CAP 74

What is the intercellular communication for

endocrines?
Cell releases a hormone through the blood to a target
cell

What is the intercellular communication for

neuroendocrines?

Neuron releases a hormone through the blood to a

target cell

What is the intercellular communication for

paracrines?
Cell releases a hormone through interstitial fluid to a
target cell

What is the intercellular communication for

autocrines?
Cell releases a hormone through interstitial fluid back
to the cell through mostly positive feedback

What are 3 classes of hormones?

Peptide & Protein Hormones

Steroid Hormones
Amine Hormones

Do steroids have a fast or slow reaction?

Slow

Do peptides have a fast or slow reaction?

Fast, Short half-life

Protein Hormones: Hypothalamus releases?

Releasing hormones, TRH, GnRH, CRH, GHRH,
Somatostatin

Protein Hormones: Anterior Pituitary releases?

ACTH, TSH, FSH, LH, PRL, GH

Protein Hormones Posterior Pituitary releases?

Oxytocin, ADH

Protein Hormones:Thyroid release?

Calcitonin

Protein Hormones: Pancreas release?

Insulin, Glucagon, Somatostatin

Protein Hormones: Liver release?

Somatomedin C


Protein Hormones Parathyroid release?
PTH

Protein Hormones Placenta release?

HCG, HCS or HPL

Protein Hormones Kidney release?

Renin?

Protein Hormones Heart release?

ANP

Protein Hormones G.I. release?

Gastrin, CCK, Secretin, GIP, Somatostatin, GLP-1

Protein Hormones Adipocyte release?

Leptin

What are the different types hormone families?

Insulin Family

Glycoprotein Family

POMC Family

Secretin-Glucagon Family

Growth Hormone Family

Neurohypophyseal Family

Synthesis & Secretion of Peptide Hormones

DNA is synthesized to RNA through transcription, RNA
to ribsomes through translation to make protein. When
you have stimuli activates the vesicles release the
hormones

Are peptides receptors on the surface of the cell?

Yes

Cyclic Adenosine Monophosphate (cAMP) Second

Messenger Mechanism

Hormone attaches to receptor releaseing alpha to GTP

which activates cAMP leading to a cell's response

What is the 2nd messenger for Insulin?

Tyrosine Kinase

If a protein is bounded to a hormone is it inactive or

active?
Inactive by phosphorylation release the active part of
the hormone

Thyroid

Thyroxine

Triiodothyronime

protein binding 99%

plasma half life 6-1 days

Steroids

Cortisol
Testosterone
Aldosterone

protein binding 94-15%

plasma half life 100-25 min

Proteins

Thyrotropin

Insulin

Antidiuretic hormone

protein binding little %

plasma half life 50-8 min

Steroid Hormones: Adrenal Cortex releases which

hormones?
cortisol, aldosterone, androgens

Steroid Hormones: Testes releases which hormone?

testes

Steroid Hormones: Ovaries releases which hormones?

estrogens, progesterone

Steroid Hormones: Corpus Luteum releases which

hormones?

estrogens, progesterone

Steroid Hormones: Placenta releases which hormones?

estrogens, progesterone

Steroid Hormones: Kidney releases which hormones?

VD3 precursor of vitamin D

Amine Hormones?
Dopamine
T3,T4

NE, EPI

Amine Hormones: Hypothalamus release?

Dopamine

Amine Hormones: Thyroid release?

T3, T4

Amine Hormones: Adrenal Medulla release?

NE, EPI

Synthesis of Amine Hormones

Tyrosine>LDopa>Dopamine>Norepinephrine>Epinephrine
Tyrosine>Thyroid Hormone

Specific-transporting Protein Corticosteroid binding

globulin binds to?

cortisol aldosterone

Specific-transporting Protein Thyroxine binding

globulin binds to?
thyroxine, triiodothyronine

Specific-transporting Protein Sex hormone-binding

globulin binds to?
Testosterone, estrogen

Nonspecific-transporting Protein Albumin binds to?

Steroids, Thyroxine, Triiodothyronine

Nonspecific-transporting Protein Transthyretin binds

to?

thyroxine, some steroids

Is hormonal release rhythms constant?

No...different levels are release at different times of the

day.

The feedback mechanisms positive or negative feedback

from endocrine to target cells?

Both positive and negative feedback

What are causes of endocrine hyperfunction?

Neoplastic

Autoimmune: Graves' Disease

Iatrogenic: Cushing;s syndrome, hypoglycemia

Infectious/Inflammatory: Subacute thyroiditis

Activating Receptor Mutations: TSH

What are causes of decreased endocrine function?

Addison's Disease: can produce enough hormones

Sheehan's syndrome: occurs in pregnant women

Hormone Resistance: Mutations in the receptors

CAP 75

Cell and Action: Adrenocorticotropic hormone

(ACTH)
Cell: Corticotropes
Action: Stimulates production of
glucocorticoids and androgens by the adrenal
cortex; maintains size of zona fasciculata and
zona reticularis of cortex

Cell and Action: Thyroid-Stimulating hormone

(TSH)
Cell: Thyrotropes
Action: Stimulates production of thyroid
hormones, T3 and T4, by thyroid follicular
cells; maintains size of follicular cells

Cell and Action: Follicle-Stimulating hormone

(FSH)
Cell: Gonadotropes
Action: Stimulates development of ovarian
follicles; regulates spermatogenesis in testes

Cell and Action: Lutenizing hormone (LH)

Cell: Gonadotropes

Action: Causes ovulation and formation of

corpus luteum in the ovary; stimulates
production of estrogen and progesterone in the
ovary; stimulates testosterone production in
the testis

Cell and Action: Prolactin (PRL)

Cell: Mammotropes, Lactotropes
Action: Essential for milk production by
lactating mammary gland

Cell and Action: Growth Hormone

(somatotropin,GH)

Cell: Somatotropes

Action: Stimulates postnatal body growth;

stimulates secretion of IGF-1, stimulates
triglyceride lipolysis; inhibits actions of insulin
on carbohydrate and lipid metabolism

What are adenohypophyseal hormones?

-ACTH
-TSH

-FSH

-LH

-PRL

-GH

How is the size of the adrenal cortex

maintained? And why is this significant?

The adrenal cortex (its 3 parts) are responsible

for production of sex hormones and
maintaining the size of the cortex. It does this
by producing regular amounts of ACTH

What structure is considered the "big boss" in

the endocrine system?

The hypothalamus

TRH is poduced by what?

The hypothalamus


What manufactures ADH/oxytocin?
The hypothalamus!

Where is ADH/oxytocin stored?

In the posterior lobe of the hypophysis

What are hypophysiotropic hormones?

-TRH
-GnRH

-CRH
-GHRH

-Somatostatin

-dopamine

What is the action of Throtropin-releasing

hormone (TRH) on the anterior pituitary?

Stimulates secretion of TSH by thyrotropes;

stimulates expression of genes for a and b
subunits of TSH thyrotropes; stimulates
synthesis of PRL by lactotropes

What is the action of gonadotropin-releasing

hormone (GnRH) on the anterior pituitary?

Stimulates secretion of FSH and LH by

gonadotropes

What is the action of corticotropin-releasing

hormone (CRH) on the anterior pituitary?

Stimulates the secretion of ACTH by

corticotropes; stimulates expression of gene for
POMC in corticotropes

What is the action of growth hormone

releasing hormone (GHRH) on the anterior
pituitary?
Stimulates the secretion of GH by
somatotropes; stimulates expression of gene
for GH in somatotropes


What is the action of growth hormone
inhibiting hormone (somatostatin) on the
anterior pituitary?

Inhibits the secretion of GH by somatotropes

What is the action of prolactin-inhibiting

hormone (PIH) on the anterior pituitary?

Inhibits biosynthesis and secretion of PRl by

lactotropes

Almost all secretion by the pituitary gland is

controlled by either hormonal or nervous
signals from what?

Hypothalamus

What is a collecting center for information

concerning the internal well-being of the body,
and much of its information is used to control
secretions of the many globally important
pituitary hormones

Hypothalamus

What are the only 2 things that growth

hormone decreases?

The uptake of glucose & adiposity

Name a system that growth hormone does

NOT effect.

CNS

Name some things that growth hormone

increases.

