API_Exam 3 Flashcards
what are the function of the kidneys
-excretion of waste: urea, cratinine
-excretion of foreign chemicals: drugs, toxins
-secretion/metabolism/excretion of hormones: erthryopoetic facotr
-regulation: acid base balance
-gluconeogensis: from amino acids
-controls arterial pressure
-regulation of water and electrolyte secretion
what are some waste products the kidneys excrete
urea
creatinine
bilirubin
hydrogen
what are some foreign chemicals the kidney excretes
drugs
toxins
pesticides
food additives
what are some hormones the kidneys secrete/metabolize/excrete
renal erythropoietin factor
vitamin D3
renin
what do kidneys perform gluconeogenesis with
amino acids
what does excess BUN indicated
kidney disease
what is a normal BUN level
20
what is a byproduct of proteins being broken down
urea
what is 100% excreted by the kidneys
creatinine
what type of metabolism is creatinine metabolized from
muscle metabolism
what type of metabolism is urea metabolized from
protein metabolism
what type of metabolism is uric acid metabolized from
nucleic acid metabolism
what type of metabolism is bilirubin metabolized from
hemoglobin metabolism
what is the byproduct of ammonia
is all of urea excreted in urine
what is byproduct of RBC breakdown
bilirubin
how long does a RBC live for
120 days
what is RBC broken down into
heme and globin
then into bilirubin
is bilirubin conjugated or nonconjugated when it is first formed
non conjugated
where is bilirubin conjugated
liver
after bilirubin is conjugated where does it go
into bile which then goes into the bowel
what makes urine yellow
bilirubin
once liver detoxifies blood, where does part of the waste go
kidneys to be excreted
what drug class is commonly excreted through kidney
antibiotics
what is a common issue with halothane
nephrotoxic and HEPATOtoxic
what hormones are produced in the kidney
vitamin D3
renal erythropoetic factor
renin
what hormones are metabolized and excreted in the kidney
most peptide hormones such as insulin, angiotensin II
what hormone stimulates RBC production from kidney
renal erythropoetic factor
what causes pink puffer COPD
polycythemia from low O2 levels in blood which stimulates kidney to make more RBCs
what allows absorption of Ca in digestive tract and puts calcium into bone
vitamin D3
how does erythropoietin stimulate RBC production
stimulates erythrocyte production in the bone marrow
what ion metabolism is vitamin D3 important in
phosphate and calcium
what are the only means of excreting non-volatile acids
kidneys
how does the kidney regulate the body fluid acidity
bicarbonate
what is the carbonic acid formula
h2o + co2 <—> H2CO3 <—> HCO3 + H
what is carbonic acid
H2CO3
how is most CO2 carried in the blood to the lungs
bicarbonate
what actually drives respiration
H+ ions around pons in CSF
where does H+ have to be formed to be able to drive respiration
CSF from CO2
what does low and high bicarb mean
low= metabolic acidosis (high H+)
high= metabolic alkalosis (low H+)
why does high CO2 cause acidosis
creates H+ through carbonic acid equation thus a build up of excessive H+ ions
how is CO2 breathed off if carried through body as bicarb
combines with H+ to make carbonic acid which gets broken down into CO2 and water
what does the liver use for gluconeogenesis
glycogen
what does the kidney use for gluconeogenesis
amino acids
how does the kidney regulate arterial pressure
raas
prostaglandins (inflammatory)
bradykinin (inflammatory
controls extracellular fluid volume
raas, bradykinin, and prostaglandins are the _________________ function of the kidney
endocrine
what electrolytes balance the kidneys
Na
K
H+
Ca
Phos
Mg
with increased intake of Na, how many days does it take the kidneys to balance the Na level
4-6 dyas
8 days on the graph
what part of the kidney has no glomeruli
medulla
what surrounds on the kidney and provide protection
capsule of the kidney
where are nephrons found in the kidney
renal pyramids
are nephrons located in the medulla and the cortex?
YES in both
what is the flow of urine
nephron (renal pyramid)
papilla
minor calyx
major calyx
renal pelvis
ureter
what is in between the renal pyramids
renal columns
where is hydronephrosis found
underneath the renal capsule
what surrounds the kidney
fat
what is normal GFR per min and per day
125 ml/min
180L/day
how many times per day is plasma volume filtered
60x
does albumin or other proteins get filtered
NO
what is the filtration fraction equation
GFR / renal plasma flow= 0.2 (.20 x plasma filtered)
what is role of renal columns
extension of renal cortex that gives stability to kidney
what drives renal filtration
renal blood supply
what do renal arteries/veins branch out into
interlobar arteries and veins
what do interlobar arteries/veins branch into
arcuate arteries/veins
when does interlobar turn into arcuate
at turn of renal pyramid at the top
what branches off arcuates
interlobular
how many glomerulus does a nephron have
1
what does glomerulus look like
bundle of vessels
what encases the glomerulus
bowmans capsule
what is the filtration apparatus of the kidney
glomerulus
what brings blood to the glomerulus and what artery does it come from
afferent arteriole brings it in
branches off interlobular or arcuate artery
what takes blood away from the glomerulus
efferent arteriole
why does the glomerulus coil
increases surface area
what attaches to bowman’s capsule carrying filtration content away
proximal tubule
what does proximal tubule turn into
descending loop of henle
finish the sequence–
proximal tubule-loop of henle–
distal tubule
where does collecting duct terminate
renal papilla
what does efferent arteries wrap around
loop of henle
when does efferent arteriole attach to arcuate vein
