. what are some "high" risk factors for breast cancer?
11. what are some "medium" risk factors for breast cancer?
12. what are some factors that can protect against breast cancer?
13. what is one common denominator in the risk factors for breast cancer?
14. describe estrogen's role in the pathogenesis of breast cancer.
15. describe pregnancy's role in decreasing susceptibility to breast cancer.
16. what are the PE findings commonly associated with breast cancer?
17. what are the three main types of breast cancer?

types of breast cancer...
18. what is the most common type of breast cancer? how common is it?
19. what is IDC characterized by?
20. what is the second most common breast cancer and how common is it?
21. LC is associated with...
22. how common is paget's disease of the breast?
23. what is a common presentation of paget's disease?
24. how does the paget's disease present in its later stages?
25. what is inflammatory breast cancer?
26. what is notable about the PE of IBC?

answers
1. adenosis is increased glandular component aggregation while adenoma is a more organized but still benign form.
2. fibroadenoma.
3. generally a non tender, firm, freely movable mass.
4. well encapsulated, with hyperplasia of intraductal epithelial cells.
5. hormones during pregnancy and late menses.
6. generally benign with an miminally increased risk for carcinoma.

7. found in 1-3% of all biopsy specimens.
8. spontaneous nipple discharge from a single duct.

9. glandular tissue (includes both lobular and ductal tissue).
10. old age, prior history of breast cancer, positive family history (especially if mother and sister both had breast cancer), alcoholism, high IGF-1 levels premenopause, high estrogen levels postmenopause. [old history family alcohol insulin estrogen] [the old story of my family involves alcohol and hormones]
11. a late first pregnancy or nulliparity, family history, smoking, history of other benign lesion.
12. late menarch, breast feeding, exercise, low alcohol/tobacco, diet rich with monounsaturated fats.
13. most involve lifetime levels of endogenous estrogen exposure.
14. because estrogen has a cell-proliferating effect, it inherently increases the possibility for gene mutations to occur, which cause breast cancer.
15. pregnancy decreases the breast tissue susceptibility to mutation (unknown reasons) and thus can shorten the "susceptibility period" that begins at menarche.
16. firm, fixed, not painful, irregular borders, skin dimples, nipple retraction, galactorrhea.
17. ductal/intraductal, lobular, Paget's disease of the nipple.

18. infiltrating ductal carcinoma. 80% of breast cancers.
19. single hard mass with irregular borders, not easily movable.
20. lobular carcinoma, 5-10%.
21. multiple loci in affected breast, increased risk for bilateral involvement.
22. uncommon compared to ductal and lobular.
23. persistent change in sensation of nipple, itching/burning. might have eczematous changes on overlying skin.
24. may present much differently than earlier stage: with ulceration and destruction of nipple.
25. a form of ductal carcinoma that is characterized by aggressive inflammation of the affected breast.
26. might present without a palpable lump.

pathology III: breast pathologies, part I

this pathology lecture covered various pathologies of the female breast. first we covered normal breast histoanatomy and physiology: breast tissue is made up of on a microscopic level of different cells such as luminal epithelial cells and myoepithelial cells, which produce milk and assist in milk ejection during lactation, respectively. "lobules" are formations of cells that are involved in milk production that are largely absent prepuberty and after menopause but appear during puberty and are copious during pregnancy. breast tissue structure and growth is directed by hormonal influences, in particular estrogen (stimulating duct elongation, branching and elasticity, as well as increased connective tissue and fat) and progesterone (lobule formation).

breast tissue is subject to various congenital anomalies: amastia is absence of breast tissue, nipple or areola, while amazia is absent mammary glands with normal outer anatomy. supernumerary nipple is an extra nipple in an ectopic location and supernumerary breast tissue is ectopic breast tissue, generally along the milk line. inverted nipple can be physiological in a small percentage of women, but can be pathological in cases of breast cancer.

galactorrhea is nipple discharge and can be simply from hormonal dysregulation or a side effect from drugs, or can be cause for concern if unilateral or accompanied by a breast mass. mastitis is an inflammation of the breast tissue parenchyma, called puerperal mastitis in lactating mothers. infectious mastitis can be caused from staph or strep epidermitis, and periductal mastitis is characterized by a painful mass in the sub-areolar area with an overlying erythema. periductal mastitis also has a strong correlation with smoking and nipple inversion.

mammary duct ectasia results from the dilation of sub-areolar ducts that appears histologically as dilated lactiferous ducts with granular debris such as lipid laden macrophages. it presents in the 5th or 6th decade of life, generally unilateral, with a palpable peri-areolar mass, thick nipple secretion, breast pain, and erythema. 30-40% of cases are associated with nipple inversion.

