6-23-14 p.

1
Human Kidney = two of them= bilaterally = kidney shaped
Descending abdominal aorta farther up is LV
CO out of LV in resting = 5L/min
Three major portion of kidney
1. outside = renal cortex = in latin means bark
2. medulla
3. pelvis
Pelvis has finger like projections called calix. Avg humans have 5-7 calix
There are striations renal pyramids 5-7 per kidney. Come down and touch onto calix
Pyramids are located inside the medulla
Carbohydrates in mitochondria = metabolize carbs = produce co2 and we can exhale it
End products of fat are co2 and water
Metabolize proteins = have C, H, O, and N = Nitrogen products cannot be excreted as a
gas
Nitrogen in air we breath is inert = breath in breath out
Metabolize proteins, we have to figure way to get rid of nitrogen
Urea = has C, O, and N
To get rid of nitrogen products is via our urine because we can expire it in gas form
Carbs + fats = we get rid of stuff by exhaling
Three big products have Nitrogen 1. Urea 2. Uric acid 3. Creatinine = we have to urinate
these three things out of our blood stream
Kidney fail = renal failure
1. pre-renal
2. intra-renal
3. post renal = after kidneys
No blood flow to kidneys urea, uric acid, creatinine = go up. = Pre-renal fail
Intra- renal = something damaged in kidney
Coming out of each of pelvis is a tube that go to bladder called ureters. There is a
urethra that attached to bladder
B.U.N. = blood test = blood urea nitrogen = how much urea in bloodstream and if it is
elevated you must be having renal failure
Post renal failure = problem in ureters = some people can have stones called renal
calliculi in pelvis which can go into ureters and get stuck which would lead to blood
urea nitrogen levels going up = fluid get back up and pelvis get enlarged
hydronephrosis
Hydronephrosis = pelvis gets enlarged = renal pelvis smashes onto renal pyramids =
fluid cant get out of the ureters
Descending abdominal aorta > L+R renal arteries that bring blood flow to kidneys = renal
blood flow
Renal Blood F = 1L/min , 5L out of aorta,
L into L +R renal arteries = 1L/ min or 20% of blood flow going to L+R renal arteries
Urea, uric acid, creatinine = produced from protein metabolism (amino acid break
down)
Elevation of these three = marker of renal fail
Ex. Bucket make creatine and lose creatinine = creatinine stays low
But if you cant get rid of it
Renal artery stenosis = narrowed = RBF would less = creatine and other two elevated =
renal failure = pre-renal failure
Lower CO = less RBF to kidney = creatinine increases = example of pre-renal fail because
you cant excrete the N components
Nephron = 1 mil per kidney
Prof = 700,000 neph
Need 200,000 per kidney = to get rid of N waste
We have 5 x buffer zone
Diabetics = High glucose can destroy nephrons
Half of nephron destroyed = never know have renal fail
Drop below 200,000 neph = N waste goes ^ = too late to do anything
Options 1. Renal trans 2. Dialysis 3. Die
Microalbumin = test tell you that you lose nephrons
Blood vessel leads to nephron called afferent arteriole > small group capillaries called
glomerulus, leads out of glomerulus = efferent arteriole
Surround glomerulus = bowmans capsule which leads to small tube called proximal
convoluted tubule
Convoluted = curvy , proximal = next to
PCT> Loop of Henle = 180 deg loop
Loop of henle has two parts 1. Descending limb 2. Ascending limb >distal convoluted
tubule (located in cortex)? > comes down which is called collecting duct
Glomeruli = located in cortex so are PCT
Descending limb = medulla = descend through medulla = then ascends back through
medulla > makes final turn and comes down to hit calix
Collecting duct hits the calix
What makes up the renal pyramid = loop of hendle, and collecting ducts from 1 mil
nephrons
Pelvis > ureters > bladder > urethra > exterior = excretion
Things from bloodstream coming in to afferent
1. RBC (not filtered = too big)
Plasma
2. H2O
3. PP= albumin (not filtered = too big)
4. Urea
5. U.A.
6. Cr
7. Glucose
8. Na+ = 140 mmol/L
9. Ca
10. K
Afferent arteriole = brings blood flow
Filtration = separation under pressure
Ex. Coffee = put filter thorw coffee grounds = allow water through and leave behind
coffee grounds
Glomerulus purpose = filter
Hematuria = RBC filtered = red urine (RBC in urine)
1. glomerular = damage to glomerulus = red cells gain access to nephron @glomerulus
2. non-glomerular = gain access other than glomerulus
Helps pick out where damage is
Proteinuria = plasma proteins filtered
Bladder infection = non-glomerular hematuria
Collect urine sample = hematuria = microscope, normal healthy blood cells is bi concave
disk, enter at glomerulus the RBC have to squeeze through and they get damaged and
you get dysmorphic RBC
Normal morphology = bi concave. Damage it passing through nephron the urine sample
under microscope the RBC would be dysmorphic RBC
Bladder cancer = cause blood enter to bladder = hematuria = RBC not dysmorphic =
enter after nephron
Protein called Tamm-Horsfall protein = produced by collecting duct = put in urine
