Translational Physiology Block 7 Flashcards
1
Q
What is a paraneoplastic syndrome?
A
ability of nonendocrine tissues to produce hormones (primarily peptide)
examples: different types of lung cancers may cause hypercalcemia (secretion of PTH-related peptide), or hyponatremia (secretion of AVP)
2
Q
Describe pseudohypoparathyroidism
A
abnormality in Gs g protein
impairment in PTH signaling (low serum calcium, high serum phosphate, and increased circulating PTH; increased risk of hypothyroidism and female gonadal dysfunction
3
Q
How are steroid receptors quantified in cancer patients?
A
labeled immunoassay; Scatchard plot: y-axis is steroid/free hormone, x-axis is bound hormone concentration; slope is dissociation constant
4
Q
Is a high expression of estrogen and progesterone receptors in breast tumors a favorable prognosis?
A
Yes; suggests advanced state of differentiation and predicts favorable response to hormone therapy
5
Q
What is Cushing’s syndrome? What causes it?
How is it treated?
A
truncal adiposity, hypertension, loss of subcutaneous adipose and connective tissue in the extremities with associated bruising, loss of bone mineral, muscle wasting and weakness, and hyperglycemia
primary cortisol-producing adrenal tumor or secondary pituitary tumor
treatment depends on the elucidating the cause and eliminating it
6
Q
Treatment of glucocorticoid therapy is used in what clinical setting?
A
chronic inflammatory and neoplastic disorder
7
Q
What is Addison disease?
What causes it?
Treatment?
A
increases in circulating concentration of ACTH and other products of POMC (skin hyperpigmentation), hypoglycemia, hypotension, and hyperkalemia
caused by tuberculosis or autoimmune disorders
treated with glucocorticoid and mineralocorticoid therapy
8
Q
Describe 21alpha-hydroxylase deficiency.
A
inadequate production of both glucocorticoid and mineralocorticoid hormones
symptoms: hypotension and dehydration; hypoglycemia; body responds by increasing ACTH secretion resulting in: hyperplasia of adrenal gland, greater than normal activity of SCC enzyme, 3beta-HSD, 17alpha-hydroxylase, and 11beta-hydoxylase (net effect is production of adrenal androgens)
9
Q
Describe the consequences of glucocorticoid therapy.
A
rounding of the face (moon facies), thinning of the skin, and fragility of cutaneous blood vessels; osteopenia (or osteoporosis; pathologic fractures); increased frequency and severity of infections; wasting of muscle leading to generalized muscle weakness; glucose intolerance (antagonist of insulin); does not result in hypertension
10
Q
What are common treatment modalities for hypertension?
A
spironolactone: weak diuretic that directly antagonizes the effects of aldosterone on the renal tubule (patients present with ascites; may be combined with common thiazide diuretics in treatment of hypertension or congestive heart failure to prevent potassium wasting)
ACE inhibitors: captopril and AT1-receptor targeted therapies (most common side effect of ACE inhibitors is chronic cough)
11
Q
Describe pheochromocytoma. How is it diagnosed?
How is it treated?
A
tumor caused be hyperplasia of either adrenal medullary tissue or extra-adrenal chromaffin tissue that failed to involute after birth
may be benign or malignant
symptoms: paroxysmal (sudden outburst) hypertension, tachycardia, headache, episodes of sweating, anxiousness, tremor, and glucose intolerance
diagnosis: history, evidence on physical examination of excessive adrenergic tone, and laboratory detection of increased amounts of urinary catecholamines and their metabolites
treatment: locate and resect tumor (if bilateral adrenalectomy is elected, glucocorticoid and mineralocorticoid therapy is required); no therapy is routinely given to replace the adrenal medullary function
12
Q
Why are patients weaned off of cortisol or its derivatives?
A
Too allow for the normal CRH-ACTH-cortisol axis to reinitiate
13
Q
Can beta blockers decrease renin release?
A
Yes
14
Q
What pathologies affecting the CRH-ACTH-cortisol axis are ACTH-dependent? independent?
A
dependent: Cushing, ectopic ACTH, or ectopic CRH
independent: adrenal adenocarcinoma, adrenal adenoma, adrenal hyperplasia, and exogenous steroid administration
15
Q
Describe pseduo-Cushing’s.
A
(exogenous steroid) a consequence of obesity, depression, poorly controlled diabetes, alcoholic liver disease, and poly-cystic ovarian syndrome
16
Q
What is metyraprone?
