Microanatomy Test 4

Front 1

secretion

Back 1

cell will take simple molecules and use E to make a more complicated molecule and then release it

- synthessis and release and sometimes storage

Front 2

organization of endocrine cells

Back 2

- glands - cells packaged into glands w/ CT capsule. Example = thyroid

collection of glands - bunch of little glands spread out

collections of cells - hypothalmus

unicellular glands - enteroendocrine cells

Front 3

islets of langerhans

Back 3

reticular fibers outside it

- mini endocrine glands
ex- of a collection of glands - pancreas

Front 4

pancreatic duct

Back 4

starts at tail of pancreas and runs through it
carries bile and pancreatic enzymes that empty into same space (duodenum)

sphincter of oddi - surround two tubes (pancreatic duct and bile duct) at ampulla that regulates secretion

Front 5

what is peristalis regulated by?

Back 5

autonomics n in gut

Front 6

starling's law of the heart

Back 6

states that the greater the volume of blood entering the heart during diastole (end-diastolic volume), the greater the volume of blood ejected during systolic contraction (stroke volume) and vice-versa.

This allows the cardiac output to be synchronized with the venous return, arterial blood supply and humeral length[1] without depending upon external regulation to make alterations.

Front 7

starling's law of the intestines

Back 7

A stimulus within the intestine, i.e., the presence of food, initiating a band of constriction on proximal side and relaxation on distal side. This results in a peristaltic wave.

Front 8

pavlov and the vagus n

Back 8

The R vagus n is responsible for pancreatic secretions

Front 9

baylys and starling

Back 9

stripped mucosa of duodenum and made water excretion from gut
then injected it into animal which caused pancreatic secretions

called it secretin -1902

Front 10

starling

Back 10

coined term hormone 1905

a chem molecule released in one part of the body affects another part - enteroendocrine system

Front 11

control of digestion

Back 11

regulation via
hormones
autonomic nervous system
enteric nervous system

Front 12

relationships btwn gut hormones and hypothalamus, pituitary and pancreas

Back 12

1 gut hormone acts on the anterior pituitary gland to control growth hormone secretion

2 gut hormones are also secreted by the hypothalamus to control growth hormone secretion

Most gut hormones are also synthesized by brain where they act as neurotransmitters

2 gut hormones act on the exocrine pancreas

3 to 4 gut hormones act on the endocrine pancreas

The endocrine pancreas secretes some gut hormones

Front 13

regulation of GI hormones to fn

Back 13

1. Hunger (ghrelin) - stimulates eating and growth hormone

2. Break up food in stomach (gastrin)

3. Decrease motility (decrease in motilin)

4. Duodenal mediation of exocrine pancreas and gall bladder secretions to digest food (secretin and cholecystokinin)

5. Duodenal stimulation of endocrine pancreas to release insulin (GLP-1 and GIP)

6. Duodenal stimulation of endocrine pancreas to release glucagon (likely gastrin and/or CCK)

7. Inhibit all of the above by paracrine action (somatostatin)

Front 14

Ghrelin

Back 14

- 28 aa (8-42)
- Syn - stomach and the hypothalamus (less)

- Stimulus to release = low levels of metabolic substrates in blood - when fasting

- Action - stimulates:
1. hypothalamic control of food intake - stimulates feeding center
2. growth hormone secretion from anterior pituitary gland

- Negative feedback (increase in metabolic substrates in blood due to eating and to GH)

- passes through liver first where it may or may not be broken down or inactivated
then passes through the heart and body where it only reacts with cells that have a receptor on its PM

Front 15

gastrin

Back 15

Different peptide forms
- Synthesized in G cells primarily in stomach

- stimuli to release (oligopeptides, distension)

- Action - travels via blood to:
1. promote mucosal growth of GI tract,
2. parietal cell hydrogen ion and intrinsic factor release,
3. chief cell pepsinogen release;
4. possibly stimulates islet glucagon release

- Negative feedback (meal moves into duodenum and acid is no longer buffered; acid acts on G cells to inhibit gastrin secretion)

- Acid also causes somatostatin release which inhibits gastrin release by paracrine action

Front 16

Secretin

Back 16

1st hormone discovered

- 27 aa

- Synthesized in S cells primarily in duodenum and jejunum

-Stimulus to release (acidic chyme)

Action - stimulates:
1. pancreatic centroacinar and intercalated duct cells,
2. biliary duct cells - to increase bile secretion
3. cells of Brunner’s gland to release bicarbonate ions in a watery juice
4. possibly closure of pyloric sphincter

- Negative feedback (bicarbonate neutralizes duodenal acid)

Front 17

Cholecystokinin (CCK)

Back 17

- Different peptide forms

- Synthesized in I cells primarily in duodenum and jejunum

- Stimulus to release (peptides and fatty acids)

- Action - stimulates :
1. pancreatic acinar cells to release zymogen granules,
2. gall bladder to contract,
3. sphincter of Oddi to relax;
4. possibly stimulates closure of pyloric sphincter
5. possibly islet glucagon release

- Negative feedback (absorption and movement of digestive products down the intestine)

Front 18

Glucagon-like polypeptide - 1

Back 18

(7-36) - secreted as big long protein then chopped up and this one is cleaved differently that glucagon is cleaved

- 30 aa

- GLP-1 is synthesized in L cells primarily in duodenum and jejunum

- Stimulus to release (protein meal)

- Acts on B cells in islets to increase insulin secretion

- Negative feedback (absorption of aa)

Front 19

Gastric inhibitory peptide (GIP)

Back 19

- 42 aa

- Synthesized in K cells primarily in duodenum and jejunum

- Stimulus to release (glucose and fat)

- Pharmacological doses (inhibits gastric secretion and motility)

- Physiologically (acts on B cells in islets to increase insulin secretion)

- Negative feedback (absorption of glucose and fat)

Front 20

Motilin

Back 20

- 22 AA
- syn- in Mo cells primarily in duodenum and jejunum

- stimulus to relase - interdigestive state

- acts to contract smooth m in stomach and intestines

- neg feedback - ingestion of a meal

Front 21

somatostatin

Back 21

- 14 and 28 AA forms

- synthesized in D cells along entire GI tract

- stimulus to release - acid

- acts primarily as a paracrine factor to inhibit all hormones in gut

- negative feedback - decrease in acid

Front 22

Islets of langerhans

Back 22

contain 4 major cell types:
A or alpha cells - secrete glucagon
B or beta cells - secrete insulin
D or delta cells - secrete somatostatin (paracrine factor)
F cells secrete pancreatic polypeptide
most islets have many A cells at the expense of F cells or vice versa

= 1 islet has more of one type of cell

Front 23

beta cells

Back 23

islets of langerhans- 1-2 million

- secretions enter hepatic portal v

- most common and concentrated in center of islets

- secrete insulin (2 polypeptide chains connected by disulfide bonds)

- glucostats - increase in glucose stimulates insulin secretion - GIP and glucagon also glucostats -- can sense glucose levels in blood

Front 24

alpha cells

Back 24

- located at periphery of islets and along islet capillaries

- secrete glucagon (29aa)

- decrease in blood glucose stimulates glucagon release - so does norepi and insulin inhibits it

- glucagon increases blood glucose
- a glucostat

Front 25

a small peptide

Back 25

10-40AA

Front 26

F cells

Back 26

secrete pancreatic polypeptide (PP) - 36aa

PP is stimulated by protein meal or low blood glucose

- it slows absd of food primarily by decreasing bicarbonate secretion

Front 27

delta cells

Back 27

secrete somatostatin in response to increased glucose and glucagon

exerts paracrine actions to suppress secretion of insulin, glucagon, and pp

Front 28

paracrine interactions w/in islets

Back 28

glucagon stimulates insulin and somatostatin release - and is inhibited by both

insulin inhibits glucagon and is inhibited by somatostatin

somatostatin inhibits insulin, glucagon, and PP

Front 29

insulin

Back 29

anabolic hormone

increases storage of glucose, fatty acids and aa

excess causes hypoglycemia which may lead to convulsions and death ( glucose is the fuel used by nervous tissue)

- deficiency leads to diabetes mellitus w/elevated blood glucose - effects of acidosis, dehydration, and hyperosmolarity on brain leads to coma and death

Front 30

diabetes mellitus

Back 30

- urine is sweet

Type 1 - insulin dependendl insulin deficiency often caused by autoimmune sdestruction of beta cells; usually develops before 40 years of age

type 2 - non insulin dependent - insulin resistance - usually develops after 40 and in overweight ppl, characterized by abn regulation of insulin release and insulin resistance in mm, liver, and other tissues

exercise - causes glucose to enter skeletal m by insulin-independent mechanism
= regular exercise increases insulin sensitivity
- if diabetic exercises may need to consume more glucose or reduce dose of insulin

Front 31

glucagon

Back 31

catabolic hormone

increases blood levels of glucose fatty acids and aa

excess makes diabetes worse

deficiency leads to hypoglycemia

Front 32

somatostatin in excess

Back 32

caused by tumor on islet

- increases blood levels of glucose
- makes diabetes worse

hypoglycemia as soon as it is taken out

Front 33

fat cells

Back 33

are endocrine cells
secrete leptin (167aa)

the more fat = the more leptin

leptin binds to receptor in small blood vessels in brain that appear to play a role in leptin crossing the blood brain barrier

- acts on hypothalamus to decrease food intake and increase energy consumption

Front 34

Fat and type II diabetes

Back 34

adipocytes signal (hormone) muscle and liver to become insulin resistant

signal not leptin but could be due to fat releasing another peptide hormone or fatty acids themselves

fat is diabetogenic - makes diabetes worse

Front 35

hypothalmus

Back 35

inf portion of diencephalon at inf surface of brain

- controls pituitary gland and thereby hundreds of fns
-

Front 36

pituitary

Back 36

aka hypophysis

post to sphenoid sinus

lies in depresion in body of sphenoid bone called sella turicica

connected to hypothalamus by pituitary stalk

ant - glandular tissue
post - neural tissue
seperated by - intermediate pituitary (sometimes contains cyst)

-surrounded by CT capsule

Front 37

Embryology of pituitary gland

Back 37

infundibulum - outgrowth of brain - neural tissue
rathke's pouch - outgrowth of pharyngeal cavity - glandular cells

lots of growth anteriorly

sphenoid bone grows together to close off pharyngeal area

pouches grow together

Front 38

adenohypophysial tissue

Back 38

ant. ppituitary gland - (AKA - ant lobe, pars distalis, or pars anterior)

pars tuberalis - forms part of pituitary stalk

- at least 5 cell types that secrete different hormones classified as chromophobes or chromophils based on wheter they take up dye or not

Front 39

chromophobes

Back 39

ant pituitary cell type

- primarily degranulated chromophils

some may be stellate cells

secrete interleukin 6

acts in paracrine fasion to stimulate growth hormone and prolactin release

Front 40

chromophils

Back 40

divided into basophils and acidophils

- basophils secrete either ACTH, LH and FSH, or TSH

- acidophils - secrete prolactin or GH

the specific cell thype can be ided by immunocytochemistry (ICC)

Front 41

pharyngeal hypophysis

Back 41

most humans have remnants of adenohypophyseal tissue in pharynx

almost always consists of non active cells

Front 42

pars tuberalis

Back 42

part that grows up and makes the stalk

adenohypophysial tissue surrounding anterior and sumtimes all of the infundibular stalk

unknown fn

contains primarily gonadotropes that do not contribute significantly to LH or FSH levels in peripherial blood

Front 43

pars intermedia

Back 43

present at birth then disappears

adenohypophysial tissue post to rathke's cleft

virtually gone by the time you start med school

in adults represented by small cells surrounding colloidal cysts - which rarely enlarge to become a matter of concern - supercellous cyst or rathke's cyst

secretes melanocyte-stimulating hormone in other mammals - skin darkening 0 imp in fish, reptiles ,and amphibians

don't make it but if injected w/it our skin will darken

Front 44

neurohypophysial tissue

Back 44

median eminence
infundibular stalk - stem

post pituitary (aka pars nervosa, neural lobe, or inifundibular lobe)

Front 45

blood supply to pituitary

Back 45

sup hypophysial a -> stalk ( capillary plexus in median eminance) -> portal v -> ant lobe capillary plexus
inf hypophysial a -> capilary plexus in neural lobe

2 capillary plexus drain to a common v -> R side of heart -> lungs -> l side of heart -> carotid -> inf and sup hypophysial a

Front 46

nucleus

Back 46

collection of nerve cell bodies w/in central nervous system

Front 47

tract

Back 47

bundles of axons traveling together or as a group within the CNS

often named after both origin and termination

Front 48

infundibulum

Back 48

funnel

Front 49

nuclei that feed into pituitary

Back 49

paraventricular nucleus - next to 3 rd ventricle -which is very thin runs like nose down middle


arcuate and other nuclei -> ant pituitary - through capilary plexus in stalk - hypothalamohypophysial tract

supraoptic and paraventricular nuclei - to post pituitary hiormones - straight into post pituitary - tuberoinfundibular tract


supraoptic nucleus

suprachiasmatic nucleus - circadian rhythms

arcuate nucleus - outside blood brain barrier

Front 50

neurosecretory neurons

Back 50

do not make synaptic contacts w/other neurons or w/muscle - they release hormone

vasopressin-containing and oxytocin containing - 1st to be described

Front 51

blake's rule

Back 51

With the exception of prolactin and partial exception of FSH, each anterior pituitary gland hormone stimulates the release of a target organ hormone which, in turn, acts at both the hypothalamus and the anterior pituitary gland to exert negative feedback on release of the anterior pituitary gland hormone.