Small amounts of tamm horsfall protein = found in urine = normal
Tamm horsfall protein can bind RBC (glomerular of origin) when they are in collecting
duct = RBC cast
Collect urine sample = RBC cast
Two indicate that hematuria is coming from glomuleral origin 1. Dysmorphic RBC 2. RBC
casts
No red cells in cast with non-glomelular
Glomelular = dysmorphic RBC , and RBC casts = glomelular origin
Tamm horsfall protein = stops formation of kidney stones
Hyline casts are clear casts made from tamm forsfall proteins = healthy
Albumin in urine proteinuria = starlings forces = descrease pp = edema formation
High glucose , hypertension = can damage glomerulus = can damage it a lot means you
can get proteinuria and hematuria so you have to be on dyalisis
Type 1 type 2 = urine samples = to see if you have microalbumin = see if glomerulus
damaged
Renal colliculi = kidney stones
5L coming from aorta > 1L to kidneys > Portion of fluid that is filtered = glomerular
filtration rate which is 125 mL/min which is 12.5 % of 1L called ultra filtrate
Inside of ultra filtrate is everything except 1. RBC 2. Albumin
180 L/day Ex. Garbage cans = 120 L + half garbage can = 180 L
Filtration occurs in glomerulus
We need to reabsorb 179 L/day
Fluid filtered after glomerulus = 180 L/day glomerular filtration rate and 179 L is
reabsorbed so you excrete 1L per day or 1 ml per min
Filter > reabsorb > excrete
Anything increase urine production rate = diaureses
Any drug that makes you diaurese = diaretic
End of 30 min only have 2ml produced = going into renal failure
Urine production> 1 ml per min = diauresis = diaretics
6-23-14 p.2
GFR= 180 L/day
Reabsorb = 179 L/day leaving ultra filtrate going back to bloodstream
Filtration = leaving bloodstream going to ultra filtrate
Filter reabsorb = excrete
Creatinine is filtered and not reabsorbed
100% of what is filtered is excreted
Creatine and uric acid are not reabsorbed so they are excreted
urea = 50 % reabsorbed 50% excreted
Water, cr, RBC (not filtered, not excreted)
If dont reabsorb h2o you lose plasma so you get thrombo emboli from polycythemia
How water reabsorbed
Filter 180L/day = Only reabsorb 178L/day = diauresis because urine production rate
would be 2L a day
Anything slow water reabsorp = increase excretion
Reabsorption of water 1. Proximal convoluted tubule = 80% of water occurs in PCT =
80% of Na reabsorbed. Na in bloodstream and so it is filtered. 2.
There is no water pump found in animals. Water reabsorbed = 1. Na+ reabsorbed by a
pump? and 2. water follows it by osmosis
Thyasid diauretics = diaurese = work by = only reabsorb 70% of Na ions reabsorbed (80%
supposed to be reabsorbed from tubules.), means you reabsorb less water so more
water has to be excreted
Thyasid diauretics = decrease the Na reapsorption from nephron = decrease resultant
osmotic reabsorption of water = diaurese
Healthy people dont have thyasid and we reabsorb 80% of Na and so 80% of water
follows by osmosis
6-24-14 p.1
http://www.bing.com/images/search?q=bowman%27s+capsule&FORM=HDRSC2#view=
detail&id=C7C85A30A9C9E6E3A8448314A3D01FE0857EC149&selectedIndex=0
Surrounding glomerulus = bowmans capsule
The glomeruli and the proximal and distal convoluted tubules are located in the cortex of the
kidney, but the loops of Henle run in parallel as straight sections down into the renal medulla
and back up to the cortex. Collecting ducts run from the cortex to the inner surface of the
medulla, where they open into the ureter.
Couple hundred thousand nephrons in each pyramid
Border between pelvis and medulla = where collecting duct and calix meet
Filtered not reabsorbed = uric acid and creatinine
Filtered and reabsorbed = Na and water
GFR = how much is filtered
Dont filter N waste build up in = build up in bloodstream
GFR = 125 mL/min or 180 L/day
Renal fail is when GFR is less than 30 mL/min = dialysis
GFR of 10? Cr is high and urea is high because you cant filter it out
179L/day reabsorbed along nephron = 1L/min (excreted) gets to caliyx
Urine production rate = 1L/day or 1mL/min
Anything greater than 1 mL/min = diureses = drugs are called diaretics
Filter 180 L but only reabsorb 177 L urine production will be 3L
Diaretics slow water reabsorption
How reabsorb the water and how drugs mess up
Water reab
1. mandatory water reabsorp
2. facilitated water reabsorp
Mandatory water reabsorp occurs in PCT (80% of Na filtered is reabsorbed so 80% of
water is reabsorbed)
1. Na+ reabsorbed
2. H2O will also be reabsorbed and follows Na by osmosis
Cr and UA are filtered but not reabsorb so they are urinated
80% of 180 L is 144 L. So 144 L/day is reabsorbed from PCT. Be urininate 36L/day
Purpose of filter is to clear 144L/day of. Because Cr and UA (not reabsorbed)
No water reabsorbed til it gets to collecting duct
We can have water reabsorp from collecting duct facilitated water rebsorp
Facilitated = variable = dont fixed amount of water reabsorb= depends on fluid needs of
animal
