renal Flashcards
what are the main functions of the kidneys?
- regulation of water, Na/K balance and blood pH
- removal of metabolic from the blood and their excretion in the urine
- removal of foreign chemicals from the blood
- hormone/enzyme production
what types of hormones are produced by the kidneys?
erythropoietin
renin
1,25 dihydroxyvitamin D3
what is the function of erythropoietin?
production of RBC
What is Renin
enzyme that controls the formation of angiotensin and influence sodium balance.
what is the function of vitamin d in the kidneys
influences calcium balance, precursor enters the kidneys to be activated
how big are each kidney?
size of fist, 150g
where are the kidneys located?
Behind the peritoneum on either side of the vertebral column against the posterior abdominal wall
what is the outer layer of the kidneys?
renal cortex
what is the inner layer of the kidneys?
renal medulla
how is the renal medulla divided into?
pyramids
what do the renal pyramides converge into?
renal pelvis
where is the renal A relative to the renal vein?
A is above V
what is the first arterial branch of the renal a
interlobar A
how does the interlobar A travel?
turns 90 degrees and artery, turns back 90 degrees
what does the interlobar A branch off into?
into the interlobular
what branch gives blood to the nepheron
afferent arteriole
how many nepherons are contained in each kidnet
~1 million
what is the nepheron composed of?
tubule renal corpuscule (glomerulus and bowman’s capsule)
how does the nephron get blood supply?
afferent arteriole –> glomerulus –> efferent arteriole
where is the bowman’s spae located?
around the glomerulus in the bowman’s casule
in what does urine travel through?
through the tubule
how does urine travel through the tubule
proximal tubule in the cortex will then enter the medulla in the loop of henle, will leave the medulla and will come in contact with the arterioles and enter the distal convoluted tubule which will merge with other nephrons into a collecting duct system found in both the cortex and the medulla.
where is renin formed in the kidneys?
Juxtaglomerular apparatus
what are the holes found in the glomerular capillary wall?
Fenestrae
what covers the holes of the glomerular capillary wall?
podocytes
what is the function of the glomerular capillary wall?
acts as a filtration barrier
where are the fenestrae located?
in the endothelial cells of the glomerular capillary wall
how does blood circulate through the glomerular capillary wall (pathway)
capillar lumen > endothelial cells > glomerular basement membrane > visceral glomerular epithelial cells
what is another name given to the glomerular epithelial cells?
podocytes
what is the function of the glomerulus?
filter blood to produce urin
what is another name given to the tubule epithelial cells?
peritubular capillaries
what are the 3 basic processes of urine formation?
- glomerular filtration
- tubular secretion
- tubular reabsorption
what is the function of glomerular filtration?
filtration of plasma from the glomerular capillaries into Bowman’s space
what is glomerular filtrate ?
fluid found in bowman’s space which is cell free but contains substances or plasma except for large proteins
what is the function of tubular secretion?
peritubular capillaries to tubules blood becomes urine
what happens are the glomerular filtrate passes through the tubules?
As the glomerular filtrate passes through the tubules, its composition is altered by movements of substances.
what does tubuar reabsorption invole
reabsorbin urine into the blood by the tubule to the peritubular capillaries
what is the amount of urine excreted?
its the sum of the amount filtered + amount secreted - amount reabsorbed
where does everything get filtered?
at the glomerular capillaries.
how is glucose filtered?
100% reabsorbed
how is sodium and water filtered?
reabsorbed to some extent and then the rest is secreted
how is PAH filtered?
what isnt filtered continues in the blood and gets fully secreted
what does the rate of filtration, reabsorption and secretion depend on?
physiological state of the body such as (When the body content of a substance goes above or below normal, homeostatic mechanisms can regulate the substance’s bodily balance by changing these rates)
what gets filtered in the bowman’s space of the glomerulus?
filtrate
what type of molecules are freely filtered?
Water and low-molecular weight substances
what type of molecules are not freely filtered?
Not freely filtered: cells, proteins (i.e. albumin, globulins), protein-bound substances (i.e. 1/2 of Ca ion, fatty acids)
what are the main forces involved in filtration?