Front 52

IGF-1

Back 52

insulin-like growth factor- one
insulin like b/c the polypeptide amino acid sequence but not the 3D structure is similar in addition to acting on its own receptor it exerts a weak action on the insulin receptor

primarily secreted from hepatocytes

acts on many tissues to stimulate growth

first called sulfation factor because stimulated incorporation of sulfate into cartilage and then called somatomedin C b/c it stimulatied collagen formation

causes hypertrophy -

Front 53

difference between IGF-I and insulin

Back 53

insulin has a c [e[tode omotoa;;u bit os c;eaved pff om tje secretopm grami;e amd secreted separately

measurement of C peptide indicates beta cell function in people recieving exogenous insulin

c= connectin protein from the alpha strand carboxy terminis to the hydroxy terminus of the beta strand

the insulin structure doesn't have it but the IGF-I has it

Front 54

hypersecretion

Back 54

abnormally high secretion over time

Front 55

why does the liver hypersecrete IGF - I

Back 55

hepatocytes are hyperstimulated by another hormone that is secreted by adenomas (in ant pituitary most frequently)

- if caused by promary disease to liver then liver transplant

Front 56

acidophils

Back 56

2 types
lactotropes aka (mammotropes - secrete prolactin

somatotropes secrete growth hormone

Front 57

somatotrope

Back 57

acidophil that secretes growth hormone

there are different forms of hGH

they are polypeptides

main one in ant pituitary has 191 AA and a MW = 22,000 so called 22k hGH or hGH-N

Front 58

What causes AP to secrete excess GH?

Back 58

usually primary disease - due to a tumor in AP -adenomas 0 benign epithelial tumors that form glandular structures

prevalance ~ 50/million population an annual incidence of ~3/million for GH secreting tumor - 2nd most common type of AP adenoma

Front 59

AP adenomas

Back 59

GH-secreting - 2nd most common

prolactin secreting -most common

sometimes it can secret both prolactin and GH

GH - 20-40% secrete PRL as well

called acidophil adenomas

many chromophobe adenomas (70%) are PRL - secreting - not storing

Front 60

hypopituitarism

Back 60

tumor

if tumors grow too large they can destroy the pituitary itself or the hypothalamus that controls the pituitary - leads to hypopituitarism

Front 61

why would a young child w/ prolactinoma might be short in stature?

Back 61

b/c prolactin secreting cells are taking up all the cells and not a lot of space for cells secreting GH or TSH

Front 62

acromegaly - primary disease

Back 62

primary

GH-secreting tumor (technically after adolescence) that causes hypersecretion of liver IGF-I

acral (hands and feet) parts are enlarged and prognathism is present

women may develop galactorrhea (abn lactation). Males do too infrequently

- the internal organs enlarge

-headaches! and tunnel vision can occur

headaches bc enlarged adenoma presses on dura

tunnel vision - bc n fibers cross and can become impinged or killed from pressure from the tumor

Front 63

galactorrhea

Back 63

can be due to growth hormone exerting a weak effect on prolactin receptor - similar molecules

can be due to the adenoma secreting prolactin in addition to growth hormones ( 20-40% of acromegalics)

Front 64

Gigantism

Back 64

soft CT - poor blood supply
extremely tall

immediate cause is hypersecretion of IGF-I before end of adolescent period

often hypopituitarism - low gonadal steroid secretion and failure to close epiphysial plate - thickening of bones (skull)

Front 65

puberty vs adolescence

Back 65

pubert - first reproductively fertile

adolescence - final maturation period

Front 66

epiphysial plate

Back 66

GH causes chondrogenesis and widening of epiphysial plates

effected by GH causing IGF-I release from liver and from chondrocytes

estrogen and testosterone responsible for closing epiphyseal plates

Front 67

treatment for pituitary adenomas

Back 67

surgery -by highly skilled physicians

somatostatinanalogues (octreotide) for GH adenomas

GH receptor antagonists

- ergot drugs (dopamine agonists) for adenomas secreting both PRL and GH - from mushroom - dopamine supressor

radiation - last resort

Front 68

microadenoma vs macroadenoma

Back 68

macro - errodes through sella turica and pushes clinoid process up

micro - scooped out during surgery

Front 69

what is the primary stimulus for the AP to secrete GH

Back 69

hypothalmus secretes GHRH, somatostatin, and ghrelin

ant pituitary gland then secretes GH

which stimulates liver to secrete IGF-I which stimulates growth in many tissues and provides a negative feedback on AP hormone release to the Hypothalmus and to the ant pituitary gland
trope
at the hypothalmus IGF-I stimulates increased somatostatin release and shuts off GHRH release and at the ant pituitary it shuts off cell directly - somato

Front 70

acromegaly (secondary disease)

Back 70

GHRH (44 aa) discovered in pancreas ( neuroendocrine tumors)

growth hormone releasing hormone - comes out of neuroendocrine cells in ilets of langherhans

rarely a GHRH secreting tumor in hypothalmus and rarely there may be a GH secreting tumor in the hypothalmus or other areas of the body like a pharyngeal hypophysis

Front 71

Somatatostatin n braini

Back 71

GHIH or GIH

- a 2nd hypothalmic hormone that affects GH release. it supresses it

- 14 or 28 AA

- doesn't get into peripheral blood in appreciable amts enabling it to be secreted elsewhere in the body to exert local inhibitory actions - conservation biology

Front 72

ghrelin

Back 72

primarily from stomach

a 3 hypothalamic hormone that affects GH release - 28 AA

- secreted by hypothalamus and stimulates GH release

- fasting causes increased GH secretion - likely due to hypothalamic release of ghrelin but also definitely due to release of ghrelin from stomach cellls in response to fasting

Front 73

measurement of hypothalmus hormones

Back 73

portal blood cannot be collected to measure hypothalmic hormones in humans

measurement of AP hormones reflect the secretrions of hypothalamic hormones

thus GHRH assesment is done by measurement of GH in peripherial blood

Front 74

Episodic hormone release

Back 74

GHRH is released in pulses 1- 3 hrs apart

these pulses cause GH to be released in pulses which in turn cause IGF-I to be released in pulses - sleep increases the requency of pulses

most hormones are released this way because most hypothalamic neurons synthesizing a particular hormone synchronize the release of the hormone episodically

this mechanism involved in the synchronization is not fully known

the frequency of pulsations is different for the different hypothalamic hormones

Front 75

what happens if some hormones are released continuously

Back 75

continuous elevated levels can cause downregulation of the hormone receptors - may not occur in disease states

downregulation is a decrese in the number of active receptors for a hormone in cells exposed to continuously high levels of hormone - common for cell membrane receptors for peptide/protein hormones

Front 76

pituitary dwarf

Back 76

hyposecretion of IGF-I prior to adulthood (pituitary dwarf)

can be due to low GHRH, GH, or IGF-I

ameliorated before closure of the epiphysial plates by administration of GH

GH works down but not up the phylogenicc scale - works in all other animals but not us for other animals

cadavers, synthesized in lab and bioengineered GH - cadavers GH is dangerosu

laron dwarfism - insensitifity to GH - mutation in receptor

Front 77

Creutzfeldt-Jakob disease

Back 77

cadavers as a source of GH

prions - cause proteins to loose their fold

Front 78

dwarfism - other types than pituitary

Back 78

1. low thyroid hormone secretion
2. precocious puberty - early closing of epiphyseal plates
3. achondroplasia - genetic lack of receptor for fibroblast Growth factor receptor - norm trunk, short limbs
4. kaspar hauser syndrome - psychosocial

Front 79

direct actions of GH

Back 79

increases blood glucose and fatty acids and stimulates cellular uptake of aa

anabolic hormone

diabetogenic hormone - increasing liver glucose release and exerting an anti-insulin effect on muscle

Front 80

factors that stimulate GH secretion

Back 80

1. exercise
2. fasting
3. low blood glucose
4. decrease in metabolic substrates in blod

cause increase in GH release
mediated by ghrelin release from stomach and hypothalamus

arginine or GHRH often used to test for GH release

Front 81

GH and aging

Back 81

GH and IGF-I secretion decreases in old age

administration of GH in the aged decreases body fat

in young and old adults administration of GH does not increase muscle strength, endurance, or mental status but does provide a small increase in bursts of energy such as employed for sprinting

Front 82

Pre-POMC

Back 82

prepromoplomelanocortin syn in corticotropes (a basophil) in pars distalis as well as pars intermedia (humans don't have a well developed pars intermedia)

-265 AA - after cleavage of the single peptide it is caled pre-POMC

Front 83

Pre-POMC in pars distalis

Back 83

split into ACTH and beta-lipotropinwhich are secreted but prior to release small amts of beta-lipotropin are split into gamma-lipotropin and beta endorphin which are secreted - w/unknown fns
-ACTH is a stress hormone
-beta-endorphin is also a neurotransmiter that binds to openoid receptors in stomach, spine and brain

Front 84

Pre-POMC in pars intermedia

Back 84

in other animals

POMC split to ACTH and beta lipoprotein and sml amts are secreted but most is cleaved to form alpha MSH, CLIP, gamma lipotropin, and beta endorphin which are secreted, fn of CLIP unknown

pars intermedia is regressed in adult humans, alpha MSH stimulates melanin synthis in melanocytes earalier in life

in nonmamalian vertebrates alpha MSH stimulates expanson of melanin granules in melanophores - causing skin darkening

first 13 AA of ACTH = mSH
so ACTH can cause skin darkening particulary on face

Front 85

CRH-ACTH - Adrenal axis

Back 85

Corticotromin- releasing hormone (41 AA ) from hypothalmus stimulates ACTH secretion - stress molecule in brain

CRH release during the later part of sleep cycle and in response to strong emotions and some stressors

ACTH stimulates the adrenal cortex to release glucocorticoids which can feed back on the hypothalamus to inhibit CRH release and at the corticotrope to suppress the action of CRH

Front 86

Development of adrenals

Back 86

cortex develops from mesoderm and contains a large fetal cortex that regresses rapidly after birth

the medulla develops from neural crest

Front 87

fetal adrenal cortex

Back 87

in the fetus fetal CRH stimulates fetal corticotropes to release fetal ACTH. Fetal ACTH stimulates:
1. fetal zone in the fetal adrenal cortex to use pregnenolone (made in placenta) to make dehydroepiandrosterone and then sulfate it

2. the sona fasiculata to use progesterone made in the placenta or during late pregnancy by its own cells to make corticosterone and cortisol

Front 88

accessory adrenal tissue

Back 88

right and left glands are about 2 inches apart in fat on superior ends of kidneys

medullary and less commonly cortical tissue can be found in additional sites often ant to the abd aorta

Front 89

zones of the adrenal

Back 89

zona glomerulosa
zona fasciculata
zona reticularis

Front 90

zona glomerulosa

Back 90

thin layer internal to capsule wher cells are in whorls

sinusoids

Front 91

zona fasiculata

Back 91

cells in cords running froom surface towards medulla - sinusoids

Front 92

zona reticularis

Back 92

cords of cells going in different directionsl
blood often pools in this layer during fixation

sinusoids

Front 93

secretions of adrenal cortex

Back 93

zona glomerulosa- mmineral corticoids - aldosterone

zona fascicilata and zona reticularis - glucocorticoids, cortisol, androgens, aldosterone,

zona retiuclaris secretes more androgens than fasciculata

corticosterone is converted to aldosterone in zona glomerulosa

Front 94

ACTH affects on adrenal cortex

Back 94

stimulates glomerulosa to undergo hyperplasia to replace cells in all three layers

also stimulates fasciculata and reticularis to secrete cortisol, corticosterone, dehydroepiandrosterone and androstenedione

Front 95

Angiotensin II and potassium affects on adrenal cortex

Back 95

stimulates glomerulosa to secrete aldosterone

Front 96

actions of coritical hormones

Back 96

-mineralcorticoid aldosteroone stimulates reabs of sodium ions in kidneys

- glucocorticoids coritsol and corticosterone affect carb and protein metabolism and defend against stress - small amts prime cells to respond to norepi - need them also when you have severe stress - need a ton to survive stress

- androgens promote growth in prepubertal and adolescents

-if you remove adrenal gland - die - b/c cant control BP = shock

Front 97

adrenal medulla

Back 97

cords of cells called chromffin cells because they turn brown w/ chromaffin rxn

Front 98

chromaffin rxn

Back 98

exposure of catecholamines to chromium salts causes them to oxidize and polymerize and turn brown - the chromaffin rxn

Front 99

catecholamine synthesis

Back 99

tyrosine is actively concentrated in the chromaffin cell cytoplasm

- there it is converted to dopa and then to dopamine which enters secretion granules

- in the granules some of the dopamine is converted to norepinephrine and most iof it is converted to epinephrine (by an enzyme that is a glucocorticoid-induced )

Front 100

adrenal blood supply

Back 100

3 aa supply an arterial plexus w/in CT capsule of each gland

- arterioles enter the cortex and either travel directly to the medulla or enter sinusoids which carry blood to the medulla

blood is drained by a center v to the adrenal v

Front 101

control of medulla secretions

Back 101

catecholamine secretion is stimulated by acetylcholine from a n (pregang parasymp - all release acetylcholine)
- enzyme converting norepi to epi is glucocorticoid induced

- opioid peptides (enkephalins are secreted ing cells - they may reduce pain sensation from epi-secreting cells - they may reduce pain sensation - stimulated by acetylcholine - bind opiod receptors in gut etc

Front 102

catecholamine

Back 102

an aa derivative

- epi and nonepi can mimic most effects of symp nervous sys

- they provide E sources by converting glycogen to glucose in liver and skeletal m and increasing free fatty acid in blood

physiologic fn of dopamine if any is unclear - used clinically for ppl in shock
effects systolic BP w/o effecting diastolic

Front 103

adrenal cortex insufficiency

Back 103

adrenal cortex removal (surgery) or destruction (cancer, TB, or autoimmune dx) can lead to death

primary adrenal cortex insufficiency = addison's dx (John F Kennedy) - assoc w/ marked pigmentation and minor stresses can cause an addisonian crisis

decreased cortisol = dedreased neg feedback = inc in ACTH release but structure damaged

Front 104

Addison's dx tx

Back 104

tx - w/cortisone
more pigmentation before tx b/c incrreased CRH and ACTH levels

primary adrenal cortex insufficiency

Front 105

secondary adrencortical insufficiency

Back 105

not making enough ACTH

Front 106

Cushings dx

Back 106

- leads to cushings syndrome
-moon face
- poor m development
- fat accumulates in upper back - buffalo hump, abd wall, and face (moon face)

- individuals bruise easy and striae are present

AP microadenoma (cushings dx) adrenal tumors or CRH or ACTH neuroendocrine tumors

technically - when prob restricted to ant pituitary

Front 107

Conn's syndrome

Back 107

excess aldosterone (mineralcorticoid secretion) leads to Conn's syndrome - hypertension and decreased potassium in body

Front 108

adrenogenital syndrome

Back 108

excess androgen secretion leads to masculinization and the condition in women - hirsutism - receding hiarline males escutcheon (pattern of distribution of male pubic hair , enlarged clitoris

does nothing in males

Front 109

secretions of the pituitary stalk

Back 109

GH ACTH and TSH approach zero
b/c w/o hypothalmic factors to stimulate doesn't stimulate

Front 110

pheochromocytoma

Back 110

tumpr pf adrenal medulla secreting catecholamines

episodic secretion of catecholamines
-BP morn then all of the sudden through the roof

Front 111

TRH-TSH-Thyroid axis

Back 111

Thyroid stimulating hormone (TSH) is a glycoprotein w/alpha and beta chains (100AA disulfide bonds) secreted by thyrotropes (a basophil) of pars distalis

- alpha chain is identical to that of LH, FSH, and human chorionic gonadotropin (hCG)

- hypothalamic thyrotropin-releasing hormone (TRH) is a tripeptide that stimulates TSH release

-TSH acts on thyroid to secrete hormones T3 and T4 which feed back to the hypothalmus to suppress TRH release and at thyrotropes to inhibit TRH action

Front 112

where are TRH receptors?