after it wraps around loop of henle
what is ascending loop of henle attached to
descending loop and distal tubule
what is descending loop of henle between
proximal tubule and ascending loop
what does the distal tubule feed into
juxtaglomerular apparatus
what does juxtaglomerular apparatus dump into
connecting duct which dumps into collecting duct which dumps into papilla
do nephrons replace themselves
no
1.2 million nephrons per kidney
lose 1% per year after 40
what is glomerulus always in and what is loop of henle always in
g=cortex
LoH= medulla
which loop of henle has important function with water
-juxtamedullary- concentrate urine (pull water into back system)
what are portions of ascending/descending loop of henle
thick and thin
what are two types of nephrons
cortical and juxtamedullary
where are all glomeruli vs all loop of henle
glomeruli= cortex
loop of henle= medulla
which nephron has shorter loop of henle
cortical
which nephron has longer loop of henle
juxtamedullary
should there be protein or glucose in the urine
NO
what are systems of peripheral nervous system
ANS
Somatic
what is the receptor and neurotransmitter of somatic motor
Ach
nicotinic
what is the receptor and neurotransmitter of sns
epi/norepi- ,
alpha 1,
alpha 2,
beta 1,
beta, 2,
beta 3,
role of alpha and beta receptors
alpha 1= constrict
alpha 2= inhibit constriction
beta 1= increases HR
beta 2= dilationin lung smooth muscle, dilate muscle vessels
beta 3= neutralizer
role of nicotinic vs muscarinic
N= muscular
M= organs/glands
how many neurons does a response have to go through
2 neurons
what is the receptor and neurotransmitter of pns
ach
nicotinic= n1, n2
muscarinic= m1, m2, m3
does sns have long or short pre ganglionic
short
does sns have long or short post ganglionic
long
does pns have long or short pre ganglionic
long
does pns have long or short post ganglionic
short
what are muscarinic receptors usually on
glands and organs
what is neurotransmitter for preganglionic in pns or sns
acetylecholine
by default what are all receptors in 1st synapse in pns or sns
nicotinic
what are neurotransmitters and receptors post ganglionic for pns (second synapse)
cholinergic (nicotinic/muscarinic)
Ach
what are neurotransmitters and receptors post ganglionic for sns (second synapse)
adrenergic receptors (alpha/beta)
epi/norepi
what nicotinic receptor is post ganglionic in somatic nerve
N1
what is the bladder muscle
detrusor muscle
what are receptor sites on bladder and nerves that synpase with them
M3- PNS- Pelvic nerve
Beta 3- SNS- hypogastric
what is the external sphincter in
urogenital diaphragm
what separates internal from external sphincter in male
prostate
what receptor is on internal sphincter
alpha 1 -SNS- Hypogastric
what receptor is on external sphincter
somatic- pudenal
what muscle is voluntarily controlled in urethra
external sphincter
do women have an internal sphincter
Yes, but does not have constricting ability like males do
just a thickening into neck of bladder
is male internal sphincter voluntarily controlled
NO
what is the sensory nerve attached to the bladder and how does it sense things
pelvic- baroreceptors- senses stretch
what regions do nerves come out of that innervate bladder and urethral muscles
sacral and thoracic region
how does empty bladder signaling work
baroreceptors signal slowly which causes beta 3 to neutralize contraction and alpha 1 to constrict internal sphincter for urine to collect- m3 is also inhibited in bladder to stop contraction and nicotinic signals external sphincter to constrict
what receptor neutralizes contraction of the bladder
Beta 3
full bladder signaling
stretched bladder activates baroreceptors on pelvic sensory nerve which goes to pons (micturition center) which signals m3 (detrusor muscle to constrict), beta 3 is inhibited to bladder can constrict, alpha 1 is inhibited so internal sphincter can relax, and pudendal signals external sphincter to relax and let urine out
what nerve does sensation to urinate come from and where does it go to in the brain
pelvic sensory- pons
when does voiding reflex happen
after initiation- to completely empty bladder
how does voiding reflex work
baroreceptors keep signaling via pelvic nerve to have pelvic motor nerve to to keep detrusor muscle (m3) to constrict
what are the 4 mechanisms of urine formation
filtration
reabsorption
secretion
excretion
filtration, reabsorption, excretion of water
180
179
1
filtration
reabsoprtion
excretion
of glucose
180
180
0
filtration, reabsorption, excretion of creatinine
1.8
0
1.8
is any creatinine reabsorbed
NO
what is equation for excretion
excretion=filteration-reabsorption + secretion
how much renal plasma is filtered
20%
what is normal Renal blood flow, GFR and reabsorption
RBF= 625 ml/min
GFR= 125ml/min
reabsorption= 124ml/min
what is gfr in ml/min and l/day
125 ml/min and 180/day
should albumin/amino acids/rbc be in urine
No should be filtered
who is more likely to develop proteinuria
diabetic patients
what are tiny holes inside endothelium of glomerulus that filter
fenestrations
what has negatively charged heparin sulfates that repels proteins and amino acids back into circulation
basement membrane
what is found in epithelium that has smaller holes than fenestrations
split pores
what is a split pore in
podocytes
when basement membrane is damaged, what happens
proteinuria
what is not a very accurate proteinuria test
dipstick
what is the equation for net filtration pressure
net filtration pressure = glomerular hydrostatic pressure- bowman’s capsule pressure- glomerular oncotic pressure
what is normal net filtration pressure
10
(60-32-18)
what pressure push opposite of glomerular hydrostatic pressure
glomerular colloid osmotic and bowman’s capsule pressure
