Pbl Exam 7 Case 6

Front 1

1. What are three reasons for the failure of the mother to reject the fetus?

Back 1

1. The absence or low density of MHC antigens on placental cells
2. A covering of antigens w/blocking antibody
3. Subtle defects in the maternal immune responses

Front 2

2. Once the fetus is infected, what are three reasons why it is very susceptible?

Back 2

1. IgM and IgA antibodies are not produce din significant amts until the second half of the pregnancy
2. There is no IgG antibody synthesis
3. Cell-mediated immune responses are poorly developed or absent, with inadequate production of the necessary cytokines

Front 3

3. What are the 11 important causes of congenital infections?

Back 3

1. Rubella virus
2. CMV
3. HIV
4. VZV
5. HSV
6. HBV
7. Parvovirus B19
8. Treponema pallidum
9. Toxoplasma gondii
10. Listeria monocytogenes
11. Mycobacterium leprae

Front 4

4. What are the effects of the human parvovirus B19?

Back 4

Parvovirus B19 during pregnancy causes fetal damage or death in 5-10% of cases following maternal infection in early pregnancy. The infected fetus develops severe anemia with ascites and hepatosplenomegaly (hydrops fetalis) as the virus infects progenitor erythroid stem cells.

Front 5

5. What is congenital rubella?

Back 5

The fetus is particularly susceptible to rubella infection when maternal infection occurs during the first 3 mos of pregnancy.

At this time, the heart, brain, eyes and ears are being formed and the infecting virus interferes with their development.

Front 6

6. What are the clinical manifestations of congenital rubella?

Back 6

These include low birth weight and eye and heart lesions. Effects on the brain and ears may not become detectable until later in childhood, in the form of mental retardation and deafness.

Up to 80% of infants eventually suffer from deafness. About 25% of congenitally infected children develop insulin-dependent diabetes later in life, but rubella is a very uncommon cause of this disease. There is a 15% mortality in infants showing signs of infection at birth, often associated with hypogammaglobulinemia.

Front 7

7. Where are fetal rubella antibodies found?

Back 7

Fetal rubella IgM is found in cord and infant blood. Infected fetuses produce their own IgM molecules to rubella virus, which can be detected in cord and infant blood.

Maternal IgG antibodies are also present and together with interferons help control the spread of infection in the fetus. Virus can be isolated form the infant's throat or urine. The infant sheds virus into the throat and urine for several months and can infect susceptible individuals.

Front 8

8. Is congenital rubella preventable?

Back 8

Yes, completely. Vaccination with live attenuated virus vaccine is given during childhood, usually in the MMR vaccine.

*Pregnancy is a contraindication to vaccination, and the only safe time during reproductive life is in the immediate postpartum period.

Front 9

9. What are the organ involvement and effects associated with congenital rubella?

Back 9

1. Small brain size
2. Mental retardation
3. Cataracts
4. Microphthalmia
5. Hearing defect (organ of Corti affected)
6. PDA, patent interventricular septum
7. Hepatosplenomegaly, TTP, anemia
8. Low birth weight
9. Failure to thrive
10. Increased infant mortality

Front 10

10. What is congenital CMV infection?

Back 10

Mothers with a poor T-cell proliferative response to CMV antigens are more likely to infect their fetus. After primary maternal infection during pregnancy, about 40% of fetuses are infected. Of those women with a primary infection in the first trimester, up to 30% of babies may develop CNS sequalae.

Front 11

11. What are the clinical features of congenital CMV infection?

Back 11

1. Mental retardation
2. Spasticity
3. Eye abnormalities
4. Hearing defects
5. Hepatosplenomegaly
6. Thrombocytopenic purpura
7. Anemia

*Deafness and mental retardation may not be detectable until later in childhood.

Front 12

12. How is congenital CMV infection detected?

Back 12

Dx is by detecting CMV-specific IgM antibodies in infant blood w/in 3 weeks of delivery, and by detecting and quantifying CMV DNA in the blood or urine during this period.

Front 13

13. What is congenital syphilis?

Back 13

It is rare, but more common in resource-poor countries.

Clinincal features in the infant include rhinitis (snuffles), skin and mucosal lesions, heaptosplenomegaly, lymphadenopathy, and abnormalities of bones, teeth,

Front 14

14. How is congenital syphilis detected?

Back 14

Pregnancy often masks the early signs of syphilis, but the mother will have serological evidence of treponemal infection, and treponemal IgM will be detected in the fetal blood.

Front 15

15. How is congenital syphilis spread to the fetus?

How is it treated?

Back 15

Vertical transmission most commonly takes place after 4 months of gestation, therefore treatment of the mother before the 4th month of pregnancy should prevent infection.

Front 16

16. What is congenital toxoplasmosis?

Back 16

Acute asymptomatic infeciton by Toxoplasma gondii during pregnancy can cause fetal malformation. Clinincal features in teh fetus include convulsions, microcephaly, chorioretinitis, hepatosplenomegaly and jaundice, with alter hydrocephaly, mental retardation and defective vision.

There are often no detectable abnormalities at birth, but signs (e.g., chorioretinitis) generally appear within a few years.

Front 17

17. How is congenital toxoplasmosis detected?

What is the treatment?

Is there a vaccine?

Back 17

Toxoplasma-specific IgM antibodies may be detected in cord blood. Treatment of a pregnant woman or an infected infant is with spiramycin or (w/care to avoid toxicity) sulfonamide + pyrimethamine + folinic acid.

There is no vaccine. Prevention is by avoidance of primary infection which occurs via ingesting cysts from cat feces or lightly cooked meat during pregnancy.

Front 18

18. Where does congenital HIV infection occur?

Back 18

In resource poor countries, approx 1/4 of infants born to mother with HIV are infected; about 1/3 of these in utero and the rest perinatally.

Front 19

19. What are the symptoms of congenital HIV infection?

Back 19

Clinically, congenital HIV infection manifests as poor weight gain, susceptibility to sepsis, developmental delays, lymphocytic pneumonitis, oral thrush, enlarged lymph nodes, hepatosplenomegaly, diarrhea and pneumonia, and some infants develop encephalopathy and AIDS by 1 year of age.

Front 20

20. How can congenital HIV infection be prevented?

Back 20

Since most infections take place during late pregnancy or during delivery, transmission rates are reduced by lowering the HIV load by offering antiretroviral drugs during pregnancy, especially during the last trimester or during labor, carrying out an elective c-section, and avoiding breast feeding.

Front 21

21. How is congenital HIV infection Dx?

Back 21

IgG antibodies present in the neonatal blood sample may be maternal in origin and can persist for at least 1 year.

*The mainstay of Dx therefore involves detection of HIV-1 proviral DNA or HIV-1 RNA by PCR, although these tests may not be positive until several months after birth, in conjunction with HIV antibody and antigen detection using the combination assay.

Front 22

22. What is listeriosis?

Back 22

Listeriosis is caused by Listeria monocytogenes, a small Gram-positive rod, which is motile and beta-hemolytic. Its distro is worldwide in a great variety of animals including cattle, pigs, rodents and birds, and the bacteria occur in plants and in soil.

Its transmission to human is by:
1. Contact w/infected animals and their feces
2. Consumption of unpasteurized milk or soft cheeses or contaminated vegetables

Front 23

23. What are the features of listeriosis infection during pregnancy?

Back 23

L. monocytogenes in the pregnant woman causes a mild influenza-like illness or is asymptomatic, but there is a baceremia.

This may cause abortion, premature delivery, neonatal septicemia or pneumonia with abscesses or granulomas. The infant can also be infected shortly after birth, for instance from other babies or from hospital staff, and this may lead to a meningitic illness.

Front 24

24. How is listeriosis Dx?

What is the Tx?

How is it prevented?

Back 24

L. monocytogenes is isolated from blood cultures, CSF, or newborn skin lesions.

Treatment is w/ampicillin, which may need to be combined w/gentamicin to achieve a bactericidal effect. There are no vaccines.

Pregnant women should avoid exposure to infected material, but the exact source of infection is generally unknown.

Front 25

25. What are the features of viral infections in the fetus and neonate?

Back 25

Viral infections (e.g. rubella, CMV), are generally less damaging to the fetus when the maternal infection occurs late in pregnancy.

Primary infection w/VZV in the first 20 weeks of pregnancy can lead to limb deformities and other severe lesions in the newborn.

HSV infection in this setting is underdiagnosed and can lead to neonatal morbidity and mortality.

Front 26

26. What about bacterial infections in the fetus and neonate?

Back 26

Bacterial infections originating from the vagina and perineum late in pregnancy, especially those occurring when the fetal membranes have been ruptured for more than 1-2 days, may result in chorioamnionitis, maternal fever, premature delivery and stillbirth.

Infants of low birth weight (<1500g) tend to be more severely affected.

Front 27

27. What are the bacteria involved in fetal and neonate infections?

Back 27

1. Group B hemolytic streptococci; 10-30% of pregnant women are colonized in the rectum or vagina
2. E. coli
3. Klebsiella
4. Proteus
5. Bacteroides
6. Staphylococci
7. Mycoplasma hominis

*These infections may also be acquired after delivery to give later onset disease.

Front 28

28. What are the features of neonatal septicemia?

Back 28

Neonatal septicemia often progresses to meningitis. Bacterial meningitis is frequently fatal unless treated.

Dx is difficult b/c the infant shows generalized signs such as respiratory distress, poor feeding, diarrhea and vomiting, but early Dx is essential and emergency treatment is required.

Blind antibiotic treatment should be started as soon as CSF (gram stain and culture) and blood samples have been taken.

Front 29

29. What are the features of fetal infection with HSV?

Back 29

Fetal infection w/HSV must be considered in a baby who is acutely ill w/in a few weeks of birth.

Cutaneous lesions of HSV may develop 1 week after delivery, w/generalized infection and severe CNS involvement.

Babies < 4 weeks of age may present w/neonatal HSV as acutely ill and septic but classically there are three well-defined clinical presentations.

Front 30

30. What are the three well-defined clinical presentations of neonatal HSV?

Back 30

1. Those with infection affecting the skin, eye, and/or mouth (SEM)
2. Encephalitis with or w/o skin involvement
3. Disseminated disease involving the lungs, liver, CNS, adrenal glands, and SEM

Front 31

31. What is the Dx for neonatal HSV infection?

Treatment?

Back 31

The Dx may be missed as neonatal HSV infection may present w/o skin lesions in up to 39% of babies. Therefore, there must be a low threshold for considering this Dx and aciclovir therapy should be started ASAP.

Morbidity and mortality rates are higher in those w/encephalitis and disseminated disease.

Front 32

32. What are the features of gonoccoal, chlamydial, or staphylococcal infection?

Back 32

Gonoccoal, chlamydial, or staphylococcal infection can infect the eye to cause ophthalmia neonatorum.

Infection w/group B streptococci generally occurs at this time.

Front 33

33. What about HBV infection and the neonate?

HCV?

Back 33

In countries w/high HBV carrier rates, maternal blood is a major source of infection during or shortly after birth. More than 90% of infants from carrier mother become infected and then carry the virus. This is preventable by giving the vaccine plus specific immunoglobulin to the newborn.

HCV, in contrast, is not usually transmitted in this way, and < 5% of children w/carrier mothers are infected.

Front 34

34. Can human milk carry pathogens?

Back 34

Yes, human milk may contain rubella virus, CMV, human T-cell lymphotropic virus (HTLV), and HIV.

Virus titers are generally low and, except in the case of HTLV and HIV, milk is not thought to be an important source of infection.

Front 35

35. What is puerperal sepsis?

Back 35

After delivery, a large area of damaged vulnerable uterine tissue is exposed to infection. Puerperal sepsis was a major cause of mortality back in the 1800's.

It was caused by Group A beta-hemolytic streptococci (major culprits***), and other possible organissm which include anaerobes such as C. perfringens, or Bacteroides, E. coli, and group B streptococci and originate from the mother's own fecal flora.

Front 36

36. What were the major predisposing factors to puerperal sepsis?

Back 36

These include immature rupture of the membranes, instrumentation and retained fragemetn of membrane or placenta. Poor aseptic techniques were a major contributor.

High vaginal swabs and blood cultures should be taken if there is postnatal pyrexia or an offensive discharge.

Front 37

37. What are three types of infections that may be transmitted to the newborn infant during the first 1-2 weeks after birth?