Back 112

ant pituitary

Front 113

where are TSH receptors?

Back 113

PM of follicular cells in thyroid

Front 114

Where are T3 and T4 receptors?

Back 114

most cells of the body

binding increases O2 utilization and inhibits feedback at hypothalmus

T3/T4 are AA derived and do not bind to receptors in PM bind to cytoplasmic receptors which are then transported to nucleas or bind to nuclear receptors

Front 115

immunohistochemically-stained TRH cells in paraventricular nucleus of hypotalamus

Back 115

diffusely localized in the hypothalamus

- skattered
-not many

Front 116

thyroid develompment

Back 116

endodermal cells migrate through floor of oral cavity and reach anterior side of trachea to form the follicular cells - from foramen cecum - becomes bilobar as it grows
connected by thyroglossal duct - which is normally formed in

- neural crest cells and neural ectoderm - migrate to the ant side of the trachea to form the C cells

Front 117

thyroid gland gross anatomy

Back 117

pyramidal lobe grows sup in 50% of ppl

accessory tis shown sup to pyrmamidal lobe

gland is supplied by sup and inf thyroid arteries

Front 118

thyroid microanatomy

Back 118

follicles - roundish structures w/CT capsule that sends septa into gland to divide it into lobulles which contain blood vessels and surround follicle

follicles are filled w/colloid and are surrounded by follicular cells a single layer of cells around follicles that secrete thyroid hormone

C or parafollicular cells that secrete calcitonin (aka thyrocalcitonin) are located between follicles and appear as larger plae cells

Front 119

syn of thyroid hormonees

Back 119

made extracellulary

- thyroperoxidase is synthesized in the RER and thyroglobulin (a glycoprotein) is syn in the RER and golgi

- both are packaged in apical vesicles and transported to the colloid

- blood iodine is actively transported into the cells and travels down an electrical gradient to the colloid through a Cl-/I- exchanger and uses 2nd active transport Na+/I+ symport to get into cell from blood

Front 120

MITs and DITs

Back 120

tyrosines in thyroglobin are iodinated to form mono and diiodotyrosines (MIT and DIT) under influence of thyroperoxidase

MIT and DIT combine to form T3 and DIT and DIT combine to form T4

MIT + DIT = 3,5,3' - triiodothyronine (T3) + alanine
DIT + MIT = reverse T3 (3',5',3) + alanine - biologically inactive
DIT + DIT = 3,5,3',5' - tetraiodothyronine (T4=thyroxine) + alanine

T3 is active and the most potent one

Front 121

thyroid hormone release

Back 121

pseudopods (come out when stimulated by TSH) of the follicular cells grab colloid and pull it into cell to form phagosomes which fuse with lysosomes to form phagolysosomes

lysosomal enzymes break down thyroglobulin and T3 and T4 diffuse through basal plasma membrane

deiodinases take of I from MITS and DITs but T3 and T4 are resistant and don't get chopped

Front 122

TSH actions on follicular cells

Back 122

TSH stimulates
1. iodine transport,
2. thyroglobulin and thyroperoxidase synthesis
3. pseudopod activity

under norm conditions increased TSH release is associated w/increased release over storage
but poorly stimulated cells store thyroid hormone in colloid = flat and squamous cells - hypothyroid

highly stimulated cells are columnar and have little colloid this MAY be hyperthyroid

Front 123

different physiological states of thyroid

Back 123

hypothyroidism = follicular cells flattened and colloid relatively abundant

hyperthyroidism columnar follicular cells and little colloid

exceptions - iodine deficiency there is a hypothyroid state assocciated w/columnar cells

Front 124

hyperthyroidism

Back 124

- aka - thyrotoxicosis can lead to hypertrophy and hyperplasia of follicular cells and goiter

due to a TSH -secreting tumor (VERY rare) - main type Grave's disease associated w/low serum TSH levels

Front 125

graves' dx

Back 125

autoimmune dx which antibodies are made that recognize the TSH receptor and activate it

they are clalled TSH receptor stimulating antibodies and used to be called LATS ( long acting thyroid stimulation where it acts like TSH and activates follicular cells and neg feedback shuts of TSH but this antibody is still there

associated w/ exopthalmos (no white above eyes=norm, white abv eyes - prob b/c fibrocytes in orbit subgroup destened to become adipocytes has TSH receptors and are activated - 1/2 the time and goiters

Front 126

Hypothyroidism

Back 126

during neonatal period results in cretinism which is irreversible

if mom is hypothyroid babay may be = lack of brain development or growth = dwarf

during adulthood it results in myxedema which can be assoc w/low or high serum TSH levels

iodide-deficient diet or compromised pituitary gland can cause myxedema

give a little bit of thyroid hormone and everything is back to norm

w/o thyroid everything slows down but not nec. for life

Front 127

Myxedema

Back 127

thickened dry flacking skin - puffy

plae often yellow skin -due to jaundice b/c carotenes are converted to vit a and need thyroid hormones to do this if not build up of carotens

autoimmune in most cases in US - most common are Ab against thyroglobulin or thyroid peroxidase or TSH receptor-blockiing antibody but not in the rest of the world

-severe cases can be diagnosed over the phoen- husk voice slow mentation and memory

Front 128

iodine deficiency

Back 128

2.2 bil ppl (38% of worlds pop) live in iodine-deficient areas mainly africa and east asia

113,000 kids w/severe iodine deficiency (Cretins) are born each day

-iodine deficienccy is the number 1 cause of preventable mental retardation in the world today

-universal salt iodinization can be accomplished at a cost of 4cents per person per year

iodine deficiency occurs in places like Ethiopia where the soil has low iodine content and seafood is not readily available

the easiest way to eliminate prob is fortify foods such as bread,milk, warter and salt w/iodine

Front 129

pineal gland

Back 129

gland in adults is difficult to see in section b/c of concretions of calcium phosphate and calcium carbonate make tissue brittle = brain sand

part of diencephalon

neural gland connected to the top of the brain by a stalk

pinealocytes (not neurons) - make melatonin in response to darkness (may take many hours of darkness)- stimulated by neurepi and glial cells (astrocytes)- stalk contains postgang symp

corpora arenacea increase w/age and are useful in interpreting x=rays

derived from neural ectoderm

Front 130

melatonin and pineal gland

Back 130

melatonin appears to act as a timing signal to keep internal processes synchronized w/those of the light/dark cycle of the enviro

melatonin injection in blind ppl entrains their free runing circadian rhythms

it was previously believed that the pineal inhibited the onset of puberty as pineal tumors were assoc w/ early puberty - only occurs when tumor is assoc w/ hypothalamic damage

Front 131

neurohypophysial hormones

Back 131

hormone is syn as part of a larger protein molecule that is packaged into secretion granules

accumulation of these secretion granules are called herring bodies

large protein molecules are cleaved into hormone and neurophysin

individual neurons contain either vasopressin and its assoc neurophysin or oxytocin and its assoc. neurophysin

neurophsins have no effect and are released into the blood

the prohormone is made in cells, packaged into secretion bodies that carry it down the axon as it is cleaved big masses of secretory granules = herring bodies that are stored at axon terminals cause axons to bulge -

increase in firing rate = release of hormone

Front 132

what nucleuses send axons into the post . pituitary

Back 132

supraoptic
and paraventricular

Front 133

vasopressin

Back 133

aka ADH (antiduretic hormone

primary fn is to act on collecting diucts of the kidneys to conserve loss of water in the urine

also in pharmacological amts acts on smooth m in walls of sml blood vessels to cause contraction to raise blood pressure

nicotine increase and alcohol decreses vasopressin secretion

- osmoreceptor cells in ant hypothalmus sense an increase in osmolality of blood (1% rise abv 285 mosm/kg) - they stimulate vasopresssin- containing neurons to increase their firing rate - vasopressin is released from axon terminals - water is conserved which decreases the osmolality of blood

decreases in blood volume (sweating) are sensed by neurons in atria and largge veins of the heart this information is carreid to the vasopressin containing neurons to increase their firing rates

hemorrhage sensed by vagus n in large vessesl of heart to increase ADH release

Front 134

direct or indirect effects on ADH system

Back 134

direct - cut pituitary stalk - severe diabetic or MVA

indirect - damage to osmoreceptors = from tumpors

ADH is only one aspect of the osmoregulation of water "metabolism" - sto,i;ates dromlomg

- neurons may come back or drip ADH from ending

Front 135

diabetes insipidus

Back 135

not enough ADH
- in diabetes insipidus there is an excessive loss of water in the urine (polyuria)

- injury to the hypothalamo-hypophysial tract can lead to a decrease in vasopressin secretion and diabetes insipidus, insipidus = tastless

individuals w/diabetes insipidus drink large quantities of water (polydipsia)

Front 136

congenital diabetes insipidus

Back 136

one cause is a mutation in the neurophysin for ADH = familial central diabetes insipidus

Front 137

acquired diabetes insipidus

Back 137

one cause is Sheehan's syndrome (vascular collapse during birth

Front 138

nephrogenic diabetes insipidus

Back 138

ADH norm but kidneys don't respond well

one cause is loss of V2 receptor for ADH or norm aquaporin-2 (fails to form water channel

Front 139

diabetes insipidus during pregnancy

Back 139

the placenta makes vasopressinase

the increased clearance of ADH that it causes may cause diabetes insipidus

vasopressinase breaks down ADH so increases the clearance of it

Front 140

Syndrome of inappropriate hypoersecretion of ADH (SIADH)

Back 140

common

caused by
1. tumor ADH production and secretion
-carcinoma
- lung
- duodenal
-pancreatic
-uretral
-bladder
- lymphoma
-thymoma

leads to low plasma osmolalarity

2. trauma
- pulmonary disease
- CN II disorders
- Drugs
cause inapropriate ADH secretion which leads to inappropriately high urinary osmolality

Front 141

development of parathyroids

Back 141

number ranges from 2-6 - norm in pairs - arise from endoderm

- inf parathyroids come from 3rd pharyngeal pouch and and sup parathyroids come from 4th

they migrate to the post lobes of the thyroid

Front 142

location of parathyroids

Back 142

individual parathyroids are .5 cm in diameter

CT capsule forms septa but no distinct lobules

-supplied by inf thyroid aa

inf ones have variable location

usually lie outside the thyroid capsule int to thyroid sheath but can be found in the meiastinum

- recurrent laryngeal n lies adjacent to them

Front 143

cells of parathyroid

Back 143

1. cheif cells - aka principle cells
- found at all ages and often arranged in cords
- detect low blood calcium levels directly and secrete parathyroid hormone (84aa)
- secrete parathyroid hormone related peptide (PTHrP 140aa) that binds to one type of parathyroid hormone receptor is secreted by many other tissues and is imp for skeletal dev in utero
- darker on slides

2. oxyphil cells (OC)
- first appear in childhood
- are often are in clumps
-unknown fn
- tons of mitochondria
- lighter on slides
3. fac cells - become numerous w/aging

Front 144

fn of parathyroid hormone

Back 144

increased blood calcium and lowers blood phosphate

increase resorption of calcium and phosphate from bone

stimulates reabsorption of calcium from distal convoluted tubeules = 99% rreabs. b/c 60% reabs in prox tubules

- inhibits reabsorption of phosphate in prox tubules

- act on kidneys tp increase blood calcium indirectly - enhances prox tubules to secrete 1,25 dihydroxycholecalciferol - active form of vit D a(a metabolite of vit D) which is a secosteroid ( one ring is opened up) - that acts on gut to increase calcium abs

Front 145

Vit D

Back 145

sulight converts 7-dehydrocholesterol in skin to previt D3 (fast) which in turn forms D3 (slow)

w/high plasma calcium parathyroid hormone decreases and 24,25-dihydroxy forms

other sources of Vit D = diet like plants but don't get enough to be used - ergocalciferol (D2)

Front 146

Vit D deficiency

Back 146

in kids - rickets - knock knees and bow legs
- osateomalacia in adults
- defective calcification of bone matrix

Front 147

hypoparathyroidism

Back 147

-assoc w/ hypocalcemia and hyperphosphatemia

- hypocalcemia leads to m spasms and convulsions (tetany) of larynx = choke

- caused usually by unknowing surgeons

- in pseudohypoparathyroidism plasma parathyroid hormone levels are norm or high - caused by defects in receptor for the hormone

-hypocalcemia can be caused by vit D deficiency or renal dx

rarely occurs unless thyroid has been removed

Front 148

hypocalcemia

Back 148

chvostek's sign - tap on facial n = ipsilateral contraction of face mm usually abv lip

trousseau's sign - comes up self or w/blood cuff on flexion of wrist, thumb , ext of fingers

hyperparathyroid b/c all 4 adenomas - removed all 4 -= hypocalcemia = put one of 4 glands into forearm and one gland grows if not to big - easy to take out or cut of part if tumor returns

Front 149

hyperparathyroidism

Back 149

assoc w/ hypercalcemia and hypophosphatemia

-leads to destruction of bone and formation of kidney stones

- primary cause is benign adenoma in one gland - cancer in one or more glands is less common

Front 150

parafollicular cells (C cells)

Back 150

pale appearance due to poor staining on slide

synthesize catecholamines and calcitonin (32aa) - imp of calcitonin is unclear

- high blood Ca+ stimulates cells directly to secrete calcitonin

acts on bone to suppress osteoclast activity and on kidney to increase calcium excretion
0lowers blood ca and phosphate levels

-derived from neural crest cells

Front 151

Norepi acts on gut to ...

