Histo Final 10 In 10"

Front 1

Accumulation of immune complexes in the subepithelial zone of glomerular capillaries. GBM material projects around the subepithelial deposits. Glomeruli are normocellular.


“spikes are present” in the GBM – Stage II. Spikes also called tram tracks

Back 1

Stage II Membranous Glomerulopathy

Front 2

GBM thickening or widening and expansion of the mesangial matrix, mild mesangial hypercellularity. Sometimes focal, segmental, nodular lesions appear, for example in Kimmelstiel-Wilson nodules. Capillaries & mesangial cells are pushed to the periphery in Kimmelstiel-Wilson. DG is the leading cause of end-stage renal disease in the U.S.

Back 2

Diabetic Glomerulosclerosis

Front 3

proliferation of parietal epithelial cells of Bowman’s capsule; cellular buildup resembles a crescent pushing on the glomerulus. This proliferation can cover about 50% of the entire urinary space. Fibrin and macrophages are also a component of “crescents”. This condition is not a disease but is a morphological component of an active disease.

Proliferation of the parietal cells of Bowman's capsule and also infiltration of macrophages, producing a crescent-like mass in most glomeruli

Back 3

Crescentic Glomerulonephritis

Front 4

also known as Type I membranoproliferative glomerulonephritis -- hypercellularity (increase in mesangial cells) and subendothelial deposits, glomeruli are enlarged

Back 4

Mesangial Glomerulonephritis

Front 5

Results from mutations in either of two genes: PKD1 and PKD2, encoding polycystin1 and polycystin2 proteins. These proteins are found predominantly in the cilium of principal cells of the collecting ducts.

A complete loss of P1 or P2 leads to extensive cyst formation. Cysts are derived from dilation of CD. Hypertension and renal failure are clinical presentations.

Polycystin 1 and 2 are mechanosensors

Back 5

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Front 6

Mutation of genes encoding AQP-2 and ADH receptors. Kidney does not respond to ADH because of defective AQP-2 and ADH receptor proteins synthesized by the collecting duct epithelial cells. Copious dilute urine is produced.

Back 6

Nephrogenic diabetes insipidus

Front 7

tubular function due to poor oxygenation, following a fall in blood pressure. Cells swell as a result of failure of NaK. ATPase pumps, leading to inadequate excretion of H2O into interstitium.

Result: oliguria or anuria hyperkalemia – raised K+ in blood acidosis – raised H+ in blood

Back 7

Acute Tubular Necrosis Failure

Front 8

Most common bladder cancer, male dominant, replacement of normal epithelial cells with ones that are enlarged, crowded with enlarged hyperchromatic nuclei and prominent mitotic figures; epithelium is not thickened. Epithelium changes are likely to progress to invasive.

Enlarged cells, prominent mitotic figures, dark nuclei

Back 8

Transitional Cell Carcinoma (TCC)

Front 9

7-dehydrocholesterol Vitamin D3 (skin): usually a half to 2 hours of sunlight exposure to sunlight per day can provide enough vitamin D to fulfill daily body requirements for this vitamin. Vitamin D is absorbed by the small intestin in association with chylomircrons

Vitamin D3 -> 25-OH Vitamin D3 (Hydroxylation in Liver)

25-OH Vitamin D3 -> 1,25-(OH)2 Vitamin D3 (hydroxlation in kidney): this process is regulated indirectly by an increase in plasma Ca concentration, which triggers secretion of PTH, or directly by a decrease in circulation phosphates which trigger this hydroxylation cascade. It is necessary for normal development and growth of bones and teeth.

Vitamin D deficiency results in rickets, a disease that causes abnormal bone ossification.

Back 9

Role of kidney in Vitamin D Synthesis and Role of other Organs

Front 10

Mutation in the nephrin gene leading to absence or structural malformation of the slit diaphragm, leads to proteinuria and edema.

Congenital Nephrotic Syndrome – Caused by a mutation in the nephrin gene leading to the absence or malfunction of the podocyte slit filtration diaphragm. Affected children have massive proteinuria and edema.