Back 37

1. Group B beta-hemolytic stroptococci and Gram-negative bacilli acquired by cross-infection in the nursery, can still cause serious infection at this time, often w/meningitis
2. HSV from cold sores or herpetic whitlows of attending adults
3. Staphylococci from the noses and fingers of adult carriers may cause staphylococcal conjunctivitis or "sticky eye", skin sepsis, and sometimes staphylococcal scalded skin syndrome due to a specific epidermolytic staphylococcal toxin.

Front 38

38. Can the mother's nipple become infected?

Back 38

During the first 1-2 weeks of life, the nose of the neonate becomes colonized w/Staphylococcus aureus, which can enter the nipple during feeding to cause a breast abscess.

These infections are preventable if hospital staff pay vigorous attention to hand washing and aseptic techniques.

Front 39

39. What can infect the umbilical stump?

Back 39

If hygienic practices are poor, the umbilical stump, especially in resource-poor countries, may be infected w/Clostridium tetani, usually b/c instruments used to cut the cord are contaminated w/bacterial spores, resulting in neonatal tetanus.

It can be prevented by immunizing mothers w/tetanus toxoid.

Front 40

40. What is the function of PTH in supporting serum calcium levels?

5 things...

Back 40

1. PTH activates osteoclasts, thereby mobilizing calcium from bone
2. It increases the renal tubular reabsorption of calcium, thereby conserving free calcium
3. It increases the conversion of vitamin D to its active dihydroxy form in the kidneys
4. It increases urinary phosphate excretion, thereby lowering serum phosphate levels
5. It augments GI calcium absorption

Front 41

41. What is the most common cause of clinincally apparent hypercalcemia?

Back 41

Malignancy. Hypercalcemia of malignancy is due to increased bone resorption and subsequent release of calcium

Front 42

42. What are the two major mechanisms that cause hypercalcemia of malignancy?

Back 42

1. Osteolytic metastases and local release of cytokines
2. Release of PTH-related protein (PTHrP)

Front 43

43. What is RANK and RANKL?

Back 43

RANK is a critical osteoclastogenic pathway. It stands for receptor activator of nuclear factor kB. Its ligand is RANKL. It's decoy receptor is osteoprotegerin.

RANKL is also know as "osteoclast differentiation factor", and by binding with the RANK receptor, it promotes all aspects of osteoclast function.

Front 44

44. What does RANK and RANKL have to do with hypercalcemia of malignancy?

Back 44

RANKL is secreted by tumor cells and peritumoral stromal cells in metastatic foci and causes osteolysis.

Osteoprotegerin inhibits this pathways of osteoclastogenesis and has emerged as a possible therapeutic agent in CA pts w/hypercalcemia of malignancy.

Front 45

45. What is the most freq cause of hypercalcemia in nonmetastatic solid tumors?

Back 45

The release of PTHrP. This protein is different from PTH yet it is similar enough to permit binding to identical receptors and stimulation of cAMP.

Classically, PTHrP-induced hypercalcemia was known as "humoral hypercalcemia of malignancy" to distinguish it from hypercalcemia arising from osteolytic metastases. However, PTHrP contributes to hypercalcemia of malignancy irrespective of the presence or absence of metastases.

Front 46

46. What is primary hyperparathyroidism?

What are the three main causes of it?

Back 46

Primary hyperPTH is one of the most common endocrine disorders, and it is an important cause of hypercalcemia.

It comes from:
1. Adenoma (75-80%)
2. Primary hyperplasia (10-15%)
3. PTH CA (less than 5%)

Front 47

47. What is the prevalence of primary hyperparathyroidism?

Back 47

Primary hyperparathyroidism is usually a disease of adults and is more common in women than in men by a ratio of 3:1. Most cases occur in the fifties or later in life.

Front 48

48. What is the pathogenesis of primary hyperparathyroidism?

Back 48

In more than 95% of cases, the disorder is caused by sporadic PTH adenomas or sporadic hyperplasia.

Front 49

49. What are the 3 genetic syndromes associated with familial primary hyperparathyroidism?

Back 49

1. MEN-1
2. MEN-2
3. Familial hypocalciuric hypercalcemia (FHH)

Front 50

50. How is MEN-1 related to primary hyperparathyroidism?

What causes it?

Back 50

The MEN1 gene on chromosome 11q13 is a tumor suppressor gene inactivated in a variety of MEN-1 related PTH lesions, including PTH adenomas and hyperplasia.

In addition to familial cases, MEN1 mutations have also been described in sporadic PTH tumors.

Front 51

52. How is MEN-2 related to primary hyperparathyroidism?

What causes it?

Back 51

The MEN-2 syndrome is caused by activating mutaitons in the tyrosine kinase receptor, RET.

Primary hyperparathyroidism occurs as a component of MEN-2A.

Front 52

53. How is familial hypocalciuric hypercalcemia related to primary hyperparathyroidism?

What causes it?

Back 52

FHH is an autosomal dominant disorder characterized by enhanced PTH function due to decreased sensitivity to EC calcium.

Mutations in the PTH calcium sensing gene (CASR) on chromosome 3q are a primary cause for this disorder. Pts w/homozygous CASR mutations present in the neonatal period w/severe hyperparathyroidism.

Front 53

54. Are sporadic PTH adenomas monoclonal or polyclonal?

Back 53

Most, if not all, sporadic PTH adenomas are monoclonal, suggesting that they are true neoplastic outgrowths from a single abnormal progenitor cell.

Front 54

55. What is the parathyroid adenoma 1 (PRAD1) molecular defect?

Back 54

PRAD1 encodes cyclin D1, a major regulator of the cell cycle. A pericentromeric inversion of chromosome 11 resutls in relation of PRAD1 protooncogene so that is directs overexpression of cyclin D1 protein, forcing the cells to proliferate.

10-20% of adenomas have this clonal genetic defect.

Front 55

56. What is the MEN1 molecular defect?

Back 55

Approx 20-30% of PTH tumors not associated with the MEN-1 syndrome demonstrate mutations in both copies of the MEN1 gene.

The spectrum of MEN1 mutations in the sporadic tumors is virtually identical to that in familial PTH adenomas.

Front 56

57. What is the morphology of PTH adenomas?

Back 56

PTH adenomas are almost always solitary and may lie in close proximity to the thyroid gland or in an ectopic site.

It usually averages 0.5 - 5.0 gm; is a well-circumscribed, soft, tan to reddish-brown nodule; and is invested by a delicate capsule.

Front 57

58. Are the PTH glands enlarged with PTH adenomas?

Back 57

In contrast to primary hyperplasia, the glands outside the adenoma are usually normal or somewhat shrunken due to feedback inhibition by elevations in serum calcium.

Front 58

59. What are the microscopic features of PTH adenomas?

1/2

Back 58

Microscopically, PTH adenomas are often composed predominantly of fairly uniform, polygonal chief cells w/small, centrally placed nuclei.

In most instances, at least a few nests of large cells containing oxyphil cells are present as well. (Uncommonly, entire adenomas are composed of this cell type and are called oxyphil adenomas).

Front 59

60. What are the microscopic features of PTH adenomas?

2/2

Back 59

The chief cells are arranged in a variety of patterns; follicles reminiscent of those seen in the thyroid are present in some cases.

Mitotic figures are rare. A rim of compressed, non-neoplastic PTH tissue, generally separated by a fibrous capsule, is often visible at the edge of the adenoma.

*It is not uncommon to find bizarre and pleomorphic nuclei even within adenomas (called endocrine atypia), and this should not be used as a criterion for malignancy.

Front 60

61. What is the morphology of primary PTH hyperplasia?

Back 60

Primary hyperplasia may occur sporadically or as a component of MEN syndrome. Although classically all four glands are involved, there is freq asymmetry w/apparent sparing of one or two glands, making the distinction btwn hyperplasia and adenoma dfficult.

The combined weight of all glands rarely exceeds 1 g.

Front 61

62. What are the microscopic and histologic features of PTH hyperplasia?

Back 61

Microscopically, the most common pattern seen is that of chief cell hyperplasia, which may involve the glands in a diffuse or multinodular pattern. Less commonly, the constituent cells contain abundant water clear cells called "water-clear cell hyperplasia".

In many instances, there are islands of oxyphils, and poorly developed, delicate fibrous strands may envelop the nodules.

Front 62

63. What is the morphology of PTH carcinomas?

Back 62

PTH CAs may be fairly circumscribed lesions that are difficult to distinguish from adenomas, or they may be clearly invasive neoplasms.

*These tumors enlarge one PTH gland and consist of gray-white, irregular masses that sometimes exceed 10 gm in weight.

*The cells are uniform, and are arrayed in nodules or trabecular patterns with a dense, fibrous capsule enclosing the mass.

Front 63

64. What are the criterion for Dx of malignancy with PTH CAs?

Back 63

A Dx based on cytologic detail is unreliable, and invasion of surrounding tissues and metastasis are the only reliable criteria of malignancy.

Front 64

65. What are the skeletal changes associated with primary hyperparathyroidism?

Back 64

These include prominence of osteoclasts, which, in turn, erode bone matrix and mobilize calcium salts, particularly in the metaphyses of long bones.

In many cases, the resultant bone contains widely spaced, delicate trabeculae reminiscent of those seen in osteoporosis.

Also includes osteitis fibrosa cystica and brown tumors.

Front 65

66. What is osteitis fibrosa cystica?

Back 65

In more sever cases, teh cortex of the bone is grossly thinned, and the marrow contains increased amts of fibrous tissue accompanied by foci of hemorrhage and cyst formation.

Front 66

67. What are brown tumors of hyperparathyroidism?

Back 66

Aggregates of osteoclasts, reactive giant cells, and hemorrhagic debris occasionally form masses that may be mistaken for neoplasms called brown tumors of hyperparathyroidism.

Front 67

68. What are the renal complications of hyperparathyroidism?

Back 67

PTH-induced hypercalcemia favors formation of urinary tract stones (nephrolithiasis) as well as calcification of the renal interstitium and tubules (nephrocalcinosis).

Front 68

69. What is the clinical course for primary hyperparathyroidism?

Back 68

It may present in one of two ways:

1. It may be asymptomatic and be identified after a routine chemistry profiles
2. Pts may have the classic clinical manifestations of primary hyperparathyroidism

Front 69

70. What is the clinical course for asymptomatic hyperparathyroidism?

Back 69

Routine serum calcium determinations in medical evaluations have resulted in the Dx of most cases of primary hyperparathyroidism at an early stage.

***In pts w/primary hyperparathyroidism, serum PTH levels are inappropriately elevated for the level of serum calcium, whereas PTH levels are low to undetectable in the hypercalcemia resulting from non-PTH diseases.

Front 70

71. What is the clinical course for symptomatic primary hyperparathyroidism?

Back 70

The signs and symptoms of hyperparathyroidism reflect the combined effects of increased PTH secretion and hypercalcemia.

Primary hyperparathyroidism has been traditionally associated with a constellation of symptoms including "painful bones, renal stones, abdominal groans, and psychic moans".

Front 71

72. What are the six major clinical manifestations that can present with symptomatic primary hyperparathyroidism?

Back 71

1. Bone disease includes bone pain secondary to fractures of bones weakened by osteoporosis or osteitis fibrosa cystica
2. Nephrolithiasis, and chronic renal insufficiency, polyuria, and secondary polydipsia
3. GI disturbances include constipation, nausea, peptic ulcers, pancreatitis, and gallstones
4. CNS alterations include depression, lethargy, and eventually seizures
5. Neuromuscular abnormalities include complaints of weakness and fatigue
6. Cardiac manifestations include aortic or mitral valve calcifications (or both)

Front 72

73. What causes secondary hyperparathyroidism?

Back 72

Secondary hyperparathyroidism is caused by any condition associated w/a chronic depression in the serum calcium level b/c low serum calcium leads to compensatory over-activity of the PTH glands.

***Renal failure is by far the most common cause of secondary hyperparathyroidism.

Front 73

74. What is the morphology of secondary hyperparathyroidism?

Back 73

***The PTH glands in secondary hyperparathyroidism are hyperplastic.

The degree of glandular enlargement is not necessarily symmetric.

Microscopically, the hyperplastic glands contain an increased number of chief cells, or cells with more abundant, clear cytoplasm (water-clear cells) in a diffuse or multinodular pattern.

Front 74

75. What is the pathogenesis of secondary hyperparathyroidism?

Back 74

Renal failure is related to phosphate retention and hypocalcemia, with compensatory hypersecretion of PTH.

Impaired GI calcium absorption b/c of reduced 1,25-(OH)2D3 synthesis and skeletal resistance to the effects of PTH and vitamin D may also contribute.

