Renal Physiology Flashcards
functions of the kidney
- Regulation of extracellular fluid volume (ECF) & blood pressure
- Regulation of osmolarity
- Maintenance of ion balance
- Maintenance of body pH, if the pH is too low or high, the kidney assists the lungs to bring it back to normal
- Excretion of wastes: some waste products – urea broken down proteins, ammonia broken down proteins and nucleic acids, creatinine broken down creatine
- Production of hormones – erythropoietin, vitamin D is also a hormone, travels in the blood and changes body functions, vitamin D becomes fully activated through the kidney
- Gluconeogenesis – produces new glucose from non-carbohydrate sources like proteins or lipids if there isn’t a sufficient supply of glucose from the diet
kidney anatomy
nephron
- functional unit of the kidney
- approx. 1 million nephrons per kidney
composed of 2 major structures:
- renal corpuscle
- where filtration of blood occurs - tubule
- where the filtered fluid is processed
nephron anatomy
cortical nephron
the cortical nephron has it’s renal corpuscle located in the cortex of the kidney closer to the outer section of the cortex
has a short loop of henle which decends into the medulla and acends back into the cortex
the capillaries that surround the nephron are called peritubular capilliaries and reabsorb filtrate
then connects to a connecting duct
cortical nephron make up 80% of all nephrons
juxtamedullary nephron
the juxtamedullary nephron’s renal corpuscle is located in the cortex beside the medulla
the loop of henle decends into the medulla and acends back into the cortex like the cortical nephron, but is longer
the capillaries that surround the nephron looks different and is called the vasa recti which reabsorbs filtrate and help concentrate urine
20% of the nephrons are juxtamedullary nephrons
renal corpuscle
- glomerulus has many pores (fenestrations) in capillary cells (endothelial)
- podocytes wrap around the glomerulus and prevents some filtration
- podocytes are part of Bowman’s capsule, fused with the glomerulus by basal lamina preventing filtration of larger items
renal corpuscle filtration
- glomerulus has small pores
- inbetween is the basal lamina which is a mesh with negatively charged glycoproteins
- attached to the basal lamina are podocytes which have gaps to reduce filtration
- small molecules, ions are filtered
- big proteins can’t fit through the glomerulus pores, but small proteins can, however the small proteins are negatively charged and are repeled by the basal lamina
- glucose and amino acids are filtered, but are reabsorbed very well back to the blood through the peritublar capillaries
blood vessels around nephron
- capillaries can constrict and dilate
nephron processes
filtration
- from blood in glomerulus into Bowman’s space (filtrate)
reabsorption
- from filtrate in the tubule into surrounding capillaries
secretion
- from surrounding capillaries into the filtrate in the tubules
amount filtered (F) - amount reabsorbed (R) + amount secreted (S) = amount of solute excreted (E)
Glomerular filtration
- healthy kidneys produce a large volume of filtrate per day
- ability to produce large volumes of filtrate are due to a number of pressures in the renal corpuscle
- sum of these forces produces is called the NET FILTRATION PRESSURE
- if net filtration pressure is approximately 10 mmHg, then proper filtration can occur
calculating net filtration pressure
PBC - hydrostatic pressure of Bowman’s capsule (into glomerular capillaries)
PGC - hydrostatic pressure of glomerular capillaries (into Bowman’s capsule)
πBC - colloid osmotic pressure of Bowman’s capsule (into Bowman’s capsule) in healthy kidneys proteins dont get filtered, so pressure is zero
πGC - colloid osmotic pressure of glomerular capillaries (into glomerular capillaries)
net filtration pressure = (PGC + πBC) - (PBC + πGC)
net filtration pressure = (55 mmHg + 10 mmHg) - (30 mmHg + 25 mmHg)
net filtration pressure = 5 mmHg
normal net filtration pressure = 10 mmHg
glomerular filtration rate (GFR)
- the amount of fluid filtered in a day by the kidneys
- normal value of 180 L/day (125 mL/min)
Affected by:
Netfiltration pressure
- mostly affected by the renal blood flow and blood pressure (PGC)
Filtration coefficient
- mostly affected by the spaces in between podocytes and integrity (permeability) of the basal lamina
two autoregulatory mechanisms that function to keep GFR mostly constant throughout the day
- Myogenic Response
- Tubuloglomerular Feedback
myogenic response
- afferent arteriole stretches
- stretch sensitive ion channels open
- smooth muscle cells depolarize
- voltage-gated calcium channels in smooth muscle open
- smooth muscle of the afferent arteriole contracts (constricts afferent arteriole)
- blood flow decreases in the glomerulus
tubuloglomerular feedback
- GFR increases
- flow through tubule increases
- flow past macula densa cells increases
- paracrine from macula densa to afferent arteriole
- afferent arteriole constricts
- resistance in afferent arteriole increases
- hydrostatic pressure in glomerulus decreases
- GFR decreases
*if [Na] too high at distal convoluted tubule then that means GFR is too fast so it counters and vice versa
regulation of GFR by blood flow
GFR can be increased or decreased quickly by constricting or dilating the arterioles surrounding the corpuscle
if the afferent arteriole is constricted then the blood flow is decreased which decreases the hydrostatic pressure of the glomerular capillaries and decreases GFR
what would happen if the efferent arteriole is constricted?