Back 151

1. constict the sphincters
2. inhibit contraction of longitudinal and circular smooth m
3. constrict blood vessels
4. suppress acetlcholine release from prostganglionic sympathetic neuron synapse on terminal of postganglionic parasymp
- in non flight orfight situation these postgang parasymp are frequently activated by pregang parasymp in vagus n or pelvic splancnics
- acetylcholine acts to increase gut motility and causes hyperemia of gut via activation of vasoactive intestinal peptide (VIP) and nitric oxide (NO)_ in the submucosal plexus
-unclear whether the source of the acetylcholine is from postgang parasymp or from cells intrinsic to submucosal plexus
- VIP and NO also are the 2 imp molecules that cause increased blood flow to penis - est an erection

5. acts on submucosal plexus to supress enteroendocrine secretion

= shuts down gut during flight or fight

Front 152

symp nervous system discharge and the pancreas

Back 152

postgang symp release norepi which acts on islets to stimulate glucagon release and inhibit insulin and somatostatin release - overrides the glucagoninduced stimulation of somatostatin release - result increase in blood glucose conc

Front 153

symp nervous system discharge and adrenal medulla

Back 153

all pregang smp neurons release acetylcholine including those that synapse on chromaffin cells of adrenal medulla which stimulates them to release catecholamines

adrenal medullary norepi that circulates to the gut has the same effect as norepi released from postgang symp

- epi that circulates to the gut exerts some of the effects that norepi does

Front 154

male reproductive system

Back 154

hormone producing:
-brain
- ant pituitary gland
- testes

non-hormone producing:
- epididymius
- ducts - assoc glands
- penis

Front 155

testis

Back 155

seminiferous tubules contain sertoli cells and germ cells
leydig cells and blood vessels lie btwn tubules

tunica albergina send septum to divide the testes into lobules - 200-300 lobules/testes
-each lobule has 3-4 seminiferous tubules - sertole cells and germ cells

ant/lat - thin layer of peritoneum called tunica vagionsus and right under that is the tunica alborgenia
posteriorly it is broken up by rete testes -> mediastinum testes (subdiv of tunica alborgenia

Front 156

LHRH - LH - Testicular axis

Back 156

- hypothalmic LH-releasing hormone (LHRH) - 10 AA
- decapeptide binds to its receptor in PM of gonadotropes and stimulates lutenizing hormone (LH) secretion (and FSH)
-no hypothalmic inhibiting hormone has been IDed

- LH a glycoprotein w/alpha and beta chains
-LH is a protein hormone and thus it acts on plasma membranes of cells that have recepetors for LH

-LH stimulates leydig cells (aka interstital cells ) in testes to secrete testosterone which exerts neg feedback on LH

Front 157

LHRH-LH-Testicular axis neg feedback

Back 157

testosterone acts on hypothalmus to inhibit LHRH release

- testosterone acts on ant pituitary to suppress the action of LHRH on gonadotrope

- decrease in testosterone if hypotalmus is destroyled b/c ant pituitary doesn't secrete LH => no stimulation of gonadotromes = no testosterone

- if testes are removed LH and LHRH levels rise

- If testicular extracts or androgens are administered decrease in serum LH

testosterone is broken down in the liver

Front 158

LHRH - FSH - Testicular axis

Back 158

LHRH also stimulates Follicle stimulating hormone (FSH) secretion from gonadotropes - same ones that secrete LH
-FSH is also a glycoprotein w/alpha and beta chains

LHRH aka gonadortropin releasing hormone (GnRH)

FSH stimulates sertoli cells to secrete inhibin ( a hormone), androgen binding protein - not a hormone, and other factors

Front 159

LHRH - FSH- Testicular axis neg feedback

Back 159

testosterone feeds bacvk neg at the hypothalamus to suppress LHRH release and at gonadotrope to suppress the action of LHRH tro release LH and FSH

physiological circulating levels of testosterone are insufficient to exxert complet suppression of FSH secretion

Front 160

Inhibins

Back 160

Inhibin A - consists of an alpha chain and a beta A chain conned by disulfide bond

Inhibin B consists of an alpha chain and a beta B chain connected by disulfid bonds -and acts on the gonadotrope to suppress FSH release in the presence and absence of LHRH by competing w/ activin for the activin receptor

Front 161

activins

Back 161

secreted by sertoli cells and act on gonaddotropes to stimulate FSH secretion

also secreted by gonadotropes

are the 3 possible beta chains of inhibin (AA, BB, and AB)

Front 162

Follistatins

Back 162

secreted by sertoli cells and is a glycoprotein which bind activin and inactivate it and therefore decrease FSH release

also secreted by gonadotropes

Front 163

androgen binding protein

Back 163

ABP is concentrated in the seminiferous tubules

binds testosterone and testosterone reaches very very high conc w/in the tubules

- high androgen conc are essential for spermatogenesis

testosterone is a steroid and is lipid soluble as long as it is not bpound to a protein - by binding to this it is not as soluble and makes it stay in the tubule

Front 164

LHRH-LH/FSH-Testicular Axis and anabolic steroids

Back 164

androgenic steroids which bind to androgen receptor are taken by ppl who want to enhance performance and or phys appearance

they decrease LH secretion = not making own testosterone or androgen binding protein anymore => testosterone levels in tubules is same as in blood = difficulty making sperm

anabolic steroids reach conc in testes that are less than 1/100 to 1.500 times those of the endogenous levels of testosterone of tthe testes

Front 165

side effects of anabolic steroids

Back 165

- psychiatric including aggression, mood swings, violence, depression, paranoid gealousy, delusions, and impaired judgement

- may lead to other drugs

- hair loss at temporal recession, acne, weight gain, deeper voice - permant
- high BP, blood clots, incresed blood cholesterol, liver toxicity, stress on heart

- short stature when taken during adolescence by either sex b/c causes epiphyseal plates to close by aromatase that converts androgen to estrogen

no permanat effects on sperm production

Front 166

Adrenal anadrogens

Back 166

all androgens act on a single type of androgen receptor

dehydrepiandrosterone and androstenedione are secreted by adrenal cortex - both bind androgen receptor and they have abt 10% and 20% activity of testosterone - very little masculinizing effects when secreted in normal amts

- they promote some protein anabolism and growth

-adrenal or exogenous adrostenedione can be converted to testosterone in testes

Front 167

Testosterone metabolism

Back 167

a c19 steroid w/hydroxy group in the 17 position

secreted by and not stored in leydig cells

- 98% bound in blood to albumin or sex-hormone binding globulin

-only 2% unbound testosterone is activa and bound and unbound are in equilibrium

- can activate nuclear androgen receptor but is often converted to DHT a more active androgen or estradiol by enzymes in peripherial tissues

- some is converted to 17 keto steroids, andosterone, and etiocholaolone in the liver which are excreted in the urine

some are conjucated w/sulfate or glucuronate in liver and excreted - how you can check pee for drugs

Front 168

dihydrotestosterone

Back 168

DHT

- circulating conc are abt 10% of those of testosterone

- formed by 5 alpha reductase esp in skin, the male repro tract, and male accessory glands

- non aromatizable and often amplifies the effects of testosterone

- 2 types of 5 alpha reductases - type I - present in skin including scalp and type 2 in genital skin, prostate, and other genital tis

Front 169

estriol

Back 169

E3 primary estroge during pregnancy

Front 170

estradiol

Back 170

E2 primary estrogen in malese and females who are not pregnant

Front 171

Estrogen

Back 171

androstenedione from adrenals and testosterone from testes are aromatized to estrone (E1_ and 17-beta estradiole (main form of estrogen)

occurs in fat cells, brain, sertoli cells, and skin

- leydig cells also make sml amts of estradiol

norm ration of testosteorne to estrogen protects males from becoming feminized - gynecomasstia (breast enlargment) as may occur in atheletes taking anabolic steroids

- estrogen receptor s in hypothalmus and AP of males as there is in females and testosterone can exert neg feedback on LH release through estrogen

Front 172

testosterone and male sex accessory glands

Back 172

maintains the structure of male sex accessory glands and their secretions
1. prostrate
2. bulbourethral
3. seminal vessicles

shrivel up w/o testosterone

Front 173

testosterone and secondary sex characteristics and growth

Back 173

- lipid soluble steroid that acts on cells that contain nuclear androgen receptor

during puberty and after testosterone promotes masculine pheonotype:
1. growth of larynx and thickening of vocal cords,
2. penis enlargement
3/. scrotum becomes rugose and pigmented
4. shoulder broaderning
5. m development
6. bone growth
7. aggressive behavior
8. interest in opposite sex
9. male sex accessory glands enlarge and secrete
10. effects on hair'

anabolic - promoting growth - it also stimulates growth of long bones and causes growth spurts and subsequently causes closure of epiphysial plates and cessation of growth in height - effect by aromatization of testosterone to estrogen oin chondroceoblasts in both sexes ytes and ost

Front 174

action of testosterone on skin

Back 174

acts to promote growth of facial, chest, axillary, and pubic hair but also on the temporal recession of hairline
- hair loss on the vertex is genetic and due to the presence of type I 5- alpha reductase

cacts via conversion to dihydrotestosterone to stimulate sebaceous glands to secrete a thick secretion in both sexes on face, chest and shoulder, can cause acne vulgaris

in women excess androgen secretion leads to adrenogenital syndrome

Front 175

Gonadotropin releasing hormone neurons

Back 175

develop in the nodes medial and migrate through cribiform plate and follows olfactory bulb back to diencephalon

800-1000 of them

Front 176

kallmann syndrome

Back 176

LHRH neurons do not migrate from the olfactory regions to the medial basal hypothalmus bc of agenesis of the olfactory bulbs - prob x-linked inheritance and individuals are usually anosmic - stuck in septal area or front paprt of brain

so the ant pituitary isn't stimulated by LHRH and gonadotropin secretion is hypogonadotropic - don't make gonadotrope hormones

= testes are not stimulated and the person is hypogonadal

Front 177

hypopituitarism

Back 177

caused by ant pituitary tumor any kind but gonadotropin - so hypogonadotropic and hypogonadal

Front 178

hypergonadotropic and hypogonadism

Back 178

occurs after puberty due to testicular dx

increase in FSH and LH
prir to puberty - no LH -> hypergonadotropic befoere puberty

Front 179

eunuchoidism

Back 179

minimal leydig cell testosterone secretion before puberty

tall w/female body configuration

no closure of epiphyseal plates
- no secondary sex characteristics

Front 180

gross anatomy of testis

Back 180

descent during late gestation from abdomen to the inguinal region requires mullerian inhibiting substance (MIS) secreted by sertoli cells
-descent through inguinal canal to be located outside the body caity in scrotum req testosterone secreted by leydig cells

- the gubernaculum is a lig connecting inf pole of each testis with the respective developing scrotum - it shortens under the influence of androgens

sperm are produced below body temp

there is an air cooling and heat exchange system between the tortuous testicular a and the pampiniform plexus of blood vessels

Front 181

impaired spermatogenesis

Back 181

cryptorchidism in one or both sides occurs in 10% of newborn males ( non-descended testis may require surgica intervention and should be performed well before puberty

- prolonged heat can curtiail spermatogenesis ( clothing) - hot bath, insulated underwear

- sperm counts increase in winter regardless of temp of testis in scrotum

- testis descends a day or 2 after bith usually inguinal canal if it hasn't descended

- if not by the first couple of years then surgery
if it stays in the abd susceptible to become malignant and steril

Front 182

lobules of testis

Back 182

1-4 twenty inch long seminiferous tubules per lobule

tubules are like non-connected garden hose open at both end

sperm are made in tubules

androgen is made by leydig cells external to the tubules

Front 183

sperm travels in testis and epididymis

Back 183

from seminiferous tubules to tubuli recti (straight tubules) to the anastomosing channels of rete testis to efferent ductules to epididymal duct w/in epididymis

- plug in at both ends changes histologically as it goes

Front 184

Seminiferous epithelium

Back 184

stratified epithelium

- sertoli cells are supporting oclumnar cells that span the distance from basal lamina to the lumen - surround germ cells and undergo mitotic divisions primarily until shortly after birth and then again just prior to the start of puberty when they cease to divide
- number of sertoli cells determines the max size of testies

- germ cells become sperm

-leydig cells are located btw tubules - some of the testosteroe they secrete diffuses into sertoli cells and binds to androgen binding protein to reach high conc and promote latter stages of spermtogenesis

Front 185

Germ cells

Back 185

- puberty is initiated by the onset of LHRH pulsatility

- germ cells undergo progressive development at puberty

- spermatogonia are adjacent to basal lamina

- spermatids are adjacent to lumen

- spermatocytes are often in the iddle

- external to the basal lamina is the lamina propria also called the tunica propria and contains the myoic cells

prior to puberty primative germ cells on basement membrane

Front 186

myoid cells

Back 186

in lamina propria external to basal lamina of seminiferous epithelium -

- smooth m like cells not innervated by n in other mammals they contract in response to circulating factor - not sure if it happens in humans