PGC = glomerular capillary blood pressure is the favoring filtration force. PBS = fluid pressure in bowman’s space, an opposing filtration force. piGC = Oncotic pressure = osmotic force due to proteins in plasma, the other opposing filtration force.
what is the net glomerular fitration pressure?
PGC – PBS – piGC
~16 mm Hg
what is the Glomerular filtration rate (GFR)?
the volume of fluid filtered from the glomeruli into
Bowman’s space per unit time
how if GFR regulated?
net filtration pressure (only one accounted for in this class but also memebrane permeabiluty and surface area availible for filtration)
what is the normal GRF in a standard patient?
180L/day
how often is the entire plasma of a person filtered daily?
over 50 times
how can GRF be decreased?
- Constrict the afferent arteriole, thus less blood flowing per time, decreasing PGC.
important) - Dilate efferent arteriole, thus decreasing the PGC
how can GRF be increased?
- Constrict Efferent arteriole, slowing down the blood flow away from glomeruli, increasing PGC. 2. Dilate afferent arteriole, more blood arrives at the same time, increasing PGC.
what is the filtered load?
total amount of any freely filtered substance per unit time. GFR x plasma concentration of the substance (if freely filtered)
what happens if filtered load > amount excreted?
net reabsorption has occurred
what happens if filtered load < amount excreted?
net secretion has occurred
where does reabsorption take place?
from the tubular lumen to the peritubular capillary
what keeps the tubular epithelial cells together?
tight junctions
what faces the tubular lumen?
the tubular membrane
what faces the peritubular capillaries
basolateral membrane
how do parcellular solvents travel?
go between the cells from tubular lumen to peritubular capillary
how do transcellular solvents travel?
go through the cells from tubular lumen to peritubular capillary
what has the highest percentage of reabsorption?
Water, sodium and glucose
why are urine and potassium not fully reabsorbed?
urine is a waste product (44% reabsorbed)
potassium if found in large doses may be toxic (86.4%)
is reabsorption of waste products complete?
no, relatively incomplete
is reabsorption of most useful plasma components complete?
yes
is the regulation of glucose and AA regulated?
no
is the reabsorption of water and inorganic ions regulated?
yes
are the filtered loads big or small?
they are enormous
through what process does reabsorption occur?
diffusion and mediated trabsort
how does reabsorption by diffusion function/?
ften across the tight junctions connecting the tubular epithelial cells. Secondary to sodium diffusion.
what happens when urea is reabsorbed through the proximal tubules?
- ->In the proximal tubule, water reabsorption occurs and urea follows water.
- ->Urea concentration in the tubular fluid becomes higher.
- ->Urea diffuses into the interstitial fluid and peritubular capillaries.
how does reabsorption by mediated transport function?
occurs across tubular cells Requires the participation of transport proteins in the plasma membrane of tubular cells.
what is reabsorption by mediated transport usually coupled with?
Na+ reabsorption
how does mediated transport function?
Na/K-atpase pumps Na from the cell into the capillary and K from the capillary to the cell. Low Na in the cell drives Na+ in the lumen of the cell
Na/glucose cotransporter allows for Na and Glucose to drive into the cell
Na/AAs channels allow Na to drive in with AAs
Glucose/AAs channels let glucose and AAs diffuse out into the ISF and eventually back into the capillaries
what is the transport maximum attained?
When the membrane transport proteins become saturated causing the tubule to be unable to reabsorb anymore
how is Tm exceeded in diatbetic patients?
uncontrolled diabetes= high [glucose] in plasama, where filtered load > capacity of tubules to reabsorb glucose causing glucourea
what is moved by tubular secretions?
moves substances from peritubular capillaries into the tubular lumen
what is tubular secretion mediated by?
diffusion and transcellular mediated transport.
what are the most important substances secreted by the tubules?
H+ and K+
what is tubular secretion generally coupled with?
eabsorption of sodium
what is the function of the proximal tubule?
reabsorbs most of this filtered water and solutes. It is also a major site of secretion for various solutes, except K+.
what is the function of Henle’s loop of the tubules?
eabsorbs relatively large quantities of the major ions (less water).
what is the function of DCT/CD of the tubules?