since the exit arteriole is constricted, the hydrostatic pressure of glomerular capillaries increases which increase GFR
how to measure GFR?
- excretion = filtration - reabsorption + secretion
- we can determine an individuals GFR by selecting the correct substance to evaluate in their urine
- rate of creatinine excretion from the body is equivalent to the GFR
MEASUREMENTS:
[Creatinine]plasma = 1 mg/L
[Creatinine]urine = 90 mg/L
urine/day = 2 L
CALCULATION:
([Creatinine]urine * urine/day) / [Creatinine]plasma = 180 L/day = GFR
renal handling
- filtered load calculates how much of a substance filters into Bowman’s space in a day
- determined by the concentration of that substance in the blood and individuals GFR
- filtered load X = [X]plasma x GFR
- renal handling is then determining how much of that substance gets into the urine and hypothesizing how that substance was handled
filtered load of glucose
Example glucose
- filtered load X = [X]plasma x GFR
- [glucose]plasma = 1 mg/mL
- GFR = 180 L/day or 125 mL/min
- filtered load glucose = 1 mg/mL x 125 mL/min
- filtered load glucose = 125 glucose excreted per minute
- evaluate glucose in urine and observe no glucose. What happened to all the glucose that filtered?
filtered load
proximal tubule
65% of the total filtrate volume gets reabsorbed
- water, ions (Na, Cl, K), glucose and amino acids
- filtrate volume is reduced, but osmolarity stays the same
- epilethial cell [Na+] = ~5 mM
LUMINAL
sodium/amino acid symporter ([amino acid] is low in cell)
sodium/glucose symporter
sodium/hydrogen exchanger (Na+ enters the cell and H+ is excreted, Angiotensin II changes how fast the exchanger works)
aquaporin I (osmosis)
BASOLATERAL
Na+/K+ ATPase (going against [] gradients, regulated by Angiotensin II)
aquaporin I (osmosis)
aminoacid uniporter (high [] -> low [] into interstitial -> blood)
glucose uniporter (high [] -> low [], facilitated transporter)
PARACELLULAR REABSORPTION
water, potassium and chloride can be absorbed inbetween cells
descending and ascending limbs of henle
20% of the filtrate is reabsorbed from the descending and ascending limb together
descending limb absorbs
- highly permeable to water and water is reabsorbed through osmosis since the medulla is progressively more concentrated the lower (300 mOsm -> 1400 mOsm)
ascending limb absorbs
- ions, impermeable to water (has protein carriers to like Na/K ATPase to keep the luminal membrane cells low on ions, so ions can continue to be reabsorbed)
luminal sodium channel, protein carrier moving sodium, 2 chlorides and a potassium
basolateral sodium/potassium symporter, sodium/potassium ATPase
distal tubule
between dixtal convoluted tubule and collecting duct about 14% of the filtrate is reabsorbed
- sodium, chloride and potassium
- filtrate is about 100 mOsm
distal convoluted tubule
- no aquaporin
- no paracellular absorption
- reabsorbs the same ions as ascending limb of loop of henle, but also calcium
- calcium reabsorption is regulated by PTH
difference between distal tubule and ascending limb of loop of henle
- distal absorbs Ca2+
- distal has no paracellular absorption
- distal is regulated by PTH
collecting duct
Luminal
aquaporin II (regulated by ADH)
Na+ channel (regulated by aldosterone)
K+ channel (K+ is low in lumen and high in cell, regulated by aldosterone)
Basolateral
aquaporin III
Na+/K+ ATPase (regulated by aldosterone)
cells of the tubule
tubule is a single layer of polarized epilethial cells meaning that one side of the cell looks and acts differently than the other side
the lumen side is called luminal membrane (different particles can go through these membranes)
the outer side is called basolateral membrane
reabsorption in the tubules
reabsorption can happen:
inbetween the epilethial cells (paracellular reabsorption)
through the cells (transcellular)
molecules like glucose will be transported through the membrane by an protein transporter embedded on the epilethial cell
secondary active transport
transports substances through membrane against gradient, but doesn’t use ATP
ex) Na+/glucose symporter (transports 2 substances in the same direction), sodium goes along it’s concentration gradient and glucose is against
diabetes mellitus
issue with insulin and increased [glucose] in blood
- > increased level of glucose filtration into Bowman’s space
- > saturates sodium/glucose symporter
- > the nephron cant reabsorb all the glucose
symptoms: glucose in urine (glucosoria), increased urine volume, low glucose absorption means low osmosis of water
what if you drank too little or too much water?
