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Glucose Receptor types:
GLUT-1
GLUT-2
GLUT-4

1: insulin INdependent (RBCs, brain)
2: BIdirectional (B islet cells, liver, kidney, small intestine)
4: insulin DEpendent (fat, skeletal muscle)

1

Mech of glucose as insulin stimulator

1. Glucose into cell, metabolized --> ATP
2. ATP => close K+ channels -> depolarize
3. open volt-gated Ca2+ channels --> Ca2+ influx => insulin secretion

2

Effects of insulin (on ALL parts of body!) "anabolic"

1. skel. m/fat: increase glucose uptake, increase protein synthesis
2. liver: increase glycogen synthesis, and TG synthesis/storage
3. kidneys: increase Na+ retention
4. increase cell uptake of K+ & AAs
5. decrease glucagon release

3

Effect of adrenergic signalers on insulin secretion

B2 antagonists: increase insulin

Alpha2 agonists: decrease insulin

4

3 types of pancreatic cells

1. alpha --> glucagon
2. beta --> insulin
3. delta --> somatostatin *inhibits glucagon and insulin secretion

5

regulation of growth hormone ("somatotropin")

secretion = in pulses, increases during exercise and sleep

Inhibitors: glucose, somatostatin

6

Case:
Child with hypertension, hypokalemia and ambiguous genitalia/lack of secondary sex characteristics

congenital bilateral adrenal hyperplasia (CAH), w/ 17a hydroxylase def.
=> high mineralcorticoids, low cortisol and sex hormones
Male: undescended testes, ambig. genitalia (insuff. DHT)
Female: normal int. & external sex genitalia, no secondary sex features

7

Case:
young female with hypotension, hyperkalemia, increased renin activity & volume depletion, and pseudohermaphroditism

CAH (congenital adrenal hyperplasia) w/ 21-hydroxylase def.
*most common form of CAH
low mineralcorticoids & cortisol, high sex hormone levels
--> masculinization bc shunting of products towards testosterone

8

Case:
Young adult female with hypertension and masculinization

CAH (congenital adrenal hyperplasia) w/ 11B-hydroxylase def.
=> low aldosterone! but high 11-deoxycorticosterone, low cortisol, HIGH sex hormone levels
Masculinization bc shunt products toward testosterone

9

major functions of cortisol (4)

1. maintain BP (upregulate a1 Rs in arterioles)
2. inhibit Bone formation & fibroblasts
3. Immune-suppression/anti-inflam. (--l leukotrienes, prostaglandins, histamine, eosinophils, IL-2, and leuk adhesion)
4. Increase Gluconeogenesis and insulin resistance

10

function of PTH (parathyroid hormone)

Goal: increase serum Ca2+
1. increase bone reabsorption
2. increase renal reabsorption of Ca2+ & decrease renal PO4- reabs.
3. increase 1,25-D3 production (stimulate renal 1a-hydroxylase)
*opposed by calcitonin*

11

effect of 1,25D3 on gut absorption

active Vit D (1,25D3 aka calcitriol) acts on gut to increase Ca2+ AND PO4- absorption!
(vs PTH acts on kidney, increases Ca reabs. & decreases PO4- reabs.)

12

Function of T3 (thyroid hormone)
"4 B's"

1. Brain maturation
2. Bone growth
3. B1 adrenergic (increase CO, HR, SV, contractility)
4. increase Basal metabolic rate (via Na+/K+ ATPase --> incr. O2 consumption, RR, body temp; also incr. glycogenolysis/gluconeogen.)

13

Wolff-Chaikoff effect

excess iodine in system --> temporarily inhibits thyroid peroxidase
=> less iodine processing = less T3 & T4 production

14

Distinguishing between types of abnormal ACTH secretion
(Cushing's syndrome)

use dexamethasone suppression test (low and high dose)...
normal: cortisol suppressed by low OR high dose.
Pituitary adenoma: high ACTH, low - elevated, high - suppressed.
Ectopic tumor: high ACTH, low - elevated, high - still elevated.
Cortisol tumor (adrenal): less ACTH, low - elevated, high - elevated.

15

symptoms of Cushing's disease/syndrome

HTN, weight gain, truncal obesity and buffalo hump, hyperglycemia, stria/thin skin, osteoporosis, amenorrhea, immune suppression

16

Conn's syndrome

aldosterone-secreting adrenal adenoma (primary hyperaldosteronism)
=> HTN, hypOK+, metabolic alkalosis, low plasma renin
Tx: spironolactone and/or surgical resection

17

primary vs. secondary hyperaldosteronism

Primary: too much aldosterone (adrenal hyperplasia or ectopic)
=> LOW plasma renin
Secondary: overactive RAAS bc kidneys percieve low volume
=> HIGH plasma renin level (ie: renal a stenosis, CHF, cirrhosis, etc)

18

Primary vs. Secondary adrenal insufficiency

Primary (Addison's disease): adrenal destruction bc disease process
=> hypotension, hyperK+, acidosis, skin hyperpigmentation (bc MSH)

Secondary: NO skin hyperpigmentation or hyperK+

19

Case:
Child with swollen belly & diarrhea, also generalized fatigue, etc. Testing shows increased HVA (Homovanillic acid) in urine.

= Neuroblastoma (of adrenal medulla/sympathetic chain)
*over-expression of n-myc => risk rapid tumor progression
*similar to pheochromocytoma but HTN less likely

20

Types of hypOthyroidism

#1: Hashimoto's: autoimmune, w/ HLA-DR5 & anti-thyroiglobulin Abs
2. congenital (Cretinism): hypotonic, poor feeding, umbilical hernia
3. Subacute/DeQuervain's: post-flu, self limited w/ granulomatous inflamm. Very tender thyroid.
4. Riedel's: replace thyroid w/ fibrous tissue, "rock hard" & immobile.