A
a drug used to diagnose adrenal insufficiency and occasionally used in the treatment of Cushing’s syndrome;
Metyrapone blocks cortisol synthesis by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels (ectopic ACTH-producing tumors do not increase ACTH secretion in response to metyraprone)
17
Q
What happens to the contralateral adrenal gland in the case of a adrenal adenoma in the right hemisphere?
A
the left adrenal gland will atrophy (due to the feedback inhibition on ACTH secretion by the increased cortisol production the right adrenal gland)
18
Q
What is a common symptom of pituitary adenomas?
A
Papilledema (compression of optic chiasm from below)
19
Q
How is primary aldosteronism diagnosed?
A
findings of hypernatermia, hyporeninemia, hypokalamia (muscle weakness and polyuria), metabolic alkalosis, ST-depression and U wave elevation
20
Q
What is Conn’s syndrome? Barrter syndrome?
A
Primary aldosteronism secondary to an adrenal adenoma
Secondary hyperaldosteronism as a result of increased renin secretion from renal artery stenosis, congestive heart failure, renal salt-wasting, juxtaglomerular hyperplasia
21
Q
What are characteristics of iodine deficiency? (geography and pathology)
A
common in inland areas (seawater and seafood contains large amounts of iodine; Andes Mountains in South America, central Africa, and Southeast Asia); goiter formation; cretinism- mental retardation
22
Q
How do you calculate the amount of free T4 in the circulation?
A
[T4 ] free = concentration of T4 bound to TBG divided by the binding constant (T4TBG/T4 x TBG) multiplied by the concentration of TBG
23
Q
Describe Grave’s disease.
What are key clinical features of this disease that are not associated with the thyroid?
A
activation of TSH receptor by antibodies secreted from B lymphocytes (not regulated)
increased iodide trapping; increased synthesis of T3 and T4; goiter; Increased metabolic rate with associated weight loss, sweating and heat intolerance, a rapid and more forceful heartbeat, muscle weakness and wasting, tremulousness, difficulty concentration, and changes in hair growth and texture; palpable isthmus
Antibodies are also able to stimulate connective tissue in the extraocular muscles and in the dermis of the lower extremity to synthesize mucus (exopthlamos and pretibial myxedema)
24
Q
Describe hypothyroidism. (trends, symptoms, causes)
A
more common in women; peripheral edema, constipation, headache, joint aches, fatigue, and, in women, anovulation (hypothermia and coma in elderly patients); caused by iodine deficiency (sometimes autoimmune disorder known as Hashimoto thyroiditis)
25
How is thyroid function assessed clinically?
the level of TSH reflects the amount of free, biologically active thyroid hormone in the target tissue (RAI); The health of the thyrotrophs themselves can be tested by injecting a bolus of synthetic TRH and monitoring changes in plasma [TSH] (in hypothyroid patients, there is a larger increase due to decreased negative feedback); radioactive iodine uptake can show whether a solitary thyroid nodule, detected on physical examination, is “hot” (functioning) or “cold” (nonfunctioning; malignant); radioactive iodine uptake can show whether hyperthyroidism is the result of thyroid inflammation (i.e., thyroiditis), in which tracer uptake is minimal, or Graves disease, in which tracer uptake is increased.
26
What are clinical manifestations of hypoglycemia?
early: palpitations, tachycardia, diaphoresis (sweating), anxiety, hyperventilation, shakiness, weakness, hunger, and nausea
late: confusion, unusual behavior, hallucinations, seizures, hypothermia, focal neurologic deficits, and coma
27
What are clinical manifestations of hyperglycemia?
early: weakness, polyuria, polydipsia, altered vision, weight loss, and mild dehydration
late: (accompanied by metabolic acidosis or diabetic ketoacidosis): Kussmaul breathing, stupor, coma, hypotension, and cardiac arrythmias
NOTE: severe hyperglycemia produces osmotic diuresis and can lead to severe dehydration, hypotension, and vascular collapse)
28
Describe nonhuman insulin.
Pork and beef insulin differ from human insulin by one and three amino acids, respectively. The difference, although small, is sufficient to be recognized by the immune system, and antibodies to the injected insulin develop in most patients treated with beef or pork insulin
29
Describe mutant insulin.
abnormal insulin possesses a single amino acid substitution in either the A or B chain. In each case that has been described, these changes lead to a less active insulin molecule
results in glucose intolerance or diabetes
30
What is the effect of sulfonylureas?
| Can they treat type I diabetics?