how does glomerular colloid osmotic pressure cause pressure
draws water/proteins back into glomerulus against glomerular hydrostatic pressure
how does bowman’s capsule cause pressure
funneled to pushes pressure upward
does net filtration rate = GFR
NO
what is normal GFR
125ml/min
what is kf a measure of
measure of surface area and permeability
-more surface area= bigger glomerulus=more filtering
what is kf
filtration coefficient
what diseases cause reduced kf and GFR
HTN
DM
Obesity
glomerulonephritis
what does cast noted mean in UA
tubular necrosis
does bowman’s capsule pressure regulate gfr
no- changes because of ghp and gcop
what has most significant/important effect on gfr
GHP
what can influence bchp beside gcop and ghp
obstruction- stones, bph (urine backs all the up into bowman’s pressure which increases pressure)
what influences glomerular hydrostatic pressure
arterial pressure, afferent/efferent arteriole resistance
what does increased afferent arteriole resistance do to ghp
decreased ghp thus decreasing gfr
decreased flow
when efferent arteriole resistance is increased what happens
fluid backs up, increasing ghp and gfr
where does angiotensin II constrict
efferent arteriole- backs up blood so ghp and gfr increase
what does increased ghp cause
increased GFR
what does kidney need a lot of oxygen/atp for
tubular reabsorption of sodium (active transport)
can you decrease renal blood flow and increase gfr
yes- constriction of efferent arterioles by angiotensin II
kidney consumes o2 at _____________ rate of brain but receives ______________ times the blood flow
twice
7
how much cardiac output goes to kidney
22%
what does sns do to gfr
vasoconstriction= increased resistance, decreased renal blood flow so decreased gfr
what does angiotensin II do to arterioles
increases efferent arteriole resistance, which backs blood up in glomerulus
overall what does angiotensin II to do gfr
holds at normal- since angiotensin II is indirectly released by renin (which is only released with low blood pressure) the gfr would already be low. So angiotensin II raises gfr but gfr was already low to begin with so it brings it to normal
how do prostaglandins/nitric oxide affect gfr
decreases resistance= increased blood flow= increased gfr/renal blood flow
how does ibuprofen affect kidneys
blocks prostaglandins- so afferent and efferent arterioles are not as dilate= decreased gfr
what is auto-regulator to stop complete vasoconstriction
endothelial derived nitric oxide
nitric oxide
vasodilator
makes o2 more soluble
how does endothelin impact gfr
decreases it by vasoconstriction (increased resistance)
what are autoregulation control of gfr/renal blood flow
myogenic mechanism- increase bp=increase calcium=increased contraction=increased increased resistance= decreased flow/gfr
macula densa feedback=
angiotensin II=
myogenic autoregulation
increase bp=increase calcium=increased contraction=increased increased resistance= decreased flow/gfr
where is macula densa
juxtaglomerular apparatus
what makes renin
juxtaglomerular cells
what cells line distal tubule
macula densa- come close to afferent and efferent arterioles
what does macula densa measure
sodium and chloride in distal tubule (which is urine)
when sodium chloride is decreased in macula densa, what happens
decreases afferent arterial resistance so more blood gets into glomerulus to filter more sodium/chloride out
what does low gfr cause sodium to be in distal tubule, low or high
low
more gets absorbed
how does angiotensis II affect GFR
decreased gfr= low macula densa nacl= increases renin= angiotensin II= increases efferent arteriole resistance= raises GFR
where does angiotensin II have effect on kidney
efferent arterioles
other factors that influence GFR
increase= fever, STEROIDS, hyperglycemia, high diet protein
decrease= age, low diet protein
what are the four mechanisms of urine formation
filtration
reabsorption
secretion
excretion
what kind of cells do aldosterone antagonists and sodium channel blockers work on
principal cells
what location do aldosterone antagonists and sodium channel blockers work
collecting duct
what is the equation for excretion
filtration - reabsorption + secretion
what is the equation for resborption
filtration- excretion
what is the equation for secretion
excretion - filtration
what is excretion
removing wastes and drugs
what is the process of filtered components going back into body
reabsorption
what is the process of stuff coming from body going into lumen to get excreted
secretion
is most of water reabsorbed or excreted from body
reabsorbed
where does stuff that get filtered go to for excretion
lumen
where does the lumen lead to
collecting duct
what does the connecting tubule connect
glomerulus and collecting duct
what is the filtered material in the lumen
urine
what are the ways molecules get reabsorbed into the body
active transport,
passive transport (diffusion),
osmosis
paracellular/transcellular paths
what is between the peritbular capillary and lumen
tubular cells
what do molecules have to pass through to be reabsorbed in the kidney
tubular cells
where do transporter mechanisms occur for reabsorption
tubular cells
what ions travel in paracellular path
Ca
Mg
what ions travel in the transcellular path
Na
K
Cl
what drives diffusion
concentration or electrical gradient
how can sodium move against concentration/electrical gradient
active transport
what are the 3 methods of transport sodium is reabsorbed in the kidney
diffusion
active transport
osmotic pressure
does secondary active transport use ATP
NO
gets energy from Na to move molecules
how does secondary active transport work
It takes advantage of a gradient that has already provided energy.