Lipolysis
RNA synthesis
DNA synthesis

Protein synthesis
Gluconeogenesis
Somatomedin

Amino acid uptake

Protein synthesis
Cell Size & Number; Organ size & function
Collagen

Chondroitin sulfate

Linear growth

Lean body mass

T/F Carbohydrates are required for growth

hormone to work.

TRUE--Carbs and insulin are needed inorder

for GH to work because they provide the
energy needed for the metabolism of growth
and insulin plays a role in enhancing the
transportation of amino acids

What are the metabolic effects of GH on the

plamsa?

Increased glucose, free fatty acids, ketoacids

Decreased amino acids

T/F Growth hormone inhibits almost all facets

of amino acid uptake and protein synthesis by
cells, while at the same time increasing the
breakdown of proteins.

FALSE! Growth hormone ENHANCES almost

all facets of amino acid uptake and protein
synthesis by cells, while at the same time
DECREASING the breakdown of proteins

Does GH increase or decrease fat metabolism?

Increase

Circulating IGF-I is produced where and in

response to what?
Produced in the liver in response to GH (its
local production is in tissues)

What does IGF-I stimulate?

Chondrocytes which increases linear growth

What does IGF-I inhibit?

GH secretion

What is IGF-I highly bounded to?

Plasma proteins--T1/2

What does somatostatin typically inhibit?

EVERYTHING

What are some factors that stimulate GH

secretion (increase the need for GH)?
glucose decrease
free fatty acid decrease

amino acid increase (arginine)

Fasting
Prolonged carb depletion

Stress Exercise

Puberty
Androgens and estrogens

SLeep

What factors inhibit GH?

Somatostatin

Glucose increase
Free fatty acid increase
Somatomedins
Growth hormone
Senescence

What may occur with too much GH?

Gigantism or acromegaly

What may occur with too little GH?

dwarfism

What can cause acromegaly?

A acidophilic tumor that occurs after
adolescence...after the long bones have stopped
growing--resulting in thicker bones and soft
tissue growth

What are some clinical features of acromegaly?

-Increased cranial pressure causing headaches

& problems with vision

-acral enlargement, prognathism, carpal tunnel

-ventricular hypertrophy, cardiomyopathy

-sleep disturbances/sleep apnea

-can be insulin resistant

CAP 76

What are thyroid metabolic hormones

stimulated by?
Thyroid-stimulating hormone (TSH)

Thyroxine

-Also called T4
-93% of thyroid gland secretion

-Increase metabolic rate of body

Triiodothyronine
-Also called T3

-7% of thyroid gland secretion

-Much more potent than thyroxine
-Persists in blood for shorter duration
-Usually smaller quantities in blood

-Increase metabolic rate of body

What does thyroxine eventually convert

into?
Triiodonthyronine

Iodine

Needed to make thyroxine

-50 mg needed per year (1 mg/week)

-Most table salt is supplemented with

iodine
Iodine pumped via active transport into
thyroid cells

Thyroglobulin precursor
Makes and stores thyroid hormones


What is the storage of thyroid hormones
like?

-Thyroxine & triiodothyronine remain

stable inside thyroglobulin proteins
-Thyroid gland can store large amounts of
thyroglobulin in follicles
-2-3 months storage supply
-Iodine deficiency not noticed for at least
this amount of time

What is the delivery of thyroxine and

triiodothyronine like?
-They combine with several plasma
proteins in the blood
-Because T4 and T3 bind tightly to plasma
proteins, they are released slowly and
gradually cells
-Enter cells, bind tightly with proteins
inside the cells
-Once again stored

When thyroxine injected, how long does it

take for person to notice a difference?

2-3 days
-Triiodothyronine effects are faster and
stronger

What are the first two functions of thyroid

hormones?
Increase transcription of large numbers of
genes

-Some protein production increased 6X

-Some protein production increased only

slightly
Increase cellular metabolism
-Utilization of food for energy increases

-Growth rate of young people increases

-Mental processes are excited

-Other endocrine glands more active

-Mitochondria increase in number and

size
-Increases active transport of ions

What are five other functions of thyroid

hormones?

Growth

-Essential for growth in children

-Essential for brain development in

fetuses (without thyroid treatment within
days of birth, child will remain mentally
deficient throughout life)

Stimulation of carbohydrate metabolism

-Affects nearly every aspect

Stimulation of fat metabolism

-All aspects affected

-Esp. increases mobilization of fat from

adipose tissue

Increased requirement for vitamins

Increases heart rate and heart strength

What are even more functions of thyroid

hormones?

Increases gastrointestinal motility

Excites nervous system

-Too little thyroid hormones: slow brain

function
-Too much thyroid hormones: extreme
nervousness and/or worry, anxiety
complexes, paranoia

Muscles react more energetically

-Limited because of protein catabolism

induced by thyroid hormones

-Muscle tremor

-Can lead to constant feeling of tiredness

Required for normal sexual function

-Too much in men: impotence results
-Too much in women: abnormally
reduced menstrual bleeding

Decreases body weight

Describe the regulation of the thyroid

hormone secretion

-Temperature change affects

hypothalamus (esp. cold)
-Hypothalamus releases thyrotropin
releasing hormone (TRH)

-Nervousness, anxiety or excitement can

decrease the amount of TRH released
-TRH causes pituitary to release thyroid
stimulating hormone (TSH)

What releases TSH?

Anterior pituitary gland

What happens after TSH is released?

-T4 and T3 released from thyroglobulin

-Iodine pump increases function

-Increased production of T4 and T3
-Increased number of thyroid cells

-^^^^Negative feedback system

What is a five step summary of the TRH

control system?

1. Hypothalamus stimulated

2. Releases TRH

3. Blood carries TRH to anterior pituitary

4. Anterior pituitary releases TSH
5. Thyroid gland stimulated

Hyperthyroidism

-High state of excitability

-Intolerance to heat

-Increased sweating

-Mild to severe weight loss

-Diarrhea

-Muscle weakness

-Extreme fatigue, but cannot sleep

-Tremor in the hands
-Exophalmos (autoimmune disorder
brought on by too much thyroid
hormones)

Goiter

Insufficient iodine in diet

-Swiss Alps, the Andes, Great Lakes
region of USA lack of iodine in soil
-Develop endemic goiters without iodine
substitute
Pituitary secretes too much TSH (no
feedback mechanism from T4 and T3

Hypothyroidism

-Opposite of hyperthyroidism
-Hair growth reduced
-Skin becomes scaly (cannot repair itself
adequately)

-Myxedema (increase in interstitial fluids)

What are the the three main diseases of

the thyroid?
-Hyperthyroidism
-Goiter

-Hypothyroidism

CAP 77

Describe the adrenal glands

-Also called suprarenal glands

-About 4 grams each

-Medulla in the middle (functionally related to

sympathetic nervous system; secretes
epinephrine and noepinephrine)

-Cortex on outside (secretes corticoidsteroids

like aldosterone and cortisol)

What are the hormones produced by the zona

glomerulosa?
Mineralocorticoid, mainly aldosterone

What are the hormones produced by the zona

fasciculata?
Glucocorticoids mainly cortisol and androgens
like DHEA and androstenedione

What are the hormones produced by the zona

reticularis?
Androgens like DHEA and androstenenedione


What are the hormones produced by the
medulla?
Epinephrine and noepinphrine

What are the adrenal hormones made of?

Cholesterol

-Chemically similar
-Change in one enzyme can cause production
of the wrong hormone

What are the two general classes of

adrenocortical hormones?
Mineralocorticoids

-Aldosterone is the most important

-Promotes salt and water retention in kidney

Glucocorticoids

-Cortisol is most important

-Increases plasma glucose levels

Aldosterone and cortisol are structurally very
similar
Their funcitons are dramatically different
At high hormone levels, their functions
overlap somewhat

What happens with aldosterone deficiency?

Potassium ion concentration rises

Sodium and chlorine lost

Mostly a result of the loss of aldosterone

-Increases reabsorption of sodium in renal
tubules (kidneys)
-Increased sodium retention causes water to
be retained

-Extra water causes blood pressure to rise

Lack of aldosterone allows 10-20 grams of
sodium to leave the body daily

What else does aldosterone do?