Enhance insulin secretion by beta cells by binding to the SUR subunits of ATP-dependent potassium channels (decreasing the probability of the channel being open)
No
31
What is Leprechaunism?
mutation in insulin receptor that markedly affects growth in utero and after birth (generally fatal within first year of life)
32
Can people develop antibodies against their insulin receptor?
Yes
33
Describe pathologic activation of the insulin receptor.
activation of inflammatory pathways involving p38 MAP kinase and nuclear factor-κβ can lead to phosphorylation of the insulin receptor (and of IRS proteins), principally at serine residues. This serine phosphorylation occurs commonly in animal models of insulin resistance and type 2 diabetes, as well as in human diabetes.
34
Describe diabetes mellitus type 1.
hallmark: elevated blood glucose concentration; caused by an immune-mediated selective destruction of beta cells of the pancreas; osmotic diuresis and metabolic acidosis
death may occur by dehydration and diabetic ketoacidosis
35
Describe diabetes mellitus type 2.
early presentation: hyperplastic beta cells; Beta cells do not respond normally to increases in plasma glucose by increasing insulin secretion (in addition to resistance of insulin receptor)
comorbidities: hypertension, obesity, and dyslipidemia (elevated triglycerides and low HDL); increased risk for atherosclerosis
36
What is a clinical measure of excess growth hormone secretion?
an increased circulating concentration of IGF-1 (occurs in cases of acromegaly and gigantism)
37
Describe Laron dwarfism
| How is it treated?
mutation in growth hormone receptor; characterized by normal or elevated plasma growth hormone
treatment with GH is ineffective; treated with recombinant IGF-1
38
Describe anabolic-androgenic steroids (what are examples, what are the affects, what are the adverse effects?)
testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone (DHEA) (as well as growth hormone)
"performance enhancers": increase muscle mass and strength
adverse effects: oily skin, acne, hair growth, liver abnormalities, aggressive behavior, and hepatocellular carcinoma
(in addition to alteration in growth and sexual maturation)
39
What is BMI? what is considered underweight? normal weight? overweight? obese?
Weight in kilograms divided by the height in square meters
underweight: less than 18.5
normal: 18.5-24.9
overweight: 25-29.9
obese: 30 or more
40
What are some causes of obesity?
most obese persons are not leptin deficient (some may be leptin resistant and eventually respond to sufficiently high levels of the hormone)
Some obese individuals have a mutated leptin receptor gene and other may have a mutation in the POMC gene (leading to loss of the anorexigenic alpha-MSH); others may have a mutation in MC4 receptor
41
What is the response of lean individuals to administration of leptin?
loss of weight
42
What drugs have been approved to treat obesity? what may eventually be approved?
serotonin re-uptake inhibitor and an agent that blocks fat digestion (limited by side effects and have minimal effect)
cannabinoid receptors
43
Describe familial hypocalciuric hypercalcemia (what are the symptoms? treatments?)
Mutation in calcium-sensing receptor on the parathyroid cell; set point at which the calcium turns off PTH secretion is shifted toward higher plasma calcium concentration; similar calcium sensing receptor may be expressed in distal convoluted tubule of the kidney
Remarkably few symptoms (present with decreased calcium excretion through kidney)
treated with CaSR agonist
44
What is Rickets? What is osteomalacia?
both are result of vitamin D deficiency resulting in unmineralized osteoid of both cortical and trabecular bone (Rickets in children and osteomalacia in adults)
May have impaired ability in the kidney to 1-hydroxylate the 25-hydroxyvitamin D, synthesized in the liver (rare autosomal recessive disorder or consequence of chronic renal failure); this particular type of disorder may be treated with vitamin D
children have bowing of bones; adults have decreases bone strength (prone to fractures); recruitment of new osteoclasts may be diminished resulting in hypocalcemia and sensations of numbness, tingling, or burning (in addition to motor nerve tetany)
may result in secondary hyperparathyroidism leading to bone resorption and worsening osteoporosis (mild deficiency; common in elderly)
45
Describe osteoporosis. What are risk factors? What are possible treatment options?
weakening of bones; hip fractures are responsible for much of the morbidity associated with osteoporosis
Major risk factor is declining estrogen levels in aging women (in addition to hyperthyroidism, hyperparathyroidism, and Cushing); other risk factors include adequate dietary calcium intake, alcoholism, and lack of exercise
estrogen or calcitonin therapy; bisphosphonates are powerful inhibitors of bone resorption (suggested to take at low doses to prevent impairment of mineralization); vitamin D, and PTH agonists
46
What is Paget disease of bone? How is it treated?
