Reproductive Pathology

Reproductive System Pathology

Delayed Puberty

Kallman Syndrome = tall teenage male (46XY) with poorly developed secondary sex characteristics and anosmia (loss of sense of smell). Low GnRH -> low FSH, LH, and testosterone -> infertility (both males & females)

due to failure of migration of olfactory & GnRH producing neurons

Turner Syndrome = short female (46XO) with primary amenorrhea and premature ovarian failure (low estrogen, but high FSH & LH). May also have: webbed neck, swollen hands & feet, horseshoe kidney, coarctation of aorta/ aortic valve abnormalities. Increased risk of ovarian cancer, so remove ovaries

due to SHOX gene mutation --> skeletal abnormalities & short stature. No extra X means no barr body.

Links: 1, 2, MCC objectives

Infertility

Klinefelter's syndrome = tall young man with infertility (trying to conceive for 1 year and no success), long extremities & wide hips, gynecomastia, small shrunken testes (azoospermia i.e. no sperm production), low testosterone but high FSH & LH. May also have: learning difficulties, behavioral problems.

due to nondisjuntion or translocation --> 47XXY, (extra X -> barr body)

Ambiguous Genitalia

5-alpha-reductase deficiency = genetically male (46XY) infant with ambiguous genitalia until puberty. Normal testosterone, FSH, LH.

due to inability to convert testosterone to dihydrotestosterone (DHT) --> disruption of external male genitalia formation (penis, scrotum, prostate gland), but normal internal genitalia (regulated by testosterone). During puberty, testosterone rapidly increases external genitalia development

Aromatase deficiency = genetically female (46XX) infant with ambiguous genitalia. Mother of infant will present with transient masculinization (facial hair, etc) as excess androgens cross from placenta to maternal blood.

due to inability to convert androgens to estrogens (occurs in placenta then later in many tissues) --> disruption of external female genitalia formation.

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Chronic Myeloid Leukemia (CML)

Quick Review Patient is often older, and can no symptoms or have B symptoms (night sweats, etc), fatigue, and weight loss (caused by early satiety due to enlarged spleen). On physical exam, an enlarged spleen can be palpated. CBC shows very high WBC count (typically >100,000) with elevated basophils on differential. Peripheral smear shows early, immature neutrophil precursors (myelocytes, metamyelocytes) as well as many basophils. It is important for CML to know the details of the genetic abnormality because it relates to the treatment. CML is due to a translocation of BCR and ABL on chromosomes 9 and 22 resulting a fusion BCR-ABL gene that produces a tyrosine kinase that is always active. The treatment of choice is a tyrosine kinase inhibitor e.g. imatinib. They work to suppress the tyrosine kinase and can induce disease remission. Relevant Images Immature neutrophil precursors on peripheral smear BCR-ABL translocation

Chemotherapy

Terminology Adjuvant therapy - given in addition to standard therapy Consolidation therapy - given after induction therapy with multidrug regimens to further reduce tumor burden Induction therapy - initial dose of treatment to rapidly kill tumor cells and send the patient into remission Maintenance therapy - given after induction and consolidation therapies or after the initial standard therapy to kill any residual tumor cells and keep the patient in remission Neoadjuvant therapy - given before the standard therapy for a particular disease Remission - less than 5% tumor burden Salvage therapy - given when standard therapy fails Adjuvant therapies in various cancers Metastasis to bone - bisphosphonates (e.g. zoledronic acid) are given to prevent lytic lesions and pathologic fractures as well as malignant hypercalcemia. Bisphosphonates work by inhibiting osteoclasts and thereby preventing bone breakdown. Breast cancer Tamoxifen , a selective estrogen recep...

Heparin

Mechanism Unfractioned heparin (UFH) has a pentasacharide sequence that binds to antithrombin to form a complex. The UFH-antithrombin complex is better at inactivating factor Xa then antithrombin alone. This is because once bound to UFH, antithrombin undergoes a conformational change. The UFH-antithrombin complex can also inactivate thrombin by binding to it. Low moleculer weight heparin (LMWH) also has a pentasaccharide sequence that binds to antithrombin to form a complex. The LMWH-antithrombin complex also inactivates factor Xa, however, it doesn't work on thrombin. This is because the pentasaccharide sequence on LMWH is too short to both complex with antithrombin and bind thrombin. LMWHs typically end in "parin", examples include enoxaparin and dalteparin . Adverse effect: Heparin-Induced Thrombocytopenia (HIT) Heparin is a common cause of thrombocytopenia. LMWH (e.g. enoxaparin) is less likely than unfractioned heparin to cause HIT. There are two m...

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