Fine-tuning. Determines the final amounts excreted in the urine by adjusting the rates of reabsorption, and, in a few cases, secretion.
where does most homeostatic controls take place int he tubuules
DCT/CD
what is clearence?
the volume of plasma from which that substance is completely removed (“cleared”) by the kidneys per unit time.
what does clearence dependent on?
Mass of S excreted in urine per unit time/
Plasma concentration of S (Ps)
what equation is used to calculate clearence?
Mass of S excreted per unit time = Urine concentration of S (Us) x Urine volume per unit time (V).
Cs = UsV / Ps
what is inulin?
polysaccharide that gets freely filtered at the glomerulus but isn’t reabsorbed, secreted or metabolized by the tubule
what is the clearance of inulin equal to?
is equal to the volume of plasma originally filtered (GFR).
what is the most accurate marker for GFR?
INULIN CLEARENCE
Why is inulin clearence not ideal?
requires to keep patient on IV over a certain time period
what is creatinine?
Creatinine is a waste product produced by muscle.
is creatinine filtered and reabsorbed by glomerulus?
It is filtered freely at glomerulus and is NOT reabsorbed.
is creatinine metabolized by the tubule?
no
what is an advantage of measuring creatinine clearence?
naturally found in the body hence doesnt need to be administered to patient
how to calculate creatinine clearence?
Urine concentration of creatinine (UCr)*Urine volume (V)/Plasma concentration of creatinine (Pcr)
what happens when clearence > GFR
secreted at the tubule
what happens when clearence < GFR
its reabsorbed at the tubule
how can partial reabsorption or total absorption be described as?
clearence < GFR
What needs to be maintained to sustain normal BP and life?
total body balance of Na and water
how do we intake water?
food, liquids and metabolism
how does water leave our bodies?
insensible losses of the skin and lungs
urine
feces
how do we intake Na
through food
how does the body excrete sodium?
sweat
feces
mostly urine
how much can sodium and water intake vary daily?
h20 can vary from 0.4 L/day to 25 L/day
sodium chloride output can vary from 0.05 g/day to 25 g/day
is sodium and water secreted?
no, both are freely filtered and ~99% gets reabsorbed
where does the majority of sodium and water reabsorption occur?
2/3 occurs in the proximal tibule
where does the hormonal control of reabsorption of sodium and water take place?
DCT and CD
where does Na reabsorption take place?
tubular segments except for he descending thin limb of Henle’s loop
where does H20 reabsorption take place?
occurs via diffusion
what is H20 reabsorption dependent on?
on Na reabsorption
where does Na active reabsorption take place?
cortical collecting duct
how does Na/K atpase function in Na reabsorption?
allows for Na to be reabsorbed into the tubular lumen
what does Na diffuse through in the cortical collecting duct to reach the tubular lumen?
sodium channels
what is the role of Na/K-atpase on the basolateral membrane?
pumps sodium out of the cell and keeps the intracellular concentration of sodium low
what happens to sodium on the apical (lumenal) side of the membrane
Na moves downhill from the tubular lumen into the tubular epithelial cells
what is different about each tubular segment in regards to Na reabsorption
function under different mechanisms in different segments
what happens when sodium intake goes uo?
urinary sodium excretion goes up
what happens when sodium intake goes down?
urinary sodium excretion goes down
what is the body’s major extracellular solute?
Na
what do changes in the body’s sodium result in?
similar changes in the Body’s ECF volume
what is the total body sodium sensed by?
baroreceptors in the cardiovascular system.
what is the total body sodium sensed as?
sensed as intravascular fillin (amount of plasma in the blood vessels)
is plasma concentration of sodium a marker for total body sodium?
no
what does Pna reflect?
relative relationship of the total body Na and water
what is the amount of sodium excreted?
sodium filtered-sodium reabsorbed
what regulates sodium excretion
GFR (minor) sodium reabsorption (major)
what happens when the body loses a high amount of sodium or water?