Stimulates sodium and potassium transport in

sweat glands, salivary glands, and intestinal
epithelial cells
-Sodium reabsorbed

-Potassium excreted

Release of aldosterone controlled by

potassium and angiotensin

What happens when you have an excess of

aldosterone?

Potassium removed from plasma

-Excreted in urine

-Transported into cells

Hypokalemia
Muscle weakness results

-Action potentials screwed up because of

depolarized cell membranes

What happens when you have an aldosterone

deficiency?

-Too much potassium in plasma

-Cardiac toxicity results

Describe glucocorticoids

Cortisol is the most important

-Also called hydrocortisone

Corticosterone also important

Stimulates gluconeogenesis (conversion of

proteins into glucose for synthesizing ATP)

-Increase in protein --> glucose enzymes in

liver

-Mobilization of amino acids from muscle

-Excess cortisol causes extreme muscle

weakness
-Depresses immune function of lymphatic
tissues

Decreased glucose utilization by cells

-Moderate

-Cells less sensitive to insulin

Outcome of these two --> "Adrenal diabetes"

-Excessive glucose in blood

What are some other important things about

cortisol?

-Increases liver and plasma proteins

-Increases mobilization of fatty acids from

extremities
-For unknown reasons: some fat is deposited
centrally (Cushing's syndrome)

Describe the relationship between cortisol and

inflammation

Sometimes inflammation is more damaging

than an actual infection

Cortisol injection can reduce swelling

-Lysosome membranes stabilized (proteolytic
enzymes in lysosome that would normally
cause swelling are reduced in quantity

-Decreases permeability of capillaries

-Decreases migration of white blood cells into
damaged tissue

When does cortisol concentration reach its

peak?
An hour after waking in the morning

CAP 78

What are the three main pancreatic

hormones?
1. Insulin

2. Glucagon

3. Somatostatin

What does the pancreatic acini secrete?

Hormones and fluid

Glucose cannot be taken into the cell

without...
Insulin

Main is the function of glucagon?

Brings blood plasma glucose levels up

Proinsulin
Precursor; what the insulin will be made of

How is insulin made?

C-peptide is detached from proinsulin and
what is left is insulin

C-peptide
Measuring it can allow us to clinically
diagnose if there is a production problem with
insulin

Tyrosine Kinase
-Second-messenger only to insulin reception

-After activated, causes phosphorylation of

enzymes that causes glucose transport,
protein synthesis, fat synthesis, glycogen
synthesis, and growth and gene expression

What needs to happen for glucose receptors to

open up on the cell membrane?
Insulin (alpha cells) needs to attach to beta
cells embedded in the cell membrane to open
up glucose channels

What are the conversions to get glucose to

cholesterol?
1. Glucose

2. Glucose-6-P

3. Fructose-6-P

4. Fructose-1,6-diP

5. Phosphoenolpyruvate

6. Pyruvate

What are the steps to convert glucose into

triglycerides?
Same steps as cholesterol but go one more
step to Acetyl CoA


What are the four key enzymes influenced by
insulin?
1. Glucokinase

2. Glucose-6-phosphatase

6. Fructose-1,6-diphosphatase
7. Pyruvate kinase

What happens to glucose immediately after it

enters the cell and what is the significance of
this?
It becomes phosphorylated so it cannot exit
the cell

What blocks glucose uptake into the cell?

What does it do to blood glucose levels?
Cortisol and growth hormone; increased blood
glucose levels

What hormones stimulate the conversion of

triglycerides to fatty acids?
-Growth hormone

-Cortisol

#VALUE!

Why does T3 help stimulate the conversion of

triglycerides to fatty acids?

Because it increases metabolism overall

What hormone blocks lipase and the

conversion of triglycerides to fatty acids?

Insulin

What is the storage form of glucose in the

muscle?

Glycogen


What is the main transporter available in the
liver?

GLUT2 transporters in hepatocytes

What is the role of glucokinase?

It is an enzyme that stores glucose in the form
of glycogen in the liver (glycogenesis);
decrease glucose release and G6Pase

What happens with an increase in glycolysis?

-increased acetyl CoA

-increased FA synthesis

How does the insulin transfer of glucose affect

triglycerides and proteins in the liver?
-increased triglyceride storage and export
(VLDLs)

-increased protein synthesis

-decreased protein degradation

What happens when the liver receives too

much glucose?

Converts it into adipose tissue for a rainy day

What are the transporters in lipid cells?

GLUT4 transporters

What happens when glucose enters an

adipocyte?

-increased glycolysis
-increased alpha-glycerol phosphate
-increased acetyl coA and FA synthesis

-increased triglyceride production

-decreased hormone sensitive lipase

-increased lipoprotein lipase

What is the major difference between liver

and muscle when it comes to converting
glucose into glycogen, protein, or triglyceride?
The transporter is GLUT4 and the major
storage form is PROTEIN

-increased glycogen

-increased glycolysis

-increased protein synthesis

-decreased protein degradation

-increased triglycerides (FA's from
circulation)

What are the metabolic effects diabetes

mellitus?
Insulin Deficiency

-Increased blood glucose concentration

-Increased blood FFA and ketoacid

concentration - fat depletion

-Increased blood amino acid concentration protein depletion

Why is there an increased blood FFA, ketoacid

concentration, and amino acid concentration
with diabetes mellitus?
Glucose is not taken into the cell because of
insulin deficiency SO glycolysis cannot happen
and triglycerides/protein cannot be made for
storage; build up of fats, ketoacids, and amino
acids result

Why does ketoacidosis occur when blood

glucose is high?
Lactic acid from anerobic glycolysis builds up
and releases ketones into the blood

What causes osmotic diuresis?

Glycosuria increases the amount of glucose

dispelled creating an osmotic gradient;
amount of urine goes up

Polydipsea in diabetes mellitus

Frequent thirst

Hyperphagia in diabetes mellitus

Overeating; feel hungry all the time because

glucose cannot enter the cell and the kidney
gets rid of it. Body feels like it cannot
metabolize anything

Hypovolemia and hypotension in diabetes

mellitus
Osmotic diuresis keeps get ridding water in
urine; if BP falls below a certain level, coma
and death can occur

What level of plasma glucose must be

obtained to begin the secretion of insulin in
the body?
80 mg/dl

What is the maximum plasma glucose level

one can reach for 100% insulin response?

240 mg/dl

Why do amino acids, FFA's, and keto acids

stimulate insulin secretion?
They are absorbed in the GI and are useless
until they are taken into a cell and used
towards glycolysis

What are the gastro-intestinal hormones that

stimulate insulin secretion?
-Glucagon-like peptide 1 (GLP-1)

-Gastric inhibitory polypeptide (GIP)

What parasympathetic mechanisms stimulate

insulin secretion?
Release of acetylcholine

What are the inhibitory factors affecting

insulin secretion?
-Somatostatin
-Fasting (not enough glucose in the blood so
why secrete insulin)

-Exercise
-Alpha-adrenergic stimulation (NoEp and Ep)

What effect does glucagon have on insulin

secretion?

Stimulatory

What is glucagon's second messenger?

Cyclic AMP

How does glucagon increase blood glucose?

1. Cyclic AMP

2. Protein kinase A
3. Triggers GLYCOGENOLYSIS creating more
glucose and pyruvate as products

What happens in the liver with glucagon?

Creates glucose to either:

1. Be phosphorylated and stored as glycogen
2. Be converted to pyruvate for the Kreb's
Cycle

What happens when we have glucagon

secretion?
Keeps glucose from entering the liver cells and
stays in the blood

What is the relationship between plasma

blood glucose and glucagon response?
Opposite to that of insulin; as plasma glucose
hits 80 mg/dl, glucagon stops responding.
Anywhere below 80 mg/dl, glucagon is 50100% functioning

What are the stimulatory factors affecting

glucagon secretion?

Opposite of insulin:

-Hypoglycemia

-Fasting

-Exercise
-Acetylcholine

-Beta-adrenergic stimulation (NoEp and Ep)

What are the inhibitory factors affecting

glucagon secretion?