Front 75

76. What are the clinical features of secondary hyperparathyroidism?

Back 75

The clinical features are usually dominated by those associated w/chronic renal failure. Bone abnormalities and other changes associated with excess PTH are less severe.

Front 76

77. What is calciphylaxis??

Back 76

The vascular calcification associated with secondary hyperparathyroidism may occasionally result in significant ischemic damage to skin and other organs, a process sometimes referred to as calciphylaxis.

Front 77

78. What is tertiary hyperparathyroidism?

Back 77

In a minority of pts, PTH activity may become autonomous and excessive, with resultant hypercalcemia.

Parathyroidectomy may be necessary to control the hyperparathyroidism in such pts.

Front 78

79. What are the causes of hypoparathyroidism?

Back 78

1. Surgically induced
2. Congenital absence of glands (22q11.2 syndrome)
3. Familial hypoparathyroidism*
4. Idiopathic hypoparathyoidism

Front 79

80. What is associated with familial hypoparathyroidism?

Back 79

Familial hypoparathyroidism is often associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency.

This syndrome is known as autoimmune polyendocrine syndroem type 1 (APS1) and is caused by mutations in the autoimmune regulator (AIRE) gene.

The syndrome typically presents in childhood with the onset of candidiasis, followed several years later by hypoparathyroidism and then adrenal insufficiency during adolescence.

Front 80

81. What causes idiopathic hypoparathyroidism?

Back 80

Idiopathic hypoparathyroidism most likely represents an autoimmune disease w/isolated atrophy of the glands.

60% of the pts with this disorder have autoantibodies directed against the calcium-sensing receptor (CASR) in the PTH gland. Antibody bind to the receptor may prevent the release of PTH.

Front 81

82. What are the clinical manifestations of hypoparathyroidism?

Back 81

1. The hallmark of hypocalcemia is tetany which is characterized by neuromuscular irritability
2. Mental status changes
3. Intracranial manifestations include calcifications of the basal ganglia, Parksonian-like movement disorders
4. Ocular disease results in calcification of the lens leading to cataract formation
5. Cardiovascular manifestations include a conduction defect, which produces a characteristic prolongation of the QT interval
6. Dental abnormalities

Front 82

83. What are the two classic findings on physical exam of pts with neuromuscular irritability?

Back 82

Chvostek sign and Trousseau sign.

Chvostek sign is elicited in subclinical disease by tapping along the course of the facial nerve, which induces contractions of the muscles of the eye, mouth, or nose.

Occluding the circulation to the forearm and hand by inflating a BP cuff about the arm for several minutes induces carpal spasm, which disappears as soon as the cuff is deflated (Trousseau sign).

Front 83

84. What is pseudohypoparathyroidism?

Back 83

In this condition, hypoparathyroidism occurs b/c of end-organ resistance to the actions of PTH. Serum PTH levels are normal or elevated.

Front 84

85. What is the pathogenesis of pseudohypoparathyroidism?

Back 84

Its related to mutations in GNAS1, the gene encoding Gsα, a G-protein that mediates PTH action on cells.

As a result, there is loss of responsiveness to PTH in target tissues. This situation results in hypocalcemia, compensatory PTH hyperfunction, and a variety of skeletal and developmental abnormalities.

Front 85

86. What are the two types of pseudohypoparathyroidism?

Back 85

1. Pseudohypoparathyroidism type 1A

2. Pseudopseudohypoparathyroidism

Front 86

87. What is pseudohypoparathyroidism type 1A?

Back 86

Type 1A is associated with multihormone resistance and Albright hereditary osteodystrophy (AHO), a syndrome characterized by skeletal and developmental defects.

Pts with AHO often have short stature, obesity, short metacarpal and metatarsal bones, and variable mental deficits.

***The mutation in this disorder is inherited on the maternal allele, severely impeding the actions of PTH on the kidney in maintaining calcium homeostasis.

Front 87

88. What is pseudopseudohypoparathyroidism?

Back 87

In this disorder, the mutation is inherited on the paternal allele, and is characterized by AHO w/o accompanying multihormonal resistance.

As a result, serum calcium, phosphate and PTH levels are normal.

Front 88

89. Maturation of the ovum

Back 88

While still in the ovary, the ovum is in the primary oocyte stage. Shortly before it is released from the ovarian follicle, its nucleus divides by meiosis and a first polar body is expelled from the nucleus of the oocyte.The primary oocyte then becomes the secondary oocyte. In this process, each of the 23 pairs of chromosomes loses one of its partners, which becomes incorporated in a polar body that is expelled.

This leaves 23 unpaired chromosomes in the secondary oocyte. It is at this time that the ovum, still in the secondary oocyte stage, is ovulated into the abdominal cavity. Then, almost immediately, it enters the fimbriated end of one of the fallopian tubes.

Front 89

90. How does the ovum enter the fallopian tube?

Back 89

The fimbriated ends of each fallopian tube fall naturally around the ovaries. The inner surfaces of the fimbriated tentacles are lined w/ciliated epithelium, and the cilia are activated by estrogen from the ovaries, which causes the cilia to beat toward the opening, or ostium, of the involved fallopian tube.

*Ova can even enter the opposite fallopian tube.

Front 90

91. Fertilization of the ovum - where does it occur?

Back 90

Fertilization normally takes place in the ampulla of one of the fallopian tubes soon after both the sperm and the ovum enter the ampulla.

Front 91

92. What is the acrosome reaction?

Back 91

Before the sperm can enter the ovum, it must first penetrate the multiple layers of the granulosa cells attached to the outside of the ovum (the corona radiata) and then bind to an penetrate the zona pellucida surrounding the ovum itself.

Proteolytic enzymes released from sperm dissolve zona pellucida - takes about 30 minutes to penetrate zona pellucida

Front 92

93. Once a sperm has entered the ovum, what happens?

Back 92

Once a sperm has entered the ovum (which is still in the secondary oocyte stage of development), the oocyte divides again to form the mature ovum plus a second polar body that is expelled.

The mature ovum still carries its nucleus (now called the female pronucleus) 23 chromosomes. One of these chromosomes is the female chromosome, known as the X chromosome.

Also, the fertilizing sperm has also changed. On entering the ovum, its head swells to form a male pronucleus. Later, the 23 unpaired chromosomes of the male pronucleus and the 23 unpaired chromosomes of the female pronucleus align themselves to re-form a complete complement of 46 chromosomes (23 pairs) in the fertilized ovum.

Front 93

94. What determines the sex of the fetus?

Back 93

After formation of the mature sperm, half of these carry in their genome an X chromosome (the female chromosome) and half carry a Y chromosome (the male chromosome).

Therefore, if an X chromosome from a sperm combines with an X chromosome from an ovum, giving an XX combination, a female child will be born. But if a Y chromosome from a sperm is paired with an X chromosome from an ovum, giving an XY combination, a male child will be born.

Front 94

95. What happens to the fertilized ovum after fertilization takes place?

Back 94

After fertilization has occurred, an additional 3 to 5 days is normally required for transport of the fertilized ovum through the remainder of the fallopian tube into the cavity of the uterus.

This transport is effected mainly by a feeble fluid current in the tube resulting from epithelial secretion plus action of the ciliated epithelium that lines the tube; the cilia always beat toward the uterus.

Weak contractions of the fallopian tube may also aid the ovum passage.

Front 95

96. What causes the contractions of the fallopian tubes?

Back 95

The fallopian tubes are lined with a rugged, cryptoid surface that impedes passage of the ovum despite the fluid current. Also, the isthmus of the fallopian tube (the last 2 centimeters before the tube enters the uterus) remains spastically contracted for about the first 3 days after ovulation.

After this time, the rapidly increasing progesterone secreted by the ovarian corpus luteum first promotes increasing progesterone receptors on the fallopian tube smooth muscle cells; then the progesterone activates the receptors, exerting a tubular relaxing effect that allows entry of the ovum into the uterus.

Front 96

97. Why is this delayed transport of the fertilized ovum important?

Back 96

It allows several stages of cell division to occur before the dividing ovum, now called a blastocyst, enters the uterus.

During this time, the fallopian tube secretory cells produce large quantities of secretions used for the nutrition of the developing blastocyst.

Front 97

98. When does implantation occur?

Back 97

After reaching the uterus, the developing blastocyst usually remains in the uterine cavity an additional 1 to 3 days before it implants in the endometrium; thus, implantation ordinarily occurs on about the fifth to seventh day after ovulation.

Before implantation, the blastocyst obtains its nutrition from the uterine endometrial secretions, called “uterine milk.”

Front 98

99. What causes implantation to occur?

Back 98

Implantation results from the action of trophoblast cells that develop over the surface of the blastocyst.

These cells secrete proteolytic enzymes that digest and liquefy the adjacent cells of the uterine endometrium.

Some of the fluid and nutrients released are actively transported by the same trophoblast cells into the blastocyst, adding more sustenance for growth.

Once implantation has taken place, the trophoblast cells and other adjacent cells (from the blastocyst and the uterine endometrium) proliferate rapidly, forming the placenta and the various membranes of pregnancy.

Front 99

100. What provides nutrition for the early embryo?

Back 99

Progesterone - when the conceptus implants in the endometrium, the continued secretion of progesterone causes the endometrial cells to swell further and to store even more nutrients.

These cells are now called decidual cells, and the total mass of cells is called the decidua.

Front 100

101. How does the embryo obtain its nutrients in the first 8 weeks?

Back 100

As the trophoblast cells invade the decidua, digesting and imbibing it, the stored nutrients in the decidua are used by the embryo for growth and development.

During the first week after implantation, this is the only means by which the embryo can obtain nutrients; the embryo continues to obtain at least some of its nutrition in this way for up to 8 weeks, although the placenta also begins to provide nutrition after about the 16th day beyond fertilization (a little more than 1 week after implantation).

Front 101

102. Anatomy of the placenta

Back 101

While the trophoblastic cords from the blastocyst are attaching to the uterus, blood capillaries grow into the cords from the vascular system of the newly forming embryo.

By the 16th day after fertilization, blood also begins to be pumped by the heart of the embryo itself. Simultaneously, blood sinuses supplied with blood from the mother develop around the outsides of the trophoblastic cords. The trophoblast cells send out more and more projections, which become placental villi into which fetal capillaries grow.

Thus, the villi, carrying fetal blood, are surrounded by sinuses that contain maternal blood.

Front 102

103. Blood flow through the placenta

Back 102

The fetus’s blood flows through two umbilical arteries, then into the capillaries of the villi, and finally back through a single umbilical vein into the fetus.

At the same time, the mother’s blood flows from her uterine arteries into large maternal sinuses that surround the villi and then back into the uterine veins of the mother.

Front 103

104. How do substances pass through the placental membrane?

Back 103

The total surface area of all the villi of the mature placenta is only a few square meters—many times less than the area of the pulmonary membrane in the lungs.

Nevertheless, nutrients and other substances pass through this placental membrane mainly by diffusion in much the same manner that diffusion occurs through the alveolar membranes of the lungs and the capillary membranes elsewhere in the body.

Front 104

105. What is the major function of the placenta?

Back 104

To provide for diffusion of foodstuffs and oxygen from the mother's blood into the fetus's blood and diffusion of excretory products from the fetus back into the mother.

Front 105

106. How does the permeability of the placental membrane change throughout the pregnancy?

Back 105

In the early months of pregnancy, the placental membrane is still thick because it is not fully developed. Therefore, its permeability is low. Further, the surface area is small because the placenta has not grown significantly. Therefore, the total diffusion conductance is minuscule at first.

Conversely, in later pregnancy, the permeability increases because of thinning of the membrane diffusion layers and because the surface area expands many times over, thus giving a tremendous increase in placental diffusion.

Front 106

107. How does oxygen diffuse through the placental membrane?

Back 106

The dissolved oxygen in the blood of the large maternal sinuses passes into the fetal blood via simple diffusion, driven by an oxygen pressure gradient from the mother's blood to the fetus's blood.

The mean pressure gradient for diffusion of oxygen through the placental membrane is about 20 mm Hg.

Front 107

108. What are the three reasons why the low partial pressure of oxygen is capable of allowing the fetal blood to transport almost as much oxygen to the fetal tissues as is transported by the mother's blood to her tissues?

Back 107

1. The Hb of the fetus is mainly fetal Hb, a type that can carry 20-50% more oxygen than maternal Hb can (shifts O2-Hb curve to the left)

2. The Hb concentration of fetal blood is about 50% greater than that of the mother

3. The Bohr effect provides another mechanism to enhance the transport of oxygen by fetal blood. That is, Hb can carry more O2 at a low pCO2 that it can at a high pCO2. Loss of the CO2 makes the fetal blood more alkaline, whereas the increased CO2 in the maternal blood makes it more acidic.