what happens to gfr with hyperglycemia and hyperproteinemia
increases
how is glucose/amino acids reabsorbed in the kidney
secondary active transport
what is it called when a substance reaches its maximum rate of tubular transport in ALL nephrons
transport maximum
when the transport maximum is reached for all nephrons, what happens when more substance comes through
NOT reabsorbed- excreted
what is it called when transport maximum is exceeded in SOME nephrons
threshold
t or f- individual nephrons may have lower transport maximum’s than others
True
what are some examples of substances that have a transport maximum
glucose
amino acids
phosphate
sulfate
what happens to lumen potential when sodium is reabsorbed
negative potential increases (since sodium is positive)
what happens to chloride and urea when sodium and water are reabsorbed in proximal tubule
increased concentration–>passive reabsorption due to concentration gradient
how much of all sodium is reabsorbed in proximal tubule
65%
what is reabsorbed in proximal tubule
sodium
chloride
potassium
bicarb
water
glucose
amino acids
where is most of sodium reabsorbed in kidney
proximal tubule
what is excreted out of proximal tubule
hydrogen
organic acids
bases
what are the byproducts of metabolism and are most toxic
hydrogen
organic acids
bases
what are kidneys key in balancing
balance fluid through sodium renetion
acid-base balance through h+ and bicarb
what is the thin descending loop of henle very permeable to
water 20%
which nephron is responsible for concentration of urine
juxtamedullary nephrons
which nephron absorbs most of water
juxtamedullary nephrons
where is 25% of sodium reabsorbed
thick ascending loop of henle
what is reabsorbed in the thick ascending loop of henle
sodium
chloride
potassium
bicarb
calcium
magnesium
what is the ratio of molecules for the transporter in the thick ascending loop of henle
1 sodium, 2 chloride, 1 potassium
is the proximal tubule isosmotic or hyposmotic
isomotic
is the thick ascending loop of henle isosomtic or hyposmotic
hyposmotic
what does the thick ascending loop of henle secrete
Hydrogen
what is the thick ascending loop of henle NOT premeable to
H2O
where is h2o not permealbe to in the kidney
thick ascending loop of henle, early distal tubule
when sodium-hydrogen exchanger in thick ascending loop of henle moves sodium into tubular cells, what does it initiate
triple transporter to move into tubular cell
what is the pathway of sodium when reabsorbed in the kidney
tubular lumen- tubular cell- renal interstitial fluid
where is 5% of sodium reabsorbed
distal convoluted tubule
what pump is responsible for sodium being reabsorbed in early distal tubule
sodium chloride transporter
in the sodium chloride pump on the early distal convoluted tubule, does chloride come into lumen or go into renal interstitial fluid
from tubular lumen into tubular cell then into renal interstitial fluid
what are the two types of transporters/exchangers on the early distal tubule and where are they located
sodium potassium exchanger- between renal interstitial fluid and tubular cells
sodium/chloride transporter- between tubular cells and tubular lumen
where do thiazide diuretics work
early distal tubule- on sodium chloride transporter
what does thiazide diuretic inhibit
sodium chloride transporter- so sodium stays in lumen and draws water into lumen for excretion
in early distal tubule, where does sodium and chloride travel from and to
from tubular lumen to tubular cell and then to renal interstitial fluid
what structure has a similar functional to the thick ascending loop of henle
early distal tubule
is the early distal tubule permeable to water
NO
where are macula densa located
early distal tubule
where does active reabsorption of sodium, chloride, calcium, and magnesium occur
early distal tubule
what is actively reabsorbed in early distal tubule
sodium
chloride
potassium
magesium
what is called the diluting segment
early distal tubule
what is the macula densa responsible for
Na Cl balancing
what part of tubule is not very permeable to urea
early and late distal tubule/collecting tubule
what does permemability of water in late distal tubule/collecting tubule depend on
ADH
where are principle cells located
late distal tubule/collecting tubule
another name for ADH
vasopressin
where are type a intercalated cells located
late distal tubule/collecting tubule
what do intercalated cells play a role in
acid base balance
in the principal cell, when sodium potassium exchanger puts sodium into renal interstitial fluid (blood), what does that cause
sodium leaky channel brings in sodium from tubular lumen
what is renal interstitial fluid
blood
in the principal cell, when sodium potassium exchanger puts potassium from renal interstitial fluid in the cell, what does that cause
potassium leaky channel to take potassium from inside cell and put into tubular lumen
what does the principal cell work primarily off of
sodium potassium transporter
leaky channels- k and na
what are some aldosterone antagonists
spironolactone, eplerenone
what are some sodium channel blockers
amiloride, triamterene
how do aldosterone antagonists work
bind sodium potassium transporter between renal interstitial fluid and tubular cell, so sodium isn’t pulled from cell into interstitial fluid, so then sodium leaky channel doesn’t bring sodium from tubular lumen into cell. Sodium stays in tubular lumen and draws water into tubular lumen
what cell does aldosterone have greatest impact on
principal cell
what does aldosterone stimulate
sodium potassium exchanger- so more sodium is reabsorbed
what are the potassium sparing diuretic classes
aldosterone antagonists- sprinolactone
sodium channel blockers- amiloride
where do sodium channel blockers work
blocks leaky channels on principal cells (which are in late distal tubule/collecting tubule)
what do the type a intercalated cells help with
acidosis- help to decrease h and save bicarb
what do the type b intercalated cells help with
alkalosis- increase h and decrease bicarb
where are the intercalated cells a-b found
late distal tubule/collecting tubule
where does adh act
medullar collecting duct
what is reabsorbed in medullary collecting duct
sodium
chloride
water
urea
bicarb
what is secreted into medullary collecting duct
hydrogen
what is peritubular capillary reabsorption
pressure needed to move from interstitial fluid into capillary
when is aldosterone produced
low bp, or low extracellular fluid
how does aldosterone work
acts on sodium potassium exchanger to increase sodium moving from principal cell into interstitial fluid
what cell does aldosterone work in
principal cell
what are the factors that increase aldosterone secretion
angiotensin II
increased potassium
adrenocorticotrophic hormone (acth)
where is aldosterone secreted from
adrenal cortex
what are factors that decrease aldosterone secretion
atrial natriuretic factor
increased na concentration
why does increased potassium increase aldosterone
too high potassium= sodium-potassium exchanger isn’t pumping enough potassium out- so it releases to pump more potassium out and more sodium in
what is the permissive role of acth
release aldosterone
what does high atrial natriuretic factor mean