Back 10

Congenital Nephrotic Syndrome

Front 11

1. 98% of affected fetus result in miscarriages; accounts for 10% of all spontaneous abortions in US; affects 1:2500 live female births
2. Appearance: short stature, lymphoedema, broad chest, low hairline, low-set ears, webbed neck, gonadal dysfunction including amenorrhea and infertility (ovarian failure)
3. No cognitive effects but problem with visual-spatial relationships – math issues
4. Additional medical issues: ~ 1/3 thyroid disorders (hypothyroidism – autoimmune); ~1/3 kidney malformation; 5 – 10% constriction of aorta; Xp deletion results in lymphedema
5. IDed by Henry Turner (OK endocrinologist) in 1938
6. No cure – treat with GH, estrogen replacement, thyroid replacement, etc.

Back 11

Turner Syndrome

Front 12

1. Characterized by bilaterally enlarged ovaries with numerous follicular cysts.
2. AKA Stein-Leventhal syndrome when associated with oligomenorrhea (scanty menstruation).
3. Infertile due to lack of ovulation
4. Morphology: ovaries resemble small, white balloon filled w/ marbles
5. Cause: fluid-filled follicular cysts & atrophic secondary follicles beneath an unusually thick tunica albuginea.
6. Pathogenesis unclear but related to defect in regulation of androgen synthesis  excess production of estrogen
7. Abnormal selection process in follicle maturation; progesterone not produced  failure of mature follicle to transform into progesterone-producing corpus luteum.
8. Treatment of choice: hormones to stabilize & reconstruct estrogen:progesterone ratio; surgical intervention - incision into ovary cortex to allow oocyte exit following hormonal treatment.

Back 12

Polycystic ovarian disease:

Front 13

1. Oocytes fail to enter uterine tube usually degenerate in peritoneal cavity
2. If fertilized, oocytes that fail to enter uterine tube can implant on surface of ovary, intestine or inside the rectouterine pouch; ~95% implant in uterine tube wall
3. Most ectopic implantations do not develop past early fetal stages
4. May be fatal to mother & need to be removed surgically

Back 13

Ectopic implantation or pregnancy: implantation of embryo in abnormal site

Front 14

1. Associated w/ hormone-induced changes in ectopic endometrium during menstrual cycle.
2. As endometrium is shed, bleeding occurs in peritoneal cavity, causing severe pain, formation of cysts, scar tissue and adhesions.
3. May lead to sterility; ovaries and uterine tube become deformed & embedded in scar tissue.
4. No cure; Diagnosis by US, laparoscopy, CA-125 levels in blood
5. Treatment involves decreasing pain symptoms w/ medication; shrinking and/or slowing endometrial growths by blocking ovulation w/ hormones; restoring fertility by removal of growths by conservative surgery and hormonal treatment; prevention of recurrence by complete removal of growths and ovaries by hysterectomy.

Back 14

Endometriosis: uterine endometrial tissue in pelvic peritoneal cavity

Front 15

1. Non-cancerous growths of uterine tissue forming mass or polyp protruding into uterine cavity; sensitive to estrogen so  estrogen during cycle   growth of polyp
2. Present in ~10% of women; ID most in 40- 50 year olds
3. If blocks cervix or uterine tube  fertility issues; if IVF then  risk of miscarriage
4. Symptoms include: irregular bleeding; bleeding between menstrual cycles; excessively heavy bleeding during menstrual cycle; bleed post-menopause
5. At  risk if obese; tamoxifen (breast cancer drug); high BP; cervical polyps
6. Treatment: surgical removal but can recur

Back 15

Uterine fibroid

Front 16

1. 80 – 90% originate from stratified squamous epithelial cells
2. 10 – 20% originate from cervical glands (adenocarcinomas)
3. HPV infection now recognized as main cause (80% of cases) (~16 strains considered high-risk for development of cervical cancer) V16 found in ~50% of cases – although majority of infections do NOT result in cancer
4. In 2006 – 10,000 women in US diagnosed (half a million world-wide) & 4,000 women (~250,000 world-wide) die
5. Carcinoma in-situ: contained within epithelium, does not invade underlying stroma
6. Invasive carcinoma: penetrates basal lamina & metastasizes to other regions of body
7. Occurs at relatively high frequency
8. Cervical lesions may exist in noninvasive stage for as long as 20 years
9. Pap (Papanicolaou) smear used to detect variation in cells (from cervical or vaginal lining) with stages of menstrual cycle
10. May be cured by surgery if discovered before it becomes invasive