Opposite of insulin:
-Glucose
-Somatostatin

-Insulin
-FFA's and ketoacids

-Alpha-adrenergic stimulation

Anabolic State (Anabolism)

Storage of Energy!
-Increased insulin
-Decreased glucagon

-Diet fuel source

-Processes include glycogen, triglyceride, and

protein synthesis
-Example would be athletes using anabolic
steroids to increase ability to store energy

Catabolic State
Release of Energy!

-Decreased insulin
-Increased glucagon
-Fuel source is storage depots
-Processes are glycogenolysis, lipolysis,
proteolysis, and ketogenesis
-Examples include AIDS and cancer patients
that are "wasting away"

How do glucocorticoids and growth hormone

effect glucose production and glucose
consumption?

-It increases glucose production in the liver

-Decreases glucose consumption in muscle
and adipose tissue

What are the responses to decreasing plasma

glucose concentration at 80-85 mg/dl?

Decreased insulin

What are the responses to decreasing plasma

glucose concentration at 65-70 mg/dl?
1. Increased glucagon

2. Increased epinephrine

3. Last resort is cortisol and GH

-After that brain glucose uptake is at very low
levels and deadly coma and convulsions may
occur

Why is osteoporosis more prevalent in

women?

Menopause decreases the amount of estrogen

in the blood (which protects the bone) and
without it, osteoclasts chew off the bone

What is the normal glucose tolerance in

fasting glucose diabetic patients?
<110 mg/dl

What is the impaired glucose tolerance

(prediabetes) in FPG diabetic patients?

110-125 mg/dl

What is a diabetic glucose level in FPG

patients
less than or equal to 126 mg/dl

What are the levels associated with

administering glucose 2 hours after patient
has fasted and is suspected of having
diabetes?
Normal: <140 mg/dl

Impaired glucose tolerance (prediabetes):

140-199 mg/dl

Diabetes: greater than or equal to 200 mg/dl

What are the characteristics of type I diabetes

mellitus?

-Autoimmune destruction of Beta-cells

-Insulinpenia: lack of insulin in blood
-Ketoemia: high conc. of ketones in blood
-Dependent on insulin to sustain life and
prevent ketoacidosis

-Usually very thin and very young patients;

cannot take oral insulin

What are the receptors like in Type II DM?

Resistant to insulin

CAP 79

What does PTH do in terms of calcium metabolism?

Increases calcium and decreases phosphate

How does PTH increase calcium?

Increases absorption of calcium from the GI,
increases reabsorbtion from nephrons, and finally
from the bone by stimulating osteoclasts (chew off
bone and release calcium into the blood)

What is the relationship between acidemia and

ionized calcium
-Release of calcium from albumin
-Increased hydrogen ions attached to albumin
-Increased ionized calcium in blood

What is the relationship between alkalemia and

ionized calcium?
-Increased attachment of calcium to albumin
-Decreased hydrogen ions attached to albumin

-Decreased ionized calcium in the blood

Osteoblast
Make bone

Osteoclasts

Chew off bone

What form of vitamin D do we ingest?

-7-Dehydrocholesterol
-Inactive

What does UV light convert 7-dehydrocholesterol

(provitamin) into?

-Vitamin D3 aka cholecalciferol

-Inactive

Liver hydrolyzes Vitamin D3 into what and with

what?
-Into 25-(OH)-cholecalciferol

-With 25-Hydroxylase

-Still inactive

Which organ converts 25-(OH)-cholecalciferol and

what are the active forms?

-Kidney

-With the help of PTH

-1,25-(OH)2-cholecalciferol
-24,25-(OH)2-cholecalciferol

-Both active forms of vitamin D

How does PTH affect the tubular reabsorption of

calcium?

-65% in proximal tubule

-25% in thick ascending loop of henle

-0.5% of calcium secreted in urine

Calcitonin
Opposite effects of PTH!
-Receptors on osteoclasts

-Decreased osteoclast activity and number

-no role in chronic regulation of plasma [Ca2+]

-Thyroidectomy and C-cell tumors

What are two main causes of vitamin D deficiency?

Dietary and deficient synthesis

What are the other causes of vitamin D deficiency

tied with dietary and deficient synthesis?

-GI disorders

-Hereditary: vitamin D-dependent rickets type I and

II

-Chronic renal failure

-Phosphate depletion (dietary or renal)

Rickets

Vitamin D deficiency in kids

Osteomalacia

Vitamin D deficiency in adults

What are the treatments for Rickets-Osteomalacia?

-Vitamin D2 (ergocalciferol) or D3 (cholecalciferol)

-Calcium

-Sunlight

-1,25-(OH)2-D3 (calcitriol)

Osteoporosis

Aging

-Decreased estrogen
-Decreased testosterone

-Decreased GH

-Increased glucocorticoids
-Also caused by immobilizatoin

What are the treatments for osteoporosis?

Antiresorptive Therapy:

-biphosphates

-estrogen
-SERMs (raloxifene, tamoxifen)
-calcitonin

Anabolic Therapy
-PTH (expensive)

In surgical hypoparathyroidism (hypocalcemia),

what happens to plasma PTH and plasma
phosphate?

-Decreased plasma PTH

-Increased plasma phosphate

In vitamin D deficiency (hypocalcemia), what

happens to plasma 1,25-(OH)-D3 and plasma
phosphate?

-Decreased active form of vitamin D3

-Significant decrease of plasma phosphate

In chronic renal failure (hypocalcemia), what

happens to plasma 1,25-(OH)2-D3 and plasma
phosphate?

-Decreased active form of vitamin D3

-Increased plasma phosphate (because kidney
cannot get rid of it)

In primary hyperparathyroidism, what happens to

plasma PTH and plasma phosphate?
-Increased plasma PTH

-Decreased plasma phosphate

CAP 80

What is the penis comprised of?

Venous network

Where does the ejaculatory duct pass through?

Prostate

What is the immature form (inital cell) of sperm?

Spermatogonium

What is the division of spermatogonium?

Meiosis

What is the range of onset for puberty in males?

9-14 years of age


How long does it take for males to complete
puberty?
2-4.5 years

What is the first sign of puberty in males and what

causes it?

-Enlargement of testes greater than 2.5 cm

-Due to increase in size of seminiferous tubules,
Leydig cells

What is the driving force for secondary sex

characteristics?
Androgens/adrenal testosterone

What are the secondary male sex characteristics

caused by testosterone?
-Body hair

-Voice: hypertrophy of laryngeal mucosa and

larynx

-Skin: thickens

-Muscle development

LH pairs with what kind of cells?

Leydig cells

FSH pairs with what kind of cells?

Sertoli cells

Function of the leydig cells?

Convert cholesterol into testosterone

What happens to the testosterone produced by the

leydig cells?

It can either be converted into DHT or estrogen

What is the enzyme that allows testosterone to be

converted into DHT?

5alpha-reductase

What is the enzyme that allows testosterone to be

converted into estrogen?

Aromatase

What are the two functions of sertoli cells?

1. Convert testosterone into estrogen

2. Responsible for spermatogenesis

What happens when levels of androgen increase in

the female body?
Facial hair becomes apparent as well as acne

What happens when inhibin is released from the

sertoli cells?
LH and FSH levels are controlled through the
inhibition of the anterior pituitary gland

What is the precursor to all steroid hormones

(estrogen, progesterone, androgen, DHT, etc.)

LDL (cholesterol)

We make testosterone from cholesterol but what

other two steroids are derived from cholesterol?

DHEA and androsterone

What gland has the capability of converting

cholesterol to androstenedione?

The adrenal glands

Where in the body is testosterone converted into

either DHT or estrogen and where can it not be
produced and why?

-Peripheral tissues
-It cannot be produced in the adrenal glands b/c it
lacks the enzyme aromatase

What body part has the capability of converting

cholesterol to testosterone

The testis

Where in pregnancy/fetal is testosterone the

highest?

Mid-pregnancy; 2nd trimester


Where in the neonatal phase of life is testosterone
again the highest?

About 6 months old

What age in male puberty does testosterone spike?

12-20 years old

After what age does testosterone decline in males

but doesn't completely deplete?

60 years old

What is 45% of testosterone bound to?

Sex hormone-binding globulin (SHBG)

What is 55% of testosterone bound to?

Albumin and corticosteroid-binding globulin

What percentage of testosterone moves freely in

the blood stream?
2% (most important biologically)

What are the plasma concentrations of

testosterone, androstenedione, and DHT?