fibrocystic breast disease is an extremely common disorder and is the number one cause of surgical breast procedures. it is a non cancerous fibrotic change of breast tissue that results in lumps and cords and discomfort that can be exacerbated by hormonal or lifestyle influences. it will present during 20-40 years old and generally affect the upper outer quadrant of the breast. mammography will be interfered with because of the dense nature of the fibrotic tissue.

fat necrosis of the breast occurs in response to injury or surgery: rupture of adipocytes causes hemorrhage into the affected tissue, leading to lipolysis, conversion to fatty acids and glycerol, fibroblastic proliferation and walling off / vascularization of damaged tissue. it presents as a painless mass or area of skin accompanied by breast tissue retraction and skin thickening, and may show areas of high density (from fat) or calcifications on a mammogram.

lymphocytic mastopathy is characterized by single or multiple masses which are made up of collagenized / fibrotic stromal tissue that surrounds atrophic ducts and lobules. histologically, lymphocytic infiltrates surround the epithelium and blood vessels of the affected tissue. there is a strong correlation between lymphocytic mastopathy and type 1 DM and autoimmune thyroiditis and in general a sense that LM might be related to autoimmune dysfunction.

the last breast disorder in this lecture is granulomatous mastopathy, a mastitis characterized by giant cell / epitheloid cell granulomas with an idiopathic origin. this disorder can be seen in conjunction with other diseases such as breast carcinoma or TB, in which case the granulomas are caseating. in immunocompromised patients, granulomatous mastopathy is likely due to mycobacterial or fungal infection.

questions
normal breast anatomy...
1. how many ducts does the lactiferous duct system of the breast generally consist of?
2. what makes up the remainder of the non-milk producing breast tissue?
3. what are the two cell types in the lactiferous ducts and lobules and what do they do?
4. where does lymph from the breast flow to?
5. describe the changes that occur on the histological level during breast development through puberty.
6. what happens to the breast tissue on a histological level during a woman's 3rd decade of life and after menopause?
7. what effect does estrogen have on breast tissue?
8. what effect does progesterone have on breast tissue?
9. what are Montgomery tubercles?

congenital breast conditions...
10. what is amastasia?
11. what is amazia?
12. what is a supernumerary nipple? how common is it?
13. what is supernumerary breast tissue? where is it generally located?
14. what is inverted nipple and what is it caused by?
15. the diagnosis of a patient with inverted nipple must rule out what?

various pathologies...
16. what is galactorrhea and what is it caused by?
17. when might galactorrhea be a cause for concern?
18. what is mastitis?
19. what is "puerperal mastitis"?
20. cases of infectious mastitis are found to be due to which microorganisms?
21. what is periductal mastitis?
22. more than 90% of periductal mastitis patients are...
23. what is a common sequelae for periductal mastitis?
24. ∂escribe the histomorphology of periductal mastitis.

mammary duct ectasia...
25. what is mammary duct ectasia?
26. when does mammary duct ectasia generally affect women?
27. is mammary duct ectasia unilateral or bilateral?
28. what is the characteristic clinical presentation of mammary duct ectasia?
29. how common is nipple inversion associated with mammary duct ectasia?
30. what are the histologic findings of mammary duct ectasia?

fibrocystic breast disease...
31. what is fibrocystic breast disease?
32. fibrocystic tissue changes may cause...
33. how common is fibrocystic breast disease?
34. what age is fibrocystic breast disease generally diagnosed?
35. where are fibrocystic breast changes most often found?
36. why is mammography of limited value in diagnosing fibrocystic breast disease?

fat necrosis...
37. how does fat necrosis of the breast present?
38. what are the common causes of FN?
39. describe the pathogenesis of FN in breast tissue.
40. what is deposited within the affected area of FN?
41. what does mammography of the affected FN area reveal?

lymphocytic mastopathy...
42. what is lymphocytic mastopathy?
43. what are the histologic features of lymphocytic mastopathy?
44. why is it hypothesized that LM is an autoimmune disease?

granulomatous mastopathy...
45. what is granulomatous mastopathy?
46. what is the etiology of most granulomatous mastopathy?
47. granulomas may be seen in association with...
48. caseating granulomas of the breast may be due to...
49. breast granulomas in immunocompromised patients is likely due to...