Ex. Drank excess you want to urinate. Dont drink for couple days =
Mandat
ory = dont control
Ex. Prof stupid = climb up grand canyon in august 117 degrees so hot= want to reabsorb
tremendous amounts
Vs. prof drinkin lots = want to urinate to get rid of Cr
Filter 180 in both
Reabsorbed 80% of Na and 80% of H2o in both
Can control how much of 36 L
Facilitiated = something has to help it
Portion of brain = hypothalamus, hooked by pituitary stalk which is called infundibulum,
hooks to pea size gland called pituatary gland. Rod through ear rod through nose =
pituitary gland.
Pituatary gland broken in half. There is anterior pituitary and the posterior pituitary.
Posterior pituitary secretes hormone called ADH. Have effect on collecting duct. Cover A
if you had Diuretic hormone it would make you diurese. Diratics would make you diruses
more and stop you reabsorbing water. Anti diuretics would therefore come down and
promote water reabsorption so you stop diuresing.
Hormone is biological substance that is made in one place and has effect in some place
different
ADH is aka vasopressin
Lining the collecting duct= phospholipid bilayer = receptor located in bilayer called V2
receptor
V2 receptor= vasopressin receptor made in posterior pituitary have
Collecting duct cell (made of phospholioid) , 1. Lumanal or apical membrane is where
fluid is flowing by because it is next to lumen where fluid is passing, 2. basolateral
membrane
V2 receptors are located on the basolateral portion
There are phospholipid bilayer vesicle that can exocytose into the cell membrane.
Proteins embedded in phospholkipid bilayer vesicle called aquaporins
36 L h2o flowing through collecting duct per day > ADH comes down and binds to V2
receptor > signals vesicle membrane to come to luminal membrane and fuse and
aquaporin protein get inserted to cell membrane and allow water to reabsorb.
No ADH = aquaporins go right back into intracellular pool remains unattached to
collecting duct cell because no signal
Lots of ADH lots of aquaporins inserted lots of water reabsorbed
No adh = you have aquaporins but they are useless because they are in the intracellular
pookl
Diabetes insipidus = Latin diabetes means cyphen which is referring to urine = hear
diabetes it is saying urine = insipidus in latin is large and void. So diabetes insipidus
means large clear empty urine
Diabetes insipidus = pituitary disorder. Stop producing ADH. GFR = 180 L/day.
Mandatory = 144 L/day. Cant have facilitated water reabsorpt if you dont produce
ADH. Should urinate 36 L/day
> 20 L/day = symptomology of diabetes insipidus
ADH is one of the smallest hormones is only 9 amino acids.
They have recombinant engineering to use e coli bacteria to make ADH.
Medication called DDAVP which come in spray bottle.
Spray it up their nose so it goes to the muscous membrane so it can be reabsorbed in
bloodstream through nasal cavity. This goes down to V2 receptors and causes
aquaporins to insert into luminal membrane and you can have water H2O reabsorb.
Patients use DDAVP = diabetes insipidus patients
12 year old urinate a lot = give DDAVP
Scuba dive = urinate because body has all fluid it needs = so you diurese
PCT = Na and water rebabsorb = occur simultaneously
Na goes down the loop and goes up the loop
Na+ come along and as they go up loop of henle there are pumps that will take Na and
pump Na out and they pumps dont do it equally. Pumps that see Na first will pump the
most out. Vs. Fluid flows through the loop of henle more sodium are pumped out down
and little Na pumped out up because little sodium left. Lopp of henle creates medulla
osmotic gradient. Na+ accumulate out. PCT is permeable to water. Thick ascending
limb of loop of henle do not allow water to be reabsorbed.
High conc at bottom of loop of henle which is in medulla. Very low Na absorbed towards
the top of ascending limb.
The loop creates gradient. Why have gradient ADH comes down binds to collecting duct
inserts aquaporins and water can be reabsorbed by osmosis toward sodium that has
already been reabsorbed previously at the loop of henle.
Mandatory water reabsorp = coupled. Na reabsorp water folllwo by osmosis
Na reabsorp from ascending loop of henle. Water reabsorption from collecting duct if
ADH is available
In someone with diabetes insipidus do they still have an osmotic gradient? Urinate a lot.
So Yes they do have osmotic gradient but they cant use it because they cant get
aquaporins to insert into luminal membrane and have water reabsorption.
Why do we need a gradient? Fluid comes up and water is reabsorbed and conc of Urea
cr starts to concentrate because you are removing water. So you need more gradient so
as it passes down water can still be reabsorbed.
6-24-14 p.2
5 classes of diaretics (for edema) (plasma volume goes done) (cause lower BP)
1. thyozide = decrease Na reabsorption, decrease water reabsorption work in PCT/DCT
2. anti-adh diuretics = alcohol (ethanol) better have lots of bathrooms = lower ADH and
you diureses = dehydrated