too much fluid
what is the opposite of renin
atrial natriuretic factor
what does angiotensin II stimulate the release of
aldosterone
where does angiontensin II directly increase sodium reabsorption
distal, and collecting tubules
what does angiotensin II do to the efferent arterioles
constricts them
what happens when angiotensin II constricts efferent arterioles
-decreased peritubular capillary hydrostatic pressure
-increases filtration fraction which increases peritubular colloid osmotic pressure
what is the important thing to remember with angiotensin II
vasoconstriction
what are the pumps that angiotensin II affects on tubular cells to increase sodium reabsorption
sodium-potassium-exchanger
sodium-hydrogen-exchanger
sodium-bicarb-transporter
what do ace inhibitors, arbs and renin inhibitors decrease
decreases:
aldosterone
sodium reabsorption
efferent arteriolar resistance
what is a renin inhibitor example
aliskirin
where is ADH secreted from
posterior pituitary gland
what does adh increase permeability to and where does it do this
water- distal and collecting tubules
what is an important controller of extracellular fluid osmolarity
ADH
what hormone allows for differential control of water and solute secretion
ADH
what is the most important renal action of adh
increase water permeability in distal tubule/collecting tubule
what does adh attach to on tubular cell
V2 receptor
when adh binds to v2 receptor, what happens
increases formation of cAMP
what does camp activate after creation by adh
protein kinase
what does protein kinase stimulate prodction of
protein phosphorylation
what does protein phosphorylation stimulate to move to lumen side
aquaporin 2
where does aquaporin 2 attach to
wall of tubular cell on the tubular lumen side
where are aquaporin 3 and 4 found
tubular cell wall on interstitial fluid side
what is the gateway for water to flow from tubular lumen into interstitial fluid
aquaporins
what does anp increase excretion of
Na
what are the 3 things anp inhibits
sodium reabsorption
renin release
aldosterone formation
what impact does anp have on gfr
increases
how does diabetes cause diuresis
osmosis
water follows glucose
does an increase or decrease of unreabsorbed solutes in tubules decrease water reabsorption
increase
what tests measure plasma concentration of waste products
BUN
creatinine
what measures urine concentrating ability
urine specific gravity (1-2)
what measures albumin excretion
microalbuminuria
what describes rate at which substances are removed from plasma
clearance
what is the volume of plasma completely cleared of a substance per min by kidney
renal clearance
clearances of different substances
glucose- 0
albumin- 0
sodium- 0.9
urea- 70
inulin- 125
creatinine- 140
pah-600
what should renal clearance be equal to
GFR
what does efferent arteriole turn into
vasa recta- which wraps around loop of henle
what is between the bowman’s capsule and the descending loop of henle
proximal convoluted tubule
what is the between the ascending loop of henle and the collecting duct
distal convoluted tubule
what gets reabsorbed in proximal convoluted tubule
sodium
chloride
potassium
glucose
amino acids
urea
water
bicarb
where do juxtaglomerular nephrons lie
bottom of cortex right near medulla
which nephrons concentrate urine
juxtamedullary nephrons
what is main thing loop of henle reabsorbs
water
what is reabsorbed at thick ascending loop of henle
na, cl, k, bicarb, ca, mag
where is the sodium potassium exchanger located in the nephron
collecting duct
where is the sodium chloride transporter found in nephron
distal convoluted tubule
how does sodium potassium exchanger work in dct
sodium is moved from dct to blood
potassium is moved from blood to dct
what is reabsorbed from late distal convoluted tubule
sodium
chloride
potassium
bicarb
water (adh)
what is reabsorbed from collecting duct
sodium
chloride
bicarb
urea
water (adh)
what are parts of nephron where things are primarily secreted
proximal convoluted tubule
how is creatine removed from body
urine
what is the byproduct of breakdown of muscle and protein
creatinine
what is secreted into proximal convoluted tubule (lumen)
hydrogen, organic acids, bases, creatinine, drugs
what is secreted into distal convoluted tubule
hydrogen
potassium
where is most (65%) of sodium reabsorbed from in kidney
proximal convoluted tubule
where is a high concentration of sodium bicarb reabsorbed from
proximal convoluted tubule
what does the triple transporter transport and where does it do so
thick ascending loop of henle
Sodium
2 chloride
potassium
where is 25% of sodium reabsorbed from in kidney
thick ascending loop of henle
what is reabsorbed in the early distal convoluted tubule
sodium
chloride
calcium
magesium
where is 5% of sodium reabsorbed from
distal convoluted tubule
in the sodium potassium exchanger in the collecting duct, what is also secreted into collect duct with potassium
hydrogen
where is 1-2% of sodium reabsorbed from
collecting duct
where does osmotic diuretics work
proximal convoluted tubule
what transporter do loop diuretics work on
triple transporter
what ions are transported paracellularly from lumen to blood
Ca
Mg
what channel does sodium channel blocking diuretics block
sodium leaky channel- so sodium can’t get out of lumen and into cell
where does aldosterone antagonist have effect and on what transporter
collecting duct- on sodium potassium exchanger
what does aldosterone increase the number of
sodium potassium exchanger- so more sodium gets out of cell into blood
how do lungs play a role in hydrogen regulation
increased hydrogen= increased ventilation to increase co2 exhalation
how do kidneys regulate hydrogen ions
secrete H
reabsorb bicarb
generates new bicarb
what is the most important extracellular fluid buffer
bicarb
what kind of buffers are phsophate and ammonia
renal tubular buffers
what is the intracellular buffer
proteins (Hgb)
what does phosphate and hydrogen form
phosphuric acid
what does ammonia and hydrogen form
ammonium
what does proteins and hydrogen form
hydrogen-hemoglobin
why does hydrogen have to be buffered instead of excreted
fixed amount of hydrogen that can be directly excreted from kidneys
what is the most important kidney hydrogen buffer system
bicarb
what is pk
concentration of hydrogen at a certain ph
what is a normal pk level
6.1- this is when bicarb and co2 are balanced
what enzyme is necessary for the carbonic acid equation
carbonic anhydrase
what systems closely regulates the bicarbonate buffer system
lungs and kidneys
what is the most important buffer in extracellular fluid
bicarbonate buffer system
how much co2 is carried in the blood as bicarbonate
70%
what happens to alveolar ventilation when there is an increase in hydrogen ions
increases ventilation
does increased co2 lead to increased or decreased aciditiy
increased
what can reabsorb, produce new, filter, or excrete bicarb
kidney
what are some non volatile acid the kidneys eliminate
sulfuric acid, phosphoric acid
what does the kidneys conserve or excrete depending on body needs
bicarb
if the body is in an alkalotic state, what will the kidney excrete MORE of
bicarb
if the body is an acidosis state, what will kidney excrete LESS of
bicarb