-6.5 micrograms/L

-1.5

-0.5

Where is testosterone metabolized?

Liver = 17-ketosteroids
Kidney = urine (2%)

What is the first difference between

spermatogenesis and oogenesis?

-In females, mitotic proliferation of germ cells

occurs PRIOR to birth

-In males, spermatogonia proliferate only AFTER

puberty

What is the second difference between

spermatogenesis and oogenesis?

-In females, meiotic division of oocyte produces

only ONE MATURE OVUM

-In males, meiotic divisions of primary

spermatocyte produces 4 mature spermatozoa

What is the third difference between

spermatogenesis and oogenesis?
-In females, second meiotic division is completed
only upon fertilization
-In males, the products of meiosis (spermatids)
undergo substantial differentiation in the maturing
process

What is the acrosome of a sperm?

-The cap at top of sperm head

-Contains hyaluronidase and proteolytic enzymes
which are important in penetration of ovum

Why is it important for sperm to have

mitochondria?
It is arranged around the body so it can move

What is the tail of a sperm called?

Flagellum

-Outgrowth of centriole
-Two microtubules in center

-Nine around the outside

What structures produce semen?

-Seminal vesicles

-Prostate
-Mucus glands (bulbourethral gland)

What makes up semen?

-Fructose

-Vit. B, C, and E
-Electrolytes: Na, K, Mg, Ca, Cl, and HPO3

-LMW (low-molecular weight) polypeptides,

proteins

What is the pH of semen?

7.5 final

What is the amount of semen in one ejaculation

and sperm count?
-2-6 ml
-20-200 million sperm

- <20 million = infertile

What is the function of testosterone in fetal

development?

-Present at 2nd month of embryonic life

-Presence or absence of testosterone determines
development of genital organs and characteristics
- + testosterone = penis, scrotum

- - testosterone = clitoris and vagina

-Also development of prostate, seminal vesicles,

and vas deferens
-Causes descent of testes into scrotum during last
2-3 months of pregnancy

What happens with when testicles don't descend

into the scrotum?
The testicles will overheat (37 degrees C) and the
sertoli cells will not be able to produce sperm
causing infertility

What are some other functions of testosterone?

-Fetal development of epidydimis, vas deferens,
and seminal vesicles

-Pubertal growth of penis, seminal vesicles,

musculature, skeleton, larynx, and
spermatogenesis

What are the functions of DHT?

-Fetal development of penis, penile urethra,
scrotum, and prostate
-Pubertal growth of scrotum, prostate, sexual hair,
and sebaceous glands
-Prostatic secretion

-Causes male pattern baldness

What can we do to prevent male baldness?

Use medications that are antagonists to 5alphareductase so testosterone cannot be converted into
DHT (controls hair growth)

What are other important functions of

testosterone?
-Bone growth and calcium retention: thought to
inhibit production of osteoclasts
-Red blood cells which cause increase in
erythropoetin and stimulates RBC production

-Stimulates sodium and water reabsorption in PT

of kidney (BP goes up)

Why is being a male increase your risk of coronary

heart disease?
-Increases LDL to produce testosterone and
decreases HDL
-Hypertension occurs because of increased blood
pressure

Where are androgen receptors found in

reproductive tissue?
-Prostate

-Testis (sertoli, leydig, and myoid cells)

-Epididymis

-Seminal vesicles

Where are androgen receptors found in nonreproductive tissues?

-Neurons in CNS
-Anterior pituitary
-Thyroid skin

-Adrenal cortex

-Live kidney tubules

-Bladder cardiac and striated muscle

-Bone
-Vasculature

Where are androgen receptors found in females?

-Ovary (interstitial and granulosa cells)
-Mammary glands

-Uterus

What controls erections in males? (POINT)

Parasympathetic NS (decrease in sympathetic

activity)

What exactly does the parasympathetic NS do to

the vasculuture of the penis?
Vasodilation of the arterioles and erection

Emission (SHOOT)
-Movement of ejaculate into proximal part of
urethra under sympathetic control
-Causes sequential peristalic contraction of smooth
muscle of vas deferens (closing of bladder
sphincter)

Ejaculation

-Spinal reflex
-Triggered by entry of semen into urethra; causes
nerve impulses to activate perineal muscles
forcibly expel semen from urethra

Orgasm

Culmination of sexual excitation

Detumescence
Flaccidity
-NE from sympathetics, edothelin = contraction of
smooth muscle and inc. venous outflow

What is male-pattern baldness caused by and how

can it be treated?
-Caused by DHT
-Treated by 5alpha-reductase inhibitor

What causes benign prostatic hypertrophy and how

can it be treated?

-Caused by DHT
-Treated with 5alpha-reductase inhibitor

What are possible treatments for cancer of the

prostate?
-Androgen receptor antagonists

-Radiotherapy

-Radical prostatectomy

What do tumor of testis produce a lot of?

Testosterone


What is unique about germinal epithelial tumors?
They produce no hormones

Prostatic Specific Antigen (PSA)

Tumor marker; surface antigen
-not used to diagnose disease!! Used to screen and
follow-up with patients to measure future PSA
levels
-indicator of carcinoma of the prostate

What is the age range that suffer from erectile

dysfunction?

40-70 years old

What percentage of men suffer from erectile

dysfunction?

What can cause erectile dysfunction?

-Diabetes Mellitus
-Hypertension
-Radiation
-Surgery for prostate cancer
-Lower spinal cord injury
-Stress from unemployment or performance
anxiety

52%

-Drugs such as diuretics, antidepressants,

antilipidemics, antihypertensives, tranquilizers,
hormones, EtOH (alcohol), cocaine, and marijuana

What is the difference between libido and erectile

dysfunction?
With libido, you want to have sex but with erectile
dysfunction, the male cannot physically have an
erection

What are some common medications for erectile

dysfunction?
Phosphodiesterase-5 inhibitors:
-sildenafil
-citrate
-vardenifil
-tadalafil

What are the main mechanisms of

phosphodiesterase-5 inhibitors?
To increase NO release and cause vasodilation in
the venous system of the penis

What are the treatments for erectile dysfunction?

-Androgen therapy to create more testosterone
-Vacuum constriction devices-noninvasive; draws
venous blood into penis constriction ring prevents
venous return

-Injections of PGE1
-Surgical implantation of prostheis

-Sex therapy

Vasectomy
-Small segment of the vas deferens is removed
-May be reversed unless interstitial fibrosis of
testes occurs.
-Normal sexual response
-May be reversible

What is hormonal birth control like for males?

-Testosterone and progestagen in clinical trials in
Europe
-Azospermia within 6-8 wks - easily reversible

What are male birth control vaccines like?

-Not reversible

-Targets: gamete production (hormones), gamete

function (zona pellucida, sperm), and gamete
outcome (hCG - in phase II and II trials)

What happens to testosterone when males age?

-Decrease slowly after age 40
-Decreased bone formation and muscle mass
-Decreased growth of facial hair, appetite, and
libido
-LH not changed; FSH increased with aging in men
(unknown reason)

Testosterone Supplements
Beneficial or not, in lieu of side effects; yes and no

CAP 81

Female reproductive functions

1. Preparation for conception and pregnancy

2. Pregnancy

What are the main reproductive organs in a female?

-Ovary

-Uterine Tube
-Uterus
-Cervix
-Vagina

How many eggs does a mature ova carry starting at

birth?
400-500

Menopause
Remaining ova degenerate

In the female hormonal system, what are the 3

hierarchies of hormones?
1. Gonadotropin-releasing hormone (GnRH); released
by hypothalamus
2. Follicle-stimulating hormone (FSH) and Luteinizing
hormone (LH); secreted by anterior pituitary gland
3. Estrogen and progesterone secreted by ovaries and
LH and FSH respectively

Menarche
Time of first menstrual cycle

What is the average length of a menstrual cycle?

28 days

How do we identify the first day of menstruation?

When the bleeding begins

When does puberty usually begin in females?

9-12 years old

What is the first phase of menstrual cycle?

The follicular phase; day 0-14

What is the second phase of menstrual cycle?

The luteal phase; day 14-28 (set, does not vary)

What happens on the 14th day of menstrual cycle?