Characterized by localized regions of bone resorption and reactive sclerosis
may be asymptomatic or may cause pain, deformity, fractures, vertigo, and hearing loss if bony overgrowth occurs in the region of the eight cranial nerve
treated with calcitriol (vitamin D) and bisphosphonates
47
What are the consequences of decline in serum testosterone in aging males? What are treatments?
decreases in bone formation, muscle mass, growth of facial hair, appetite, and libido (decrease in hematocrit); levels of LH are frequently not elevated (some degree of hypothalamic-pituitary dysfunction accompanies aging)
may be counteracted by testosterone replacement
48
Describe Sertoli cell-only syndrome (what is the cause, is Leydig cell function preserved, what hormones are elevated, and does this affect the entire organ?)
Virilized men whose testes are small bilaterally and whose ejaculates contain no sperm cells (azoospermia; complete absence of germ cells)
single gene defect or acquired as a result of orchitis, alcoholism, and toxic agents
YES
FSH levels are elevated (plasma testosterone and LH levels are normal)
NO
49
Describe congenital and acquired ductal obstruction (what are epididymal changes, is spermatogenesis normal, what are hormone levels, and what is the hallmark of the disease?)
Acquired as a result of stricture, infection, or vasectomy (epididymitis, smallpox, Young syndrome, and cystic fibrosis)
congenital absence of the vas deferens (common in patients with cystic fibrosis)
varies from incomplete epididymis to the presence of only small portions of the epididymis (seminal vesicles are absent)
Yes (presence of germ cells on biopsy)
Testosterone and gonadotropin levels are normal in most patients
azoospermia in men with normal testes
50
Descibe vasectomy. What are pathologic consequences?
a simple surgical procedure in which a small segment of the vas deferens is removed to ensure male infertility, is currently the leading cause of ductal obstruction
Interstitial fibrosis: increased thickness of the tubule wall, an increase in cross-sectional tubular area, and decreased numbers of the Sertoli cells are usually noted
51
What are medications to treat erectile dysfunction (what are the results, what is the mechanism of action, and what are side effects, and can they work on women?)
sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)
experience significant improvement in rigidity and duration of erections
Highly selective, high-affinity inhibitors of cGMP-specific phosphodiesterase type 5
sudden death (if taken with other vasodilators) and "blue vision"
Sildenafil may improve sexual function in women by increasing blood flow to the accessory secretory glands
52
Describe retrograde ejaculation (etiology, treatments and their mechanism of action)
occurs when internal urethral sphincter fails to constrict allowing semen to enter the urinary bladder
diabetes mellitus, multiple sclerosis, antagonists of sympathetic tone, or nerve damage following surgery
sympathomimetic drugs: phentolamine (an alpha adrenergic agonist), ephedrine (enables norepinephrine release), and imipramine (inhibits norepinephrine re-uptake)
Increase the tone of the vas deferens (propelling the seminal fluid) and the internal sphincter (preventing retrograde movement); no effective treatments for nerve damage resulting from surgery
53
Is erectile capacity preserved in men with lesions of the premotor neurons? Is ejaculation more significantly impaired by upper or lower motor neuron lesions? What site of nerve damage disrupts reflexic erection?
Yes;
upper (loss of the psychogenic component)
damage to the lower spinal cord
54
Does an upper motor neuron lesion affect reflexogenic erection? psychogenic erection? What is the overall effect?
No, Yes (absent); significantly impaired ejaculation
55
Does a lower motor neuron lesion affect reflexogenic erection? psychogenic erection? What is the overall effect?
Yes (absent), No; less impaired ejaculation compared to upper motor neuron lesion
56
What disease requires pulsatile GnRH administration in women?
Kallman syndrome (caused by disordered migration of GnRH cells during embryonic development; X-linked; characterized by absence of gonadotropins and hypogonadism (in addition to anosmia)
57
What disease requires continuous GnRH administration in women?
endometriosis (aberrant presence of endometrial tissue outside the uterine cavity; source of pain and potential infertility)
58
What are Leiomyomas? What hormone are they dependent upon? How can they be treated?
smooth muscle tumors of the uterus; estrogen dependent; can be effectively treated by continuous administration of GnRH analogues
59
What is the treatment regimen of most birth control pills? What is the net effect of oral contraceptives? How are progestin-only OCPs different from other contraceptives? What are side effects of these pills?
take pills 21 days out of the 28-day cycle (monophasic and fixed-combination OCPs, OR multiphasic and varying-dose OCPs, OR progestin-only)
suppression of FSH and LH secretion (insufficient to stimulate normal folliculogenesis)
thickening of the mucus in the uterus, impaired uterine motility, and decreased glandular production of glycogen; Because they are inconsistent inhibitors of ovulation, the progestin-only OCPs have a substantially higher failure rate than does the combined type of OCP.
nausea, edema, headaches, and weight gain; progestin-specific (androgenic actions): depression, breast pain or tenderness (mastodynia), acne, and excessive hair (hirsutism)
new progestins have decreased androgenic effects increasing sex-hormone binding globulin concentrations, improving glucose tolerance, and increased HDL to LDL ratio
60
Why can excess estrogen and progesterone cause weight gain?