where is most of bicarbonate reabsorbed in nephron (85%)
proximal convoluted tubule
for each bicarbonate reabsorbed, there must be a _________ secreted
hydrogen
where is 10% of bicarbonate reabsorbed in
ascending thick portion of loop of henle
where is 5% of bicarbonate reabsorbed
late-distal-tubule
when pco2 is increased, such as in respiratory acidosis, what happens to hydrogen secretion
increases
when extracellular hydrogen increases, what happens to h+ secretion
increases
when tubular fluid buffers and increased, what happens to H+ secretion
increases
what factors increase h+ secretion and hco3 reabsorption
increased: pco2, hydrogen, aldosterone, agiotensin II
decreased: bicarb, extracellular fluid volume, potassium
when the body is increasing h+ secretion and hco3 reabsorption, what state is the body in
acidosis
how do aldosterone and angiotensin II increase h+ secretion and bicarb rebsorption
increase sodium uptake which increases h+ secretion via sodium-hydrogen exchanger
what conditions in body drive angiotensin II and aldosterone release
low bp,
low extracellular fluid
how does hypokalemia lead to increase hydrogen secretion
on intercalated cell, there is a hydrogen potassium exchanger, so when there is low potassium, body tries to reabsorb more potassium, so then more hydrogen gets secreted out
what happens to hydrogen secretion, bicarb reabsorption, and bicarb production during acidosis
H= increased secretion
bicarb= increased reabsorption
bicarb= increase production
what happens to hydrogen secretion, bicarb reabsorption, and bicarb in urine during alkalosis
h= decreased secretion
bicarb= decreased reabsorption
bicarb= increased in urine
can enough free hydrogen be removed by only secretion/excretion
no- needs buffers
what is the minimum urine ph
4.5,
any more acidic will damage tissues
t or f- kidney is not limited to amount of free hydrogen that can be excreted
false
what is NH3
ammonia
what is NH4
ammonium
what is made from metabolism of amino acids in the liver
glutamine
is ammonium or phosphate buffer system more important
ammoinum
makes more bicarb
is NH3 or NH4 more permeable
NH3
what is the goal ratio of hco3 to co2
20 : 1
normal bicarb range
22-26
normal PaCO2
35-45
what is majority of cations
Na
what are anions
Cl
bicarb
t or f- cations and anions are usually equal in the body
true
what are unmeasured anions
proteins
phosphates
sulfate
lactate
what are unmeasured cations
K
Mg
Ca
normal anion gap
8-16 mEq/L
what causes abnormal anion gap
dka
ethylene glycol poisoning
what are normal cation and anion levels
142 Cation
132 Anion
when there is an increase in anion gap, what is being thrown off
the unmeasurable anions or cation
what are preventions of blood loss
-vascular constriction
-Formation of a platelet plug
-Formation of a blood clot
-Healing of vascular damage (clot remodeling/repair)
-fibrinolysis
what are the key events in hemostasis
- severed vessel
- platelets agglutinate
- fibrin appears
- fibrin clot forms
- clot retraction occurs
what causes vascular constriction
Myogenic spasm
Local autocoid factors from damaged tissues and platelets
Nervous reflexes
Smaller vessels: thromboxane A2 released by platelets
characteristics of platelets
Released by fragmentation of megakaryocytes
normal level: 150–300,000 per µL
Half-life in blood of 8–12 days
what are platelet funtions
Contractile capabilities
-Actin, myosin, thrombosthenin (contractile protein)
Residual ER and Golgi
-Synthesize enzymes, prostaglandins, fibrin-stabilizing factor, PDGF, store Ca++
Mitochondria/enzymes
-Produce ATP, ADP
what are the platelet membranes
surface glycoprotein
membrane phospholipids
what is the function of surface glycoproteins
Repels intact endothelium
Adheres to injured endothelium and exposed collagen
what is the function of membrane phospholipids on platelets
activate blood clotting
what is the process of formation of the platelet plug
-contact with damaged endothelium
-adhere to collagen and vWF
-other platelets accumulate, adhere, and contract, form plug, initiate clotting
what does contact with damaged endothelium result in
-assume irregular forms
-endothelium contracts and release granules (ADP and thromboxane A2)
what can very low platelets present like
petechiae
bleeding gums
in severe vascular trauma, how long for clot formation
15-20 seconds
how quickly can an occlusive clot form
within 3-6 min unless very large vascular defect
how long does it take for clot retraction
20-60 min
what happens within 1-2 weeks of clot formation
-invasion by fibroblasts
-organization into fibrous tissue
what are the effector proteins for clotting
prothrombin
fibrinogen
characteristics of prothrombin
-α2 globulin,
-15 mg/dL in plasma
-Vitamin K-dependent synthesis in liver
-Cleaved by PT activator to thrombin
characteristics of fibrinogen
-100–700 mg/dL in plasma
-Synthesized in the liver (acute phase reactant)
-Usually intravascular; can extravasate with increased vascular permeability
what cleaves 4 small peptides from fibrinogen
thrombin
fibrin monomer-> spontaneous polymerization
what helps to form clot reticulum
long fibrin fibers
characteristics of fibrin stabilizing factor
In plasma and released from platelets
Activated by thrombin
Covalent cross-linking of fibrin monomers and adjacent fibrin fibers
what is bound to platelets and trapped in the clot
thrombin
what system does thrombin and clot formation work on
positive feedback
___ produces more prothrombin activator by acting on other clotting factors
thrombin
what is generated at the periphery of the clot
additional fibrin monomers and polymers
when does clot retraction begin
within 20-60 min
what binds to the damaged vessel wall
fibrin
what causes clot contraction
actin, myosin and thrombosthenin
describe clot retraction
clot tightens expressing serum and closes the vascular defect
what are the two clotting pathways
Extrinsic pathway—Trauma to vessel wall and adjacent tissues
Intrinsic pathway—Trauma to the blood or exposure of the blood to collagen
what factor activates the extrinsic pathway
tissue factor
what factor activates the intrinsic factor
exposure to factor XII
exposure of platelets to collagen
what is the time to clot for extrinsic pathway
<15 sec
how long for clotting in intrinsic pathway
1-6min
what prevents clotting
-smoothness of endothelial surface
mucopolysaccharide coating (glycocalyx) repels platelets and clotting factors
thrombomodulin
protein C
how does mucopolysaccharide coating (glycocalyx) prevent clotting
it repels platelets and clotting factors
how does thrombomodulin prevent clotting
Thrombomodulin bound to endothelium binds (competes for) thrombin
how does activated protein C prevent clots
Thrombin-thrombomodulin activates Protein C→ inactivates factors V and VIII
how does thrombin become localized to the clot
Fibrin fibers bind 85–90% of thrombin and localize it to the clot
how does antithrombin III work in the negative feedback system
Antithrombin III combines with the remainder and inactivates it over 12–20 minutes.
what is the charge of heparin
highly negative
MOA of heparin
Binds anti-thrombin III and increases its effectiveness 100–1000-fold
Heparin-antithrombin III removes free thrombin from the blood almost instantly.