The ova within the follicle is released

Corpus luteum

Remnant of follicle turns into yellow body and if

sperm are around, will turn into white body and
maintain levels of estrogen and progesterone to
support pregnancy (and development of placenta)

Placenta

Sack that connects pregnant woman's uterus to the

fetus

What stimulates ovulation?

Tremendous increase in LH

What is release of LH and FSH like?

Pulsatile

Where does LH hit its peak in a menstrual cycle?

Day 14

Where does FSH hit its peak in the menstrual cycle?

Day 14

Estrogen is prevalent in which phase of the menstrual

cycle?

The follicular phase

Progesterone is prevalent in which phase of the

menstrual cycle?

The luteal phase


Estrogen subtly declines the first five days of the cycle
because...
It is still low from the previous cycle because
pregnancy did not take place. By the time it
encounters the effects of the LH surge, it is around day
14

What is the union of the sperm and the egg?

Zygote

What happens to the follicle after it ruptures and

releases the ovum?

-It becomes the corpus luteum (yellow body) Lasts

about 12 days after ovulation, then degenerates
becoming corpus albicans which finally is absorbed

What can the corpus luteum produce?

Estrogen and progesterone

What happens to LH in the luteal phase?

It decreases consistently

What is responsible for the production of estrogen and

progesterone initially after conception?
Initially corpus luteum but once the placenta develops,
it takes over as the main producer of estrogen and
progesterone

What is required to grow the endometrium and the

placenta?

Progesterone

What causes anterior pituitary to limit FSH and LH

secretion?
Estrogen (and to a lesser extent, progesterone) in a
negative feedback loop

What happens when the corpus luteum degenerates?

Estrogen and progesterone production drops

-results in menstruation
-FSH and LH production increases again, starting a
new ovarian cycle

What are estrogen's effects on puberty?

-Increases size of ovaries, fallopian tubes, uterus,
vagina, mons pubis, and labia

-Increases resistance of vaginal epithelium to infection

-Endometrium (lining) of uterus becomes thicker, and
more glandular

-Fallopian tubes contain more cilia and thicker tissue

What are estrogen's effects on the breast?

-Development of connective tissues

-Growth of ductile system

-Deposition of fat

-Not enough to convert breast into milk-producing

organ (need prolactin)

What is estrogen's effects on the skeleton?

-Osteoclastic activity inhibited

-Also causes epiphyses (growth plates) of bones to

fuse: This is one of the reasons why female growth
ends sooner than male growth; menopause leads to
osteoporosis due to decreased Ca++ deposition

What is estrogen's effect on body metabolism?

-Increases

-1/3 as much as testosterone

What is estrogen's effect on fat deposition?

-Increases especially in breast, gluteal region, and

thighs

What is estrogen's effect on hair distribution?

-No significant effect; hair growth in pubic
region/axilla
-Caused by increased ANDROGENS from adrenal
glads

What is estrogen's effect on skin?

-Smoother, softer, but thicker than child's
-More vascular; hence warmer and bleed more than
men during cut injuries

What are the functions of the progesterone?

-Promotes secretory changes in uterine endometrium
during last half of ovarian cycle
-Prepares uterus for implantation of fertilized ovum
-Cause breasts to swell, alveolar cells to proliferate
-Decreases uterine contractions; prevents expulsion of
implanted ovum


Why is menses considered the onset of the menstrual
cycle?

Because it is something we can physically see

What are the steps of menstrual phase?

1. Corpus luteum stops producing estrogen and
progesterone
2. Endometrium degenerates
3. Blood vessels supplying endometrium undergo
vasospasm (decreased nutrient supply to
endometrium)
4. Endometrium undergoes some necrosis

5. Blood seeps into endometrium

6. Tissue breaks loose from uterus

What is the composition of normal menstruation

fluids?
-About 40 mL blood
-35 mL serous fluid

-Nonclotting
-Leukorrhea can occur

Leukorrhea

White discharge (can be seen during menstrual phase)

Anovulatory Cylces

If LH surge in preovulatory stage is insufficient,

ovulation does not occur

What are the effects of anovulatory cycles?

-Failure of development of corpus leuteum

-No secretion of progesterone

-Cycle is shortened but rhythm continues

When do anovulatory cycles usually occur?

First few cycles after puberty and before menopause

When does menopause happen and what exactly

happens?
-Occurs at 40-50 years

-Sexual cycle becomes irregular

-Ovulation fails to occurs over months or years

What causes menopause?

-"Burning out" of ovaries

-Few primordial follicles remain to produce estrogens
that is insufficient to inhibit FSH and LH hence, FSH
and LH levels increases

What are the symptoms of menopause

-Hot flashes (hot flushes)

-Irritability

-Fatigue
-Anxiety (occasional)

-Various psychotic states

-Decreased strength and decreased calcification of
bones

What are some other physical changes that happen to

a woman experiencing menopause?
-Headaches and hot flashes
-Teeth loosen and gums recede

-Risk of cardiovascular disease

-Backaches

-Body and pubic hair becomes thicker and darker

-Bones lose mass and become more fragile
-Vaginal dryness, itching and shrinking
-Stress or urge incontinence; urethra loses its tonicity
-Abdomen loses muscle tone
-Skin and mucous membranes become drier, skin
develops a rougher texture

-Nipples become smaller and flatten

-Breasts droop and flatten

-Hair becomes thinner and loses luster

What does a successful female sexual act depend on?

-Local stimulation

-Psychic stimulation: similar nerve pathways as men

Sexual thoughts lead to desire based on what?

-Psychological and physiological drive

-Peaks during ovulation (high estrogen = high libido)

What does local stimulation include?

-Massage
-Other types of stimulation of clitoris, vulva, vagina,
and perineal regions

What is sensory stimulus transmitted through in the

female sexual act?

Pudendal nerve and sacral plexus to spinal cord and

then to cerebrum; local reflexes are also involved
mostly controlled by spinal cord

What can we recommend women undergoing

menopause?
-Hormone-replacement therapy (HRT)

-Vitamin D (50,000 international units)

-Calcium

-Exercise

Perineal regions

Located between the rectum and the vagina

Female erection
-Clitoris and introitus have erectile tissue

-Clitoris is homologous to penis

-Controlled by PARASYMPATHETIC stimulation


What is released during a female erection?
Ach, NO, and VIP

What controls lubrication in female sexual act?

Parasympathetic nerves that stimulate Bartholin's

glands located beneath labia minora and secrete
mucus

What happens in a female orgasm/climax?

-Perineal muscles contract rhythmically which may
increase uterine and Fallopian tube motility; dilates
cervical canal
-Ends in relaxed peacefulness (resolution)

What is released from the pituitary that causes the

rhythmic contractions of the uterus?
Oxytocin

Do women have refractory periods?

No! Can start another sexual cycle right after

resolution

What are the main differences between male and

female sexual responses?
-Women do not require refractory time before
beginning excitation again
-Women do not ejaculate

What are the 4 phases of the female sexual response?

1. Excitement phase: NO causes vaginal congestion
2. Plateau phase: increased HR, BP, respiratory rate,
and muscle tension
3. Orgasmic phase
4. Resolution phase: returns genitalia and body
systems to pre-arousal state

CAP 82

What is the composition of blastocysts initially and

then after maturation?
Solid and then hollow (like a cyst) ball of 6-8 cells

What hormone do blastocysts and

syncytiotrophoblasts release?

hCG

When can you detect hCG in the maternal blood and

urine?
Detected within 8 days of conception (main marker)

What does hCG stand for?

human chorionic gonadotropin

What are the main functions of hCG?

1. Produced by synctiotrophoblasts (8-9 days after
fertilization)

2. Maintains corpus luteum beyond normal lifespan

3. Stimulates progesterone and E2 by CL
4. Stimulates essential DHEA-S in fetal zone of
adrenal gland
5. Stimulates testosterone production in male fetus
6. hCG receptors in endometrium and myometrium
and can inhibit contractions produced by oxytocin

7. Immunosuppressant

What is the most important function of hCG in

maintaining pregnancy?

Acts as an immunosuppressant

Why do we need to suppress the maternal immune

system?

Do not want to attack the fetus because the maternal

body thinks it is a foreign body

What cells invade the endometrium?