over hydrated: antidiuretic hormone doesn’t affect the collecting duct and aquaporins don’t connect to the membrane of the luminal cells
dehydrated: body releases antidiuretic hormone, mst aquaporins are on the membranes of the luminal cells to reaborb as much water possible
regulation of water balance
- water balance controlled independently of salt balance in humans
- urine volume can be low as 0.4 L/day and high as 25 L/day (avg. 1.5 to 2 L/day)
- most fluid intake comes from beverages and food
- most fluid output is from urine
water levels and blood pressure
- kidneys can control blood pressure through adjusting the blood volume
- if total body water decreases, the extracellular fluid volume is decreased and this causes a decrease in blood pressure
Anti-diuretic hormone (ADH)
AKA: vasopressin
- made by neuroendocrine cells in the hypothalamus
- stored: posterior pituitary
- peptide hormone
- released when triggered by the stimulus
- stimulus: high plasma osmolarity, low ECF volume
how does the body know when you are dehydrated?
there are sensors in the hypothalamus called osmoreceptors
dehydrated: osmoreceptors decrease in volume when surrounding fluid is hyperosmotic and action potentials are fired to release ADH
overhydrated: osmoreceptors increase in volume when surrounding fluid is hypoosmotic and cell stops sending action potentials to release ADH
is the extracellular volume changes then blood pressure is changes
baroreceptors located in the aortic arch and the carotid sinus
if ECF volume decreases, less action potentials sent are sent to the hypothalamus, then baroreceptors -> ADH released
actions of ADH
ADH binds to a receptors on the luminal cell and increases the number of aquaporin II channels on the luminal membrane of the collecting duct
without ADH the aquaporins are taken off the membrane of the luminal cells and water isn’t reabsorbed
diuresis
- increased urine production
- diuretics are substances or scenarios that increase urine productions (alcohol inhibits ADH)
diabetes insipidus
- produce high volume of urine and become dehydrated
- can’t release ADH in their pituitary or can’t respond to ADH
sodium balance
- sodium intake (from food) varies between people and days
- intake as low as 0.05 g/day to as high as 25 g/day
- output mostly through the urine
- output mostly through the urine
sodium levels are linked to ECF volume and therefore blood pressure
hormonal regulation of sodium balance
- two hormonal pathways to control sodium balance
- if sodium levels in the body are low, then:
Renin-Angiotensin-Aldosterone System (RAAS) is activated
Angiotensin II & Aldosterone are released
- if sodium levels are too high, then:
Atrial Natriuretic Peptide (ANP) is released
Renin-Angiotensin-Aldosterone System
Liver makes Angiotensinogen and puts into blood (floats into blood until it comes into contact with Renin)
Renin is secreted by the kidney (juxtaglomerular cells) when sodium levels are low
causes angiotensinogen to become broken into angiotensin I
Angiotensin I floats around blood until it comes into contact with an enzyme called ACE
ACE is found within the capillaries of our vasculature (part of the capillary wall) highest concentration in lung capillaries
ACE breaks angiotensin I into angiotensin II
angiotensin II (hormone)
Renin is the rate limiting step
Angiotensin II
made by: cleavage from angiotensinogen -> angiotensin I -> angiotensin II
properties: peptide hormone
stimulus: Renin release
action: increase sodium reabsorption (in the proximal tubule) by
- increasing activity of Na+/H+ exchanger and Na+/K+ ATPase
- decreasing GFR by constricting afferent and efferent arteriole
- lower flow of filtrate through tubule = more chance for Na+ to be reabsorbed
actions of angiotensin II
binds to luminal cell on the basal lateral membrane which increases the activity of the sodium/hydrogen exchanger in the proximal tubule
this increases sodium reabsorbed
angiotensin II also increases activity of the sodium/potassium ATPase
what happens when GFR is decreased?