Also removes XIIa, XIa, Xa, and IXa
where can heparin be found in the body
Mast cells,
basophils particularly abundant in pericapillary regions of liver and lung
what causes clot lysis
Plasminogen is trapped in the clot.
Over several days, injured tissues release tissue plasminogen activator (tPA).
Plasminogen is activated to plasmin, a protease resembling trypsin.
Plasmin digests fibrin fibers and several other clotting factors.
Often results in reopening repaired small blood vessels
what are some causes of excessive bleeding
Hepatocellular disease
Vitamin K deficiency
Hemophilia
Low platelet count (thrombocytopenia)
what is essential to carboxylate glutamic acid and 5 clotting factors
vitamin K
what clotting factors are affected by Vit K deficiency
prothrombin
factor VII
factor IX
factor X
protein C
what happens in vitamin K deficiency
In this process vitamin K is oxidized and inactivated.
Vitamin K epoxide reductase complex 1 (VKOR c1) reduces vitamin K and reactivates it.
where is vitamin K produced
intestines by gut bacteria
what can cause fat malabsorption and vitamin K deficiency
lack of bile production
lack of bile delivery
what can be done for patients with liver or biliary disease before surgery
In patients with liver or biliary disease, vitamin K can be injected 4–8 hours before surgery.
what can also lead to vit K deficiency
malabsorption of fats
vitamin K is fat soluble
hemophilia A
Deficiency of factor VIII
85% of hemophilia cases
1/10,000 males
Both genes are on the X chromosome (males only get one copy).
hemophilia B
Deficiency of factor IX
15% of cases
how does hemophilia effect bleeding
both A and B impair the intrinsic pathway
clinically present: bleeding after minor trauma
what factor deficiency cause hemophilia A
factor VIII
Deficiency of the small component causes hemophilia A.
→ Treat bleeding with factor VIII replacement.
what factor deficiency causes vWF disease
factor VIII large component
Deficiency of the large component causes von Willebrand disease (resembles decreased platelet function).
what are the two components of factor VIII deficiency
Large: MW >106
Small: MW ~230,000
characteristics of thrombocytopenia
Low numbers of platelets
Bleeding from small venules or capillaries
Petechaiae, thrombocytopenic purpura
Often idiopathic
< 50,000 platelets/µL—usually modest bleeding
< 10,000 platelets/µL—life-threatening
how do you treat thrombocytopenia
platelet infusion
infusion is effective for 1-4 days each time
what is a thrombus
an abnormal clot
what is an embolus
a thrombus that floats/gets dislodged
what can cause emboli/thrombi
Endothelial roughening (e.g., atherosclerosis)
Slow flow (e.g., prolonged air travel)
what is the treatment for thrombus/embolus
tPA
embolectomy
where does pulmonary embolus usually originate from
deep leg veins
what is DIC
disseminated intravascular coagulation
Occurs in the setting of massive tissue damage or sepsis
Wide-spread coagulation in small vessels
Manifested as bleeding from multiple sites because of depletion of clotting factors
what are some anticoagulants
heparin
coumarins
how does heparin work
Binds, potentiates antithrombin III
Works rapidly, generally used acutely
how do coumarins work
Inhibit VKOR c1
Deplete active vitamin K → deplete active prothrombin, factors VII, IX, X
Slower acting (days); used chronically
how do you treat over anticoagulation of coumarins
treat with FFP and vitamin K
what are calcium chelators and what are they used in
citrate, EDTA
used in blood collection and blood storage
bleeding time coag test
normal 1-6 min
reflects platelet function
clotting time coag test
-invert tube every 30 sec
normal 6-10 min
not reproducible, not generally used
Prothrombin time coag test
normal 12 sec
assess extrinsic and common pathways
Add excess calcium and tissue factor to oxylated blood, measure time to clot
tissue factor batches have to be standardized (activity expressed as “international sensitivity index” (ISI)
INR coag test
“international normalized ratio”
Normal: 0.9 - 1.3
therapeutic range 2.0-3.0
INR= PT test / PT normal
how do you test for other clotting factors
Mix the patient’s plasma with a large excess of all needed components except the factor being tested.
Compare time to coagulation with that for pooled plasma of healthy volunteers.
how is hemostasis acheived
(1) vascular constriction,
(2) formation of a platelet plug,
(3) formation of a blood clot as a result of blood coagulation,
(4) eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.
what does trauma to vessel cause
smooth muscle contract in vessel
results from
(1) local myogenic spasm,
(2) local autacoid factors from the traumatized tissues
and blood platelets,
(3) nervous reflexes
how is the nervous reflex initiated in the vessel contraction
initiated by pain nerve impulses or other sensory impulses that originate from the traumatized vessel or nearby tissues
myogenic contraction of the vessel
initiated by direct damage to the vascular wall.
the smaller vessels, the platelets are responsible for much of the vasoconstriction
by releasing a vasoconstrictor substance, thromboxane A2.