Trophoblastic cells

What are the growth factors that contribute to

trophoblast differentiation?
Growth Factors:

-IGF

-TGF

-EGF

Cytokines

What do cytotrophoblasts and syncytiotrophoblasts

form?
The placental-hypothalamic-pituitary axis

What are the spiral arteries?

Trophoblast arteries from the uterus that allow it to
attach/penetrating to the endometrium

Placenta

Bunch of cells between the uterus and fetus

How many fetal arteries and veins are established?

One artery and two veins

What are the functions of the placenta?

1. Fetal gut in supplying nutrients

2. Fetal lung in exchanging O2 and CO2
3. The fetal kidney in regulating fluid volumes and
disposing of waste metabolites
4. Endocrine gland synthesizing many steroids and
protein hormones that affect both maternal and fetal
metabolism

What is the fetus deficient in?

3Beta-hydroxysteroid dehydrogenase which is

important in making DHEA-S

How can the fetus get the needed DHEA-S?

Mom needs to provide it by eating certain foods

What does progesterone produced by the placenta

do?

1. Most important for establishment and sustenance

of morula and blastocyst
2. Maintains decidual lining of uterus to provide
nutrition for fetus
3. Produced by placenta formed from cholesterol
(90% goes to mother); is major substrate for cortisol
and aldosterone by fetal adreanal gland
4. Inhibits uterine contractions - inhibits
prostaglandin production and decreases sensitivity
to oxytocin

How does estrogen affect the pregnant uterus?

Increases blood flow

What is an index of fetal well-being?

Estrogen levels

What are the main functions of estrogen in a

pregnant woman?

1. Stimulate continuous growth of uterine

myometrium
2. Stimulates growth (w/progesterone) of ductal
tissue of breast

3. Along with relaxin, relaxes and softens maternal

pelvic ligaments and symphysis pubis of pelvic
bones - allows expansion of uterus

4. Stimulate LDL cholesterol uptake and activity of

P450 enzymes which contribute to progesterone
synthesis

When does the placenta secrete

somatomammotropin?

5 weeks into gestation

What are the main functions of

somatomammotropin?

1. May be important in breast development for

lactation
2. May promote growth (chemical structure is
similar to GH)

3. Decreases glucose usage in mother; more glucose

for fetus
4. Promote release of fatty acids from fat stores of
mother; gluconeogenesis!!

Somatomammotropin promotes what?

gluconeogenesis

What does relaxin do in a pregnant woman?

1. Produced by corpus luteum

2. Relaxation of symphysis pubis

3. May play a role in increased GFR/renal blood flow

What are the maternal responses to pregnancy?

-Blood flow to placenta requires increased cardiac
output (40% higher) until last 8 weeks
-Blood volume increases by 30% due to aldosterone
and estrogen (cause active Na and H2O retention
(also dec. atrial natriuretic peptide)
-Increased thyroxine due to hCG and hC thyrotropin
(made by placenta)

What are other maternal responses to pregnancy?

-Kidney function increases: GFR by 40%, RPF by
75%
-Inc. Na and H2O reabsorption by tubule-E2; inc.
BP slightly
-Insulin secretion increases after 3rd month of
pregnancy
-Maternal response to insulin decreased/no change
to glucagon

-TPR decreased b/c the veins need lower resistance

to hold the extra volume of blood (edema)

-Increased Ca reabsorption

-Increased alveolar ventilation

-Increased tidal volume

Supine Hypotension Syndrome

Enlarged uterus falls back and occludes the inferior
vena cava decreasing atrial filling pressure causing
cardiac output to decrease

In 95% of women, what happens after dec. cardiac

output due to supine hypotension syndrome?

Increased vascular resistance to normalize BP

In 5% of women, what happens after dec. cardiac

output due to supine hypotension syndrome?
Parasympathetic response decreases heart rate and
hypotension occurs

What percentage of pregnancies experience morning

sickness?
70%

When is the onset of morning sickness?

-4-8 weeks gestation

-Improvement before 14-16

What are the theories surrounding the cause of

morning sickness?

-Relaxation of smooth muscle of stomach

-?Inc. hCG - serum levels don't correlate well
-Higher frequency of female fetus - 56%

-Usually assciated with a more favorable outcome


What is pre-eclampsia?

Hypertension in a pregnant woman

What are the symptoms of pre-eclampsia?

Maternal hypertension, proteinuria, and generalized
edema

What is the difference between pre-eclampsia and

eclampsia?
Eclampsia occurs in pregnant women that have
seizures

What is the incidence of pre-eclampsia in the U.S.?

-Affects 7-13% of pregnancies
-Leading cause of maternal and perinatal mortality

What is amniotic fluid?

Fluid in which fetus floats in uterus

How much amniotic fluid is there?

500-100 mL

What are the 2 functions of the amniotic fluid?

1. Mechanical buffer - protects fetus

2. Mechanism by which fetus excretes waste - turns

over daily, renal excretions (75%), pulmonary
secretion

What are the four phases of parturition?

-Phase 0: From conception to beginning of labor;
quiescent uterus (main hormone available here is
progesterone)

-Phase 1: From time of uterine activation to delivery

of fetus
-Phase 2: From time of delivery of fetus (first) to
delivery of placenta (second)
-Phase 3: Postpartum, involution of uterus

What makes Phase 0 a "quiescent uterus"

-Associated with decrease cAMP, cGMP, and MLCK
activity
-Mainly due to PROGESTERONE, relaxin,
prostacyclin, PTH-related peptide, and NO

Describe Phase 1
Activation of uterus
-Upregulation of contraction-associated proteins
controlled by positive feedback loop

-Connexin-43 increases gap junctions

-50X increase myometrial oxytocin receptor

-Uterus responsive to uterotonins

-Dilation and effacement of cervic, cervical softening
due to rearrangement of collagen fibers,
glycosamingoglycans

Do we know the exact causes of uterine

contractions?

NO but we can infer


Describe Phase 2

Delivery of fetus and placenta - activated uterus

stimulated by platelet activating factor, endothelin
(via ETA Receptor), Ang II (via AT1 R)

Describe Phase 3
Oxytocin most important in postpartum bleeding
and involution of the uterus

Is oxytocin a uterus augmenter or an inducer?

Augmenter; cannot induce uterine contractions (we
do not know what causes contractions)

What are the three theories that explain the

mechanisms of starting "labor"
1. Removal of progesterone; change in estrogen:
progesterone ratio
2. Increase in uterotonins: oxytocin
3. PGF 2alpha and PGE2; not in humans but in
animals

Positive feedback theory of parturition

Stretch of cervix by fetus's head elicits reflex

increase in contractility of uterus pushing the baby
forward which in turn further stretches the cervix
setting up positive feedback loop


Braxton-Hicks contractions
Irritability of uterine muscle--weak, slow
contractions--begings about 1 month before labor

When are uterine contractions the strongest in

pregnant women?
During the 9th month of gestation; stronger
contractions stretch cervix and force baby through
birth canal

True labor has a circadian rhythm. What times do

they peak between?

12 midnight and 5am

Describe labor pains and their cause

-Due to ischemia of uterine muscle in early stage,

then stretch of cervix, perineum, and vagina
-The pressure downward on the spiral arteries by the
uterine contractions stops the bleeding and is
thought to cause some of the pains

What are good factors that can help augment labor?

Prostaglandins and oxytocin (Pitocin)


Labor Induction
Stimulate spontaneous onset of labor (uterine
contractions) with or without ruptured membranes
(amniotic sac)

What can you do when the amniotic sac of a

pregnant woman does not rupture during labor
induction?

Manually stimulate the membrane until it ruptures

and this can sometimes induce contractions to start

Labor Augmentation
-Stimulate contractions following spontaneous
rupture of membranes

-Stimulate spontaneous contractions that are

inadequate because of failure of progressive
dilatation and descent

What phase is oxytocin most important?

-Phase 3
-Women may receive extra oxytocin (Pitocin)
following placental delivery to prevent bleeding

Uterus atonia
-Uterus is exhausted after so many contractions
-Pressure on spiral arteries lifted and
bleeding/hemorrhage can occur
-Complicated labor can occur

-Give patient Pitocin

Complicated labor

When bleeding persists in, hysterectomy might be

needed if manually massaging uterus does not work

When does breast development begin?