Front 108

109. What is the double Bohr effect?

Back 108

These changes cause the capacity of fetal blood to combine with oxygen to increase and that of maternal blood to decrease. This forces still more oxygen from the maternal blood, while enhancing oxygen uptake by the fetal blood.

Thus, the Bohr shift operates in one direction in the maternal blood and in the other direction in the fetal blood. These two effects make the Bohr shift twice as important here as it is for oxygen exchange in the lungs; therefore, it is called the double Bohr effect.

Front 109

110. How does the total diffusing capacity of the entire placenta compare to the lung diffusing capacity of the newborn baby?

Back 109

The total diffusing capacity of the entire placenta for oxygen at term is about 1.2 milliliters of oxygen per minute per millimeter of mercury oxygen pressure difference across the membrane.

This compares favorably with that of the lungs of the newborn baby.

Front 110

111. Diffusion of CO2 through the placental membrane

Back 110

Carbon dioxide is continually formed in the tissues of the fetus in the same way that it is formed in maternal tissues, and the only means for excreting the carbon dioxide from the fetus is through the placenta into the mother’s blood.

The pCO2 of the fetal blood is 2 to 3 mm Hg higher than that of the maternal blood. This small pressure gradient for carbon dioxide across the membrane is more than sufficient to allow adequate diffusion of carbon dioxide, because the extreme solubility of carbon dioxide in the placental membrane allows carbon dioxide to diffuse about 20 times as rapidly as oxygen.

Front 111

112. How does glucose/food diffuse through the placental membrane?

Back 111

Other metabolic substrates needed by the fetus diffuse into the fetal blood in the same manner as oxygen does. For instance, in the late stages of pregnancy, the fetus often uses as much glucose as the entire body of the mother uses.

To provide this much glucose, the trophoblast cells lining the placental villi provide for facilitated diffusion of glucose through the placental membrane. That is, the glucose is transported by carrier molecules in the trophoblast cells of the membrane. Even so, the glucose level in fetal blood is 20 to 30 per cent lower than that in maternal blood.

Front 112

113. How do fatty acids, ions, and ketone bodies diffuse through the placental membrane?

Back 112

Because of the high solubility of fatty acids in cell membranes, these also diffuse from the maternal blood into the fetal blood, but more slowly than glucose, so that glucose is used more easily by the fetus for nutrition.

Also, such substances as ketone bodies and potassium, sodium, and chloride ions diffuse with relative ease from the maternal blood into the fetal blood.

Front 113

114. How are waste products excreted through the placental membrane?

Back 113

In the same manner that carbon dioxide diffuses from the fetal blood into the maternal blood, other excretory products formed in the fetus also diffuse through the placental membrane into the maternal blood and are then excreted along with the excretory products of the mother.

These include especially the nonprotein nitrogens such as urea, uric acid, and creatinine.

Front 114

115. How do levels of urea in fetal blood compare to that in maternal blood?

Creatinine levels?

Back 114

The level of urea in fetal blood is only slightly greater than that in maternal blood, because urea diffuses through the placental membrane with great ease.

However, creatinine, which does not diffuse as easily, has a fetal blood concentration considerably higher than that in the mother’s blood.

Therefore, excretion from the fetus occurs mainly, if not entirely, as a result of diffusion gradients across the placental membrane, because there are higher concentrations of the excretory products in the fetal blood than in the maternal blood.

Front 115

116. What 4 hormones are produced by the placenta during pregnancy?

Back 115

1. Human chorionic gonadotropin
2. Estrogens
3. Progesterone
4. Human chorionic somatomammotropin

Front 116

117. What is the importance of human chorionic gonadotropin?

Where is it secreted?

Back 116

Menstruation will begin unless human chorionic gonadotropin is secreted. Thus, the pregnancy would terminate without hCG.

Coincidental with the development of the trophoblast cells from the early fertilized ovum, the hormone human chorionic gonadotropin is secreted by the syncytial trophoblast cells into the fluids of the mother.

Front 117

118. What is the function of hCG?

Back 117

By far, its most important function is to prevent involution of the corpus luteum at the end of the monthly female sexual cycle.

Instead, it causes the corpus luteum to secrete even larger quantities of its sex hormones—progesterone and estrogens—for the next few months.

These sex hormones prevent menstruation and cause the endometrium to continue to grow and store large amounts of nutrients rather than being shed in the menstruum. As a result, the decidua-like cells that develop in the endometrium during the normal female sexual cycle become actual decidual cells—greatly swollen and nutritious—at about the time that the blastocyst implants.

Front 118

119. How does hCG affect the corpus luteum?

Back 118

Under the influence of hCG, the corpus luteum grows to about 2x its initial size, and its continued secretion of estrogens and progesterone maintains the decidual nature of the uterine endometrium, which is necessary for the development of the fetus.

Front 119

120. What happens when the corpus luteum is removed before the 7th week of pregnancy?

Back 119

Spontaneous abortion almost always occurs, sometimes up to the 12th week.

After that time, the placenta secretes sufficient quantities of progesterone and estrogens to maintain pregnancy for the remainder of the gestation period.

The corpus luteum involutes slowly after the 13-17th week of gestation.

Front 120

121. What effect does hCG have on the fetal testes?

Back 120

hCG also exerts an interstitial-cell stimulating effect on the testes of the male fetus, resulting in the production of testosterone in male fetuses until the time of birth.

Front 121

122. Secretion of estrogens by the placenta - from where does it come from?

Back 121

The placenta secretes both estrogens and progesterone. These two hormones are secreted by the syncytial trophoblast cells of the placenta.

Towards the end of pregnancy, the daily production of placental estrogens increases to about 30x the mother's normal levels of production.

Front 122

123. How is the secretion of estrogens by the placenta different from secretion by the ovaries?

Back 122

Most important, the estrogens secreted by the placenta are not synthesized de novo from basic substrates in the placenta.

Instead, they are formed almost entirely from androgenic steroid compounds, dehydroepiandrosterone and 16-hydroxydehydroepiandrosterone, which are formed both in the mother’s adrenal glands and in the adrenal glands of the fetus.

These weak androgens are transported by the blood to the placenta and converted by the trophoblast cells into estradiol, estrone, and estriol.

(The cortices of the fetal adrenal glands are extremely large, and about 80 per cent consists of a so-called fetal zone, the primary function of which seems to be to secrete dehydroepiandrosterone during pregnancy.)

Front 123

124. What are four functions of estrogen during pregnancy?

Back 123

1. Enlargement of the mother's uterus
2. Enlargement of the mother's breasts and growth of the breast ductal structure
3. Enlargement of the mother's female external genitalia
4. Relaxation of the pelvic ligaments of the mother to allow easier passage of the fetus through the birth canal

Front 124

125. Secretion of progesterone by the placenta

Back 124

In addition to being secreted in moderate quantities by the corpus luteum at the beginning of pregnancy, it is secreted later in tremendous quantities by the placenta, averaging about a 10-fold increase during the course of pregnancy

Front 125

126. What are the four special effects of progesterone that are essential for the normal progression of pregnancy?

Back 125

1. Progesterone causes decidual cells to develop in the uterine endometrium, and these cell play an important role in the nutrition of the early embryo.
2. Progesterone decreases the contractility of the pregnant uterus, thus preventing uterine contractions from causing spontaneous abortion.
3. Progesterone contributes to the development of the conceptus even before implantation, b/c it specifically increases the secretions of the mother's fallopian tubes and uterus to provide appropriate nutritive matter for the developing morula and blastocyst.
4. The progesterone secreted during pregnancy helps the estrogen prepare the mother's breasts for lactation.

Front 126

127. What is human chorionic somatomammotropin?

Back 126

A more recently discovered placental hormone is called human chorionic somatomammotropin. It is a protein and it begins to be secreted by the placenta at about the fifth week of pregnancy.

Secretion of this hormone increases progressively throughout the remainder of pregnancy in direct proportion to the weight of the placenta.

Although the functions of chorionic somatomammotropin are uncertain, it is secreted in quantities several times greater than all the other pregnancy hormones combined.

Front 127

128. What is the first proposed effect of human chorionic somatomammotropin?

Back 127

1. It causes at least partial development of the animal’s breasts and in some instances causes lactation.

Because this was the first function of the hormone discovered, it was first named human placental lactogen and was believed to have functions similar to those of prolactin.

Front 128

129. What is the second proposed effect of human chorionic somatomammotropin?

Back 128

2. This hormone has weak actions similar to those of growth hormone, causing the formation of protein tissues in the same way that growth hormone does.

It also has a chemical structure similar to that of growth hormone, but 100 times as much human chorionic somatomammotropin as growth hormone is required to promote growth.

Front 129

130. What is the third proposed effect of human chorionic somatomammotropin?

Back 129

3. It causes decreased insulin sensitivity and decreased utilization of glucose in the mother, thereby making larger quantities of glucose available to the fetus.

Further, the hormone promotes the release of free fatty acids from the fat stores of the mother, thus providing this alternative source of energy for the mother’s metabolism during pregnancy.

Front 130

131. In sum, what is the role of human chorionic somatomammotropin?

Back 130

It appears that human chorionic somatomammotropin is a general metabolic hormone that has specific nutritional implications for both the mother and the fetus.

Front 131

132. What hormones from the pituitary are secreted/inhibited during pregnancy?

Back 131

The anterior pituitary gland of the mother enlarges at least 50 per cent during pregnancy and increases its production of corticotropin, thyrotropin, and prolactin.

Conversely, pituitary secretion of follicle-stimulating hormone and luteinizing hormone is almost totally suppressed as a result of the inhibitory effects of estrogens and progesterone from the placenta.

Front 132

133. How is corticosteroid secretion different during pregnancy?

Back 132

The rate of adrenocortical secretion of the glucocorticoids is moderately increased throughout pregnancy. It is possible that these glucocorticoids help mobilize amino acids from the mother’s tissues so that these can be used for synthesis of tissues in the fetus.

Front 133

134. If aldosterone secretion increases during pregnancy, what are the possible complications?

Back 133

Pregnant women usually have about a twofold increase in the secretion of aldosterone, reaching a peak at the end of gestation.

This, along with the actions of estrogens, causes a tendency for even a normal pregnant woman to reabsorb excess sodium from her renal tubules and, therefore, to retain fluid, occasionally leading to pregnancy-induced hypertension.

Front 134

135. Secretion by the thyroid gland during pregnancy

What causes the increased secretion?

Back 134

The mother’s thyroid gland ordinarily enlarges up to 50 per cent during pregnancy and increases its production of thyroxine a corresponding amount.

The increased thyroxine production is caused at least partly by a thyrotropic effect of human chorionic gonadotropin secreted by the placenta and by small quantities of a specific thyroid-stimulating hormone, human chorionic thyrotropin, also secreted by the placenta.

Front 135

136. What is 'relaxin' that is secreted by the ovaries and placenta?

Back 135

Its secretion is increased by a stimulating effect of hCG at the same time that the corpus luteum and the placenta secrete large quantities of estrogens and progesterone.

Relaxin is a polypeptide that, when injected, causes relaxation of the ligaments of the symphysis pubis in the rat and guinea pig. This effect is weak or possibly even absent in pregnant women. Instead, this role is probably played mainly by the estrogens, which also cause relaxation of the pelvic ligaments.

Front 136

137. What are the most apparent changes in the pregnant mother?

Back 136

The increased size of the various sexual organs.

For instance, the uterus increases from about 50 grams to 1100 grams, and the breasts approximately double in size. At the same time, the vagina enlarges and the introitus opens more widely.

Also, the various hormones can cause marked changes in a pregnant woman’s appearance, sometimes resulting in the development of edema, acne, and masculine or acromegalic features.

Front 137

138. Weight gain in the pregnant woman

Back 137

The average weight gain during pregnancy is about 24 pounds, with most of this gain occurring during the last two trimesters.

Of this, about 7 pounds is fetus and 4 pounds is amniotic fluid, placenta, and fetal membranes. The uterus increases about 2 pounds and the breasts another 2 pounds, still leaving an average weight increase of 9 pounds. About 6 pounds of this is extra fluid in the blood and extracellular fluid, and the remaining 3 pounds is generally fat accumulation. The extra fluid is excreted in the urine during the first few days after birth, that is, after loss of the fluid-retaining hormones from the placenta.