the filtrate travels through the proximal tubule a little slower, allowing the sodium/hydrogen exchanger protein carrier to have a higher change to bind to Na+ and reabsorb more Na+ back into the blood
Aldosterone
made by: adrenal gland
properties: steroid hormone
simulus: angiotensin II, high levels of potassium
action: increase sodium reabsorption (in collecting duct)
- increasing the number of sodium and potassium channels (moving more channels to the luminal membrane)
- increasing the activity of Na/K ATPase
- increasing the gene expression of the Na channel - Na/K ATPase
actions of aldosterone
aldosterone binds to receptor in luminal cell and with the binded receptor, goes into the nucleus, finds the DNA sequence for the sodium channel and sodium potassium ATPase and makes more of them.
This causes an increase of Na and K channels on the luminal membrane of the collecting duct
more reabsorption of Na ions, since [Na] is lower in cells
secretion of K ions, since [K] is higher in cells
also, increases activity of Na/K ATPase to bring Na back into blood
what is there is a high level of potassium?
aldosterone is triggered and activates receptors in luminal cells to excrete more potassium
high levels of potassium is deadly
regulation of renin release
- renin released due to low sodium levels
- detection of low sodium by:
low blood pressure - baroreceptors
- in carotid sinus that reflex to juxtaglomerular cells
- at juxtaglomerular cells (these are baroreceptors)
low sodium content - chemoreceptors
- in macula densa cells
atrial natriuretic peptide
made by: cardiac artial cells
properties: peptide hormones
stimulus: high blood pressure
sensors: stretch receptors (in the atria)
action: decrease sodium reabsorption by
- inhibit aldosterone release
- dilate the afferent arteriole to increase GFR
- faster flow through tubule, less chance for Na+ to be reabsorbed
what happens when you eat something salty?
increased Na+ → increased plasma osmolarity
→ osmoreceptors in hypothalamus shrivel and the posterior pituitary releases ADH
→ water moves from cells to the ECF from increased osmolarity in plasma → increased blood volume/ blood pressure → baroreceptors fire more → release of ANP
ADH is still released, but less because the body puts osmolarity (300 mOsm) over blood pressure
→ more water absorbed and also more ANP released because more blood pressure
→ ANP causes Na+ to be excreted
cardiovascular responses to increased blood volume
increased blood volume/pressure **want to maintain Mean Arterial Pressure**
→ humoral response → ANP released → vasodilation of blood vessels
→ neural response → decreased sympathetic activity → vasodilation
→ both decrease total peripheral resistance (decreases Mean Arterial Pressure)
how do the kidneys maintain acid/base balance
acidic - pH less than 7 → acidosis
- kidneys will excrete H+ and conserve HCO3-
alkaline - pH greater than 7 → alkalosis
mechanisms to perform acid/base balance:
- secrete/excrete H+
- secrete/excrete HCO3-
- conserve filtered HCO3-
CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
the proximal tubule is important for the conservation of filtered bicarbonate
intercalated cells of the collecting duct fine-tune proton or bicarbonate secretion
convserving bicarbonate
**proximal tubule**
bicarbonate reactions with H+ to form CO2 + H2O in the filtrate
then the CO2 + H2O is reabsorbed
once in the cell an enzyme carbonic anhydrase, CO2 + H2O is formed back into HCO3- + H+
bicarbonate is then reabsorbed into the blood
type A and B intercalated cells
type A - secretes protons into the lumen by proton ATPase (blood is acidic)
type B - secrete HCO3- by bicarbonate, chloride (Cl-) exchangers (blood is alkaline)
how do the lungs maintain acid/base balance?
CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
increase rate of breathing, hyperventilation (decrease CO2) → (basic) alkalosis
decreasing rate of breathing, hypoventilation (increase CO2) → (acidic) acidosis