Front 187

tunica propria

Back 187

myloid cells are smooth m like cells that contract in many mammals but contractions may not occur in primates

- blood and lymph vessels are located external to the tunica and btw seminiferous tubules

Front 188

spermatogenic cells

Back 188

spermatogonia = stem cells (diploid - 2n)

mitosis results in more stem cells called Ad (d=dark) spermatogonia and Ap (p=pale) spermatonia that are commited to develop into sperm

- they undergo a series of mitosis and becomes B spermatogonia which undergo mitosis to become primary spermatocytes which start meiosis quickly 4n and after about 22 days exchange chromosomal segments

with the end of the first meiotic div primary spermatocytes become secondary spermatocytes which immediately start second meotic division to become spermatids 1n

cells are connected by cytoplasmic bridges until spermatzoa are released into umen

residule bodies remain and are globbled up by sertoli cells

takes 74 days and makes 512 sperm - spermatogenesis

spermiogenesis - time interval in the latter part of spermatogenesis when spermatids mature - no cell division just cell remodeling

Front 189

spermiogenesis

Back 189

- sperm is a motile cell w/head that contains mostly chromosomal material
- the acrosome contains enzymes and covers the head
- prox portion of the tail is surrounded by mitochondria

- androgen dependent
- involves elaboration of acrosome from the golgi apparatus, condensation and elongation of the nucleus formation of a motile flagellum and extensive shedding of the cytoplasm

4 general phases

Front 190

golgi and cap phases of spermiogenesis

Back 190

golgi vesicles accumulate

acrosomal vesicle forms on nuc and determines the ant end

centrioles migrate post

one centriole forms axonemal complex of the tail (flagellum)

- spreading and condensation of acromosal cap

Front 191

acrosomal phase of spermiogenesis

Back 191

condensation and elongation of nucleus

other centriole forms 9 dense fibers that surround microtubules in flagellum

mitochondria form a sheath in neck and middle piece as cytoplasm thins

fibrous sheath consisting of 2 longitudinal columns w/ connecting ribs surrounds denese fibers for the principle piece of the tail

Front 192

maturation phase of spermiogenesis

Back 192

excess cytoplasm is pinched off (residule bodies) - released into lumen

residual bodies along w/cytoplasmic bridges are phagocytized by sertoli cells

Front 193

spermatozoon

Back 193

aka sperm

appreciate the complexity of this single cell

- note acrosome covering the head

Front 194

wave of spermatogenic cells

Back 194

- cytoplasmic connections ensure synchronous development

- changing histologial picture of one Ad spermatogonium adjacent to the basal lamina becoming 512 sperm entering the lumen over a 74 day period
- another Ad spermatogonium doing the same thing in the same area of the tubule starting 16 days later - over and over again

result in assoc of specific cell types w/in the same area of the tubule that will repeat the cycle every 16 days

- result in a clone from the original Ad spermatogonium disappearing from the histological picture in 74 days or 4.6 cycles

Front 195

stages and cycles of seminiferous epithelium

Back 195

any histological picture is called a stage - 6 stages that can be ided in the cycle in man -- unique - each quadrent is different - cells not in sync

each cycle is 16 days so 4.6 cycles equal 74 days

Front 196

Waves of seminiferous epithelium

Back 196

describes distribution of stagess ALONG the tube
in non human mammals stages occur sequentially along tubule and cross section norm shows one stage in humans there are complex waves and cross section shows multiple stages

Front 197

sertoli cells

Back 197

FSH and testosterone receptors

in addition to ABP and inhibin they also secrete plasminogen activator that converts plasminogen to plasmin which assists in spermination, detachment of mature spermatids into the lumen of the seminiferous tubules

- syn transferrin an iron transport protein involved in sperm development \\syn mullerian inhibiting substance (MIS) which stimulates apoptosis and regression of mullerian ducts and likely involved in germ cell maturation - made in utero for differentation of ext genitalia

- syn aromatase which converts testosterone that diffuses to sertolic cells from leydig cells to estradiol which binds to cells in rete where it mayy stimulate reabs of fluid

= rete testes have lots of estrogen receptors which cause it to inc abs of fluid and concentrate sperm w/o = infertility

Front 198

klinefelter syndrome

Back 198

hypogonadism and infertility

accessory chrom XXY

sml testes - normally spermatogenesis doesn't go beyond primary spermatocytes -steril =- hypogonadal

Front 199

sertoli and germ cell connections

Back 199

desmosome like jncts between germ cell 0- sertoli

tight jncts between sertoli cells = location of blood testes barrier - so don't make Ab to own sperm

Front 200

Sertoli-sertoli jncts

Back 200

form basal and adluminal compartments
-basal cotains spermatogonia and early spermatocytes
-luminal contains rest of spermatogenic cells
-sertoli cells and their jnct together form blood testis barrier

- adluminal compartment is immunologically privileged site

-barrier contributes to osmotic gradient whereby fluid 0 high in potassium whch inhibits motility moves into lumen from sertoli cells

Front 201

cadmium posioning

Back 201

kills stem cells - specifically to spermatogonia - found in batteries

Front 202

vit A deficiency

Back 202

primary spermatocytes stop dividing here

Front 203

things that kill off sperm

Back 203

radiation
antibodies against own sperm proteins
- 40% of infertility is male related - causes for the most part unknown

Front 204

sperm in seminiferous tubules

Back 204

released sperm are not fully mature

they can't swim

the acrosome doesn't contain enzymes

sperm are carried by fluid secreted by sertoli cells

myoid cells do not appear to contract in primates

sertoli cells produce fluid that push them along

Front 205

straight tubules

Back 205

germ cells disappear and are lined by sertoli cells (cuboidal cells) - were tall now cuboidal

Front 206

rete testis

Back 206

anastomosing channels w/in mediastinum testis w/cuboidal epithelium

contain estrogen receptors and estrogen may play role in fluid reabs from rete

concentrate sperm

Front 207

efferent ductules

Back 207

12 efferent ductules form head of epididymus arise from rete testis and emerge on the surface of testis on each side of the body

- fuse together to from the single epididymal duct w/in head of epidiymis

after last one has fused inf. it is then called the body of the epididymis

- the corpus epidiymis changes its name to tail of the epidiymis wher the epididymis starts to separate from testis

if pulled apart = 6 meters coilked to increase serface area

epithelium has alternating groups of tall ciliated and shorter non-ciliated cells (all w/round nuclei) that give lumen festooned outline)

- layer of circularly arranged smooth m surrounds epithelium

tall cells - cillia and smooth m function to move sperm to epididymal duct

short cells abs fluid - cuboidal - microvilli - resp for conc pof sperm

pseudostratified columnar from epididymis -> membranous urethra - smooth m surrounding

Front 208

ductus epididymis

Back 208

highly convoluted duct more than 6 yards long

sperm mature in the epididymis and take their first swiming strokes but but do not show progressive mobility
-they can be stored in the tail of the epididymis and adjoining vas deferns for at least a month

= pseudostratified columnar

- principle cells w/oval nuclei and stereocillla are columnar in the head and cuboidal in the tail of the epididymis - secrete a carbohydrate decapacitation factor - glycocalyx covers head - not very tight and stereocillia (long microvilli) abs fluid

- basal cells are short and have round nuclei

-circular smooth m in head and body peristalsis indeoendent of n - longitudinal layer added ext in distal corpus - inside circular tail - longitudinal layer inside circular tail contracts in response to postganglionic sympathetics

- by tail sperm can swim and they are stored in the tail and base of vas deferens

Front 209

vas deferens

Back 209

epithelium is very similar to that of the ductus epididymis - pseudostratified - w/ sterocillia - initially but disappears further down the vas deferens

- 3 layers of smooth m continued from tail of epididymus thicken

during fixation smooth m contracts throwing lumen into major folds - not natural

Front 210

spermatic cord

Back 210

vas deferens lies w/in spermatic cord along w/testicular a, pampiniform plexus of v, lymphatics and n

- thin discontinuous layer of striated m (cremaster m surrounds the cord and continues inf to invest the testis

- w/emission sperm are propelled through vas deferens to penile urethra

-lots of fat

Front 211

vasectomy

Back 211

- bilateral ligation of vas deferens is relatively save and vonvenient for purpose of contraception

- difficult to restore patency of vas and about 1/2 men dev antibodies to sperm proteins = subseqent success for pregnancy after surgery to restore patency =50%

- sperm broken down my macrophage and protein from it enters blood so get Ab

- once sperm gets to ampulla of vas deferens can store there for 5 weeks

Front 212

ampulla of ductus deferens

Back 212

after crossing the ureter ductus deferens enlarges to form this

-distal end of it recieves the duct of the seminal vesicle and an ejaculatory duct is formed on either side of the body that enters the substance of the prostrate gland

= ampulla can store sperm = for 5 weeks

Front 213

seminal vesicles

Back 213

- outgrowth of vas deferens distal to ampulla

- highly tortuous tube abt 7 inches long w/ numerous outpockets - highly folded glands surrounded by an inner circular and outer longitudinal layer of smooth m and CT

- cells secrete a yellow viscous substance (60% of volume of seman containing:
1. flavins - pigments responsible for yellowish color of seman
2, fructose - sperm's E
3. semeogelin - gel
4. prostaglandins - large amts - 20-C penatne ring lipid found thought it was made in prostate so named this

contents are the last to be ejaculated - b/c semenogenin forms a clot and you don't want the clot in front of the sperm - also chem effect stops sperm from swimming

- pseudostratified columnar epithelium

Front 214

ejaculatory ducts

Back 214

end just lateral to the prostatic utricle - male homologue of the uterus in the post wall of the prostatic urethra

Front 215

3 different ways secretions go into the prostetic urethra

Back 215

- all empty prox to colliculus

1. mucosal glands dump in all around it
2. more laterally dump into prostatic sinuses - gutters on either side of colliculus
3. large from periphery

Front 216

prostate

Back 216

branched tubulo-acinar glands embedded in fibromuscular stroma

capsule surrounds on post and lateral surfaces

- ant surface bound by ant fibromuscular stroma

has 4 zones
- ant fibromuscular stroma- containing no glands (5%)
- Transition zone surrounds prox urethra - area around uretrha up to point of ejaculatory ducts ( 5%) - where BPH occurs - pushes in on prostatic urethra

- central zone - surrounds ejaculatory ducts (20%) - no problems clinically

- peripherial zone - no glands (70%) - post lateral - palpable by rectum = cancer - no sx

Front 217

prostrate gland secretions

Back 217

comprise abt 20% if vikyne if seneb a bd are rekeased w.soern before seminal vesicle secretion
1. clotting factor (possibly zinc) which acts on semenogelin to form a weak fibrin clot w/in 1-2 min after ejaculation - to slow down sperm
2. prostate specific antigen (PSA) - 30K serine protease that inactivates clot 15-60 min after ejaculation to liquefy the semen and simultaneously inactivates semenogelins second effect of reducing sperm motility by non-physical mechanism
- increases w/ cancer and BPH

3. spermine - gives sperm characteristic odor
4. acid phosphatase - used to be marker of prostatic cancer b/c inc in blood w/assoc w/prostate cancer

alkaline secretions are carred by several dozen ducts which empty into prostatic sinuses - sperm doesn' tlike acid - so makes vagina more alkaline

Front 218

prostate cancer

Back 218

enlargement of the glands w/their peripheral location often is not accompanied by any increased obstruction of urethra

- palpation is recommended for detection

- elevated PSA may indicate the presence of prostatic cancer - norm secreted by prostate into lumen and blood

-PSA also elevated in blood w/ BPH and prostatitis

Front 219

tx of prostate cancer

Back 219

partial or complete prostatectomy folowed by:
- chemo or radiation or both if partial gland removal
- if androgen dependent tx might include:
1. orchidectom (castration of male - take out source of testosterone)
2, estrogen tx - won't bind to androgen receptor but feedback to suppress LH release
3. antiandrogen (flutamide) - antagonist blocks androgen receptor
4. type II 5-alpha reductase inhibitor ( finasteride) = inhibition of conversion of testosterone to dihydrotestosterone
5. GnRH agonist - synthetically made long acting release of LH- keeps stimulating = decrease regulate receptors - instead of 8 hr 1/2 life = 80 day 1/2 life constant stimulation of gonadotropes = least side effects

Front 220

cowper's glands

Back 220

- bilateral glands the size of a pea

- lie deep to the UG diaphragm and adjacent to membranous urethra

- 1 inch long ducts travel in wall of membranous urethra and open into penile urethra (spongy urethra)

- erotic stimuli cause release of mucous like pre-ejaculatory fluid

Front 221

urethral glands

Back 221

some expand into deep lying glands of Littre

- mucous cells or glands in recess or outpouchings on the dorsum of the ant 2./3 of penile urethra

Front 222

penis

Back 222

2 post corpora cavernosa and 1 ant corpus spongiosum cont penile urethra

- thin skin, superficial fascia, tunica alborginea
- tunica alborginea- fibroelastic tissue that surrounds each corpora and binds the 3 together

Front 223

arterial supply to penis

Back 223

1. a to bulb of penis - corpus spongiosus
2. deep a ( a. to crus) - one out of eac copora cavernosa
3. dorsal a - collaterals bv into penis

1 and 2 supply trabecula tissue - lots of smooth m => helicine a and norm capillaries which then drain to v out through tunica alborginea

Front 224

penile erection

Back 224

-prior to sexual stimulation there is AV anastomsis and postgang. symp release of norepi which constrict helicine a

- erotic thoguhts or sexual stimulation via pudendal n are integrated in the lumbar cord - neurons then activate parasym (nerrvi erigentes in pelvic splanchnics) that activate postgang to release acetylcholine and vasoactive intestinal peptide (VIP) - potent vasodilaters that cause the smooth m of the aa to relax - but cannot produce full errection - partial