Front 138

139. Metabolism during pregnancy

Back 138

As a consequence of the increased secretion of many hormones during pregnancy, including thyroxine, adrenocortical hormones, and the sex hormones, the basal metabolic rate of the pregnant woman increases about 15 per cent during the latter half of pregnancy.

As a result, she frequently has sensations of becoming overheated. Also, owing to the extra load that she is carrying, greater amounts of energy than normal must be expended for muscle activity.

Front 139

140. What nutrients are especially important to the mother during pregnancy?

Back 139

Iron, calcium, phosphates, and proteins.

Without sufficient iron, hypochromic anemia develops. Also, vitamin D is necessary b/c calcium can't be absorbed w/o vitamin D.

Finally, shortly before the birth of the baby, vitamin K is often added to the mother's diet so that the baby will have sufficient prothrombin to prevent hemorrhage, particularly brain hemorrhage, caused by the birth process.

Front 140

141. How does blood flow through the placenta and CO change during pregnancy?

Back 140

About 625 milliliters of blood flows through the maternal circulation of the placenta each minute during the last month of pregnancy.

This, plus the general increase in the mother’s metabolism, increases the mother’s cardiac output to 30 to 40 per cent above normal by the 27th week of pregnancy

Then, for reasons unexplained, the cardiac output falls to only a little above normal during the last 8 weeks of pregnancy, despite the high uterine blood flow.

Front 141

142. How does the maternal blood volume change during pregnancy?

Back 141

The maternal blood volume shortly before term is about 30 per cent above normal. This increase occurs mainly during the latter half of pregnancy.

Therefore, at the time of birth of the baby, the mother has about 1 to 2 liters of extra blood in her circulatory system. Only about one fourth of this amount is normally lost through bleeding during delivery of the baby, thereby allowing a considerable safety factor for the mother.

Front 142

143. What causes the increase in blood volume?

Back 142

The cause of the increased volume is likely due, at least in part, to aldosterone and estrogens, which are greatly increased in pregnancy, and to increased fluid retention by the kidneys.

Also, the bone marrow becomes increasingly active and produces extra red blood cells to go with the excess fluid volume.

Front 143

144. How is maternal respiration affected during pregnancy?

Back 143

B/c of the increased metabolic rate, the total amt of oxygen used by the mother shortly before birth is about 20% above normal, and a commensurate amt of CO2 is formed. These effects cause the mother's minute ventilation to increase.

It is believed that progesterone also increases the respiratory center's sensitivity to CO2.

The net result is an increase in minute ventilation of about 50% and a decrease in arterial pCO2 to several mm Hg below that in nonpregnant women.

Also, the growing uterus decreases the diaphagmatic movement, so the respiratory rate is also increased to maintain ventilation.

Front 144

145. How does maternal urine formation change during pregnancy?

Back 144

The rate of urine formation by a pregnant woman is usually slightly increased because of increased fluid intake and increased load or excretory products.

Front 145

146. In addition to increased urine formation, what other special alterations occur in the urinary system?

Back 145

1. The renal tubules' reabsorptive capacity for sodium, chloride, and water is increased as much as 50% as a consequence of increased production of steroid hormones by the placenta and adrenal cortex.

2. The GFR increases as much as 50% during pregnancy, which tends to increase the rate of water and electrolyte excretion in the urine.

When all these effects are considered, the normal pregnant woman ordinarily accumulates only about 6 lbs of extra water and salt.

Front 146

147. Absorption and secretion of amniotic fluid

Back 146

Normally, the volume of amniotic fluid (the fluid inside the uterus in which the fetus floats) is between 500 milliliters and 1 liter, but it can be only a few milliliters or as much as several liters.

Isotope studies of the rate of formation of amniotic fluid show that, on average, the water in amniotic fluid is replaced once every 3 hours, and the electrolytes sodium and potassium are replaced an average of once every 15 hours.

A large portion of the fluid is derived from renal excretion by the fetus. Likewise, a certain amount of absorption occurs by way of the gastrointestinal tract and lungs of the fetus.

Front 147

148. What is preeclampsia?

Back 147

About 5% of all pregnant women experience a rapid rise in arterial pressure to hypertensive levels during the last few months of pregnancy.

This is associated w/leakage of large amts of protein into the urine. This condition is call preeclampsia or toxemia of pregnancy.

It is often characterized by excess salt and water retention by the mother's kidneys and by weight gain and development of edema and hypertension in the mother. In addition, there is impaired function of the vascular endothelium, and arterial spasm occurs in many parts of the mother's body, most significantly the kidneys, brain and liver. Both the renal blood flow and the GFR are decreased. The renal effects also include thickened glomerular tufts that contain a protein deposit in the basement membranes.

Front 148

149. An increased release of what factors can cause preeclampsia?

Back 148

Inflammatorycytokines such as tumor necrosis factor-alpha and interleukin-6.

This can be due to insufficient blood supply to the placenta.

Front 149

150.What is eclampsia?

Back 149

Eclampsia is an extreme degree of preeclampsia, characterized by vascular spasm throughout the body; clonic seizures in the mother, sometimes followed by coma; greatly decreased kidney output; malfunction of the liver; often extreme hypertension; and a generalized toxic condition of the body.

It usually occurs shortly before birth of the baby. Without treatment, a high percentage of eclamptic mothers die. However, with optimal and immediate use of rapidlyacting vasodilating drugs to reduce the arterial pressure to normal, followed by immediate termination of pregnancy—by cesarean section if necessary—the mortality even in eclamptic mothers has been reduced to 1 per cent or less.

Front 150

151. What is parturition, and what two major categories of effects lead up to the intense contractions responsible for parturition?

Back 150

Parturition means birth of the baby.

Two categories of effects that lead to intense contractions:
1. Progressive hormonal changes that cause increase excitability of the uterine musculature
2. Progressive mechanical changes

Front 151

152. What do estrogens have to do with uterine contractility?

Back 151

An increased ratio of estrogens to progesterone helps increase the degree of uterine contractility, partly b/c estrogens increase the number of gap junctions between the adjacent uterine smooth muscle cells.

Front 152

153. What are the four reasons to believe oxytocin increases the contractility of the uterus?

Back 152

1. The uterine muscle increases its oxytocin receptors, and therefore increases its responsiveness to a dose of oxytocin during the latter few months of pregnancy.
2. The rate of oxytocin secretion by the neurohypophysis is considerably increased at the time of labor.
3. Although hypophysectomized animals can still deliver their young at term, labor is prolonged.
4. Experiments in animals indicate that irritation or stretching of the uterine cervix, as occurs during labor, can cause a neurogenic reflex through the paraventricular and supraoptic nuclei of the hypothalamus that causes the posterior pituitary gland to increase its secretion of oxytocin.

Front 153

154. What are the effect of fetal hormones on the uterus?

Back 153

The fetus’s pituitary gland secretes increasing quantities of oxytocin, which might play a role in exciting the uterus.

Also, the fetus’s adrenal glands secrete large quantities of cortisol, another possible uterine stimulant.

In addition, the fetal membranes release prostaglandins in high concentration at the time of labor. These, too, can increase the intensity of uterine contractions.

Front 154

155. How does stretching of the uterine musculature affect uterine contractility?

Back 154

Simply stretching smooth muscle organs usually increases their contractility.

Further, intermittent stretch, as occurs repeatedly in the uterus b/c of fetal movements, can also elicit smooth muscle contraction.

Front 155

156. How does stretching or irritation of the cervix cause uterine contractions?

Back 155

The mechanism is not known. It has been suggested that stretching or irritation of the nerves in the cervix initiates reflexes to the body of the uterus, but the effect could also result simply from myogenic transmission of signals from the cervix to the body of the uterus.

Front 156

157. What are Braxton Hicks contractions?

Back 156

During most of the months of pregnancy, the uterus undergoes periodic episodes of weak and slow rhythmical contractions called Braxton Hicks contractions.

Front 157

158. What is the positive feedback theory in labor?

Back 157

This theory suggests that stretching of the cervix by the fetus's head finally becomes great enough to elicit a strong reflex increase in contractility of the uterine body.

This pushes the baby forward, which stretches the cervix more and initiates more positive feedback to the uterine body.

This process repeats itself until the baby is expelled.

Front 158

159. What are the two known types of positive feedback that increase uterine contractions during labor?

Back 158

1. Stretching of the cervix causes the entire body of the uterus to contract.

2. Cervical stretching also causes the pituitary gland to secrete oxytocin, which is another means for increasing uterine contractility.

Front 159

160. How is the positive feedback used to support false labor, in which the contractions become stronger first and then fade away?

Back 159

Remember that for a vicious circle to continue, each new cycle of the positive feedback must be stronger than the previous one.

If at any time after labor starts some contractions fail to re-excite the uterus sufficiently, the positive feedback could go into a retrograde decline, and the labor contractions would fade away.

Front 160

161. Why is it important for the contractions of labor to occur intermittently?

Back 160

Strong contractions can impede or sometimes even stop blood flow through the placenta and would cause death of the fetus if the contractions were continuous.

Front 161

162. What is the first stage of labor?

Back 161

The first major obstruction to expulsion of the fetus is the uterine cervix. Toward the end of pregnancy, the cervix becomes soft, which allows it to stretch when labor contractions begin in the uterus.

The so-called first stage of labor is a period of progressive cervical dilation, lasting until the cervical opening is as large as the head of the fetus. This stage usually lasts for 8 to 24 hours in the first pregnancy but often only a few minutes after many pregnancies.

Front 162

163. What is the second stage of labor?

Back 162

Once the cervix has dilated fully, the fetal membranes usually rupture and the amniotic fluid is lost suddenly through the vagina. Then the fetus’s head moves rapidly into the birth canal, and with additional force from above, it continues to wedge its way through the canal until delivery is effected.

This is called the second stage of labor, and it may last from as little as 1 minute after many pregnancies to 30 minutes or more in the first pregnancy.

Front 163

164. What causes the labor pains in the first and second stages of labor?

Back 163

With each uterine contraction, the mother experiences considerable pain. The cramping pain in early labor is probably caused mainly by hypoxia of the uterine muscle resulting from compression of the blood vessels in the uterus. This pain is not felt when the visceral sensory hypogastric nerves, which carry the visceral sensory fibers leading from the uterus, have been sectioned.

However, during the second stage of labor, when the fetus is being expelled through the birth canal, much more severe pain is caused by cervical stretching, perineal stretching, and stretching or tearing of structures in the vaginal canal itself. This pain is conducted to the mother’s spinal cord and brain by somatic nerves instead of by the visceral sensory nerves.

Front 164

165. Involution of the uterus

Back 164

During the first 4 to 5 weeks after parturition, the uterus involutes. Its weight becomes less than half its immediate postpartum weight within 1 week, and in 4 weeks, if the mother lactates, the uterus may become as small as it was before pregnancy. This effect of lactation results from the suppression of pituitary gonadotropin and ovarian hormone secretion during the first few months of lactation.

Front 165

166. What is lochia?

Back 165

During early involution of the uterus, the placental site on the endometrial surface autolyzes, causing a vaginal discharge known as “lochia,” which is first bloody and then serous in nature, continuing for a total of about 10 days.

After this time, the endometrial surface becomes re-epithelialized and ready for normal, nongravid sex life again.

Front 166

167. What develops the growth of the ductal system in the breasts?

Back 166

Estrogens

Front 167

168. What develops the growth of the lobule-alveolar system in the breasts?

Back 167

Progesterone - acting synergistically with estrogens.

Front 168

169. Function of estrogen and progesterone on secretion of milk

Back 168

They inhibit the secretion of milk.


Conversely, prolactin promotes it.

Front 169

170. What is necessary for maternal milk production?

Back 169

Requires adequate background secretion of hormones but most important are GH, cortisol, PTH, and insulin.

Front 170

171. Prolactin levels following birth

Back 170

After birth of the baby, the basal level of prolactin secretion returns to the nonpregnant level over the next few weeks. However, each time the mother nurses her baby, nervous signals from the nipples to the hypothalamus cause a 10- to 20-fold surge in prolactin secretion that lasts for about 1 hour.

This prolactin acts on the mother’s breasts to keep the mammary glands secreting milk into the alveoli for the subsequent nursing periods. If this prolactin surge is absent or blocked as a result of hypothalamic or pituitary damage or if nursing does not continue, the breasts lose their ability to produce milk within 1 week or so.

However, milk production can continue for several years if the child continues to suckle, although the rate of milk formation normally decreases considerably after 7 to 9 months.