answers
1. 4-18 ducts (modified sweat glands that lactate)
2. adipose, connective tissue, ligamentous tissue.
3. luminal epithelial cells (produce milk) and myoepithelial cells (assist in milk ejection during lactation, maintain normal structure and function of lobule and basement membrane)
4. 3/4 to the axillary lymph system, the rest to the para-sternal lymph, abdominal lymph, other breast.
5. before puberty: large ductal system, minimal lobules. after menarch: terminal ducts give rise to lobules, marked increase in interlobular stoma.
6. lobules and stromal tissues begin to involute, then lobules almost completely disappear after menopause.
7. estrogen stimulates duct elongation and branching, increased volume and elasticity of connective tissue, increased deposition of adipose tissue, increased elasticity of ducts. [more CT, fat, elastic ducts]
8. progesterone stimulates lobule formation.
9. glands on areola that aid in lubrication of the nipple.

10. absent breast tissue, nipple, or areola.
11. absent mammary glands but nipple and areola present.
12. presence of one or more additional nipple. 2-6% females and 1-3% males.
13. breast tissue in an ectopic location, generally along the milk line.
14. nipple that points into the breast, caused by fibrous bands of tissue.
15. breast cancer.

16. nipple discharge from hormonal dysregulation, or drug side effect.
17. if it is unilateral, bloody, or associated with a breast mass.
18. inflammation of the parenchyma of mammary gland.
19. mastitis of lactating mothers.
20. staph or strep epidermitis.
21. a painful mass in the sub-areolar area with an overlying skin erythema.
22. smokers.
23. nipple inversion.
24. keratinizing squamous epithelium, chronic granulomatous inflammation.

25. dilatation of sub-areolar ducts.
26. 5th or 6th decade of life.
27. unilateral.
28. palpable but poorly defined peri-areolar mass, thick nipple secretion, breast pain, maybe erythema.
29. 30-40% of cases.
30. dilated lactiferous ducts filled with granular debris (such as lipid laden MØ's).

31. fibrous, non-cancerous lumps and cords in the breast tissue.
32. discomfort related to hormonal cycles or life style influences.
33. single most common disorder of breast, accounts for more than half of surgical procedures for breast.
34. between 20-40.
35. upper outer quadrant.
36. because the dense fibrotic tissue will interfere with proper visualization of the breast tissue.

37. painless mass or area of skin, with breast tissue retraction, skin thickening.
38. prior breast trauma, surgery.
39. rupture of adipocytes and hemorrhage into affected area, followed by lipolysis and conversion to fatty acids and glycerol, followed by fibroblastic proliferation and increased vascularization walling off affected area.
40. calcium, hemosiderin.
41. central radiolucent, high density fat, possible calcifications at periphery.

42. single or multiple hard masses made of collagenized stroma surrounding atrophic ducts/lobules.
43. thickened/fibrotic stromal tissue, lymphocytic infiltrates surrounding epithelium and blood vessels.
44. because of its association with type 1 DM or AI thyroiditis.

45. mastitis characterized by granulomas formed by epitheloid cells and giant cells.
46. idiopathic.
47. breast carcinoma.
48. tuberculosis. (uncommon)
49. mycobacterial or fungal infection.

pathology III: CHF, cardiomyopathies, endocarditis

congestive heart failure occurs when the heart's pumping action is not able to meet the body's metabolic demands either because of increased demands, dysfunction of the heart itself, or both. the heart can compensate for this discrepancy in various ways such as tachycardia, hypertrophy; but with enough time none of these adaptations will suffice. "compensated" refers to such a case of chronic heart failure where increased heart rate or other factors have allowed the heart to maintain adequate CO and perfusion. similarly, "high output" failure refers to congestive heart failure with tachycardia to compensate, which results in peripheral vasodilation and warm extremities.

heart failure affects and is affected by many other systems of the body. generally, the sympathetic nervous system is overactive, causing peripheral vasoconstriction which shunts blood away from extremities. systemic venous congestion will also affect the renal system by way of diminished hepatic metabolism of aldosterone which will lead to increased fluid retention which will unfortunately negatively feed back into creating more pressure for the heart (note that the same heart stressing effect can happen with a patients sudden cessation of diuretics). in the lungs, heart failure cells might appear, which are macrophages full of hemosiderin.

left sided CHF, as we learned in CPD, involves dysfunction of receiving blood from the pulmonary system and thus presents with symptoms of pulmonary congestion such as pulmonary edema. on the other hand, RCHF involves dysfunction of receiving venous blood from the body and thus can present with signs of systemic congestion such as peripheral edema. LCHF is usually caused by infarction/ischemia of the left ventricle, hypertension, or mitral dysfunction whereas RCHF is most commonly caused by LCHF.