- other neurons that don't contain acetylcolien or norepi release nitric oxide synthase which ends up on endothelial cells in trabeculae and causes synthis of nitric oxide from arginine

- acetylcholine inc calcium in endothelial cells which activates the nitric oxide synthase

- nitric oxide - gas that diffuses into surrounding smooth m where it activates guanylyl cyclase to convert GTP to cyclic GMP which is a potent vasodilator= full erection

compression of ext v blocks outflow and provides turgor

Front 225

Semen

Back 225

volume 2.5-3 ml after a few days of continence

- concentration of sperm nor 100,000,000/ml

- abt 1/2 of those w/ 20-40 mil sperm are infertile (malformed - don't swim right)

- large numbers of morphologically abn sperm or immotile = sterility - most malformed of any animal

- seminal vesicle secretions last to be ejaculated

Front 226

emission

Back 226

initiated by sensory n primarily from the glans penis via pudendal n and activates pregang symp (L1) stimulating postgang symp to release norepi and causes contraction of tail of epididymis, vas deferens, seminal vesicles, prostate and cowper's glands

-oxytocin may assist in the contraction -

- seman collects in penile urethra w/in bulb of penis which causes the ejaculation reflex w/ sensory input via pudendal n

Front 227

ejaculation

Back 227

involves contraction of bulbospongiosus m (skeletal m that contracts reflexly by pudendal n)

- carbon monoxide a vasodilater may be involved w/ejaculation as blockade of the enzyme that synthesizeds it in the neural pathways concerned w/ ejaculatiion diminishes it performance

Front 228

detumescence

Back 228

decreased parasym and inc symp nerve activity cause opening of shunt and constriction of helicine a

Front 229

tx for impotence

Back 229

viagra inhibits the breakdown of cGMP by phosphodiesterases (PDEs) which have 7 isoenzyme families
viagra works on PDE 5 which is in corpora cavernosa
-also works to lesser extent on PDE6 which is in the retina and can cause temporary loss of ability to distinguis btwn blue and green

Front 230

development of gonads

Back 230

both testes and ovaries go through gametogenesis and steroidogenesis and develop from mesoderm in post abd wall which initially has a cortex and medulla

in male - short arm of Y chrom is nec for production o SRY that causes medulla to dev into testis -and cortex regresses - sertoli cells secrete MIS and leydig cells secrete testosterone

in Females - cortex dev into an ovary and medulla contains CT - no hormones are secreted by embryonic ovary

Front 231

dev of internal and ext genitalia

Back 231

- MIS and testosterone from testes acts ipsilaterlally

-MIS stimulates apoptosis and regression of mullerian ducts which would become the oviducts, uderus, and upper 1/3 of vag

-testosterone stimulates dev of wolffian ducts which become the epididymides, vas deferens, seminal vesicles and ejaculatory ducts

testosterone is converted to dihydrotestostern (DHT) by 5-alpha reductase in genital tissue DHT is more active than testosterone and converts the femal ext genitalia into male (scrotum and penis) and stimulates dev of prostate

Front 232

pseudohermaphroditism

Back 232

gonads of their genetic sex and int and or ext genitalia of other

Front 233

female pseudohermaphrodites

Back 233

ovaries and male ext genitalia due to exposure to androgens btwn the critical 8-13th week in utero - androgen exposure after the 13th week causes clitoral enlargement
-cause usually are maternal exposure to androgens or congenital adrenal hyperplasia due to 21 beta or 11 beta hydroxylase deficiency - lots of androgens coming out of adrenal gland

Front 234

male pseudohermaphrodites

Back 234

have testes and female ext genitalia

cause:
- 5-alpha reductase type II deficiency - male int genitalia and testies internally to int to labia majora and female ext genitalia - at puberty testosterone causes male body and libido and they have an enlarged clitoris large enough to have sex w/a woman and usually change gender identy - common in dominican republic - no DHT

- mutations in androgen receptor gene - if complete loss - testicular feminizing syndrome occurs - female genitalia where vagina ends in a bouch w/no female or male internal genitalia - testosterone is converted to estrogen at puberty and feminization occurs - seek medical help b/c failure to start menstration

- deficiency of 17 alpha hydroxylase

- defective testicular development in genetic males can lead to female ext and int genitalia = w/o MIS = female int and est genitalia

Front 235

what would happen if a norm pregnant woman took finasteride?

Back 235

a type II alpha reductase inhibitor

- or progar- used to treat BPH 5 mg
- or propesia - 1 mg to treat male pattern baldness

= genetic male fetus = female ext genitalia
but no effect to a genetic female fetus

Front 236

primordial germ cells ovary

Back 236

as in male primordial germ cells migrate from yolk sac into gonad

oogonia 2n undergo mitosis to form more oogonia until 5th month in utero when the y start meiosis and become primary oocyte whic hreplicates its DNA and stops in proohase and is 4n

Front 237

ovary

Back 237

attached to post aspect of broad lig by mesovarium

n and blood vessels travel w/in suspensory lig

lig of ovary is homologue of upper part of gubernaculum

oocytes are housed w/in follicles w/in cortex

alternates btw R and L ovary every month

Front 238

germinal epithelium

Back 238

covers ovary single layer of cuboidal cells

originally thought to be where germ cells came from

- extension of mesothelium

Front 239

tunica albuginea

Back 239

thin but tough layer underlying germinal epithelium = very thin barrier for oocytes

Front 240

primordial follicle

Back 240

primary oocytes surrounded by single layer of flattened cells that is surrounded by basal lamina and embedded in stroma

- nuc and 1 or more nuclolei may be present
-stromal cells lie ext to follicular cells

- follicules degenerate (undergo atresia) during estation, and after birth, a few survive and grow after puberty and few of those ovulate

7 mil by 5th month in utero

birth = 2 mil 1/2 go through atresia

puberty = 1 mil

Front 241

early primary follicle

Back 241

unilaminar

unknown stimulus causes some primordial follicles to become primary follicles continuously from in utero to menopause

- primary oocyte gets larger

- follicular cells become cuboidal

-zona pellucida - secreted glycoproteins - start to form btwn oocyte and follicular cells

basal lamina and stroma outside

Front 242

primary follicle

Back 242

multilaminar

- follicular cells become cuboidal and through mitosis multilaminar - called granulosa cells

- dev of multilaminar primary follicles does not req gonadotropin stimulation

Front 243

late primary follicle

Back 243

basal lamina separates the ext layer of granulosa cells from stromal cells - stromal cells have concentrated around the follicle and are called thecal cells - theca interna and externa

theca interna cells become vascular and secretory - blood is ext to basal lamina and granulaosa cells

theca externa does not secrete steroids -smooth m and CT

stroma non deferentiated

Front 244

zona pellucida

Back 244

oocyte makes cortical granules that reside internal to the oolemna they are involved in fertilization

- ensures a close relationship btwn oocyte and immediately adjacent granulosa cells

-microvilli project from oocyte and adjacent granulosa cells

= amorphous material secreted from microvilli of oocyte that forms zona pellucida

granulosa cells adjacent to zona are stuck there - processes - no gap jncts btw them and oocytes

Front 245

secondary follicle

Back 245

irregular spaces w/clear fluid (liquor folliculi) appear among the granulosa cells

-spaces come together to form crescentric cavity called the antrum - oocyte becomes eccentric

-aka antral follicle

- primary oocyte stops growing in size

Front 246

graafian follicle

Back 246

only one that releases the egg

- stratified layer of granulosa cells is thickened in one area called cumulus oophorus and contains the oocyte

the single layer of granulosa cells anchored to the zona surrounding the oocyte is called corona radiata - a subdivision of cumulous oophorus
-easily seen by eye sticks out of ovary

- enlarged 2ndary follicle that occupy the full thickness of the cortex and bulge on the surface

- liquid filled spaces increase btw granulosa cells and the ova and its corona radiata loosen to from granulosa cells in the cumulus

aka mature follicle

Front 247

ovarian follicles

Back 247

6-12 primary follicles are recruited after ovulation in the previous menstral cycle

FSH and LH stimulate growth of 2ndary follicles

-norm 1 graafian follicle forms and secretes large amts of estrogen

growing follicles move away from the surface of the ovary and deeper into the stroma

Front 248

atresia

Back 248

can happen at any stage of development
- irregular outline - cells not stacked nicely

- granulosa cells breaking apart -early atreasia
- late stage - oocyte degenerated and U shaped band surrounds the shrinkage space - remnant of zona pellucida
-area of amorphoous intercellular substance - stromal cells invade the area CT

Front 249

ovulation

Back 249

inc in LH secretion causes resumption of meosis which stops at metaphase of the 2nd meiotic div - surge from pituitary - causes inhibition of oocyte maturation factor ressumes meosis
-causes ovulation

an area on the surface of the ovary called stigma thins looses blood supply and ruptures

2ndary oocyte and its surrounding cumulus cells are extruded

Front 250

corpora hemorrhagicum

Back 250

after ovulation the wall of the follicle collapses and the granulosa cell lining is thrown into folds

there usually is extravasation of blood from the vessels of the theca interna resulting in a clot

Front 251

pain after ovulation

Back 251

minor bleeding from the corpora hemorrhagicum may occur into the abd after ovulation causing irritation of peritoneum and fleeting abd pain

germans called it mittelschmerz

Front 252

corpus luteum

Back 252

ruptured follicle is changed into this and it secretes hormones due to an increase in LH secretion and the luteinization process starts prior to ovulation
-granulosa cells thrown into folds
-basal lamina disintegrates and allows bleeding into antrum and theca cells invade the area of the granulosa cells

the granulosaluteal cells comprise the majority of the hormone secreting cells in the corpus luteum

Front 253

luteal cells

Back 253

accumulate lipids and enlarge

smaller than granulosa luteal cells - do the same thing

- secrete estrogen and progesterone that prepares uterus for implantantion

iin corpus luteum

Front 254

corpus albicans

Back 254

if pregnancy doens't occur the corpus luteum starts to decay in 10 days and menses ensues 4 days later

corpus luteum eventually replaced by this scar tissue

Front 255

polycystic ovaries

Back 255

15% of women of child bearing age
called oyster ovaries b/c never ovulated

pathogenesis due to abn androgen/estrogen ratio in ovary - increased androgen secrtion

abn thick tunica albuginea - so none of the eggs can get to surface and ovvulation cannot occur

tx- cut out wedge so ppl can get pregnant

Front 256

Sperm depositied in cervix

Back 256

deposited and pool in the ant vagina near cervical os - contains inhibitors of immune response including components that coat the sperm

- w/in 1 min the seman coagulates as a loose gel due to prostatic secretion (zinc) acting on semenogelin which also inhibits sperm motility through a chem mechanism. This protects sperm from harsh enviro of vagina (low pH and immune response)

well over 95% of sperm don't make it
- most of the spemr are not contained w/in the clot and are lost to backflow = 30 min (5min - 2 hrs)

Front 257

cervical mucus barrier

Back 257

- PSA enzymatically degrades the clot w/in 1 hr

- estrogen- induced hydration of cervical mucus is coorelated directly w/ penetrability of sperms - mucus presents significant barrier to abn sperm that can't swim properly

- transported through the uterus is likely aided by prostaglandins causing contraction of the myometrium immediately adjacent to the stratum basale - some sperm reach the ampulla w/in min but are damaged by sheer stress - motile sperm can reach the ampulla w/in an hr (swim at 3mm/min) - few sperm enter oviducts b.c sml opening and mucus barriers

- sperm cannot get in during luteal phase - cant get through mucus - too thick

Front 258

sperm are stored and activated in the isthmus

Back 258

pass through uterotubal jnct enter the isthmus where they may be trapped in a reservoir - may bind to carb moieties on the epithelium - not subject to leukocyte infiltration

- undergo 2 changes here that help them prepare for fertilization - capacitation and hyperactivation

- isthmus is more alkaline than anywhere else no immune response
- can live here for 5 days

Front 259

capacitation

Back 259

involves shedding of proteins on the surface of the sperm

facilitates the acrosome rxn

Front 260

hyperactivation

Back 260

more alkaline enviro, Ca2+ enters the sperm and they become hyperactivated - the alkalinization activates CatSpers membrane proteins in the principle piece of the sperm tail that regulate voltage gated ion channels - Ca2+ enters the sperm and they acquire hyperactivated motility providing force to free sperm from the oviductal reservoir

- swim violently in circles - help them penetrate cumulus and zona pellucida

- switch back to non-hyperactivated sperm helps them move in a forward direction

Front 261

how does the sperm find the egg?

Back 261

2 factors:
1. sperm swim towards warmer temp - the ampulla is 2 deg C warmer than the isthmus

2. odorant receptors are located on the base of the flagellum - the chemotatic odorant of the oocyte/cumulus complex has not been identified. Sperm actually turn and swim toward the ovum

Front 262

uniting of sperm and ovum

Back 262

sperms swim through the cumulus

capacitation enhances the ability of sperm to adhere to the ZP3 receptor on the zona surface causing acrosomal rxn - breakdown of acrosome (lysosomal like organelle) - acrosin released helps sperm enter zona

- 1st to reach the oolemma fuses w/it; fertilin - protein in head of sperm facilitates binding to oolemma

- reduces electrical pot of oocyte which prevents additional sperm entering

- cortical granules internal to the oolemna fuse w/it reorganize it and destroy the sperm binding receptors - in addition their enzymes are released to cause cross linking of proteins on the surface of the zona

Front 263

directly after fertilization

Back 263

1st polar body does not divide

single sperm enters oocyte - tail disintegrates

-oocyte completes 2nd meiotic div and 2nd polar body formed

- male and female pronuclei fuse to form zygote (2n)

Front 264

cell divisions of zygote

Back 264

1. 2 cell stage in oviduct - ovulation age 1.5-2.5 days,polar bodies in the zona, develops into a ball of cells called the morula that enters the uterus at 4 days ovulation age

2. 58 cell intrauterine blastocyst - cavity starts to form, zona breaks down

3. 107 cell- intrauterine blastocyst - inner cell mass formed -forms embryo (ovulation age 4.5) - rest of cells are trophoblast cells that fn in implantation and formation of placenta

Front 265

attachment of blastocyst

Back 265

zona disappears while the formation of an inner cell mass or embryoblast and outer cell mass or trophoblast

- after abt one day w.in the uterus blastocyst starts implantation through erosion of the endometrium by trophoblasts - usually in post uterine wall

Front 266

what prevents menses after fertilization?