50 years ago – leading cause of death among women
6th most common cancer of women but mortality rates
decreased 70%

2nd most common cancer in women worldwide
Leading cause of cancer-related death in women
from underdeveloped countries

Higher rate of incidence among
African-Americans, Hispanic,
and Native Americans

Back 16

Cervical carcinoma:

Front 17

1. Ductal carcinoma: originates from epithelium lining ducts
2. Lobular carcinoma: originates from epithelium lining terminal ductules
3. If not treated early, tumor cells metastasize via lymphatic vessels to axillary nodes near affected breast  via bloodstream to lungs, bone and brain
4. 180,000 new cases diagnosed annually in US (~ 2000 are men)
5. 43,000 women (~ 400 men) die yearly
6. Early detection via exam, mammography, or US reduced mortality rate
7. Deficiency or mutation in BRCA1 shown to decrease stability or elevate incidence of mutation rate of tumor suppressor genes (e.g. p53)
8. Mutations in BRCA1 incapacitate checkpoint at G2-M of cell cycle and concurrently, number of centrosomes of these cells is increased; 5-10% of women w/ breast cancer; confers very high lifetime risk of breast & ovarian cancer
Mutated cells, therefore, have capability to proliferate
9. Presence of estrogen or progesterone receptors – good prognosis; tamoxifen – estrogen receptor blocker & treatment of choice
10. Presence of c-erb B2 oncoprotein on cell surface – poor prognosis.

Intraductal carcinoma: cancerous cells proliferate
w/in lactiferous ducts

Infilitrating ductal carcinoma: most commonn~78%

Invasive lobular carcinoma: ~15% of cancers linear array of cells.

Back 17

Breast cancer

Front 18

1. Tumors comprising multiple types of cells; derived from multiple germ layers therefore commonly seen in gonads (most in ovary; fewer in testes)
2. Benign teratomas - well-differentiated (mature) cystic lesions
3. Malignant teratomas - immature & non-cystic (i.e., solid)
4. Cells differentiate along various germ lines; recapitulate any tissue of the body (e.g., hair, teeth, fat, skin, muscle, & endocrine tissue)

Back 18

Teratomas

Front 19

1. AKA Rh (D antigen) isoimmunization
2. If mom is Rh(-) and baby is Rh(+), blood from baby can enter mom’s circulation by passing thru placenta.
3. Mom makes Abs against baby’s RBC (Rh antigen) and antibodies (if IgG) can pass thru placenta and causes hemolysis of baby’s RBCs.
4. Baby suffers from jaundice and anemia and can stillbirth or death of baby shortly after birth
5. Symptoms include low muscle tone, developmental delays; increase in amniotic fluid
6. Diagnosis is fetal/newborn hemolysis; increase in bilirubin levels; (+) direct Coombs test (detects presence of antibodies on surface of RBCs)
7. Complications to baby include: hydrops fetalis (fluid accumulation in brain); kernicterus (brain damage due to high levels of bilirubin); neurological issues
8. Almost completely preventable by injections of RhoGam mid-term during pregnancy and within a few days following birth; must also get RhoGam injections during every pregnancy, following a miscarriage or abortion, following amniocentesis or chorionic villus biopsy, or following any abdominal injury during pregnancy; prior to RhoGam estimated 10,000 babies lost yearly in US
9. RhoGam is a solution of IgG directed against D antibodies. This α-D antibody binds and kills any fetal Rh D (+) RBCs that cross the placenta preventing Mom from making antibodies against Rh(+) fetal RBCs.