cardiomyopathies come in three flavors, dilated (90%), restrictive, and hypertrophic. dilated is when all four chambers are enlarged but not hypertrophic and can be caused by severe alcoholism. hypertrophic is severe hypertrophy of myocardium, especially the ventricular septum, which is generally caused by a genetic defect that causes a mutation in the proteins within sarcomeres. restrictive cardiomyopathy is generally due to hemochromatosis (excess Fe deposition) or amyloidosis (excess amyloid deposition) within the myocardium which renders it dysfunctional.

infectious endocarditis is an infection of the myocardium or heart valves, characterized by formation of "vegetations"- made up of platelets, fibrin, and bacteria. these have a high potential for embolization; septic emboli can manifest as Roth spots in the eye, petechiae on the skin, splinter hemorrhages in the fingernails. the main risk factors for infectious endocarditis include artificial valves, immunocompromise, IV drug abusers, alcoholics, procedures with catheters / grafts. endocarditis can also occur from an inflammatory origin, as in the case of Libman-Sacks endocarditis, which results in the case of SLE.

questions
introduction to CHF...
1. what is congestive heart failure?
2. how does the heart typically respond to heart failure initially?
3. why does frank starling's law not apply in cases of severe heart failure?
4. how many americans does CHF affect per year?
5. what is "compensated" or "decompensated" CHF?
6. describe the sympathetic response in acute CHF which compensates for decreased CO.
7. how can systemic venous congestion lead to fluid retention?
8. what are heart failure cells?

CHF types...
9. what is the difference between primary and secondary CHF?
10. what is a common cause of CHF related to drugs?
11. what are some common underlying conditions that can lead to CHF?
12. what can left sided CHF lead to and why?
13. what is left sided CHF usually caused by?
14. what is the most common cause of right sided CHF?
15. what is cor pulmonale?
16. describe the difference in symptom presentation between RCHF and LCHF.

high and low output failure...
17. what is the difference between high and low output heart failure?
18. what are some causes of high output heart failure?
19. how can Paget's disease cause high output heart failure?
20. what are some causes of low output heart failure?

cardiomyopathies...
21. what are the three types of cardiomyopathies and which is most common?
22. what is dilated cardiomyopathy characterized by? what is the most common cause?
23. what is hypertrophic cardiomyopathy characterized by? what is it caused by?
24. what is restrictive cardiomyopathy characterized by? what are the most common causes?

endocarditis...
25. what are "vegetations" in the context of endocarditis?
26. most common cause of endocarditis is...
27. what are some potential portals of entry for bacteria that might cause endocarditis?
28. what is the difference between acute and sub-acute infectious endocarditis?
29. the most consistent sign of endocarditis is...
30. what is a serious danger of vegetations besides their disruption of blood flow in the heart?
31. septic emboli from endocarditis can manifest in...
32. main risk factors for endocarditis.

most likely organism to cause IE in...
33. patient with native valves...
34. prosthetic valves...
35. IV drug abusers...
36. alcoholics...
37. after a cystoscopy/prostatectomy/catheters...
38. patients with colon cancer...

non-infectious endocarditis...
39. culture negative endocarditis may indicate...
40. what is the endocarditis of SLE called?
41. what is Marantic endocarditis?

answers
1. inability of the heart to pump out enough blood to meet the body's metabolic requirements.
2. increased contractility or increased heart rate.
3. if the myocardium is stretched beyond a certain point as in severe CHF, the optimum length for contractility is surpassed and the ventricles are overstretched; CO begins to decrease again.
4. 2 million.
5. compensated is CHF with adequate CO and decompensated is CHF with inadequate CO.
6. increased catecholamine activity causes peripheral vasoconstriction and shunting of blood away from extremities to internal organs.
7. systemic venous congestion leads to diminished hepatic perfusion which leads to diminished metabolism of aldosterone which leads to fluid retention.
8. hemosiderin laden macrophages in the alveoli.

9. primary is a dysfunction of the heart itself while secondary is a dysfunction of the heart due to the stress placed on it by other systems in the body.
10. cessation of certain heart medications; in particular diuretics, causes a sudden increase in fluid retention and thus stress placed on the heart.
11. conditions that cause myocardial dysfunction: coronary atherosclerosis, arterial hypertension, myocardial ischemia, infarction, inflammatory / degenerative muscle disease.
12. pulmonary congestion because of the increased pressure in the left ventricles (end-diastolic) and atrium.
13. left ventricular infarction / ischemia, hypertension or mitral dysfunction.
14. LCHF.
15. heart failure that results from an underlying lung disorder such as COPD.
16. RCHF presents with symptoms of systemic venous congestion and LCHF presents with symptoms of pulmonary congestion.