3. V2 antagonist =vaptan suffix no place for ADH to bind to so you diurese
4. Lasix = horses take diuretic because they have Pulm edema= inhibits Na reabsorption
in loop of henle = smaller osmotic gradient = destroys osmotic gradient
ALL 4 OF THESE = DOWNSIDE TIME Ex. Lasix takes lots of time
5. Mannitol = syringe directly injected into bloodstream (hence #11 in bloodstream),
body dont reabsorb this because it not naturally there, accumulated in ultra filtrate,
high conc of mannitol > than conc of Na outside water will perform osmosis which
means water will be brought into the ultra filtrate
30 sec = at kidney > filtered > 5 min water is being brought into ultra filtrate and person
will diurese
You need gradient and water to be reabsorb
Diaretics are used for edema
Curare = flaccid paralysis and antagonizes nicotinic ach receptor
Diabetics insipidus have gradient but no ADH
Lasix they got ADH but no gradient
Lasix binds to Na/K 2 cl protein
Lumenal membrane = Na/K/2Cl channel located in apical luminal membrane of
collecting duct= Na gains entrance = drug that blocked channel is lasix
Basal Lateral membrane = Na/K pump = Na pumped out
Descending limb is thin = permeable to water so mannitol can go in
Axon hillock and cell body = in hypothalamus then axon comes through the
infundibulum and terminal buttons end in posterior pituitary > cells are called
osmoreceptor neurons and they release ADH because they can sense how dehydrated
your body is so when you are dehydrated they geterate AP and ADH ^
Euhydrated = normally hydrated osmosreceptor stop generate AP and ADH goes back
down
6-25-14 p.1
Resting blood glucose = 70 110 mg / 100 ml (dL) = euglycemia (normal glucose levels in
blood
Anything over 110 is called hyperglycemia
Anything less than 70 is hypoglycemia
Getting too low = if we look look at neurons in our body brain/spinal cord they are
dependent on blood glucose = glucose has to be taken up from the bloodstream which
si done by transporter glucose transporter 1. GLUT2 TRANSPORTER located in neurons
Low levels of blood glucose there is less blood glucose going into CNS
Hypoglycemia = cns dysfunction = 40 mg/dL there is so little force drive glucose into CNS
and you stop generating AP to diaphragm and you go into coma and die of respiratory
fail.
Problem with blood glucose going too high = tissue that binds inside of blood vessel
endothelium = first cells see high glucose levels are endothelium. Glucose at higher
than 110 can bind to proteins in endothelial cells glycocylation.
Blood glucose = 300 = 3x chance of glucose bind to proteins on endothelial cells =
destroy endothelium