21

types of hypERthyroidism

1. Toxic/Multinodular goiter: focal "hot nodules" bc TSH R mutation
2. Grave's disease: IgG Ab to TSH R ("thyroid-stimulating globulins"), w/ diffuse goiter.
* complication:
Thyroid storm...catecholamine surge -> arrhythmia -> death *high AlkP

22

Common presentations for pituitary adenoma

#1: prolactinoma --> amenorrhea, galactorrhea, bitemporal hemianopia. Tx = bromocriptine (dopamine agonist)
2. Acromegaly (excess GH)
*Dx: GH doesn't suppress w/ oral glucose tolerance test

23

Diabetes Insipidus: nephrogenic vs. central

=> LOW urine specific gravity (can't [ ] urine), polydipsia/polyuria.
Nephrogenic DI: no rxn to ADH => does NOT correct w/ desmopressin
Central DI: lack ADH => DOES correct w/ desmopressin

24

Diabetes Insipidus vs. psychogenic polydipsia

BOTH have polydipsia & polyuria. Use water deprivation test:
DI: urine osmolarity does NOT increase w/ deprivation (can't [ ])
=> for DI do NOT limit H2O (will become hypovolemic)
Psychogenic: urine DOES [ ] over time w/ deprivation

25

Diabetes Insipidus & Psychogenic polydipsia vs. SIADH

DI & psychogenic polydipsia: polydipsia & polyuria, LOW urine [ ]
SIADH: high urine output w/ [ ] > serum, corrects w/ water restriction
(abnormal water retention => hyponatremia bc excrete Na+)
=> confusion, other non-specific symptoms. Coma if severe.

26

LH vs. FSH in female

LH => stimulates ovulation (rapid peak in levels)
FSH: stimulates ovarian follicle to make estrongen =>increase FSH Rs
--> endometrial proliferation

27

progression of progesterone synthesis in ovulation & pregnancy

1. Granulosa cells of follicle (estrogen before ovulation, progesterone after) *Granulosa cells become corpus luteum
2. corpus luteum/embryo
3. placenta (@ wk 5-9)

28

Effect of estrogen on cholesterol levels

HDL increases & LDL decreases w/ estrogen

29

General effects of progesterone

Goal: prepare for/maintain pregnancy (after ovulation)
- induce/maintain corpus luteum (-> spiral aa, etc.)
- thickens cervical mucus (prevent sperm entry)
- relax uterine smooth muscle
- increase body temp

30

Tanner stages of sexual development

I - childhood
II - pubic hair appears ("thelarche")
III - penis lenghtens/breast enlargement
IV - increase penis girth, raised areolae
V - adult (areolae not raised)

31

Histological evidence of Ectopic pregnancy

decidualized endometrium w/ no chorionic villi on endometrial biopsy
(implantation in Fallopian tubes => fail to dvp fully)
Sx = pain (esp. sudden, lower abdominal) +/- bleeding

32

polyhydramnios vs. oligohydramnios

Polyhydramnios: too much fluid => anencephaly
(esophageal/duodenal atresia => can't swallow fluid)
Oligohydramnios: too LITTLE fluid => Potter sequence (face deformity)
(placental insuff, bilat renal agenesis, post. urethral valves (Male)
--> can't excrete urine)

33

Types of ovarian cysts (5)

#1: Follicular cyst: UNruptured follicle, +/- endometrial hyperplasia
2. Endometrioid cyst: endometriosis in ovary *bleeds w/ menses
3. Theca-Lutein cyst: >1/bilat., from LH/FSH stim., risk choriocarc.
4. Dermoid cyst: teratoma (mature)
5. Corpus luteum cyst: persistent corpus luteum w/ hemorrhage

34

Types of gonadal germ cell tumors

#1: Teratoma: *mature = benign in F, immature always malignant
2. Yolk sac tumor: malign, yellow solid mass, "glomeruloid," high AFP
3. Dysgerminoma/Seminoma: high hCG, sheets of uniform cells
*4. Choriocarcinoma: = trophoblast -> only in mom or baby, high hCG
=> early hematog. mets to lungs

35

Benign breast masses (5)

# 1. Fibroadenoma (esp. nipple discharge
5. Phyllodes tumor: large & bulky (CT & cysts), esp. 60s

36

5 types of Malignant Breast cancer

#1: Invasive ductal (worst): firm, fibrous, "stellate"
2. Invasive Lobular: bilateral, orderly
3. Medullary: fleshy w/ lymphocytic infiltrate
4. Inflammatory: dermal lymphatic invasion, block => "peau d'orange"
5. DCIS = Ductal carcinoma In Situ/Comedocarcinoma
*Paget's disease = sign of DCIS

37

Direct vs. Indirect vs. Femoral hernia

- Direct: Hesselbach's triangle, w/ inferior epigastric vessels LATERAL, and rectus abdominus medial.
- INdirect (#1 M): INternal inguinal ring, w/ inf. epigastrics MEDIAL.
- Femoral (#1 F): femoral canal, w/ femoral v. lateral & Cooper's ligament posterior.
*Femoral = below inguinal ligament & lat. to pubic tubercle*

38

CAH vs. Aromatase deficiency

CAH (congen. adrenal hyperplasia): F ambig. genitalia & Na+ wasting
= 21-hydroxylase def.
Aromatase def: F ambig. genitalia, tall, & virilize mom during pregnancy
=> failure to convert androstenedione & testosterone to estriol/estrone