Back 19

Erythroblastosis fetalis

Front 20

loss of ovarian function prior to age 40
1. Number of women affected increases with increasing age; 1:250 at age 25 & 1:100 at age 40; can occur at any age prior to 40
2. First symptom usually missed period; later symptoms similar to menopause
3. Thought to have 2 causes: loss of follicles from ovaries; autoimmune destruction of maturing follicles but no effect on primordial follicles
4. Diagnosed by determination of blood FSH (abnormally high due to lack of release of estrogen from mature follicle); low estrogen & LH levels in blood;
5. Complications: osteoporosis; infertility; depression
6. Treatment: no cure; treat symptoms with HRT til age of 50

Back 20

Premature ovarian failure

Front 21

Most common genital problem encountered in pediatrics. 30% in premature boys, 3% of full term. May have a number of causes but seem to related to 3 areas:

(1) hypothalamus-pituitary-gonadal axis
(2) epididymis
(3) gubernaculum and genitofemoral nerve.
Descent at 28 weeks. Effect on Spermatogenesis? Testosterone Synthesis?

Back 21

Cryptorchidism

Front 22

An autosomal recessive sex-limited condition with inability to convert testosterone to DHT. DHT is required for masculinization of the external genitalia in utero. Genetic males are born with ambiguous genitalia (ie, male pseudohermaphroditism). The uterus and fallopian tubes are absent because of the normal secretion of the Müllerian-inhibiting factor. Testes are intact, as are wolffian structures (epididymis, ductus deferens, seminal vesicles).

Back 22

5α-reductase Deficiency (5-ARD)

Front 23

Observed in males with an extra X chromosome (47,XXY). They are
1) phenotypically males – presence of the Y chromosome;
2) have small testes and few spermatogenic cells are present;
3) have high FSH levels because Sertoli cell function is abnormal (failure to produce inhibin);
4) have low testosterone levels, but high estradiol levels. High levels of estradiol can lead to phenotypic feminization.

Back 23

Kleinfelter Syndrome

Front 24

Testes germ cell tumor; most common testicular cancer in men with peak incidence 30-35 years. Not found before puberty. Tumor cells have a fried egg appearance & lymphocytes infiltrate around the STubules.

Back 24

Seminoma

Front 25

Interstitial fibrosis and hyalinization of the seminiferous tubule.

Back 25

Aged Testes

Front 26

an acute inflammatory reaction of the testis secondary to infection. Most cases are associated with a viral mumps infection however, other viruses and bacteria can cause orchitis. Approximately 20% of prepubertal patients with mumps develop orchitis. In bacterial orchitis, most cases are associated with epididymitis (epididymo-orchitis), and they occur in sexually active males older than 15 years or in men older than 50 years with benign prostatic hypertrophy (BPH).

inflammation of the testis, can be associated with prepubertal mumps or bacterial or an infection of epididymis

Back 26

Orchitis (awr-kahy-tis) – orkhis is Greek for testile;

Front 27

Rare tumor, not as common as seminoma. These are functionally active tumors secreting androgens, estrogens, or both. The Reinke crystal is a characteristic rectangular, eosinophilic, cytoplasmic inclusion. Most are benign.

Back 27

Leydig Cell Tumor

Front 28

enlarged mucosal and submucosal glands, increase in PSA and PAP. DRE (“bulky feel”) also for detection. Routine treatment by TURP.

Occurs almost exclusively in the transitional and periurethral zones, leading to partial or total obstruction of the urethra. DHT is sysnthesized in the stromal cells by conversion from circulation testosterone in the presence of 5alpha-reductase. Once sysnthesized, DHT acts as an autocrine agent on the stromal cells and as paracrine hormone on the epithelial cells, causing them to proliferate.

Back 28

Benign Prostatic Hypertrophy

Front 29

enlarged main or peripheral glands. Increased PSA and PAP, increased osteoblast activity related to increase in bone formation.

PSA test was essential in early detection, management, and follow up of patients with prostate cancer, and is considered on of the best bio-medical markers currently available in the field of oncology.

Treatment is by surgery, radiotherapy both for patients with localized disease. hormonal therapy is the treatment of choice for advanced cancer with metastases. Since prostatic cancer cells depend on androgens, the goal of the therapy is to deprive the cells of testosterone by performing orchiectomy or byadministration of estrogens or GnRH agonists to suppress testosterone production.

Back 29

Prostate Carcinoma

Front 30

dilation of the veins of the pampiniform plexus, ‘bag of worms’ appearance, usually seen in left testes due to blockage of left renal vein and thus increased venous pressure

Back 30

Varicocele