At high doses they can function as mineralocorticoids in the kidney increasing sodium reabsorption and extracellular volume
61
Why can excess progesterone have androgenic effects in women?
Progesterone is converted to androstenedione and eventually testosterone
62
Can estrogen decrease the risk of cardiovascular events?
Yes
63
Oral contraceptives increase the risk for what diseases? What do OCPs decrease the risk of?
benign liver tumors, cholelithisasis (gallstones), hypertension, heart attack, stroke, deep vein thrombosis, and pulmonary embolus
ovarian cancer, endometrial cancer, ovarian retention cysts, ectopic pregnancy, pelvic inflammatory disease, and benign breast disease
64
Why do OCPs increase the risk of gallstones and liver disease?
Less absorption of cholesterol in the ovaries, through OCPs, can increase the risk of benign liver tumors and generation of gallstones
65
What is hormone replacement therapy during menopause? What is effective for? What are they not effective for? What are complications of this therapy?
estrogen and progesterone administration (administering progestins is necessary due to the high risk of endometrial neoplasia from the unopposed act; not required for women with hysterectomies)
effective against osteoporosis and cardiovascular disease (and vasomotor symptoms)
cardiovascular disease
Increased risk of breast cancer, stroke, and venous thrombo-embolism
66
What is menopausal syndrome?
a. Vasomotor instability, hot flashes, night sweats, mood changes, short-term memory loss, sleep disturbances, headaches, and loss of libido
changes in vaginal pH, atrophy of the epithelia, decrease in circulation, and pelvic relaxation
Increased risk of cardiovascular disease, osteoporosis, and Alzheimer's disease
67
What are the two most commonly used selective estrogen receptor modulators (what are outcomes)? What would be the perfect therapeutic agent?
Tamoxifen and raloxifene have beneficial effects on bone and cardiovascular system, whereas they antagonize estrogen in reproductive tissue.
The perfect SERM would alleviate the menopausal syndrome, protect against cardiovascular and Alzheimer disease, and act as estrogen agonists in certain reproductive tissues and as antagonists in others.
68
Describe Turner Syndrome.
a disorder of the female sex characterized by short stature, primary amenorrhea, and sexual infantilism
45 XO
Streak gonads: firm, flat, glistening streaks lying below the fallopian tubes (composed of connective tissues arranged in whorls suggestive of ovarian stroma)
Normal female differentiation of both the internal and external genitalia (small and immature for the patient's age)
69
Does partial deletion of the X chromosome result in full Turner phenotype?
Yes
70
What is a ring chromosome? Where does this tend to occur and what is the consequence?
A ring chromosome is a small round or oval chromosome that often appears as a single black dot without a central hole; it forms as a result of a deletion and subsequent joint of the two free ends of the chromosome
X chromosome; in effect it is a deletion of the X chromosome resulting in Turner phenotype
71
What is the genotype and gonadal phenotype of true hermaphrodites? in mixed gonadal dysgenesis? pseudohermaphrodites? pure gonadal dysgenesis?
46, XX; posses both male and female sex organs
45, XO: a testis in addition to a streak ovary
mosaic 46, XY/46, XX; only one type of gonadal tissue but morphological characteristics of both sexes; may result from translocation of the SRY gene to either an X chromosome or an autosome
46, XY: streak gonads but not somatic features of XO
72
Describe congenital adrenal hyperplasia (what is deficient, what sex is affected, and how is development of the genitalia affected?)