The more severely a vessel is traumatized, the greater the ______
the degree of vascular spasm
where are platelets formed
bone marrow from megakaryocytes
factor I
fibrinogen
factor II
prothrombin
factor 3
tissue factor
factor 4
calcium
factor 5
proaccelerin
“labile factor”
factor VII
serum prothrombin conversion accelerator (SPCA)
proconvertin
stable factor
factor VIII
antihemophilic factor (AHF)
antihemophilic globulin (AHG)
antihemophilic factor A
Factor IX
plasma thromboplastin component (PTC)
Christmas factor
antihemolitic factor B
Factor X
stuart prower factor
factor XI
plasma thromboplastin antecedent (PTA)
antihemolitic factor C
Factor XII
Hageman Factor
Factor XIII
fibrin stabilizing factor
prekallikrein
fletcher factor
High molecular weight kininogen
Fitzgerald factor
HMWK
What is required by the liver for normal activation of prothrombin and many other clotting factors
Vitamin K
Where is fibrinogen formed
In the liver
What is the reticulum of the clot
Many fibrin monomer molecules that polymerize within seconds into long fibrin fibers make up the reticulum of the blood clor
What does plasmin digest
Fibrin fibers
Fibrinogen
Factor V
Factor VIII
Factor XII
Vitamin K adds a ___ to _____ on which 5 clotting factors
Carboxylic group to glutamic acid
Prothrombin
Factor VII
Factor 9
Factor X
Protein C
name the surface glycoproteins on platelets
glycoprotein Ia
glycoprotein IIb/ IIIa
what in in the granules released when platelets come into contact with damaged endothelium
ADP
Serotonin
thromboxane A2
where is vWF produced
endothelium
ADP + thromboxane A2 does what
activates glycoproteins so that platelets stick together
what is PDGF
platelet derived growth factor
aids in the repair of muscle and connective tissue during clot retraction
what is VEGF
vascular endothelial growth factor
aids in repair of vessels and endothelium during clot retraction
what initiates/activates factor 12
negative charge on the platelet plug
what does protein C do
binds to and inactivates factor 5 and 8
what does Nitric oxide do
nitric oxide binds with PGI2 to inactivate glycoproteins on platelets
what factors are affected by heparin
XIIa,
XIa
Xa
IXa
IIa
what does tpa do
converts plasminogen to plasmin which “eats” up fibrin
what is byproduct of plasmin destroying fibrin
fibrinogen
d dimer
What substances are the kidneys the only means of excretion
Sulfuric acid and phosphoric acid generated by metabolism of proteins
Micturition reflex steps
- Progressive and rapid increase of pressure
- Period of sustained pressure
- Return of the pressure to the basal tone of the bladder
What is GFR determined by
Balance of hydrostatic and colloid osmotic forces
Capillary filtration coefficient
Filtration fraction=
GFR / renal plasma flow
What are the three layers of the glomerular capillary membrane
Endothelium
Basement membrane
Epithelial cells (podocytes)
What factors influence the glomerular capillary colloid osmotic
Arterial plasma colloid pressure
Filtration fraction
What is filtration fraction
The fraction of plasma filtered by the glomerular capillaries
What does increase in filtration fraction result in
Raised glomerular colloid osmotic pressure
Glomerular hydrostatic pressure is determined by what
Arterial pressure
Afferent arteriolar resistance
Efferent arteriolar resistance
The greater the concentration of Na in the proximal tubules, the
Greater it’s reabsorption rate
The slower the flow rate of tubular fluid the
Greater the percentage of Na that can be reabsorbed from the proximal tubules
What is the macula densa
A group of closely packed epithelial cells that is part of the juxtaglomerular complex and provides feedback control of GFR and blood flow in the nephron
Aldosterone site of action
Collecting tubule and duct
major site of action is in the principal cells of cortical collecting tubule
Aldosterone effect on tubular reabsorption
Increase NaCl and H2O reabsorption
Increase K secretion
Increase hydrogen ion secretion
Angiotensin II site of action
Proximal tubule
Thick ascending LOH
Collecting tubule
AngiotensinII effects on tubular reabsorption
Increase NaCl and H2O reabsorption
Increase hydrogen secretion
ADH site of action
Distal tubule
Collecting tubule/duct
ADH effect on tubule reabsorption
Increases water reabsorption
Atrial natriuretic peptide site of action
Distal tubule
Collecting tubule/duct
Atrial natriuretic peptide effect on tubule reabsorption
Decrease NaCl reabsorption
Parathyroid hormone site of action
Proximal tubule
Thick ascending LOH
Distal tubule
Parathyroid hormone effects on tubular reabsorption
Decreases PO4 reabsorption
Increases Ca reabsorption
What are hormones that regulate tubular reabsorption
Aldosterone
Angiotensin II
ADH
ANP
Parathyroid hormone
What the most important stimuli for aldosterone
Increased K concentration
Increased angiotensin II levels
What’s the body’s most powerful sodium retaining hormone
Angiotensin II
What are the two variables that influence sodium and water excretion
Rate of glomerular filtration
Tubular reabsorption
Where does angiotensin II constrict
Efferent arterioles and increases GFR
Filtration, reabsorption and excretion of sodium
25,560
25,410
150
What activates protein C
Thrombin-thrombomodulin
how does parathyroid hormone increase Ca reabsorption
-increases Ca reabsorption in kidneys
-increases Ca reabsorption in gut
-decreases phosphate reabsorption
-increases intracellular Ca
MOH of ADH in distal and collecting tubules
what pumps does angiotensin II work on
ATPase pump
Na Bicarb pump
Na hydrogen ion pump
Na Channel blockers work on what
leaky Na channels in late distal/collecting tubules
what do aldosterone antagonists work on
Na K atpase pump in late distal and cortical collecting tubules
what are the three steps to Na Reabsorption?
- diffuses because on concentration and electrical from lumen into tubular cells
- Na transported against electrical gradient by ATP
- Na and H2O move from ICF to capillaries by osmotic pressure
what symporter does loop diuretics work on
tri sympoter in thick ascending loop of henle
1 Na, 2 Cl, 1 K
what symporter does thiazide work on
Na Cl symporter in early distal tubule
important points on early distal tubule
-not permeable to water
-active reabsorption of Na, Cl, K, Mg
-contains macula densa
-5% of filtered load NaCl reabsorbed
trace starting from thick ascending LOH
early distal tubule
late distal tubule
connecting tubule
collecting tubule
collecting duct
where does ADH work
late/distal tubule and collecting tubule