Front 171

172. How does the hypothalamus play a role in prolactin secretion?

Back 171

The hypothalamus mainly stimulates production of all other hormones, but it mainly inhibits prolactin production.

Therefore, it is believed that anterior pituitary secretion of prolactin is controlled by an inhibitory factor formed in the hypothalamus, called prolactin inhibitory hormone; very similar to dopamine.

Front 172

173. When does the menstrual cycle resume in nursing mothers?

Back 172

Not until a few weeks after cessation of nursing b/c the same signals from the breasts to the hypothalamus that cause prolactin secretion inhibit secretion of GnRH by the hypothalamus which suppresses formation of the pituitary gonadotropic hormones.

Front 173

174. What does oxytocin have to do with milk letdown?

Back 173

The milk must be ejected from the alveoli into the ducts before the baby can obtain it.

When the baby suckles, sensory impulses travel to the hypothalamus, where they cause nerve signals to cause oxytocin secretion at the same time as prolactin secretion.

The oxytoxin is carried into the breasts, where it causes myoepithelial cells to contract and the milk can be removed by the baby.

Front 174

175. Antibodies in maternal milk

Back 174

Not only does milk provide the newborn baby with needed nutrients, but it also provides important protection against infection. For instance, multiple types of antibodies and other anti-infectious agents are secreted in milk along with the nutrients.

Also, several different types of white blood cells are secreted, including both neutrophils and macrophages, some of which are especially lethal to bacteria that could cause deadly infections in newborn babies.

Particularly important are antibodies and macrophages that destroy Escherichia coli bacteria, which often cause lethal diarrhea in newborns.

Front 175

176. How are bacterial infections in UTIs acquired?

Back 175

Bacterial infection is usually acquired by the ascending route from the urethra to the bladder. The infection may then proceed to the kidney.

Front 176

177. In what two settings are UTIs most common in?

What is the most common cause of UTIs?

Back 176

1. Community-acquired (most common)
2. Hospital acquired (associated w/catheterizations)

Most common cause of UTIs is the gram-negative rod E. coli.

Front 177

178. What 5 other members of the Enterobacteriaceae are also implicated in causing UTIs?

Back 177

1. Proteeus mirabilis is often associated w/urinary stones b/c this organism produces a potent urease, which acts on urea to produce ammonia, rendering the urine alkaline.
2. Klebsiella*
3. Enterobacter*
4. Serratia*
5. Pseudomonas aeruginosa*

*Nosocomial

Front 178

179. What 3 gram positive species are associated w/UTIs?

Back 178

1. Staphyloccus saprophyticus is common in young sexually active women
2. Staphy. epidermidis*
3. Enterococcus*

*Nosocomial

Front 179

180. What 3 species can be found when there has been hematogeneous spread to the urinary tract?

Back 179

1. Salmonella typhi
2. Staph aureus
3. Mycobacterium tuberculosis

Front 180

181. Are viral causes of UTIs common?

What are they associated with?

Back 180

Viral causes of UTI are rare, although there are associations with hemorrhagic cystitis and other renal syndromes

Front 181

182. Which viruses lead to hemorrhagic cystitis?

Back 181

Human polyomaviruses, JC and BK, enter the body via the respiratory tract and infect eptiehlial cells in the kidney tubules and ureter. During normal pregnancy, the viruses may reactivate asymptomatically with the appearance of large amts of virus in the urine. Reactivation also occurs in immunocompromised patients and may lead to hemorrhagic cystitis.

In contrast to asymptomatic shedding, some serotypes of adenovirus have been implicated as a cause of hemorrhagic cystitis.

Front 182

183. What other viruses cause renal syndromes?

Back 182

High titers of CMV and rubella may be shed asymptyomatically in the urine of congenitally infected infants.

The rodent-borne hantavirus respsonsible for hemorrhagic fever, infects capillary blood vessels in the kidney and can cause a renal syndrome w/proteinuria.

Lastly, a number of other viruses can infect the kidneys, including mumps and HIV.

Front 183

184. Which parasites/fungi cause UTIs?

Back 183

1. Candidia spp. and Histoplasma capsulatum
2. Protozoan Trichomonas vaginalis (vaginitis)
3. Schistosoma haematobium, which results in inflammation of the bladder and commonly hematuria.

Front 184

185. How does Schistosoma haematobium cause problems?

Back 184

The eggs penetrate the bladder wall, and in severe infections large granulomatous reactions can occur and the eggs may become calcified.

Bladder cancer is associated w/chronic infections, although the mechanism is not known.

Obstruction of the ureter as a result of egg-induced inflammatory changes can also lead to hydronephrosis.

Front 185

186. What three mechanical factors predispose to UTIs?

Back 185

1. Anything that disrupts normal urine flow or complete emptying of the bladder or facilitates access of organisms to the bladder.
2. The shorter female urethra is shorter than the male urethra; sexual intercourse facilitates the movements of these organisms into the urethra.
3. In male infants, UTIs are more common in the uncircumcised and this is associated w/colonization of the inside of the prepuce and urethra w/fecal organisms.

Front 186

187. What are the five main causes of obstruction to complete bladder emptying?

Back 186

1. Pregnancy
2. BPH
3. Renal calculi
4. Tumors
5. Strictures

Front 187

188. Which neurologic conditions cause one to lose control of the bladder and sphincters and thus cause a functional obstruction in urine flow?

Back 187

Spina bifida, paraplegia, or MS cause a large residual volume of urine in the bladder and such patients are particularly prone to recurrent infections

Front 188

189. What about the vesicoureteral reflux in UTIs?

Back 188

This reflux is common in children w/anatomic abnormalities of the urinary tract and may predispose to ascending infection and kidney damage.

Front 189

190. Are people w/diabetes prone to UTIs?

Back 189

People w/DM may have more severe UTIs and if diabetic neuropathy interferes w/normal bladder function, persistent UTIs are common.

Front 190

191. How is catheterization a major predisposing factor for UTIs?

Back 190

Bacteria can be pushed into the bladder as the catheter is inserted and while it is in place, bacteria reach the bladder by tracking up between the outside of the catheter and the urethra.

Contamination of the drainage system by bacteria from other sources can also result in infection.

Regardless, the duration of catheterization is directly associated w/increased probability of infection (increases 3-5% per day)

Front 191

192. What serotypes of E. coli are specific to UTIs?

How are they different from those in GI tract infections?

Back 191

The ability to cause infection in the urinary tract is limited to certain serogroups of E. coli such as O serotypes and K serotypes.

These serotypes differ from those associated w/GI tract infection which leads them to be called UPEC (uropathogenic E coli).

The success of these strains is due to a variety of genes in chromosomal pathogenicity islands that cause it to colonize in the periurethral areas.

Front 192

193. What specific virulence factor allows UPEC to adhere?

Back 192

P. fimbriae (pyelonephritis associated pili (PAP) pili).

Front 193

194. What 3 virulence factors are present in E. coli that allow it to colonize and infect the urinary tract?

What about in Proteus spp.?

Back 193

1. P. fimbriae
2. Capsular acid polysaccharide (K) antigens are associated w/the ability to cause pyelonephritis and are known to enable E. coli strains to resist host defenses by inhibiting phagocytosis
3. Hemolysin production by E. coli is linked w/the capacity to cause kidney damage; many hemolysin act more generally as membrane-damaging toxins.

Proteus spp. infections are related to their ability to cause pyelonephritis and stones via their urease production.

Front 194

195. How is the healthy urinary tract resistant to bacterial colonization?

Back 194

With the exception of the urethral mucosa, the urinary tract is excellent at ridding infections. The pH, chemical content and flushing help dispose of them.

Although urine is a good culture medium for most bacteria, it is inhibitory to some, and anaerobes and other species (non-hemolytic streptococci, corynebacteria, and staphylococci), which comprise most of the normal urethral flora, do not readily multiply in urine.

Front 195

196. What antibodies are usually found in the urine after infection of the kidney?

What about in the lower urinary tract?

Back 195

Upper:
1. IgG
2. Secretory IgA

Lower:
Low or undetectable serologic response (this reflects the superficial nature of the infection; the bladder and urethral mucosa are rarely invaded in UTIs).

Front 196

197. What are the three symptoms of acute, lower UTIs?

Back 196

1. Dysuria
2. Urgency
3. Frequency of micturition

These symptoms in the elderly and those with indwelling catheters are usually asymptomatic.

Front 197

198. Pyruria in the absence of positive urine cultures can be due...?

Back 197

Chlamydiae or tuberculosis and is also seen in patients receiving antibacterial therapy for UTI.

Front 198

199. What are the symptoms of acute bacterial prostatitis?

How does it arise?

Back 198

Acute bacterial prostatitis causes systemic symptoms (fever) and local symptoms (perineal and low back pain, dysuria, and frequency).

May arise from ascending or hematogeneous infection, and people lacking the antibacterial substances in their prostatic fluid are more susceptible.

Front 199

200. Patients with pyelonephritis present with...?

What organism is usually to blame?

Back 199

Lower urinary tract symptoms and usually have a fever.

Staphylococci are a common cause and renal abscesses are generally present.

Recurrent episodes of pyelonephritis result in loss of function of renal tissue -> hypertension

Front 200

201. Hematuria is a feature in...?

Pyuria is common in...?

Back 200

Hematuria is a feature of endocarditis and a manifestation of immune complex disease, as well as a result of infections of the kidney.

Pyuria is common in kidney infections by M. tuberculosis, which cannot be grown by normal urine culture methods and therefore the patient can appear to have a sterile pyuria.

Front 201

202. How are true infections distinguished from contaminated samples?

Back 201

Via quantitative culture methods.

Bacteriuria is defined as significant when a properly collected midstream sample is shown to contain over 10⁵ oganisms/mL.

Infected urine usually contains only a single bacterial species; contaminated urine usually has < 10⁴ organisms/mL and often contains more than one bacterial species.

These rules do not apply to samples collected via other means other than MSUs.

Front 202

203. Which two organisms require special urine samples?

Back 202

M. tuberculosis

Schistosoma haematobium

Front 203

204. Sterile pyruia is an important finding and may reflect...

Back 203

1. Concurrent antibiotic therapy
2. Other diseases such as neoplasms or urinary calculi
3. Infection w/organisms not detected by routine urine culture methods

Front 204

205. Which two agents are used only for lower UTIs?

Back 204

1. Nitrofurantoin
2. Nalidixic acid

This is because they do not achieve adequate serum and tissue concentrations to treat upper UTIs.

Front 205

206. What is the trend for the fetus gaining weight?

Back 205

THe weight remains minuscule during the first 12 weeks and reaches 1 pound only at 23 weeks of gestation. Then, during the last trimester of pregnancy, the fetus gains tremendously, so that 2 months before birth, the weight averages 2 pounds, 1 month before birth 4.5 pounds, and at birth 7 pounds.

The normal birth weight can vary from as low as 4.5 to as high as 11 pounds.

Front 206

207. How do the organ systems develop after fertilization?

Back 206

W/in 1 month after fertilization, the gross characterisitics of all the different organs of the fetus have already begun to develop, and during the next 2 to 3 months, most of the details fo the different organs are established. Beyond 4 months, the organs of the fetus are grossly the same as those of the neonate.

*Cellular development in each organ is far from complete and requires the full remaining 5 months of pregnancy for complete development.

Front 207

208. When is the circulatory system active?

Back 207

The human heart begins beating during the fourth week after fertilization, contracting at a rate of about 65 bpm.

This increases steadily to about 140 bpm immediately before birth.

Front 208

209. When are blood cells formed?

Back 208

Nucleated RBCs begin to be formed in the yolk sac and mesothelial layers of the placenta at about the third week of fetal development.

This is followed 1 week later by formation of non-nucleated RBCs by the fetal mesenchyme and also by the endothelium of the fetal blood vessels.

Then, at 6 weeks, the liver begins to form RBCs; and in the third month, the spleen and other lymphoid tissues of the body begin forming blood cells.

Finally, from the 3rd month on, the bone marrow gradually becomes the principal source of the RBCs as well as most of the WBCs.

Front 209

210. When does the respiratory system develop?

1/2

Back 209

Respiration cannot occur during fetal life b/c there is no air. However, attempted respiratory movements do take place beginning at the end of the first trimester of pregnancy.

*Tactile stimuli and fetal asphyxia especially cause these attempted respiratory movements.

Front 210

211. When does the respiratory system develop?

2/2

Back 210

During the last 3-4 mos of pregnancy, the respiratory movements of the fetus are mainly inhibited, and the lungs remain almost completely deflated.