17. high output failure characterized by peripheral vasodilation / warm extremities while low output failure characterized by peripheral vasoconstriction / cold extremities.
18. hyperthyroid, stimulants, anemia, Paget's disease.
19. in Paget's, abnormal bone mass is formed with high vascularity, increasing the demand for O2 and thereby increasing the heartrate.
20. infarction, ischemia, endocarditis.

21. dilated restrictive and hypertrophic. dilated 90%.
22. all four chambers enlarged, chronic alcoholism.
23. hypertrophy of chambers (especially ventricular septum), abnormal diastolic filling, intermittent ventricular outflow obstruction. caused by a genetic defect that affects sarcomere function.
24. abnormal tissue that obstructs blood flow. hemochromatosis (excess iron deposition) and amyloidosis are two main causes.

25. infected thrombotic masses on myocardium or valves in infectious endocarditis.
26. bacteria: chlamydia, rickettsiae.
27. dental health, GU tract infection, skin infection, pulmonary infection, any infection in blood, IV drug users.
28. sub-acute is a gradual onset and usually takes place in a heart that already has damage, whereas acute is a sudden infection with a virulent organism with a poor prognosis.
29. fever.
30. their potential for embolization.
31. roth spots in the eye, petechiae, splinter hemorrhages.
32. artificial valves, immunocompromised patients, IV drug abusers, alcoholics, catheters, grafts.

33. strep viridans.
34. staph epidermitis.
35. staph aureus.
36. anaerobes and mouth bacteria.
37. gram- microbes such as ecoli.
38. strep bovis

39. endocarditis with inflammatory origin.
40. Libman-Sacks endocarditis.
41. endocarditis that results from the hypercoagulable state resulting from Trousseau's syndrome.

pathology III: hypertension

hypertension is elevated blood pressure, subcategorized in several different ways: primary hypertension is not caused by any underlying diseases, whereas secondary hypertension is caused by a number of factors such as renal disease or pulmonary disease. the severity of hypertension can be graded according to the blood pressure level; a diastolic pressure above 120 mmHg generally indicates a very severe case of hypertension. benign hypertension refers to the gradual elevation of blood pressure over time (a misnomer because it can cause an MI, stroke, renal disease, among other things) whereas accelerated is a sudden increase in blood pressure that could indicate an emergency situation. finally, labile hypertension, also known as "white coat" hypertension, is an inconsistent elevated BP that generally only appears when measured by a doctor.

there are several proposed mechanisms for hypertension: decreased Na/K ATPase activity and/or increased cell permeability to Na+, both which lead to increased intracellular Na+ which is thought to increase the sensitivity of cells to sympathetic stimulation, causing systemic vasoconstriction and therefore increased blood pressure. another theory is that Ca+ is the causative agent since Ca+ also follows Na+ into cells.

hypertension can lead to many other serious conditions related to vessel damage. an aneurysm is a ballooning out of a vessel due to decreased wall strength combined with increased blood pressure and generally occurs in the arteries, aorta and circle of willis. aortic dissection refers to high blood pressure infiltrating the media layer of arteries (generally the aorta), causing excruciating pain resistant to painkillers. people with marfan's syndrome have an increased susceptibility to this condition because of the connective tissue abnormalities that may occur in the blood vessels as part of this syndrome.

questions
hypertension introduction...
1. how is severe hypertension defined in terms of blood pressure levels?
2. long term effects of hypertension include...
3. what are some potential mechanisms for hypertension?
4. what is the relationship of calcium in the pathogenesis of hypertension?
5. hypertension is the leading cause of which prominent diseases?
6. what percentage of americans are affected by hypertension?
7. what are some demographic / racial trends related to hypertension within the united states?
8. what is the difference between primary and secondary hypertension and in what percentage does each occur?
9. how might renal disease contribute to hypertension?

types of hypertension...
10. what is labile hypertension?
11. labile hypertension is also related to what other condition?
12. what does benign hypertension refer to?
13. what is accelerated hypertension?

complications...
14. what is an aneurysm?
15. where are aneurysms most likely to occur?
16. what is aortic dissection?
17. how will a patient with aortic dissection present and what must be done immediately in terms of treatment?
18. what is marfan's syndrome and how does it relate to aortic dissection?