1) decrease plasma volume
- decrease venous pressure which gets sensed by the baroreceptor reflex
- increases activity of the renal sympathetic nerves
2) decreased venous return thus the heart doesnt which devreases atrial pressure, EDV, SV and thus the heart cannot pump enough blood which triggers baroreceptor reflex to increase activity of the sympathetic nerves
what happens when the baroreceptor reflex to increase activtiy of the sympathetic nerves
Causes an increased constriction of afferent arterioles and then a decrease of the net GF pressure which decreases GFR thus decrease is Na and H20 excretion
what is the main hormone responsible for controling Na reabsorption?
aldosterone
aldosterone stimulates Na reabsorption where?
stimulates reabsorption in DCT and CD
how much of the filtered load is excreted when no aldosterone?
~2% thus ~35g NaCl
how much of the filtered load is excreted when high aldosterone?
~0% of filtered load gets excreted
reabsorption of Na in CCD is under what control?
hormonal control
where does Na absorption take place? in what proportions
Proximal = 67%, TAL = 25%, DT = 4%, CCD = 3%, IMCD = 1%
what gets activated/upregulated by aldosterone?
the activity of ATPases and Na channels
what system is responsible for the regulation of aldosterone secretions?
Renin angiotensin system
where does angiotensinogen begin?
in the liver and gets secreted into the blood
how is angiotensinogen converted once its in the blood? by which hormone?
angiotensin 1 by renin
what organ secretes renin?
kidneys
what is angiotensin 1 converted into? by what enzyme?
angiotensin 2 by angiotensin converting enzyme
where does angiotensin 2 go and what does it stimulate?
enters the adrenal cortex and stimulates aldosterone secretion
what may increase secretion of aldosterone?
increase plasma K or ACTH
what can inhibit secretion of aldosterone?
ANP
what are the juxtaglomerular cells wound tightly around?
afferent arteriole
what innervates the juxtaglomerular cells?
sympathetic nerves
what can be stimulated by the sympathetic nerves?
renin secretion
how can the juxtaglomerular cells be activated other than by innervation?
low afferent arteriole tension allows blood to pass through and thus can be sensed by the cells
what does the ascendinh part of the loop of henle come in touch with?
the glomerula
what is the name of the cells that touch the sude of the tube of glomerula?
macula densa
what can be detected by macula densa
when there is not enough Na and send signal to the juxtaglomerular cells
what are some other factors that may influence renal na excretion?
- arterial natriuretic peptide
- BP
what is ANP?
peptide hormone secreted by cells in the cardiac atria.
what does ANP act on?
acts on the tubules to inhibit sodium reabsorption thus increases GFR
What stimulates ANP secretion?
Increased total body sodium
what does increased blood pressure cause?
increased sodium excretion
what is osmolarity?
total solute concentration of a solution,
what is a hypoosmotic solution?
solution where the total solute concentration is less than that of the ECF (300 mOsm)
what is a isoosmotic solution?
solution where the total solute concentration is equal to that of normal ECF (300 mOsm)
what is a hyperosmotic solution?
having total solute concentration greater than that of normal ECF (300 mOsm)
what are the 3 crucial aspects of water balance?
- Water is freely filtered but ~99% is reabsorbed, no secretion.
- The majority of water reabsorption (~2/3) occurs in the proximal tubule.
- But the major hormonal control of reabsorption occurs in the CD.
what does water reabsorption depend on?
Na absorption
where is water reabsorbed into from the tubular lumen?
into the ISF across the epithelial cells
what happens to the osmolarity in the lumen and interstitium as Na is reabsorbed in the tubular lumen?
The local osmolarity in the lumen decreases (water conc becomes high), while the local osmolarity in the interstitium increases.
what does the difference in the tubular lumen and interstitium
auses net diffusion of water from the lumen into the interstitial fluid.
how does water move into the interstitium
via tubular cells’ plasma membranes
via tight junctions
through what mechanism does the interstitum move
bulk flow in peritubular capillaries
what happens in the when the water intake is small
the kidney reabsorbs more water
what happens in the when the water intake is large
the kidney reabsorbs less water
where does dynamic regulation of water take place?
in the CD
what are the 2 critical components of dynamic regulation of water?
- High osmolarity of the medullary interstitium.