The inhibition of respiration during the later months prevents filling of the lungs w/fluid and debris. Also, small amts of fluid are secreted into the lungs by the alveolar epithelium up until the moment of birth, thus keeping only clean fluid in the lungs.

Front 211

221. When does the nervous system develop?

Back 211

Most of the reflexes that involve the spinal cord and the brain stem are present by the 3rd to 4th months of pregnancy.

However, those nervous system functions that involve the cerebral cortex are still only in the early stages of development. Indeed, myelinization of some major tracts becomes complete after 1 year of postnatal life.

Front 212

122. When does the GI system develop?

Back 212

By midpregnancy, the fetus begins to ingest and absorb large quantities of amniotic fluid and during the last 2-3 mos, GI function approaches that of the normal neonate.

By that time, small quantities of meconium are continually formed in the GI tract and excreted from the anus into the amniotic fluid.

Front 213

123. What is meconium composed of?

Back 213

Meconium is composed partly of residue from swallowed amniotic fluid and partly of mucus and other residues of excretory product from the GI mucosa and glands.

Front 214

124. When does the renal system develop?

Back 214

The fetal kidneys begins to excrete urine during the 2nd trimester, and fetal urine accounts for about 70-80% of the amniotic fluid.

Abnormal kidneys development or severe impairment of kidney function in the fetus greatly reduce the formation of amniotic fluid (oligohydramnios) and can lead to fetal death.

Front 215

225. While the fetal kidneys can form urine, can they regulate fetal ECF volume and electrolytes/acid/base balance?

Back 215

These regulating systems are almost nonexistent until later fetal life and do not reach full development until a few mos after birth.

Front 216

226. What does the fetus use for energy?

Back 216

The fetus uses mainly glucose for energy, and it has a high capability to store fat and protein, much if not most of the fat begin synthesized from glucose rather than being absorbed directly from the mother's blood.

In addition, there are special problems of fetal metabolism in relation to calcium, phosphate, iron, and some vitamins.

Front 217

227. How much calcium and phosphorus are accumulated in the avg fetus during gestation?

Is it taxing on the mother?

Back 217

About 22.5 g of calcium and 13.5 g of phosphorus.

About 1/2 of these accumulate during the last 4 weeks of gestation, which is coincident with the period of rapid ossification of the fetal bones and with the period of rapid weight gain of the fetus.

*The total amts of calcium and phosphate needed by the fetus represent only 2% of the quantities of these substances in the mothers bones. Not very taxing.

Front 218

228. How does iron accumulate in the fetus?

Where is it stored?

Back 218

Iron accumulates in the fetus even more rapidly than calcium and phosphate. Most of the iron is in the form of hemoglobin, which begins to be formed as early as the third week after fertilization of the ovum.

About 1/3 of the iron in a fully developed fetus is normally stored in the liver.

Front 219

229. Small amts of iron are concentrated in the mother's uterine progestational endomentrium even before implantation of the ovum. Why?

Back 219

This iron is ingested into the embryo by the trophoblastic cells and is used to form the very early RBCs.

Front 220

230. Why is vitamin B12 and folic acid important to the fetus?

Vitamin C

Back 220

Vitamin B12 and folic acid are necessary for formation of RBCs and nervous tissue, as well as for overall growth of the fetus.

Vitamin C is necessary for appropriate formation of intercellular substances, especially the bone matrix and fibers of connective tissue.

Front 221

231. Why is vitamin D needed by the fetus?

Vitamin E?

Back 221

Vitamin D is needed for normal bone growth in the fetus, but even more important, the mother needs it for adequate absorption of calcium from her GI tract.

Vitamin E is necessary for normal development of the early embryo. In its absence in lab animals, spontaneous abortion usually occurs at an early stage of pregnancy.

Front 222

232. Why is vitamin K needed by the fetus?

Back 222

Vitamin K is used by the fetal liver for formation of Factor 7, prothrombin, and several other blood coagulation factors.

When vitamin K is insufficient in the mother, Factor 7 and prothrombin become deficient in the fetus as well as in the mother.

Front 223

233. Can the neonate produce vitamin K after birth?

Back 223

B/c most vitamin K is formed by bacterial action in the mother's colon, the neonate has no adequate source of vitamin K for the first week or so after birth until normal colonic bacterial flora become established.

Front 224

234. What causes breathing at birth?

What are the two things that may stimulate breathing?

Back 224

After normal delivery, a child begins to breathe within seconds and has a normal respiratory rhythm w/in less than 1 min.

The promptness of this indicates that breathing is initiated by sudden exposure to the exterior world, probably resulting from:
1. A slight asphyxiated state incident to the birth process
2. Sensory impulses that originate in the suddenly cooled skin

Front 225

235. What can cause a delayed onset of respiration?

Back 225

If the mother has been depressed by a general anesthetic during deliver, which at least partially anesthetizes the fetus as well, the onset of respiration is likely to be delayed.

Hypoxia frequently occurs.

Front 226

236. What are two things that can cause hypoxia in an infant?

Back 226

This can result from two effects:
1. In a few infants, intracranial hemorrhage or brain contusion causes a concussion syndrome w/a greatly depressed respiratory center.
2. *Prolonged fetal hypoxia during delivery can cause serious depression of the respiratory center.

Front 227

237. What are four reasons for why hypoxia frequently occurs during delivery/

Back 227

1. Compression of the umbilical cord
2. Premature separation of the placenta
3. Excessive contraction of the uterus, which can cut off the mother's blood flow to the placenta
4. Excessive anesthesia of the mother, which depresses oxygenation even of her blood

Front 228

238. What is the degree of hypoxia that an infant can tolerate?

Back 228

A neonate often survives as long as 10 min of failure to breathe after birth. Permanent and very serious brain impairment often ensures if breathing is delayed more than 8-10 minutes.

Front 229

239. What happens to the walls of the alveoli at birth?

Back 229

At birth, the walls of the alveoli are at first collapsed b/c of the surface tension of the viscid fluid that fills them.

More than 25 mm Hg of negative inspiratory pressure int eh lungs is usually required to oppose the effects of this surface tension and to open the alveoli for the first time.

*Once they do open, further respiration can be effected w/relatively weak respirations. Fortunately, the first inspirations are very powerful - 600 mm Hg negative pressure.

Front 230

240. How is the second breath compared to the first?

Back 230

The second breath is much easier, with far less negative and positive pressures required. Breathing does not become completely normal until about 40 minutes after birth.

Front 231

241. What happens when surfactant secretion is deficient?

Back 231

Respiratory distress. A small # of infants, especially premature infants and infants born of diabetic mothers, develop severe respiratory distress in the early hours ot first several days after birth, and some die within the next day or so.

The alveoli of these infants contain large quantities of proteinaceous fluid, almost as if pure plasma had leaked out of the capillaries into the alveoli. The fluid also contains desquamated alveolar epithelial cells.

*This condition is called hyaline membrane disease.

Front 232

242. What is one of the most characteristic findings in respiratory distress syndrome?

Back 232

Failure of the respiratory epithelium to secrete adequate quantities of surfactant.

The surfactant secreting cells (type 2 alveolar epithelial cells) do not begin to secrete surfactant until the last 1-3 mos of gestation. Therefore, many premature babies and a few full term babies are born w/o the capability to secrete sufficient surfactant, which causes both a collapse tendency of the alveoli and development of pulmonary edema.

Front 233

243. What is the ductus venosus?

What is the foramen ovale?

Back 233

Blood returning from the placenta thru the umbilical vein passes thru the ductus venosus, mainly bypassing the liver.

Then most of the blood entering the right atrium from the IVC is directed in a straight pathway across the posterior aspect of the right atrium and thru the foramen ovale directly into the left atrium.

Thus, the well-oxygenated blood from the placenta enters mainly the left side of the heart, rather than the right side, and is pumped by the left ventricle mainly into the arteries of the head and forelimbs.

Front 234

244. What is the ductus arteriosus?

Back 234

The blood entering the right atrium from the SVC is directed downward thru the tricuspid valve into the right ventricle.

This blood is mainly deoxygenated blood from the head region of the fetus, and it is pumped by the right ventricle into the pulmonary artery and then mainly thru the ductus arteriosus into the descending aorta, then thru the two umbilical arteries into the placenta, where the deoxygenated blood becomes oxygenated.

Front 235

245. About how much blood pumped by the heart pass thru the different vascular circuits of the fetus?

Back 235

About 55% of all the blood goes thru the placenta, leaving only 45% to pass thru all the tissues of the fetus.

Furthermore, during fetal life, only 12% of the blood flows thru the lungs; immediately after birth, virtually all the blood flows thru the lungs.

Front 236

246. What are the two primary changes in pulmonary and systemic vascular resistances at birth?

Back 236

1. Loss of the tremendous blood flow thru the placenta, which approx doubles the systemic vascular resistance at birth. This increases the aortic pressure as well as the pressures in the left ventricle and atrium.

2. The pulmonary vascular resistance greatly decreases as a result of expansion of the lungs. Immediately on expansion, the blood vessels in the lungs are no longer compressed and the resistance to blood flow decreases.

Front 237

247. How does hypoxia of the lungs affect the pulmonary vascular resistance?

Back 237

The hypoxia of the lungs in fetal life causes considerable tonic vasoconstriction of the lung blood vessels, but vasodilation takes place when aeration of the lungs eliminates the hypoxia.

Front 238

248. So, and increase in systemic vascular resistance and a decrease in pulmonary vascular resistance after birth does what...?

Back 238

All these changes together reduce the resistance to blood flow thru the lungs as much as 5x, which *reduces the pulmonary arterial pressure, right ventricular pressure, and right atrial pressure.

Front 239

249. What causes the foramen ovale to close?

Back 239

The low right atrial pressure and the high left atrial pressure that occur secondary to the changes in systemic and pulmonary vascular resistances cause blood now to attempt to flow backward thru the foramen ovale.

Consequently, the small valve that lies over the foramen ovale on the left side of the atrial septum closes over this opening, thereby preventing further flow thru the foramen ovale.

Front 240

250. What causes the ductus arteriosus to close?

Back 240

The increased systemic resistance elevates the aortic pressure while the decreased pulmonary resistance reduces the pulmonary arterial pressure. As a consequent, after birth, blood begins to flow backward from the aorta into the pulmonary artery thru the ductus arteriosus, rather than in the direction as in fetal life.

However, after only a few hours, the muscle wall of the ductus arteriosus constricts markedly, and w/in 1-8 days, the constriction is usually sufficient to stop all blood flow. *This is called functional closure.

Then, during the next 1-4 mos, the ductus ordinarily becomes anatomically occluded by growth of fibrous tissue into its lumen.

Front 241

251. What is the actual mechanical reason for the ductus arteriosus to close?

Back 241

The cause of the closure relates to the increased oxygenation of the blood flowing thru the ductus.

In featal life, the PO2 of the ductus blood is only 15-20 mm Hg, but it increases to about 100 mm Hg w/in a few hours after birth.

Furthermore, the degree of contraction of the smooth muscle in the ductus wall is highly related to this availability of oxygen.

Front 242

252. What causes a PDA?

Back 242

The failure of closure has been postulated to result from excessive ductus dilation caused by vasodilating prostaglandins in the ductus wall.

In fact, administration of indomethacin, which blocks synthesis of prostaglandins, often leads to closure.

Front 243

253. What causes the closure of the ductus venosus?

Back 243

Immediately after birth, blood flow thru the umbilical vein ceases, but most of the portal blood still flows thru the ductus venosus, w/only a small amt passing thru the channels of the liver.

However, w/in 1-3 hrs the muscle wall of the ductus venosus contracts strongly and closes this avenue of flow.

As a consequence, the portal venous pressure rises from near 0 to 6-10 mmHg, which is enough to force portal blood thru the liver sinuses.

Front 244

254. How does the neonate obtain nutrition after birth?

Back 244

Before birth, the fetus derives almost all its energy from glucose obtained from the mother’s blood. After birth, the amount of glucose stored in the infant’s body in the form of liver and muscle glycogen is sufficient to supply the infant’s needs for only a few hours.

The liver of the neonate is still far from functionally adequate at birth, which prevents significant gluconeogenesis. Therefore, the infant’s blood glucose concentration frequently falls the first day to as low as 30 to 40 mg/dl of plasma, less than one half the normal value.

Fortunately, however, appropriate mechanisms are available for the infant to use its stored fats and proteins for metabolism until mother’s milk can be provided 2 to 3 days later.