Ball of capillaries made up of endothelial cells.

1.Ball of capillaries in Kidney = nephropathy = destruction of nephrons. Hyperglycemia >
glycocylation > nephropathy
2. capillary beds in retina = retinopathy
3. spinal nerves are 31 pairs have little blood vessels running next to them called vasa
nerovrum. Vasa nervorum are little capillaries around all nerves of our body. Nerves
start having neuropathy because capillaries leading to nerves are damaged.

These 3 are classified as endothelial dysfunctioning

High glucose = you can have these three

Facilitated diffusion = high to low conc, hypoglycemic means you lose diffusional
gradient to be able to drive glucose in across GLUT2 to CNS. You end up with CNS
dynsfunctioning which means coma and death


20 g of carbs in apple
In blood glucose = mg
Ate apple and piece of bread = 50 g, blood glucose should go off charts = hyperglycemia
Eat = hyperglycemic= lead to death
Conversely CNS does not have ability to use fats and amino acids as fuel sources initially.
Brain and CNS has to rely on glucose from bloodstream. It is glucose dependent.
@ 2am tonight blood glucose = not eating anything = blood glucose should be dropping
to 40 mg/dL
Prevent hyperglycemia in eating
Prevent hypoglycemia when we not eat =
Pancreas = has Islet of Langerhas
Two cell types in Islet called alpha cells and beta cells
The alpha cells secrete a hormone glucagon
Ex. Control speed of car you need brake. Accelorator = speed up. Need to blend these
together
Blood glucose is controlled with antagonist contro.l Because glucagon cause blood
glucose ^. Glucagon is like accelerator. Take glucagon sample when they sleeping or
when they havent eaten.
Conversely beta cells secrete hormone called insulin which makes blood glucose go
down. Insulin can go to skeletal muscle.
Alpha cells in islet of langerhands in pancreas > secret glucagon > blood stream>
glucagon main target is liver
Euglycemic tonight at 10 pm havent been eating > blood glucose will drop to 70 mg/dL
then the alpha cells sense this and secrete glucagon make blood glucose go ^.
6 carbons in glucose
Glucose is not one straight line = glucose forms ring structure.
Can forms bond between two carbons = alpha 1-4 bond or alpha 1-6 bond
Every 10
th
glucose unit > alpha 1-6 > another string of alpha 1-4
Glucose units hooked by alpha 1-4 bond and 1-6 bonds glycogen
Located at liver in high conc = is glycogen which is 50 g/Kg
10,000 glucose units in one glycogen
Dont have 10,000 glucose untis free because it would attract water and so the liver
would be big. We prevent osmosis of water
Glucose is stored in live in form of glycogen.
Glycogen is highly branched
Glycogen in muscles in 10 g/Kg
The highest conc glycogen in body is in liver
Why we dont wake up is because we store
Enzyme that makes the alpha bonds is called glycogen synthase. Makes alpha 1-4
bonds and therefore makes glycogen.
Enzyme called phosphorolase which breaks the alpha 1-4 bond.
Located on hepatic tissue or on liver there are glucagon receptors
Low blood glucose > alpha cells >glucagon > inside liver cells there are glycogen
synthases and phosphoralyase > glucagon bind to receptor > you want glucagon to
activate phosphoralyase which breaks alpha 4-1 bonds and the glucose can leave the
liver and make blood glucose go up
Made more alpha 4-1 bonds the glucose goes down
Hers disease = genetic disorder you dont have liver phosphoralyase
1. symp = hypoglycemia = CNS disorders
2. have big liver = cant break down glycogen = hepatomeglia
100 g carbs = blood glucose rises up goes too high endothelial cells get destroyed
Blood glucosxe gets over 110 mg/dL beta cells sense this and secrete insulin.
There are phospholipid bilayer vesicles embedded in them are proteins called Glut 4
proteins. There is a receptor on skeletal muscle called insulin receptor >insulin
produced come down and bind to insulin receptor > signal >phospholipid bilayer vesicle
(Glut 4 proteins) translocates from intercellular pool to sarcolemma > vesicle inserts in
sarcolemma cell membrane > glucose taken up into skeletal muscle > glucose can be
taken up into skeletal muscle> blood glucose drops
Glut 4 proteins are located inside skeletal muscle and are insulin sensitive.
Insulin goes away vesicles go back to intercellular pool
Having glut 4 always in membrane = glucose taken up into muscle . Not eating 24/7
blood glucose taken up into the muscle = hypoglycemia
Not eating glut 4 transporters = in intercellular pool waiting for you to eat
Euglycemic range = beta cells stop produce insulin = glut 4 go back to intracellular
Glucose taken up into the sarcolemma = muscle has glycogen synthase and makes
glycogen out of glucose subunits
Insulin two things it does in skeletal muscle 1. Causes glut 4 to translocate and insert
which causes glucose to be uptake 2. Make glucose to glycogen can be used in
mitochondria to make ATP
Milidus = honey. Diabetes mellitus = honey urine
Ex. Humans urinate in woods. 100,000 years ago urinate by tree and saw insects. Reality
is 80% of Na is reabsorbed in PCT. Proteins embedded in PCT called Na glucose
transporters which transport sodium back into bloodstream and at same time take
glucose.
Protein Na glucose transporters has Transporter Max. T-Max = 200 mg/dL
Euglycemic range = 100. Glucose is filtered. 100 mg is filtered and 100% is reabsorbed
because max in 200. So 0 shows up in urine. No honey in this scenario
Blood glucose = 300. Hyperglycemic. Filtered = 300 > reabsorbed from T-max is 200 > so
there is 100 left and it goes all the way along and you urinate along the tree. The ants
want the glucose that has shown up in your urine when your blood glucose is higher
than T-max = glucose in urine.
Glucose in urine Diabetes mellitus
Two major types of diabetes mellitus
1. type 1 = juvenile onset diabetes mellitus= past 16 you are not going to get it =
autoimmune diseases antibodies that come down and destroy beta cells which means
you cant make insulin. The glut 4 are trapped intracellular pool. This is insulin
dependent mellitus. Lack of beta cells destroyed. Type 1 has no problem with receptor