answers
1. diastolic pressure above 120 mmHg.
2. heart attack, stroke, renal failure.
3. defective Na/K pump or increased cellular permeability to Na+, both of which would increase intracellular sodium and therefore make cells more sensitive to sympathetic stimulation.
4. because Ca follows Na+ into cells, it is possible that increased intracellular calcium levels is what causes the increased sympathetic sensitivity, as opposed to Na+.
5. ischemic heart disease, peripheral vascular disease, cerebrovascular disease, ventricular hypertrophy, congestive heart failure.
6. 25%
7. african americans twice as likely to have hypertension compared to caucasians.
8. primary: 95%, no underlying disease. secondary: 5% due to multiple underlying factors.
9. hypertension can stimulate renin production which can result in increased salt retention and systemic vasoconstriction.

10. inconsistent BP elevation that generally occur only when measured by a doctor. also called white coat hypertension.
11. pheochromocytoma, which presents with paroxysmal headaches, sweats, palpitations.
12. BP that has has gradually been elevated over time but is relatively stable. may still result in serious conditions such as MI, stroke, renal disease.
13. marked increase in BP (emergency) that can cause acute organ damage and CNS symptoms.

14. ballooning out of a vessel due to underlying weakness of vessel wall combined with increased blood pressure.
15. arteries, aorta, circle of willis.
16. a severe complication of hypertension that results in blood traveling in the media of vessels in addition to the lumen. usually affects ascending aorta, aortic arch, descending aorta, and abdominal aorta.
17. patient will present with severe, excruciating pain that might not be relieved by painkillers-- blood pressure must be lowered if it is elevated.
18. a connective tissue disorder that can increase the likelihood for aortic dissection due to the connective tissue abnormalities that might appear in blood vessels.
19.

pathology III: cardiovascular pathologies

this was the first lecture of the cardiac pathology series by dr. marcus miller, MD ND. we talked about the pathogenesis of coronary artery disease, atherosclerosis, and the ischemic heart diseases that can result from occlusion of the coronary artery. the first topic was atherosclerosis and the development and disruption of atherosclerotic plaques. in short, plaques are formed in the walls of blood vessels by high LDL levels which then penetrate into the intima of vessels and are oxidized, stimulating monocyte recruitment which leads to fatty streaks (clusters of macrophages that have ingested high levels of LDL). smooth muscle migration, extracellular matrix deposition, and formation of a fibrous cap around a core made largely of lipids and necrotic cellular debris eventually forms, protruding into the lumen of arteries.

if the fibrous cap of atherosclerotic plaques are disrupted by various factors such as sheer forces or simply a weakened area of the cap attracting inflammatory cells, the highly thrombogenic subendothelium and lipid core is exposed and thrombosis occurs, which generally leads to complete occlusion of the artery. if this occurs in the coronary artery, several conditions can result, such as angina pectoris refers to retrosternal chest pain that radiates to the left side that can be caused by ischemia or thrombosis.

the most severe condition results from ischemia that progresses to complete infarction of the myocardium, leading to an acute MI. infarction of the myocardium causes a switchover to anaerobic metabolism that decreases ATP levels in the myocardial cells-- this causes increased cellular permeability and decreased cellular function and eventual cell death. ATP levels can decrease as soon as 1-2 minutes and drop down to 50% of original levels in 10 minutes after the infarction. morphological changes of heart tissue include blue darkening and interstitial edema (4-12 hours), appearance of darker purple spots (12-24 hours), followed by tannish yellow areas of infarction (1-3 days), hyperemia, coagulation necrosis, decreased cell wall thickness (3-7 days). scar formation begins in 2-8 weeks and is completed in 2-3 months.

questions...
atherosclerosis...
1. where are atherosclerotic lesions usually located?
2. describe the role of smooth muscle in the development of atherosclerotic lesions.
3. what is the most commonly accepted theory of etiology for atherosclerosis?
4. what are some factors that contribute to endothelial damage?

coronary artery disease...
5. what is the most common cause of CAD?
6. describe a typical atherosclerotic plaque which might result in sudden thrombosis of the coronary artery.
7. describe the progression of the rupture of an atherosclerotic plaque in the coronary artery.

ischemic heart disease...
8. what are the four major results of ischemia of blood flow to the heart?
9. what is angina pectoris?
10. what is stable angina caused by? what are some unique symptoms?
11. An unstable angina is most likely the prodrome to what?
12. what is variant / Prinzmetal angina?