21alpha-hydroxylase deficiency reduces conversion of progesterone to 11-deoxycorticosterone (which goes on to form aldosterone) and also reduces the conversion of 17alpha-hydroxyprogesterone to 11-deoxycortisol (precursor of cortisol)
hypersecretion of adrenal androgens
The external genitalia are difficult to distinguish from male genitalia on visual inspection (clitoris resembles a penis and the labioscrotal folds are enlarge and fused resembling a scrotum)
73
Describe testicular descent. Is this androgen dependent?
prior to descent mesonephros and wolffian ducts atrophy; testes enlarge
step 1: movement of the testes into the inguinal region
step 2: Herniation of the abdominal wall adjacent to the gubernaculum (result of increased abdominal pressure; forms the processes vaginalis)
step 3: Gubernaculum increases to the approximate diameter of the testis; As its proximal portion degenerates, the gubernaculum draws the testis into the scrotum through the processus vaginalis
Yes; males with 5alpha reductase deficiency or complete androgen resistance have testicles that fail to descend
74
What happens to development of male genitalia in the case of impaired androgen receptor?
In the absence of androgens, male embryos follow a typically female pattern of sexual development
75
Describe male pseudohermaphroditism.
normal karyotype and unambiguous male gonads but ambiguous external genitalia (phenotypically appear as a female)
Deficiency in the enzyme that converts testosterone to DHT in target tissues, absent androgen receptors, qualitatively abnormal receptors, a quantitative deficiency in receptor levels, or postreceptor defects
76
Describe in vitro fertilization and embryo transfer (how are ovaries stimulated, how is ovarian/menstrual cycle monitored and manipulated, how are ovaries retrieved, how does fertilization take place, how are the cells implanted, does the women receive any hormone supplementation following the fertilzation?)
procedure in which oocytes are removed from a women and are then fertilized with sperm under laboratory conditions; early development of the embryo also proceeds under laboratory conditions; finally the physician transfers one or more embryos to the uterine cavity, where the embryo will, one hopes, implant and develop
Ovarian stimulation (must obtain multiple oocytes): physician administers some combination of FSH and LH or pure FSH preparation, either intramuscularly or subcutaneously (depresses the endogenous hypothalamic-pituitary axis)
sonographic monitoring; when ready, physician injects hCG to mimic natural LH surge; retrievals are scheduled for 34-36 hours following the administration of hCG (allow maximal follicular maturation)
The physician retrieves oocytes by aspirating them from individual follicles (under sedation)
The sperm samples is subjected to numerous washes, followed by column chromatography to separate the sperm cells from the other cells and from debris found in ejaculate; inseminated egg is incubated overnight (among couples whose male partner has very low numbers of motile sperm, high fertilization rates can be achieved by intracytoplasmic sperm injection)
After culturing the cells for 48 to 120 hours, the physician transfers three to four embryos to the uterus at the four- to eight-cell stage or fewer embryos at the blastocyst stage (ultrasonic guidance)
Women receives supplemental progesterone to support implantation and pregnancy
77
What determines success of IVF?
Success of this procedure depends on age as well as the type and severity of the disease causing infertility
78
What are indications for IVF?
disorders that impair normal meeting of the sperm and the egg in the distal portion of the fallopian tube; ovulatory dysfunction, tubual occlusion, tubal-peritoneal adhesions, endometriosis, and male-factor infertility
79
What is GIFT?
In certain cases of infertility, the physician collect the oocytes and sperm cells directly transferring the gametes to the fallopian tube, where fertilization occurs (laparoscopic)
80
What is IUGR? What pathologies are these patients at an increased risk for? how is it diagnosed?
a abnormality of fetal growth and development
Birth weight lower than the 3rd, 5th, or 10th percentile for gestational age or a birth weight that is more than two standard deviations lower than the mean for gestational age
Risk for morbidity and mortality: birth asphyxia, neonatal hypoglycemia, hypocalcemia, meconium aspiration, persistent pulmonary hypertension, pulmonary hemorrhage, thrombocytopenia, polycythemia (elevated RBCs), delayed neurologic development, and hypothermia
Diagnosed with ultrasound: predicted by biparietal diameter and abdominal circumference
81
Describe type 1 IUGR. Type 2? intermediate?
decreased growth potential (small fetus; fewer cells, etiology early in gestation from intrauterine infections, chromosomal disorders, congenital malformations, maternal drug ingestion or smoking (25% have aneuploidy)
type II: restricted growth, most frequently caused by uteroplacental insufficiency (normal, smaller, total number of cells, normal length and biparietal diameter but abdominal growth slows during late second and early third trimesters; increased cardiac flow to brain, heart, and adrenals and decreased glycogen storage and liver mass; etiology: maternal hypertension, diabetes, or kidney disease)
intermediate: combination of type 1 and 2; insult occurs during the middle phase of growth and brain is not spared (etiology: maternal hypertension, lupus nephritis, and other vascular diseases that are severe and begin early in second trimester)
82
Describe respiratory distress syndrome (who does it occur to, what are risk factors, what are the acute consequences, what are complication, how is it diagnosed, and how is it treated?