2. type 2 = adults onset diabetes mellitus = non. insulin dependent diabetes mellitus.
Insulin resistant. Problem with insulin receptor. Lipotoxicity = more more obese have
more fat cells. Fat cells will produce tnf alpha and it makes insulin receptor resistant to
insulin

Treat for type 1 is insulin inject. Blood

Biggest fear in type 1 diabetics = insulin shock = too much insulin given = all glut 4 would
insert and they quickly become hypoglycemia. So type I will have carb source incase
they have cns dysfunction. CNS dysfunction = lose social filter
Macrosomic= glucose crosses the placenta and baby grows rapidly and glucose in
amniotic fluid is much higher = fetus because macrosomic
6-25-14 p.2
Type 1 diabetes= insulin deficient = beta cella destroyed
1. Poly urea = multiple urinations. This is diureses
2. poly dipsia = thirst because he is diuresing
3. failure to thrive = measure weight and measure height =
All euglycemic is reabsorbed when filtered. Kid is 12 years old beta cells are destroyed
and no insulin. Blood glucose goes up and 100 glucose is left. Mannitol = blood glucose
can bring water into the nephron. Blood glucose exceed t-max.
Kid is lighter and havent grown = failure to thrive, thirsty all the time, take blood
sample they have type 1 diabetes
He is failing to thrive. In type 1 diabeteics blood glucose exceed t-max starts to diurese
and lose calories in the urine. Eating and losing calories means they have less calories to
put on weight.
Mannitol is osmotic diuretic you inject
Hyperglycemia = osmotic diuresis
Diabulemia = when young girls stop taking who are Type 1 diabetics purposely to lose
weight. Upside to girls is that they fail to thrive and lose weight but they become
hyperglycemic and they are risking endothelium dysfunction
6-26-14 p.1
Lining blood vessel are endothelial cells. Glucose is normally 70-110 mg/dL = does not
damage
Hyperglycemic = high glucose will bind to endothelial cells and can damage them which
is called endothelial dysfunctioning
Glucose can glycosylate or bind to proteins in endothelial cells
Protein inide bloodstream = Hb = made of alpha and beta proteins
High levels of glucose can glycosylate to endothelial cells and can also glycosylate the Hb
which is called glycosylated hemoglobin or Hb A1 C
Physicians measure Hb A1 C. Taking random blood samples = high variability = only snap
shot of what glucose is at time of blood draw.
It would be better to measure Hb A1 C. Red blood cells last 100 days in blood stream.
Looking at amount of glycosylated Hb and anything over 5.5% of Hb being glycosylated =
over last 100 days the blood glucose must have been very very high. Dont have to fast.
Glycosylated Hb tells people what blood glucose was for last 100 days. High glucose can
glycosylate the Hb around when there is high.
Glucose is bound to amino acids in the protein chains (beta and alpha chains) of Hb
Glucose binds because you must have been hyperglycemic over last 100 days
Instead of 1 time snap shot you can get 100 time snapshot of blood glucose with Hb A1 c
test
Treat someone who is type 1 diabetic = take insulin inject
Downside of insulin is that you have to inject it because it is a protein and if you eat it
gets broken down (cant be incapsulated or eaten)
Type 2 diabetic treatments 1. Lost weight, lose fat, TNF alpha levels go down, no more
lipotoxity on insulin receptor, stop being insulin resistant
Type 2 diabetics take two drugs
1. Oral hypoglycemic drugs = dont have to inject
-glipizide = zide tells you that it works on beta cells and causes you to secret more
insulin. Receptor is insulin resistant. To overcome resistance you need to produce more
insulin.
-metformin comes down and inhibits phosphoralse so you dont put so much glucose
out.
Type 2 diabetic = have problems in two places
1. insulin resistant in skeletal muscle > TNF alpha make insulin receptor insulin
receptor > have hard time translocating and inserting glut 4 proteins into sarcolemma =
blood glucose is very very high because it is not being taken up =