myocardial infarctions...
13. what is the most common pathogenesis of acute MI's?
14. what are some other possible etiologies of AMI's?
15. describe the reduction of ATP production with the amount of ischemia that leads to an MI.
16. describe the sequence of cellular injury that occurs with decreased ATP production in an MI.
17. when does irreversible cell death of myocardium occur?
18. what is the number 1 sequelae to an MI?

gross morphological changes in an MI during...
19. less than 4 hours...
20. 4-12 hours...
21. 12-24 hours...
22. 1-3 days...
23. 3 to 7 days...
24. 2 to 8 weeks...
25. 2 to 3 months...

answers
1. vessel bifurcations, large/mid sized arteries.
2. smooth muscle migrates from the media to the intima of atherosclerotic regions and builds up extracellular matrix around the plaque.
3. the "response to injury" theory in which endothelial damage causes inflammation which recruits monocytes, which then extravasate into the vessels and make fatty streaks, and then atherosclerotic plaques.
4. obesity, high LDL levels, diabetes mellitus, hyperglycemia, hypertension, turbulent blood flow, cigarette smoke.

5. fixed atherosclerotic narrowing or thrombus of disrupted atherosclerotic plaque of coronary artery.
6. the typical plaque that causes CAD is an unstable plaque that only causes mild or moderate stenosis and blocks less than 50% of the lumen prior to rupture and thrombosis.
7. a weakened fibrous cap attracts inflammatory cells which increases likelihood of rupture, which then exposes the thrombogenic subendothelium and lipid core, resulting in thrombosis.

8. myocardial infarction, angina pectoris, chronic heart failure, sudden cardiac death.
9. retrosternal chest pain that radiates to the left side and comes in paroxysmal and recurrent attacks, caused by ischemia that falls short of necrosis.
10. ischemia due to a fixed lesion; symptoms might include claudication and mesenteric angina.
11. generally a prodrome to an MI, transient ischemic attack or stroke.
12. angina caused by coronary artery vasospasm; pain at rest.

13. coronary artery plaque rupture and thrombosis.
14. coronary artery emboli from high cholesterol or infection, coronary artery vasospasm, hypoxia from underlying pulmonary disease or CO poisoning, arteritis.
15. ATP decreases starting 1-2 mins and can be reduced to 50% by 10 mins.
16. decreased ATP production inhibits action of Na/K ATPase pump which increases cell permeability. cell function further disrupted by degradative enzymes that are released from myocytes upon influx of calcium into cardiac muscle cells.
17. 15-20 minutes from onset of injury.
18. pericarditis.

19. often no change notable.
20. pale, blue, edematous.
21. darker spots of blue and purple.
22. tannish yellow areas of infarction.
23. hyperemia around infarcted areas, decreased wall thickness, coagulation necrosis.
24. greyish white scar formation.
25. scar formation complete.

pathology III: chapter 12 introduction

this chapter deals with all the major pathologies oriented around the heart. the first section is a reminder of the physiology of the heart, dividing the organ into several different aspects anatomically and physiologically: heart muscle, valves, conduction system, blood flow. to begin with cardiac muscle: as we learned in organ systems last year, cardiac muscle cells, myocytes, are structurally similar to both skeletal muscle (striations) and smooth muscle (cell size). connecting the myocytes are intercalated discs, which join the cells mechanically via adhesion molecules and electrically through gap junctions. ventricular myocytes are arranged circumferentially around the ventricles in a spiral pattern, while the smaller-celled atrial myocytes are more haphazardly arranged. atrial myocytes also contain "specific atrial granules" which contain atrial natriuretic peptide, the role of which will be discussed later on.

heart valves are specialized tissue flaps that coordinate the outflow and inflow of blood between and out of chambers. there are 4 valves: mitral and tricuspid valves control blood between the atria and ventricles of each side and the semilunar valves control the outflow of blood from the ventricles to the lungs or to the aorta. all of these valves have the same general components: a spongy loose connective tissue core, elastic layer, dense collagenous layer, endothelium. in addition, interstitial cells are scattered throughout, which produce and repair extracellular matrix, vital in the valves' ability to withstand rapidly changing mechanical conditions.

the next major aspect of heart function is the conduction system, which coordinates rhythmic contraction of the myocytes. the SA node is at the junction of the right atrial appendage and the superior vena cava and is considered to be the pacemaker because of its faster rate of spontaneous depolarization. in contrast, the AV node is situated at the right atrium, along the atrial septum, and considered the gatekeeper because it delays conduction between the atria and ventricles, ensuring that the atria contract first. the other major component of the conduction system is the bundle of His, which runs from the right atrium down to the ventricular septum and then branches further into the ventricles.