Back 266

trophoblasts secretes hCG (human chorionic gonadotropin) is similiar in structure to LH and rescues the corpus luteum to maintain pregnancy

- w/o LH stimulation of progesterone secretion by luteal cells and progesterone maintaining the structure of the endometrium - menses will ensue 14 days after ovulation

- hCG can be measured in the mothers blood by radioimmunoassy on day 6-7 after ovulation and detected in urine on day 14 after ovulation -

- hCG is also secreted by some tumors in both sexes and can be a tumor marker

very high levels of circulating hCG may be indicative of a hydatidiform mole where a non-viable embryo implants and grows - embryo can die and live as a tumor - very malignant

Front 267

Corpus luteum of pregnancy

Back 267

under the influence of hCG the corpus luteum enlarges greatly

- luteal cells secrete estrogen, progesterone, relaxin, and inhibin

-estrogen and progesterone maintain the uterus w/the implanted embryo

- fn throughout the pregnanccy but the ovaries can be removed after the 6th week of pregnancy b/c after this the placenta releases sufficient estrogen and progesterone to maintain the uterus

Front 268

feto-placental unit

Back 268

placenta can make progesterone but not estrogen from scratch

fetal adrenal cortex is stimulated by fetal ACTH to syn sulfated androgens using placental pregnenolone

- placenta aromatizes the androgen to make estrogen (estriol)

Front 269

decidua

Back 269

endometrium of the mother during pregnancy that doesn't include the stratum basale - shed at parturition

- conceptus occupies only portion of endometrium

- initially 3 areas based on relationship to implantation site

- underlying the implantation site and forming maternal placenta is decidua basalis

- thin part btw lumen and implantation site is decidua capsularis

- the rest is decidua vera

- as embryo enlarges the capsularis loses its blood supply leaving the chorion smooth (chorion laevis)

- further growth leads to amnion fusing wchorion which fuse w/vera
- villous area at base of implantation site becomes chorion frondosum which is a circular area that forms the discoid placenta

Front 270

hCS

Back 270

1. human chorionic somatotropin (hCS) was formerly called chorionic growth hormone- prolactin or placental lactogen - acts like growth hormone - little passes through placenta - reaches high levels in mothers blood
-causes lipolysis and decreases glucose utilization by mother thereby dvierting glkucose to the fetus

- low maternal plasma hCS conc are indicative of placental insufficiency

Front 271

gestational diabetes

Back 271

- the fetal pancreas secretes insulin to control glucose levels

- when there is excessive transfer of glucose across the placenta as occurs in women w/gestational diabetes the fetal pancreas releases inhibin

insulin is an anabolic and causes growth the baby will be overweight at birth

Front 272

relaxin

Back 272

hormone w/2 polypeptide chains (structure similiar to insulin) secreted by corpus luteum, uterus and placenta

- suppresses uterine contractions during pregnancy

- causes relaxation of pelvic joints and pubic symphysis and softens cervix during latter part of pregnancy

Front 273

uterine contraction

Back 273

estrogen causes smooth m to be more excitable and also more sensitive to oxytocin by inc the number of oxytocin receptors

- estrogen stimulates the syn of prostaglandins in the endometrium which causes uterine contractions

- oxytocin causes uterine cont directly and by releasing prostaglandins from decidua which in turn enhances oxytocind receptors in myometrium

- progesterone suppresses contractions directly and by inhibiting the action of oxytocin on the m of the uterus

- relaxin inhibits uterine contractions

Front 274

onset of birth

Back 274

266 days after ovulation - 280 days or 40 weeks after start of last menses

- signal likely comes from fetus
- sequential inc in fetal and placental CRH, fetal ACTH, fetal adrenal androgens, maternal placental estrogen which causes increase in uterine prostaglandins

- increased ACTH causes increased glucocorticoid secretion that in turn hastens surfactant maturation in lungs - lipid surface tension lowering agent needed to maintain lungs from collapsing after initial inspiration and expansion of lungs

Front 275

oxytocin prior to birth

Back 275

estrogen inc the number of oxytocin receptors in myometrium and decidua

- during early labor oxytocin secretion remains unchanged
- uterus itself maeks some oxytocin
-oxytocin causes myometrium to contract
- causes decidual cells to release prostaglandins that enhance oxytocin mediated contractions

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decidual cell

Back 276

implantation acts as a stimulus for stromal cells in the endometrium to change into glycogen-rich decidual cells - they fn to nurish the conceptus and facilitate dehiscence (separation) of placenta at term

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reflex release of oxytocin at birth

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- pituitary oxytocin secretion increases w/dilation of cervix

- bearing down helps expel baby

- paraplegic women give birth w/o bearing down or reflex release of oxytocin

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premature onset of labor

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assoc w/high mortality rate

- intramuscular 17-alpha-hydroxyprogesterone decreases the incidence probably by inc and stabilizing circulating progesterone activity

-progesterone like relazin relaxes uterine smooth m and suppresses the action of oxytocin

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sheehan's syndrome

Back 279

blood supply to ant pit is vulnerable - travels down stalk through rigid diaphragma - AP is enlarged during preg due to inc estrogen causing inc lactotrope number and size which may put pressure on pituitary stalk - blood supply limited

- shoch w/vascular collapse can occur in portal vessesl if there is postpartum hemorrhage - portal v first to go
- hypopituitarism develops

- only seen in males in korea w/hemorrhagic fevor

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brain pituitary ovarian axis

Back 280

1. LHRH (GnRH) - stimulates FSH and LH secretion
2. LH stimulates estrogen (17-beta estradiol) secretion from theca interna
3. estrogen inhibits LHRH release and inhibits LHRH-induced FSH and LH release

- FSH stimulates inhibin release from granulosa cells which inhibits FSH release at the gonadotrope
- prolonged high blood estrogen levels stimulate LHRH release and enhance LHRH induced FSH and LH release - 300 pg/mL and stsays there for 36 hrs

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principle sources of estrogen in blood and in follicular fluid

Back 281

- theca interna cells have receptors for LH
- androstenedoine is aromatized to estrone

- 17-beta estradiol in antrum stimulates granulosa cells to proliferate

- granulosa cells make aromatase under stimulation of FSH

- 98% bound to protein in blood to protect it from being destroyed by liver or diffuse into cells

- theca cells take in cholesterol

granulosa cells - estradiol in antrum - theca interna cells - estradiol in blood

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gonadotropin receptors on granulosa cells

Back 282

- FSH receptors are always present
- as the dominanat follicle grows, FSH stimulates the formation of additional FSH receptors and the appearance of LH receptors on granulosa cells

LH rstimulates granulosa cells to secrete meiosis inducing substance to cause luteinization of granulosa cells and effects progesterone secretion after ovulation - causes resumption of meosis

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serum hormone concentrations during mestrual cycle

Back 283

- starting w/menses LH levels are low due to neg feedback of low estrogen and FSH rises due to low inhibin levels, FSH stimulates follicles

- estrogen levels rise in response to theca interna cell secretion from follicle destined to ovulate

- high E for abt 36 hrs is effect to postive feedback at brain and gonadotropes to cause LH and FSH surges

- LH stimulates meiosis, ovulation, and progesterone release
- progesterone exerts neg feedback on LH and FSH at brain and Inhibin secreted by luteal cells suppresses FSH

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ovarian cycle

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the follicular phase precedes ovulation which occurs at 24hr after start of LH surge this is the phase when follicles grow

- lutela phase occurs after ovulation- phase when corpus luteum secretes estrogen, progesterone, and inhibin if preg doesn't occur menses starts 14 days after ovulation due to failure to maintain progesterone at high levels

- variation in length of cycle is due to variation in length of follicular phase

-progesterone is thermogenic and causes a rise in basal body temp 1-2 days after ovulation - feeds back to brain as neg feedback
-inhibin suppreses FSH

cytotrophoblasts makes hCGH

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Metaphase 1st meiotic div

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high levels of circulating estrogen stimulate the preovulatory LH and FSH surges in blood

- LH surge stimulates the resumption of meosis that has been in arrest for many years

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Metaphase 2nd meiotic division

Back 286

LH surge causes completion of 1st meiotic division and completion of the second up to metaphase before ovulation - formation of 1st polar body

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ovulation

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LH causes ovulation (rupture of the follicle and extrusion of the ovum) several hours after the 2nd meiotic metaphase is reached

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oviduct

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aka uterine or fallopian tubes

- connected to broad lig by mesosalpinx

- one ends opens into abd cavity other opens into uterus

- infundibulum w/fibria leads to ostium, ampulla, isthmus, uterine segment

- has extensive folding of lamina propria in infundibulum

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transfer of egg to oviduct

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secondary oocyte w/surrounding zona pellucida and cumulus cells is expelled into the abd cavity

- the turgid fibraie are closely applied to the surface of the ovary near the site of ovulation

- the active mvmts of the fibria and that of the cilia on their epithelial cells draw the ovum along with follicular fluid into the ostium of the oviduct - the fast stroke of the cilia beats towards the uterus - beats fast come back slow

- has littel chance of excaping traport into ampulla

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ectopic pregnancy

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- rarely ovum remains in peritoneal cavity is fertilized and implants
- norm fertilized in oviduct but

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ampulla of oviduct

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thin serosa that thickens as it merges w/mesosalpinx and surrounds a layer of longitudinal smooth m that is esterna to circular smooth m - unjdergoes peristalsis towards the uterus

- mucosa contains lamina propria and simple columnar epithelium

- not much room for egg and sperm come into contact

- has basal bodies

- secretory cells (beg cells w/ bulbous apices that protrude into the lumen
that can interconvert to ciliated cells
-estrogen rises in blood prior to ovulation and induces an increase in ciliated cells that fn to propel ovum towards uterus - after ovulation the corpus luteum makes progesterone that inc the number of peg cells that fn to secrete fluids to maintain the oocyte

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uterus

Back 292

body, fundis and cervix
- cervical canal - narrower than opening and ending
- internal and external os

- covered w/peritoneum - thi nCT serosa layer called perimetrium
-most walls in fundus and body is thick smooth m maintained by estrogen

- inner layer of mucosa (endometrium) maintained and elaborated infundus and body by estrogent then progesterone during menstrual cycle - after menarche -menses ensues montly until menopause

- cervix doesn't change w/cycle or shed it's endometrial lining

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ectocervix or portio vaginalis

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part of cervix extending into vagina

Front 294

changes in uterus during menstrual cycle

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- endometrium sloughs off during meses except for depest layer and then become thiciker form day 5-14 and the uterine glands lengthen - these changes which restore endothelium from the preceding menstration are due to inc estrogen secretion during the follicular phase of the ovarian cycle

- after ovulation the corpus luteum secretes estrogen and progesterone - estrogen induces the appearance of progesterone receptors - progesterone act on estrogen-primed tis - progesterone causes the endometrial glands to become coiled and to secrete fluid high in glycogen and growth of the spiral aa that arise from basal aa - prepare uterus for implantation

-simple tubular glands become saculated
-secretes glycogen

- if preg doesn't occyr corpus luteum starts to regress on day 24 of cycle, estrogen and progesteron secretion dec the spiral aa become spastic prob due to the release pf prostaglanding F2 alpha, leading to hemorrhages that produce menstrual flow

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phases of cycle

Back 295

uterian phases:
menstrual - day 1-5
proliferative - day 6-15
secretory - day 16- 28

Ovarian phases:
follicular - day 1-14
luteal - day 15-28

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uterine blood supply

Back 296

branches of uterine a in myometrium travel to the endometrium
straight aa supply the stratum basale

spiral a supply the stratum functionale
the stratum functionale is shed off during menses

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menstruation

Back 297

- menstrual blood is primarily arterial (75% from spiral a)

contains fibrinolysin -(so it doesn't clot) - from endometrial cells which lyses clots

lasts 3-5 days but 1-8 days considered norm

bllood loss avg 30 ml and abv 80 ml is abn

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anovulatory cycles

Back 298

ovulation doesn't occur norm occurs during first 12-18 months after menarche

- also not uncommon shortly prior to menopause

- w/o ovulation there is no corpus luteum or inc progesterone secreetion - estrogen remains high and causes the endometrium to continue to inc in height - bc thick enough to breakdown around 28 days after last onset of menses - b/c to big to maintain itself

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cervix

Back 299

- no sloughing of endometrium or spiral aa
- cervical canal lined by columnar epithelium which secrete mucus - can form infoldings (crypts) to become glands that point towards the vagina

- ducts of glands can become occluded and form nabothian cysts

- just int to the ext os the epithelium changes abruptly to stratified squamous which continues on the surface of the ectocervix and vagina

- cervical cancer usually starts where epithelium changes from columnar to stratified squamous at jnc to endocervix w/ ectocervix -

- internal os 1 inch inside
- ext os - varries - where you get cervical cancer

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vagina

Back 300

the wall has a mucous layer lined by stratified squamous non-keratinized epithelium (E)
- fibrous lamina propria , smooth m, w/ many elastic fibers and adventita

- CT form papillae at the base of the epithelium in the vaginia

- the bag has no glands but is moistened by cervical mucus, a water exudated through vag wall due to parasymp nerve release of VIP and greater vestibular gland secretions entering from thre vestibule in response to parasymp stimulation

- estrogen stimulates cornification of epithelium and progesterone causes influz of leukocytes (corn flakes) and white blood cells can be seen in smears

- estrogens stimulates glycogen secretion by epithelium which sloughs off

- glycogen is metabolized by lactobacillus acidophilus that forms lactic acid 0 which lowers pH which in turn is antimicrobial