preterm babies with patent ductus arteriosus resulting in hypoxemia
Risk factors: prematurity, male sex, C-section, perinatal asphyxia, second twin pregnancy, and maternal diabetes
Cyanosis, tachypnea, nasal flaring, intercostal and subcostal retractions, the use of accessory musculature, and grunting may be immediately apparent in the delivery room; Atelectasis with air bronchograms (air-filled bronchi standing out against the white background of collapsed lung tissue)
Increases risk for alveolar rupture with pneumothorax and pulmonary interstitial emphysema, necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia (may develop edema and respiratory failure requiring mechanical ventialtion)
Diagnosis: a ratio of lecithin to sphingomylein greater than 2.0 in the amniotic fluid is consistent with mature lungs, as is a positive phosphatidylglycerol assay
Treatment: antenatal steroids and postnatal surfactant
83
Describe fetal asphyxia (what is the etiology, what are clinical values, what is the bodies response to the insult, and what can develop following birth?)
Any insult that interferes with the ability of the placenta to exchange oxygen and carbon dioxide between the maternal and fetal circulation may lead to fetal asphyxia
Etiology: maternal hypotension, abruptio placentae (breaking away of a portion of the placenta from the uterine wall), and a prolapsed umbilical cord
Results are low fetal oxygen partial pressure, high carbon dioxide partial pressure, and acidosis (decreases myocardial function, neurotransmitter release and re-uptake, and leads to accumulation of leukotrienes and prostaglandins resulting in CNS damage through free radicals)
may lead to neonatal hypoxia
84
What are clinical signs of diabetes mellitus?
polyuria, polydypsia, and polyphagia
acanthosis nigricans
85
What is the first consequence of insulin signaling?
inhibition of gluconeogenesis
86
What is the difference between compensated and uncompensated insulin resistance? Which situation is considered diabetic?
hyperinsulinemia
hyperglycemia (abnormal beta cells and type II diabetes)
87
Describe metabolism in type II diabetics.
in the muscle, there is reduced glucose uptake and therefore utilization
in adipose tissue, there is increased lipolysis
and in the liver there is increases glucose production and VLDL synthesis
88
What are symptoms specific for type 1 diabetes?
weight loss
89
Ketoacidosis can occur in which type of diabetes?
type 1
90
How does activation of PKC represent the damaging effects of hyperglycemia?
blood flow abnormalities (decreased nitric oxide synthase), vascular permeabilty increased through VEGF, capillary occlusion through increased ECM-secreted molecules, vascular occlusion through decrease in fibrinolysis, proinflammataroy response through NFkappa beta, and increased reactive oxidative species
91
What causes polyuria and polydypsia in the hyperglycemic state?
the GLUT2 transporter is saturated
92
The autoimmune response generated against beta cells of the pancreas are a result of what type of infection?
mumps and measles virus
93
What is MODY?
mature onset of diabetes of the young (exhaustion of beta cells)
94
What is the cause of double diabetes?
administration of insulin produced by other organisms generating a B cell response
95
What is the significance of glycated hemoglobin?
Diabetic patients can be monitored by analyzing the percentage of hemoglobin that is glycated
less efficient transport of oxygen
96
What are criteria for diagnosing diabetes?
Fasting blood glucose greater than 126 (above 100 is considered criteria for prediabetes)
Postprandial blood glucose over 200 (above 140 is considered prediabetic)
Random blood glucose concentration greater than 200
A1c greater than or equal to 6.5 (greater than 5.7 is considered prediabetic)
If only one criteria is met, analysis may need to be repeated
97
What are modalities for diagnosing diabetes?
glucose tolerance test: administration of 75 grams of oral glucose with blood draws at 0 and 2 hours following administration
clamp technique: Infuse a known amount of insulin and glucose and observe changes (adjusting the concentration of infused substance to achieve target values)
98
Describe metabolic syndrome.
*three criteria must be met
```
abdominal obesity
triglycerides above 150 mg/dl
HDL below 40 or 50
hypertension
steatosis
elevated fasting glucose
```
99
How is diabetes treated?
diet: incretin effect (carbohydrates have strong effect)
exercise: glut4 activated by AMPk
pharma: sulfonylureas, GLP analogues, metformin (metabolism), glucosidase inhibitor, amylin analogue, and SGLT inhibitors
100
Are all pharmacologic agents effective in treating diabetes?