myocytes rely almost exclusively on oxidative phosphorylation for energy production, making the blood flow to the heart crucial in maintaining proper physiology. this is accomplished via the coronary arteries, which arise distal to the aortic valve, run along the surface of the heart (called epicardial arteries) and then penetrate the heart muscle itself (called intramural arteries). the main epicardial arteries are the left anterior descending artery, the left circumflex artery, and the right coronary arteries. blockage of any of these arteries by a variety of factors can prove to be fatal to heart function.

these 4 different aspects of the heart can be damaged by specific pathological stressors, and can also be the victim of age related pathological changes. epicardial fat increases with age, especially over the right anterior surface and atrial septum. atrial size increases and ventricular size decreases. valves are prone to dysfunction due to calcification and fibrosis. the myocardium itself changes, with fewer monocytes, more collagen, and possible amyloid deposition. "brown atrophy" is a particular type of pathological change associated with age that is the result of excess lipofuscin deposits in a small, atrophied heart.

questions
heart intro...
1. how much blood does the heart pump on a daily basis?
2. what is the approximate weight of the heart?

myocardium...
3. what is the heart muscle cell called?
4. describe the orientation / arrangement of ventricular myocytes.
5. describe the difference between atrial and ventricular myocytes.
6. what are the cytoplasmic granules in atrial myocytes and what do they do?
7. what are intercalated discs?

valves...
8. what are the general tissue components to all 4 heart valves?
9. describe the role of interstitial cells in valve physiology.
10. what is an example of a disturbance in semilunar valve functioning?
11. what are some factors that can disturb mitral and tricuspid valve functioning?
12. what are the three common pathologies that occur with heart valves?

conduction system...
13. what are the key components of the conduction system of the heart?
14. where is the SA node located?
15. where is the AV node located?
16. where is the bundle of His located?
17. which component of the conduction system is considered the pacemaker and why?
18. which component of the conduction system is considered the gatekeeper and why?

blood flow...
19. how do cardiac myocytes meet their energy needs?
20. describe the course of the coronary arteries along the heart.
21. what are the three major epicardial branches of the coronary artery?
22. when does most blood flow to myocardium occur during the contraction cycle?

age related changes...
23. age's effect on epicardial fat...
24. age's effect on left ventricle...
25. age's effects on valves...
26. age's effects on myocardium...
27. what is "brown atrophy"?

answers
1. over 6000 liters.
2. 250-300g females, 300-350g males.
3. the myocyte.
4. ventricular myocytes are circumferentially arranged in a spiral orientation.
5. atrial myocytes are smaller and arranged more haphazardly.
6. electron dense granules: specific atrial granules which store atrial natriuretic peptide.
7. the junctions between myocytes which link the cells mechanically and electrically (via gap junctions).

8. dense collagenous core near the outflow surface, layer of elastin near the inflow surface, central spongy core of loose connective tissue and an endothelial covering.
9. interstitial cells are spread throughout the valve tissues, where they produce and repair extracellular matrix- allowing valves to adapt and respond to changing conditions.
10. aortic root dilation interfering with coordinated cuspal closure (CCC)
11. in addition to the factors that interfere with semilunar valve closure (the leaflets themselves and the tissues they are attached to), these valves are also dependent on the tendons they are attached to as well as the papillary muscles.
12. damage to collagen tissue, nodular calcification, and fibrotic thickening. (thick chalky fibers)

13. the SA node, AV node, and bundle of His.
14. junction of the right atrial appendage and the superior vena cava.
15. right atrium, along the atrial septum.
16. from the right atrium down to the ventricular septum, and from their branches out into the ventricles further.
17. the SA node because it spontaneously depolarizes at the fastest rate, 60-100bpm.
18. the AV node, because it delays conduction between the atrium and ventricles to ensure that atrial contraction precedes ventricular contraction.

19. almost exclusively from oxidative phosphorylation
20. the coronary arteries arise immediately distal to the aortic valve and run along the surface of the heart (epicardial), then penetrate the heart muscle (intramural).
21. left anterior descending, left circumflex, and right coronary
22. during diastole, when myocardium is not compressed by contraction.

23. increased, especially over anterior surface of right ventricle and atrial septum.
24. decreased chamber size, exacerbated by hypertension or sigmoid septum; resulting in a functional outflow obstruction.
25. calcification, fibrosis, or small filiform processes.
26. fewer myocytes, more collagen and possible amyloid deposition.
27. extensive lipofuscin deposits in a small, atrophied heart.