2. insulin resistant in liver. glycogen in liver, two enzymes are glycogen synthase (make
alpha 4-1 bonds) and phosphoralase (breaks alpha 4-1 bonds)
Phosphoralase = activated by glucagon
Insulin = activates glycogen synthase
Insulin resistant in liver because insulin receptors have TNF alpha so glycogen synthases
dont work in liver. Phosphoralase works in the liver so they are constantly breaking
down liver glycogen and putting glucose into bloodstream.
No sense giving glipiside to type 1 diabetic because they dont have beta cells
Dont give type 1 diabeteic metformin because you are giving them insulin. Type 1 is not
insulin resistant and you are giving insulin to have balance of enzymes glycogen syn and
phos
Type 2 is insulin resistant you have to slow down phosphoralase so it stops produce too
much glucose
Lipizide > allows more insulin which is useless if you dont have beta cells > glut 4
inserted > glucose taken up
Metformin > inhibit phorphoralase > slow down production of glucose
Both of these lower blood glucose
Type 2 diabetics take oral hypoglycemic drugs
Wildest topic aka my mom would kill me
ADH produced by posterior pit have affect on collecting duct
1 hormone effect on one place does not work like that son!!!
hormonal axis = one hormone being produced to not have an effect but to produce
another hormone.
Reproductive endochronology
Hormones come from anterior pituitary cause production of other hormones are named
Posterior pit = secrete ADH
anterior pit = secrete LH and FSH
FSH= follicle stimulating hormone
LH= leutinizing hormone
LH/FSH have big effects on the female ovary. They cause ovary at different times during
the cycles to produce two other hormones 1. Estrodile 2. Progesterone
Reproduction. Inside lining of uterus is called endometrium.
Estrodile and progesterone have gigantic effects on endometrium lninig of uterus. This
axis is pituitary ovarian uteran axis. Pituatary has no direct effect on uteran. Without
pituitary you dont have fsh and lh. The fsh and lh are needed to cause ovary to produce
estrodile and progesterone which has effect on endometrium.
Look at ovary. There are structure inside the ovary are called primary follicles and they
consist of two parts 1. Inside part is ovum which has genetic material and feterlize to
make humans 2. And one layer of cells that surround around the ovum granulosm
cells
3 mil of primary follicles at 5-6 months of age in utero
1 mil at birth (lost 2 mil)
0.5 mil at 13
200,000 at 21-31
0 at age 55
Menopause = when women runs out of primary follicles
Dont have primary follicles you cant have ovarian cycle and cant get pregnant.
Because you dont have estrodile and progesterone
No primary follicles = decrease in estrodile and progesterone. Cant have ovarian and
uteran cycles
No estrodile and progesterone = osteoporosis, hunch back
Hormone replacement replaces estrodile and progesterone which stopped because
women have no primary follicles
Peri menopaiuse
Menarche = typically we see a cycle that occurs in ovary called ovaraian cycle. There
are three phases of this cycle
1. follicular phase (day 1-13)
2. ovulation on day 14
3. Luteal phase 15-28
On day 28 = flip back to day 1 which is the next ovarian cycle
Ovarian cycle starts typically at age 13
Menarche = 1
st
ovarian cycle at age 13
Menopause = last ovarian cycle
Most women have 40 years of reproductive cycles. Unless they are pregnant the ovarian
cycle should be repeating steps 1 to 3.
Pregnancy = shut off ovarian cycle
Graph
After day 28 = end of ovarian cycle and start over again at day 1

Ovarian cycle drives uteran cycle

Ovarian cycle occurs if not pregnant

1. follicular phase (day 1-13)
Has relation to primary follicles

2. ovulation on day 14

3. Luteal phase of ovarian cycle 15-28

Follicle is not here in this phase
Corpus Luteum= body yellow (made on day 15)
Corpus Albicans = body white (made from luteum)
corpus luteum of menstruation and is eventually transformed into a white scar, the corpus albicans