- sperm don't like acid - but have mech to bypass long expossure to acid

pH=4

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3 main ways to get lubercation of vag

Back 301

1. pelvic splanchnics - post gang release acetyl CoA and VIP resp for water exudate to go into vag
2. cervical mucous - from glands
3. parasymp - vestibular gland puts secretions into vag

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cervical mucus

Back 302

thiner and more alkaline and elastic at mid cycle (day 14) sperm can penetrate

-thicker and less tenacious after ovulation (midluteal phase)

- day 14 cells on slide have fern pattern due to estrogen and is very cellular due to progesterone

- following anovulatory cycle w/estrogen and no progesterone - to suppres estrogen induced fern pattern

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day 9 after ovulation

Back 303

cellular trophoblasts surrounds primitive mesoblasts (mesencyme) that develops from the cytotrophoblasts and in which embryo is embedded

- bilaminar disk of ectoderm and thinner endoderm
-ectoderm is cont at its margins w/thin layer of squamous cells derved from cytotrophoblasts that enclose amnoitic cavity

- endoderm is also cont w/ thin sheet of cells derived from cytotrophoblasts that form the yolk sac

- broad zone of trophoblast is the chorion

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day 11

Back 304

implantation site is covered by surface epithelium on 11th day after ovulation

entire thickness of endometrium and part of myometrium are shown

- glands are secreting; stroma is edematous

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day 14

Back 305

trophoblast dev outer syncytial layer of syniotrophoblasts (multinucleated mass of protoplasm w/no discernible cell boundaries which erode uterus) and inner layer of cytotrophoblast

- trophoblastic layer surrounding embryo becomes permeated by lacunae cont blood derived from erosion of spiral a

- cytotrophoblasts are mitotically active and form syncytiotrophoblast

- cords of trophoblasts grow out from surface of chorion to form primary chorionic villi

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day 16

Back 306

primary vilia are invaded by mesenchyme at their base to form secondary vili (mesenchyme core, cytotrophoblasts, syncytiotrophoblast on outside) they are bathed in maternal blood in merging intervillous spaces

- amnion is attached to the lat borders of ectoderm and yolk sac to lateral borders of endoderm in inner cell mass

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day 21

Back 307

cytotrophoblast cell columns grow through syncytiotrophoblast and intervilous spaces and then extend along surface of maternal tis to form trophoblastic shell

- these cytophoblastic and some syntiotrophoblastic cells determine directions of expansion of placenta

- the chorion (2 trophoblast cell types and the underlying extraembryonic somatic mesoderm arising from cytotrophoblasts) forms sphere w/chorionic villi

- fetal blood vessels dev in mesenchymal cores of secondary villli to from tertiary vil,li

- villi branch into wall of intervillous spaces containing maternal blood

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early placenta

Back 308

stem villi extend from chorionic plate

if they reach the basal plate they are anchoring villi

those that do not reacdh the basal plate are free villi

free villi may branch many times and are floating in the intervillous spaces

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placental disc 60 days

Back 309

upon maturity the villous surface is abt 10 sq m , amplified by microvili on surface of syncytiotrophoblasts to 90 sq m

spiral aa enter through holes in basal plate and pulse blood into intervillous space

Front 310

What glands or tissues secrete steroid hormones?

Back 310

adrenal glands
gonads
placenta
fetal adrenal
fetal liver

Front 311

What glands or tissues secrete peptide or protein hormones?

Back 311

GI tract
liver
kidney
heart
pancreas
adipose tissue
uterus
lung

Front 312

breasts

Back 312

accessory gands lying in the superficial fascia that differentiate similarly in the 2 sexes during gestation

- develop along mammary lines
-polymastia and polythelia are not that uncommon
- glands norm remain rudimentary after birth in males
-changes occur in femalse during adolescence , the menstrual cycle, pregnancy, and lactation, and after menopause

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Where did the cells surrounding the colloid originate?

Back 313

post wall of rathke's pouch

Front 314

breasts

Back 314

accessory gands lying in the superficial fascia that differentiate similarly in the 2 sexes during gestation

- develop along mammary lines
-polymastia and polythelia are not that uncommon
- glands norm remain rudimentary after birth in males
-changes occur in femalse during adolescence , the menstrual cycle, pregnancy, and lactation, and after menopause

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nipple

Back 315

surrounded by circular pigmented area called areola

epidermis of it is invaded by long dermal papillae caruing blood vessels that impart a pink or light brown color to the region - estrogen after puberty and to a greater extednt during pregnancy cause melanin deposition and darkening

- openings of montgomery glands (sweat glands) open into areola and form montgomery tubercles, other aerolar glands (sebaceous) secrete oily lubricant that is protective during lactation

- nipple contains longitudinal and circular sooth mm that can cause erection to assist baby in suckling
- lactiferous ducts open here
-nipple and areolar contains many sensory nn that fn in reflexes to cause oxytocin and prolactin release

Front 316

nipple

Back 316

surrounded by circular pigmented area called areola

epidermis of it is invaded by long dermal papillae caruing blood vessels that impart a pink or light brown color to the region - estrogen after puberty and to a greater extednt during pregnancy cause melanin deposition and darkening

- openings of montgomery glands (sweat glands) open into areola and form montgomery tubercles, other aerolar glands (sebaceous) secrete oily lubricant that is protective during lactation

- nipple contains longitudinal and circular sooth mm that can cause erection to assist baby in suckling
- lactiferous ducts open here
-nipple and areolar contains many sensory nn that fn in reflexes to cause oxytocin and prolactin release

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composition of gland

Back 317

20 lobes radiating from the papilla

each lobe has lactiferous duct that leads from the nipple, dilates to form the lactiferous sinus, narrows again as it travels internally w/in the gland to form a series of branching ducts
- the lobes are divided into lobules
- lobules contain alveolar ducts covered by saccular evaginations called alveoli

tubuloalveolar gland

secretory ducts and alveoli have epithelium sitting on basal lamina
- myoepithelial cells lie btw alveoli and basal lamina

Front 318

composition of gland

Back 318

20 lobes radiating from the papilla

each lobe has lactiferous duct that leads from the nipple, dilates to form the lactiferous sinus, narrows again as it travels internally w/in the gland to form a series of branching ducts
- the lobes are divided into lobules
- lobules contain alveolar ducts covered by saccular evaginations called alveoli

tubuloalveolar gland

secretory ducts and alveoli have epithelium sitting on basal lamina
- myoepithelial cells lie btw alveoli and basal lamina

Front 319

menstrual cycle changes in breast

Back 319

Estrogen causes small changes in the proliferation of the lactiferous ducts and progesterone causes small changes in the proliferation of the alveoli.

Many women experience tenderness, pain and swelling during the last 10 days of the cycle.

These symptoms are likely due to hyperemia, ductal distention, and edema. They disappear with menses.

Front 320

changes in mammary gland

Back 320

During the menstrual cycle, the duct system is minimally active.

During pregnancy, alveoli proliferate at the ends of ducts and prepare for the secretion of milk.

During lactation, alveoli are fully differentiated, and milk secretion is abundant.

Front 321

breast cancer

Back 321

~ 9% of women born in US will develop breast cancer

~ 75% arise from epithelial cells of lactiferous ducts; if metastasize to lungs, brain or bone, it becomes a major cause of death

Front 322

mammary exocytosis

Back 322

Merocrine – like other protein-secreting cells – proteins synthesized in RER and packaged in Golgi are stored in secretion granules and released by exocytosis


Apocrine – lipid droplets fuse with cell membrane and are discharged surrounded by small amount of cytoplasm and detached portion of cell membrane

Front 323

antibodies in colostrum and milk

Back 323

- Colostrum is milk low in fat secreted late in pregnancy and early after birth that contains antibodies.

- Plasma cells in lamina propria in intestine that had been exposed to intestinal pathogens migrate during latter part of pregnancy to CT in breast.

- The cells synthesize antibodies that are taken up by endocytosis by the basal and lateral plasma membrane of alveolar cells.

- the vesicles are transported o the apical end of the cell and released into the lumen.
Provides passive immunity to baby

Front 324

hormones and mammary gland

Back 324

Estrogen needed for duct development
Progesterone needed for alveoli development
Prolactin rises in blood during pregnancy
Prolactin acts to enhance breast development
Prolactin is needed for milk production

Front 325

milk production

Back 325

Estrogen inhibits the action of prolactin on breast to cause milk production
With parturition placenta is shed and estrogen decreases in blood
Administration of estrogen after birth stops lactation

Front 326

ant pituitary acidophils

Back 326

There are 2 types of acidophils.
Lactotropes also called mammotropes secrete prolactin (PRL).
Somatotropes secrete growth hormone (GH).

Front 327

prolactin

Back 327

Single polypeptide of 199 aa
Prolactin itself (its target organ does not release a hormone) feeds back negatively at the hypothalamus to inhibit its own secretion. It acts to stimulate dopamine release.
Dopamine is a PRL inhibitory hormone. It is a catecholamine that also is a neurotransmitter.
The most common type of AP adenoma is a prolactinoma!

1/3 ant pit = prl

hypothalamus secretes prolactin releasing hormone = thyrotropin releasing hormone but it is really released by a decrease in dopamine the prolactin inhibiting hormone

Front 328

prolactin in males

Back 328

Normal circulating concentrations act on Leydig cells to increase LH receptors and thereby stimulate testosterone secretion.
Elevated circulating concentrations act on Leydig cells to decrease LH receptor number and thereby suppress testosterone secretion. They also act on the hypothalamus to suppress GnRH release.
In males, hyperprolactinemia causes impotence and hypogoadotropic hypogonadism which are reversible if prolactin levels are lowered; e.g., administer the dopamine agonist bromocriptine.
Prolactin has been reported to have > 300 functions in both sexes, but it is not known if they are physiological or of importance.

Front 329

sectioning of the pituitary stalk

Back 329

prolactin increases b/c decrease in dopamine

other 5 ant pituitary inhormones approaches 0 b/c they are not receiving their releasing hormones

Front 330

suckling and prolactin

Back 330

suckling stimulates prolactin secretion and thus maintains milk production

- prolactin itself exerts neg feedback on its own secretion

- prolactin suppresses ovulation by acting at brain to suppress GnRH and at ovary to suppres action of gonadotropins - most effective in hunter gather cultures where offspring suckle at will

Front 331

oxytocin

Back 331

suckling causes oxytocin release and it causes milk to pass to lactiferous sinuses
- hearing baby cry

Front 332

myoepithelial cells

Back 332

- branching cells that occupy groovees btw the bases of the secretory cells


- contract in response to oxytocin and are located btw glandular cells and basal lamina

Front 333

chiari frommel syndrome

Back 333

persistance of lactation (galactorrhea) and amenorrhea in women who do not nurse after delivery

- rare due to increased prolactin secretion and low LH and FSH secretion

- similar to that seen in women w/ant pituitary adenomas secreting prolact

Front 334

gynecomastia

Back 334

breast dev in males
- 75% of newborns (maternal estrogen)
- mild cases in 70% of boys at puberty b/c lots of testosterone aromatized to estrogen
-number of other situations
-increase in circulating estrogen: androgen ration appears to be involved - why anabolic steroids can cause it

Front 335

puberty

Back 335

- mechanism by which pulsatile secretion of GnRH is initiated is unknown

- followed in males w/ androgen secretion, appearance of 2dary sex caracteristics and spermatogenesis

- in females - estrogen causes thelarche (dev of breasts) and androgen causes pubarche (dev of pubic and axillary hair) - assoc w
/menarche

Front 336

precocious puberty

Back 336

- early onset of puberty

occur w/hypothalamic lesions - probably destroying of the circuitry that holds episodic GnRH in check

Front 337

precocious pseudopuberty

Back 337

- early onset of puberty - secondary sex characteristics w/o gametogenesis - due to exposure of androgens or estrogens

Front 338

eunuchoidism

Back 338

delayed or absent puberty in males w/testes - often tall w/narrow shoulders

Front 339

primary amenorrhea

Back 339

term for someone who has never had a period and are older than 18

Front 340

secondary amenorrhea

Back 340

if a girl has started having periods and then stop - normal during pregnancy and menopause

= anorexia nervosa or girls who lose excessive weight from exercise - may not enter puberty until they gain weight or may stop having periods - and will go through puberty again when they gain weight

some evidence that a critical body mass must be reached to enter puberty - leptin which is a satiety hormone secreted by fat likely plays a stimulatory role in inducing puberty

runing marathons - PRL goes up

Front 341

premenstrual syndrome

Back 341

some women develop one or more sys during the last 7-10 days of the menstrual cycle -PMS

- sx can include:
1. difficulty concentrating
2. bloating
3. edema
4. irritability
5. constipation
6. emotional lability
7. headache
8. depression

Front 342

assisted reproduction

Back 342

in vitro - involves removing mature ova, putting them in culture dish and adding sperm. fertilized ova are placed in the uterus after zygote reaches 4 cell stage

intracytoplasmic sperm injection - invoves the injection of a single sperm or sperm head into an ovum

Front 343

estrogen in contraceptives

Back 343

estrogen w/epineal at 17 tripple bond btw 2 C
- liver won't break it down - makes it last long time

Front 344

post fertilization conception

Back 344

- morning after conception - large does of esrogens for 5 days which likely interferes w/implantation

- mifepristone RU 486 - cause abortion by acting as a progesterone receptor antagoinst - endometrium is not maintained

Front 345

menopause

Back 345

- occurs over a period of time and menses are irregular (45-55 years age)

- assoc w/the decline in number of primordial follicles is a decreased responsiveness of the ovaries to gonadotropins - estrogen and progesterone are no longer secreted by the ovaries

- a little progesterone is secreted by the adrenal cortex and adrenal androstenedione is aromatized peripherally to generate sml amts of estrogen

- the uterus and vagina becomes atrophic gradually

- plasma LH and FSH levels rise due to lack of negative feedback

- in some women hot flashes - coincide w/LH pulses but are not caused by gonadotropins and are prevented by estrogen

the testes decline gradually w/age and there is no male menopause but less testosterone is put out