At puberty due to estrogen stimulation; increases
during pregnancy, due to estrogen, progesterone and
prolactin

What does prolactin do?

-Promotes milk secretion
-Secreted by anterior pituitary starting from 5th
week of pregnancy until birth, then cycles


What is the 1st milk called?
Colostrum
-thick and yellowish
-same proteins and lactose as milk, but no fat
-rich in immunoglobins

What structures hold milk in the breasts?

Lobules

What is the path of the suckling reflexes using the

posterior pituitary gland?
1. Suckling
2. Mechanosensors in nipple
3. Hypothalamus
4. Nerve pathway
5. Posterior pituitary activated
6. Increases oxytocin
7. Contraction of myoepithelial cells
8. Increase milk ejection
So oxytocin = milk flow

What is the path of the suckling reflexes using the

anterior pituitary gland?

1. Suckling
2. Mechanosensors in nipple
3. Hypothalamus

4. Increase prolactin-releasing factor and decrease

prolactin-inhibitory hormone
5. Anterior pituitary activated
6. Increase prolactin production
7. Increase milk secretion
So prolactin = milk production

How is lactation initiated?

By precipitous drop in estrogen and progesterone
after delivery

How does prolactin surge?

Each time mother nurses baby due to nerve
impulses from nipples to hypothalamus
-without nursing stimulation, no prolactin surge,
and loss of milk production

What happens when women do not nurse after

labor?

-Hypothalamus prolactin inhibitory hormone

-Lactation INHIBITS FSH and LH thus lactation
interferes with reproductive function

Why do women who are lactating cannot get

pregnant?
B/c of their very low levels of LH and FSH

CAP 83

When is the fetus at a microscopic size?

First 2-3 weeks

When does the fetal heart begin beating? (CVS)

4th week

When do nucleated cells begin to form in the fetal

yolk sac? (RBCs)
3rd week

When do RBCs begin forming in the fetal liver?

6 weeks

When do RBCs begin forming in the fetal bone

marrow?
3rd month


When do fetal reflexes involve the spinal cord?
(CNS)
3rd or 4th month

Is the cerebral cortex fully developed even at birth?

(CNS)

No!; myelination completed 1 year after birth

When does fetal ingestion and absorption happen?

(GI system)

Midpregnancy

When is a fetus's GI system equal to that of a

neonate's?

During 2-3 months of pregnancy; also eliminates

meconium

Meconium

The dark green substance forming the first feces of

a newborn infant.

When does a fetus start to excrete urine?

2nd trimester

When does the respiratory system become active in

fetal life?
Does not occur during fetal life because it is
submerged in amniotic fluid

What are the percentages of fetal blood flow?

55% of all blood flows through placenta and only
45% flows through rest of the tissues

How does a fetus get blood from the mother?

One umbilical vein and two umbilical arteries

What kind of blood does the umbilical vein contain?

Oxygenated blood

What kind of blood do the umbilical arteries

contain?

Unoxygenated blood

Shunt
When the venous blood and the arterial blood is
mixed

Ductus venosus
Shunt that connects the inferior vena cava to the
umbilical vein

Foramen ovale

Shunt that connects right and left atria; this is how

blood from the inferior vena cava gets to the left
heart

Ductus arteriosus
Shunt that connects the aorta to the pulmonary
artery

What happens, after the umbilical arteries and

veins are clamped during birth?

-Shrivel up and occlude

-Loss of blood flow from placenta doubles systemic
vascular resistance, increasing left ventricular
pressure and aortic pressure, and decreasing
venous return to RA
-Ductus venosus closes 1-3 hours after birth, forcing
portal blood through liver sinuses

What do we call the umbilical arteries and vein

when they occlude?

Medial umbilical ligaments and Ligamentum teres

What happens to overall pulmonary pressure when

the umbilical vein and arteries are occluded?
-Pulmonary vascular resistance decreases due to
lung expansion, lung vasculature dilates
-Decrease in pulmonary artery pressure, RA
pressures

-Oxygenated blood from lungs enters left atrium

-Pressure in left atrium, left ventricle increases

dramatically

What is the foramen ovale called when it closes like

a door?

Fossa ovalis

What prevents the fossa ovalis from opening after

birth?
High pressure of left atrium and low pressure of RA

In what percentage of humans is the fossa ovalis a

"probe patent"
25%

When does the ductus arteriosus degenerate after

the umbilical vein and arteries are occluded? What
is it called afterwards?

-1-8 days

-ligamentum arteriosum

Failure to close the ductus arterious leads to what?

Patent ductus arteriosus (PDA)

What is the ductus venosis called when it closes?

Ligamentum venosum

What is the initial state of the fetal alveoli in the

lungs?
Collapsed under surface tension and must be
inflated with extra force

What is the first breath of an infant like?

Generates tremendous negative pressure
intrapleurally

How long does it take for normal breathing to be

established in a newborn?

40 minutes

What is the second breath of an infant like?

Considerably less effortful than the first

What is the role of surfactant in fetal life?

-Secreted during the last 1-3 months of gestation
-Reduces surface tension within alveoli and
prevents the collapse tendency of alveoli

What initiates normal breathing rhythm within a

minute after birth?

-Slightly asphyxiated state during birth

-Sensory impulses from suddenly cooled skin

-Additional stimuli are hypoxia and hypercapnia if

breathing is delayed

How long can neonates go without breathing before

damage occurs?

8-10 minutes

What are the common causes of hypoxia (delayed

breathing)?

-Compression of umbilical cord

-Premature separation of placenta

-Excessive contraction of uterus, cutting off blood
too much
-Excessive anaesthesia of mother (esp. general
anesthesia)

What is the relationship between premature babies

and surfactant?

They are born too early for surfactant to be

produced so their alveoli will remain collapsed and
they will have trouble breathing; that is why they
are put into the incubators after birth

Respiratory distress syndrome in premature infants

Due to lack of surfactant that prevents the alveoli

from collapsing

What is the gastrointestinal function of a premature

baby like?
-Difficulty absorbing fat
-Use of starch inadequate due to lack of pancreatic
amylase
-Difficulty in absorbing calcium (need diet high in
vitamin D)


What is at immature development in a premature
baby?

Liver and kidneys

Anemia in premature babies

May develop because of immature blood-forming
mechanism of bone marrow

Immune system of premature babies

-Inadequate; leads to infection

-Depressed formation of gamma globulins

Hypothalamus in premature babies

Inability to maintain normal body temperature

Kernicterus
Deposits of bilirubin occur in the brain causing
mental retardation; hyperbilirubinemia

Describe the RBC count in the first 16 weeks of life

It is at its highest right after birth, then drops

dramatically due to lack of hypoxic stimulus,
plateau around 8-10 weeks, and then starts
increasing again

Describe the bilirubin count in the first 16 weeks of

life
It is at its highest right after birth, then drops
dramatically and remains at a low level 12-16 weeks
afterwards

Physiologic jaundice
Bilirubin levels rise during first 3 days due to poor
function of liver initially; WBC count at birth is
45,000/cu.mm

Liver function details of premature babies

-Excretion of bilirubin inadequate

-Plasma proteins not synthesized in adequate
amounts
-Gluconeogenesis function deficient; infant relies
on fat stores if glucose is in short supply

-Blood coagulation factors produced inadequately

What is the rate of fluid intake and excretion in

neonate compared to that of an adult?
7X greater

What is the metabolism of neonate compared to

that of an adult?

2X greater

What is the blood and kidneys like in neonates?

-Greater acidity of blood

-Kidneys immature; cannot concentrate urine

Therefore infants can suffer from acidosis,
dehydration more readily than adults

Suckling occurs at age...

0; birth

Smiling occurs at age...

1 month

Vocalization occurs at age...

2 months

Head control occurs at age...

3 months

Hand control occurs at age...

4 months

Rolling over occurs at age...

5 months

Sitting briefly occurs at age...

6 months

Crawling occurs at age...

7 months

Grasping occurs at age...

8 months

Pulling onself up occurs at age...

9 months

Walking and supporting onself occurs at age...

10 months

Standing alone occurs at age...

11 months

Walking alone occurs at age...

12 months