Day 1 = high conc of follicle stimul hormones being produced from anter pit > goes
down to follicles > on avg 5-10 follicles start to initially grow, ovum doesnt change at all,
they start to get more granulosa cella around them > day 5 one of the follicles has
turned into the graphian follicle and it continues to grow for another 8 days > now it
has tremendous amounts of granulosa cells around it (day 13)

Called follicular phase because primary follicle > graphian follicle and getting enlarged
with more granulosa cells

What caused follicular phase was FSH

Estrodile is produced by granulosa cells

Day 1 = low levels of estrodile produced by ovary because there are no graphian follicles
around

Day 5 = estrodile increase a little because follicle turn into graphian

Between day 5 and day 13 is that estrodile will go up

During follicular phase conc of estrodile increases 10 x, increase level of estrodile has
effect on endometrium and can also feed back onto pituitary by getting into
bloodstream. Anything that feedsback onto anterior pituitary and shuts it off negative
feedback on anterior pit which shuts off LH and FSH.
Anytime something goes back to pit and speed up production positive feedback
secreting LH and FSH.
Estrodile causes negative feedback on the pit at all conc. Except for 10x greater than
normal. Estrodile affect on pit is conc dependent. Low levels of estrodile = shut of pit.
High levels of estrodile = turn on pit (day 13) (shut off the FSH but there is high FSH
production at the beginning? This seems contradictory?
Took 13 days for follicle to develop and get big enough and enough granulosa cells to
produce estrodile at 10x

FSH stays high on day 1-5 because there is low levels of estrodile = causes negative
feedback. Estrodile increases the fsh is going to decrease on day 5. We need high levels
of FSH on day 1-5 because it starts follicle growing into graphian follicle. Graphian
follicle gets bigger and estrodile ^ and FSH now drops estrodile is having negative
feedback on pit

Ens points either women gets pregnant which stops ovarian cycle or start another cycle
and see if she gets preg with next cycle

By day 5 cycle has started because a graphian follicle has started to grow. It is now time
to shut of pit and and not start another cycle and see if she gets pregnant during cycle.
Day 5 estrodile ^ because follicle is enlarging which causes high levels of estrodile >
feedsback on ant pit and shuts it off.

Oral contraceptions how does it prev pregnancy? = increase neg feedback on pit = dont
have follicular phase/develop = cant ovulate and get preg
6-26-14 p.2
Estrodile low because there are only primary follicles which cant make much estrodile
Graphian follicle forms on day 5 and grows rapidly which is called follicular phase of
ovarian cycle. This is happening because estrodile going up rapidly and it is shutting off
the pituitary because the FSH levels have dropped really low.
Want FSH to drop really low because graphian follicle is forming so there is no sense in
starting another cycle until you see one cycle through. Pregnant or not get pregnant.
Dont get pregnant
Negative feedback > By day 13 estrodile lvls increase by 10x which means it now has
become positive feedback > tremendous amounts of LH are release from pituitary
because of positive feedback > LH comes down to ovary > LH does two things 1. Cause
graphian follicle to fuse to wall of ovary 2. Ovum is now lost out of ovary 3. Tube runs
from the uterus all the way up to the ovary and doesnt actually touch it and there are
cilia that sweeps ovulated ovum down into and is called oviduct
One day estrodile is at 10 x which is day 13
LH causes ovulation to occur = day 14
Primary follicle >graphian follicle > negative feedback >estrodile increase > day 13 high
levels of estrodile cause positive feed on pituitary > day 14 pit cause big increase in LH
Only day LH is really high is day 14. What caused LH was positive feedback. Growing
follicle causes estrodile to increase
Mid cycle spike of LH = day 14
Lh does 2 things 1. Causes ovulation to occur 2. Causes leutinization. All granulosa cells
form into corpus luteum
Day 5 = graphian follicle
Day 13= big graphian follicle lots of estrodile
Day 14 = ovulation / big spike
Day 15 = all granulosa cells form into corpus luteum
Starts luteal phase = corpus luteum
Oral contraceptives = causes negative feedback Women dont have LH spike so no
ovulation and no pregnancy
Negative feedback via oral contraception stops lh spike
LH spike = tell you when you are about to ovulate and forms corpus luteum so this is
best time to sample for pregnancy
Women can have problem with pituitary infertility = pit not make enough LH
1. could inject LH = ovulate downside is bring in and inject
2. estrodile inhibits LH production = give estrodile receptor antagonist you dont have
negative feedback so women start to produce LH with a big increase in LH
This is called clomid