No; drug failure is more common is insulin sensitizers like sulfonylureas
101
What is a feature of intermediate acting synthetic insulins?
bound to a protein to increase half life
102
What are acute complications of diabetes mellitus?
hypoglycemia, diabetic ketoacidosis in type 1, and hyperglycemic coma
103
What are chronic complications of diabetes?
retionopathy, nephropathy, and neuropathy (glycation)
coronary artery disease (not improved by improved glycemia)
cerebrovascular disease, peripheral vascular disease
infections, nontraumatic lower-limb amputations
dysfunction in myelin synthesis
104
What cells can accumulate glucose?
endothelial, pericytes, and mesangial cells (cells that do not accumulate may be spared from damage)
may be converted to sorbitol
105
How does one prevent complications of diabetes?
improve glycemic index, blood pressure control, lipid control, and smoking cessation
106
How does an individual prevent type 1 diabetes? type 2?
vitamin D and breast feeding may be protective;
prevention of obesity and increased physical activity
107
What is the only effective treatment of preelampsia?
delivery of the fetus
108
What is preelampsia?
• hypertension and proteinuria with onset following the 20th week of pregnancy
109
Preeclampsia is associated with what adverse fetal outcomes?
prematurity, intrauterine growth retardation, placental abruption, and oligohydramnios (deficiency in amniotic fluid)
110
What is the pathophysiology of preeclampsia?
abnormal uterine vascular changes; vascular endothelial activation and inflammation; genetics, increased prostanoid levels (PLC) and increased lipid peroxides/free radicals
111
What is a growth factor that is associated with preeclampsia?
VEGF
112
What are risk factors for preeclampsia?
older than 40; previous miscarriage, familial history, obesity and gestational diabetes; women born small for gestational age; twins; fetal growth restriction
pre-existing conditions: hypertension, renal disease, diabetes, clotting abnormalities
113
What is HELLP? How is diagnosed?
hemolysis, elevated liver enzymes, and low platelets
peripheral smear, serum bilirubin, low serum haptoglobin, severe anemia (unrelated to blood loss), elevated AST and ALT; elevated lactate dehydrogenase; low platelets (below 100,000)
114
What is eclampsia?
convulsions (seizures) or coma along with the preeclampsia (may occur during or after pregnancy)
115
How is preeclampsia treated?
mainly to prevent eclampsia: control blood pressure to prevent stroke and magnesium to prevent seizures
116
Why do women with preeclampsia have edema?
Pathological edema due to loss of plasma oncotic pressure
Decreased venous return (congestion) from thoracic effusion?
117
What are symptoms of preeclampsia?
epigastric pain, nausea, and vomitting
118
What is administered to promote surfactant production in a newborn? Does it cross the placenta?
dexamathasone; Yes
119
What is a morbidity of children born from preeclampsia?
cerebral palsy
120
How can preeclampsia be prevented for patients that may be progressing to the condition?
high protein low salt diet
calcium, magnesium, zinc, vitamin E and C
diuretics
low dose aspirin and heparin (antithrombotics)
121
What are home remedies for impotence?
exercise, well-balanced diet, limit alcohol intake, reduce stress, cessation of smoking, and weight loss
122
Describe the anatomy of the penis.
The internal structure of the penis consists of two cylinder-shaped vascular tissue bodies (corpora cavernosa) that run throughout the penis; the urethra (tube for expelling urine and ejaculate); erectile tissue surrounding the urethra; two main arteries; and several veins and nerves
123
What is the etiology of erectile dysfunction?
Physical factors including the blood supply, nerve innervation, and hormonal insufficiencies (low levels of testosterone)
Circulatory problems and heart disease
Side effect of medications (tranquilizers, blood pressure medications including diuretics, antidepressants, and anti-inflammatory drugs)
Smoking (in its ability to cause cardiovascular disease)
alcohol, prostate and colon surgery; radiation treatment for cancer; neurologic problems (nerve damage and psychological)
124
Where are the nerves that innervate the penis located?
retropubic and perianal region
125
How is erectile dysfunction treated?
penis pump, prosthesis, and penile implant
PDE5 inhibitors, prostaglandins (injection or cream), opium (Papaverine)
126
What are adverse effects of PDE5 inhibitors?
abnormal vision
Other adverse effects include constant headache, nausea, chest pain (from vasodilation effect of the medication), dizziness if mixed with cardiovascular medications
127
How is ED diagnosed?
ultrasound, assessment of penile nerve function, presence or absence of nocturnal penile tumescence, angiography and invase cavernosometry; Penile biothesiometry