Front 245

255. What happens to the infants weight after birth?

Back 245

An infants rate of body fluid turnover averages 7x that of an adult, and the mother's milk supply requires several days to develop.

Ordinarily, the infant's weight decreases 5-10% and sometimes as much as 20% w/in the first 2-3 days of life.

Most of this weight loss is loss of fluid rather than body solids.

Front 246

256. What is a special functional problem of the respiratory system in the neonate?

Back 246

The functional residual capacity of the infant's lungs is only 1/2 that of an adult in relation to body weight.

This difference causes excessive cyclical increases and decreases in the newborn baby's blood gas concentration if the respiratory rate becomes slowed b/c it is the residual air in the lungs that smooths out the blood gas variations.

Front 247

257. What is a special functional problem of the blood volume in the neonate?

Back 247

The blood volume of the neonate avgs about 300 mL, but if the infant is left attached to the placenta for a few min after birth or if the umbilical cord is stripped to force blood out of its vessels into the baby, an additional 75 mL of blood enters the infant.

Then, during the ensuing few hours, fluid is lost into the neonate's tissue spaces from this blood, which increases the HCT but returns the blood volume once again tot he normal value of about 300 mL.

Some believe that this extra blood volume can lead to mild pulmonary edema w/some degree of respiratory distress.

Front 248

258. What is a special functional problem of the cardiac output in the neonate?

Back 248

The CO of the neonate averages about 500 mL/min, which, like respiration and body metabolism, is about 2x as much in relation to body weight as in the adult.

Occasionally a child is born w/an especially low CO caused by hemorrhage of much of its blood volume from the placenta at birth.

Front 249

259. What is the avg blood pressure of the neonate?

Back 249

The arterial pressure during the first day after birth averages about 70/50. This increases slowly during the next several months to about 90/60.

Then there is a much slower rise during the subsequent years until the adult pressure of 115/70 is attained at adolescence.

Front 250

260. What are the blood characteristics in the neonate?

Back 250

The RBC count averages about 4 million per cubic mL. The avg RBC count falls to less than 4 million per cubic mL by about 6-8 weeks of age. Few new red blood cells are formed in the infant during the first few weeks of life, presumably because the hypoxic stimulus of fetal life is no longer present to stimulate red cell production.

From that time on, increasing activity by the baby provides the appropriate stimulus for returning the RBC count to normal w/in another 2-3 months.

Immediately after birth, the WBC count of the neonate is about 45,000 per cubic mL, which is about 5x that of an adult.

Front 251

261. What is neonatal jaundice?

Back 251

After birth, the neonate's liver functions poorly and is incapable of conjugating significant quantities of bilirubin w/glucuronic acid for excretion into the bile.

Consequently, the plasma bilirubin concentration rises to about 5 mg/dL during the first 3 days of life and then gradually falls back to normal as the liver becomes functional.

Front 252

262. What is the mot important abnormal cause of serious neonatal jaundice?

Back 252

Erythroblastosis fetalis. It is caused by Rh factor incompatibility between the fetus and mother.

Briefly, the erythroblastotic baby inherits Rh-positive red cells from the father, while the mother is Rh negative. The mother then becomes immunized against the Rh-positive factor in the fetus's blood cells, and her antibodies destroy fetal RBCs, releasing extreme quantities of bilirubin into the fetus's plasma and often causing death.

Front 253

263. What is the fluid balance in the infant?

Back 253

The rate of fluid intake and fluid excretion in the newborn infant is 7x as great in relation to weight as in the adult, which means that even a slight percentage alteration of fluid intake or fluid output can cause rapidly developing abnormalities.

Front 254

264. Is acidosis a problem in infancy?

Back 254

Yes, considering the immaturity of the kidneys, together w/the marked fluid turnover in the infant and rapid formation of acid, one can readily understand that among the most important problems of infancy are acidosis, dehydration, and more rarely, overhydration.

Front 255

265. What are four effects of deficient liver function in the neonate?

Back 255

1. The liver conjugates bilirubin w/glucuronic acid poorly and therefore excretes bilirubin only slightly during the first few days of life.
2. The liver is deficient in forming plasma proteins, so that the plasma protein concentration falls during the first weeks of life to 15-20% less than that for older children
3. The gluconeogenesis function of the liver is particularly deficient. As a result, the blood glucose level of the unfed neonate falls to about 30-40 mg/dL (40% normal), and the infant must depend mainly on its stored fats for energy
4. The liver usually also forms too little of the blood factors needed for normal blood coagulation

Front 256

266. The ability of the neonate to digest, absorb, and metabolize foods is no different from that of the older child, except for three exceptions.

What are they?

Back 256

1. Secretion of pancreatic amylase in the neonate is deficient, so that the neonate uses starches less adequately than do older children.
2. Absorption of fats from the GI tract is somewhat less than that in the older child. Milk w/a high fat content is inadequately absorbed

3. B/c the liver functions imperfectly during at least the first week of life, the glucose concentration in the blood is unstable and low.

Front 257

267. Can the neonate synthesize and store proteins well?

Back 257

The neonate is especially capable of synthesizing and storing proteins.

W/an adequate diet, as much as 90% of the ingested AAs are used for formation of body proteins. This is a much higher percentage than in adults.

Front 258

268. What about the metabolic rate and body temperature of the neonate?

Back 258

The normal metabolic rate is 2x that of the adult, which accounts also for 2x as great CO and 2x respiratory volume in relation to body weight in the infant.

B/c the body surface are is large in relation to body mass, heat is readily lost from the body. As a result, the body temp falls easily in neonates.

The body temp regulatory mechanisms remain poor during the early days of life.

Front 259

269. What are 3 specific problems that occur in the early nutation of the infant?

Back 259

1. Rapid ossification needs calcium; calcium absorption requires vitamin D (premature infants are prone to severe rickets)

2. If the mother has had insufficient iron in her diet, severe anemia is likely to occur in the infant after about 3 months of life

3. Vitamin C is not stored in significant quantities in fetal tissue, yet is required for proper formation of cartilage, bone and other intercellular structures. Thus, supplementation with orange juice can help.

Front 260

270. How does the babies immune system develop?

Back 260

The neonate inherits the mothers antibodies through the placenta. However, the neonate does not form antibodies of its own to a significant extent. By the end of the first month, the baby's gamma globulins have decreased to less than 1/2 the original level.

Thereafter, the baby's own immune system begins to form antibodies, and the gamma globulin concentration returns essentially to normal by the age of 12-20 months.

Front 261

271. How long do the inherited antibodies from the mother last?

Back 261

Despite the decrease in antibodies soon after birth, the antibodies inherited from the mother protect the infant for about 6 mos against most major childhood infectious disease, including diphtheria, measles, and polio.

Conversely, the inherited antibodies against whooping cough are normally insufficient to protect the neonate; immunization is required.

Front 262

272. Do infants have allergies?

Back 262

The newborn infant is rarely subject to allergy.

Several months later, however, when the infants own antibodies first begin to form, extreme allergic states can develop, often resulting in serious eczema, GI abnormalities and even anaphylaxis.

Front 263

273. What happens if a pregnant mother bearing a female child is treated w/androgenic hormones?

Back 263

If a pregnant mother bearing a female child is treated w/androgenic hormones or if an androgenic tumor develops during pregnancy, the child will be born w/a high degree of masculinization of her sexual organs, thus resulting in a type of hermaphrodism.

Front 264

274. What causes the neonates breasts to form milk?

Back 264

The sex hormones secreted by the placenta and by the mother's glands during pregnancy occasionally cause the neonate's breasts to form milk during the first few days of life.

Sometimes the breasts then become inflamed, or infectious mastitis develops.

Front 265

275. What happens to an infant born of an untreated diabetic mother?

Back 265

The infant will have considerable hypertrophy and hyperfunction of the islets of Langerhans in the pancreas.

As a consequence, the infant's blood glucose concentration may fall to lower than 20 mg/dL shortly after birth. Fortunately, however, in the neonate, unlike in the adult, insulin shock or coma from this low level of blood glucose only rarely develops.

Front 266

276. What is the most common cause of large babies?

Back 266

Maternal type 2 DM is the most common cause of large babies.

Type 2 mothers have high insulin and these levels are believed to stimulate fetal growth factor and contribute to increased birth weight.

Front 267

277. What about babies born of an uncontrolled type 1 diabetic mother?

Back 267

Fetal growth may be stunted b/c of metabolic deficits in the mother, and growth and tissue maturation of the neonate are often impaired.

Also, there is a high rate of intrauterine mortality, and among those fetuses that do come to term, there is still a high mortality rate.

2/3'rds of the infants who die succumb to respiratory distress syndrome.

Front 268

278. What causes a child to be born w/hypofunctional adrenal cortices?

Back 268

This often results from agenesis of the adrenal glands or exhaustion atrophy, which can occur when the adrenal glands have been vastly overstimulated.

Front 269

279. How can a mother's thyroid function affect the infant?

Back 269

If a pregnant women has hyperthyroidism or is treated w/excess thyroid hormone, the infant is likely to be born w/a temporarily hyposecreting thyroid gland.

Conversely, if before pregnancy a woman had her thyroid removed, her pituitary gland may secrete great quantities of thyrotropin during gestation, and the child might be born w/temporary hyperthyroidism.

Front 270

280. What causes cretin dwarfism?

Back 270

In a fetus lacking thyroid hormone secretion, the bones grow poorly and there is mental retardation.

This causes cretin dwarfism.

Front 271

282. An immature respiratory system in the infant can cause...?

Back 271

The vital capacity and the functional residual capacity of the lungs are especially small in relation to the size of the infant.

Also, surfactant secretion is depressed or absent. As a result, respiratory distress syndrome is a common cause of death. Also, the low functional residual capacity of the premature infant is often associated w/periodic breathing of the Cheyne-Stokes type.

Front 272

283. What type of diet must a premature infant have?

Back 272

If the infant is more than 2 mos premature, the digestive and absorptive systems are inadequate. The absorption is so poor that the infant must have a low fat diet.

Furthermore, the premature infant has difficulty absorbing calcium, and there can develop severe rickets.

Front 273

284. What are 4 other effects of an premature birth on the organs?

Back 273

1. Immaturity of the liver, which results in poor intermediary metabolism and often a bleeding tendency as a result of poor formation of coagulation factors
2. Immaturity of the kidneys, which are particularly deficient in their ability to rid the body of acids, thereby predisposing to acidosis as well as to serious fluid balance abnormalities
3. Immaturity of the blood-forming mechanism of the bone marrow, which allows rapid development of anemia
4. Depressed formation of gamma globulin by the lymphoid system, which often leads to serious infection.

Front 274

285. What about the homeostatic control systems in the premature infant?

Back 274

The acid-base balance can vary tremendously, particularly when the rate of food intake varies from time to time.

Likewise, the blood protein concentration is usually low because of immature liver development, often leading to hypoproteinemic edema.

And inability of the infant to regulate its calcium ion concentration frequently brings on hypocalcemic tetany.

Also, the blood glucose concentration can vary between the extremely wide limits of 20 to more than 100 mg/dl, depending principally on the regularity of feeding.

Front 275

286. Can the premature infant regulate its own body temp?

Back 275

One of the particular problems of the premature infant is inability to maintain normal body temperature.

Its temp tends to approach that of its surroundings. At room temp, the infant’s temp may stabilize in the low 90°s or even in the 80°s F. A body temp maintained below 96°F (35.5°C) is associated with a particularly high incidence of death, which explains the almost mandatory use of the incubator in treatment of prematurity.

Front 276

287. What is a danger of excess oxygen therapy in the premature infant?

Back 276

It has been discovered that use of excess oxygen in treating premature infants, especially in early prematurity, can lead to blindness.

The reason is the too much oxygen stops the growth of new blood vessels in the retina. Then when oxygen therapy is stopped, the blood vessels try to make up for lost time and burst forth w/a great mass of vessels growing all thru the vitreous humor, blocking light from the pupil to the retina.

And still later, the vessels are replaced w/a mass of fibrous tissue where the eye's clear vitreous humor should be.

Front 277

288. What is this type of blindness called?

Back 277

Retrolental fibroplasia, and it causes permanent blindness.

Studies indicate that the premature infant is usually safe w/up to 40% oxygen in the air breathed.

Front 278

289. How does the skull and brain progress in development?

Back 278

At birth, the infant brain mass is only 26% of the adult brain mass and 55% at 1 year, but it reaches almost adult proportions by the end of the second year.

This is also associated with closure of the fontanels and sutures of the skull, which allows only 20% additional growth of the brain beyond the first 2 years of life.