2. Permeability of CD to water (regulated by vasopressin)
what mechanisms maintains high osmolarity in the medulla of the kidneys?
countercurrent multiplier system
how much urine can the kidney’s concentrate
up to 1400 mOsm/L.
where does urinary concentration take place?.
takes place as tubular fluid flows through the medullary collecting
ducts.
what does urinary concentration depend on?
the hyperosmolarity of the interstitial fluid
what happens to water in the presence of vasopressin
water diffuses out of the ducts into the interstitial fluid in the medulla
what happens to the osmolarity of the medulla as it passes through Henle’s loop
hyperosmotic
what is the function of the ascending limb of the countercurrent multiplier system?
reabsorbs NaCl but is impermeable to water
what happens to the osmolarities of the ascending limb of the countercurrent multiplier system
since Na is absorbed but not water, the fluid Osm goes from 300 to 200 and the ISF increases to 400 mOsm
what is the function of the descending limb of the countercurrent multiplier system?
Doesn’t reabsorb NaCl, permeable to water
what happens to the osmolarities of the descending limb of the countercurrent multiplier system
ISF=400 mOsm but water moves until it equilibrates and tubule fluid=400 mOsm
how does the fluid move in the from the tubule, descending and ascending limb?
Fresh fluid comes from proximal (300), fluid in descending limb moves down, turns and starts to go up (400), fluid in in the ascending limb continues up and starts to leave (200)
what are the main steps of the countercurrent multiplier system?
Step 1 NaCl is reabsorbed, changing the osmolarities
Step 2 water diffuses again to keep up with the change in interstitial osmolarity.
what is equilibrated by the descending limb
The fluid surrounding it is equilibrated with the descending limb
what are the blood vessels surround the medulla?
vasa recta
what does the hair-pin loop minimize?
minimizes excessive loss of solute from the interstitium
what factors contribute to medulla hyperosmolarity?
NaCl, urea
what does water reabsorptiin in the tubules depend on?
depends on the water permeability of the tubules
what does permeabilty of the epithelium depend on?
depends on the tubular segment
what is the permeability of water in the proximal tubule?
high permeability
what does permeability largely depend on?
ermeability largely depends on the presence of water channels
what is the key hormone that controls water permeability in the MCD, CD?
vasopressin
what is vasopressin?
Peptide hormone, also called anti-diuretic hormone (ADH)
what produces vasopressin?
posterior pituituary
what type of receptors interact with vasopressin
Couples to G-coupled Protein CReceptors V1 (smooth muscle) and V2 (kidney)
how does vasopressin function?
Vasopressin stimulates the insertion of aquaporins in the luminal membrane of the collecting duct cells and increases the water permeability.
what happens to collecting ducts when vasopressin is present?
When vasopressin is present, collecting ducts become permeable to water
what happens to collecting ducts when vasopressin is absent?
water diuresis
what my cause diabetes insipudus?
malfunction of the vasopressin system
what happens to fluid in the presence of vasopressin by the time it reaches the CCD?
Fluid is hypoosmolar by the time it gets to the cortical collecting duct. If there is vasopressin, It starts to get reabsorbed.
what happens to the fluid when it enters the medullary collecting duct?
nterstitial fluid becomes more and more hyperosmotic, until it reaches the max (1400).
what happens to fluid in the absence of vasopressin in the CD?
Fluid stays hypoosmotic through the whole collecting duct (50).
what rate is regulated by vasopressin?
Water excretion is mainly regulated by the rate of water reabsorption from the tubules
what regulates vasopressin secretion?
- Osmoreceptor control (most important)
2. Baroreceptor control (less sensitive)
what process happens in osmoreceptor control?
excess water consumption > body fluid osmolarity decreases > supresses firing of hypothalamic osmoreceptors > decrease in vasopressin secretion > decrease of vasopressin in plasma > decrease tubular permeability to water >decrease in water reabsorption > increase inwaterexcretion.
what process happens in baroreceptor control?
plasma volume decreases > decrease in venous, atrial and arterial pressures > reflexes mediated by cardiovascular baroreceptors activated > increase in vasopressin secretion > increase in vasopressin in plasma > increase in tubular permeability to water > increase in water reabsorption > decrease in water excretion
what factors cause us to feel thirsty?
- dry mouth, throat
- metering of water intake by GI tract
- decrease of plasma volume detected by
baroreceptors - high plasma osmolarity detected by
osmoreceptors
