Renal physiology Flashcards
what does renal mean?
Renal refers to the term kidney
what is the kidneys main function?
Removal of waste from the blood and urine
what do kidneys regulate?
-Blood volume and pressure
*[water] and fluid volume
**inorganic ion composition
-Acid / base balance
what do kidneys excrete?
-Urea, uric acid, creatinine, bilirubin
-foreign chemicals (drugs, food additives, pesticides)
what do kidneys synthesize?
Glucose through gluconeogenesis
-synthesis of glucose from non-carb sources
https://youtu.be/ydhr0QAyxYg?si=oPWH9CkrKcg2L0n8
what do kidneys secrete?
Hormones / enzymes
-erythropoietin
-1,25-dihydroxy vit D
-renin
what percent of the body’s weight is water?
60%
what makes up the bodily fluid compartments?
intracellular fluid - 40%
extracellular fluid - 20%
-plasma
-interstitial fluid (larger)
what is the volume of total body water?
42L
what ions are in greater [ ] in the ECF compared to ICF?
140mM Na+ , 100mM Cl-, 24mM HCO3-
what ions are in greater [ ] in the ICF compared to ECF?
150mM K+, 12mM Mg+, 40mM Pi, 4mM protein
inside the ECF where is protein found? why?
in the plasma
- plasma proteins are too large to cross the capillary membrane into the interstitial fluid
what factors play a role in diffusion across the the fluid compartments?
-distance
-chemical properties of cell membrane
-chemical nature of molecules (polar vs non-polar)
-channels and transporters
what does osmolarity measure?
the number of solutes per unit volume of solution (mol/ L)
what is 1 osmole equal to?
1 mole of solute particles
what are aquaporins?
water channels that influence the rate of diffusion
-diffusion is guided by [water]
If osmolarity is high, is the [solution] high or low?
high osmolarity indicates low [water] and high [solute]
low osmolarity indicates high [water] and low [solute]
how does diffusional Eq occur?
what is osmosis?
the diffusion of water across a selectively permeable membrane
- high [water] to low [water]
what is osmotic pressure?
the pressure needed to prevent solvent movement
-prevent osmosis
what is the difference between osmosis and the diffusion of water across a cell membrane?
in osmosis, the membrane is only permeable to water; not solutes
what is tonicity?
the ability for a solution to modify the volume of it’s cells by altering water content
what determines tonicity?
the [non-penetrating solutes] (NPS) of an extracellular solution relative to intracellular environment of the cell
what determines cell volume in regards to tonicity?
[solute]
what is isotonic (isoosmotic)? what happens to the cell?
same [non-penetrating solutes] inside and outside the cell
-same cell volume
what is hypertonic (hyperosmotic)? what happens to the cell?
higher [non-penetrating solutes] outside than inside the cell
-cells shrink
what is hypotonic (hypoosmotic)? what happens to the cell?
lower [non-penetrating solutes] outside than inside the cell
-cell swells
what direction does water flow in osmosis?
from lower osmolarity to higher osmolarity
*high osmolarity = high [solute] low [water]
what is normal osmolarity inside the cell?
300 mOsm/L
how does osmolarity values change in relation to changes in tonicity?
300 isotonic (normal)
400 hypertonic
200 hypotonic
what is movement of solutes and water out of the blood (plasma) called?
filtration
what is movement of solutes and water into the blood (plasma) called?
absorption
what factors influence fluid movement along capillaries? what direction does it push fluid?
-capillary hydrostatic pressure (Pc); out of cell
-interstitial fluid hydrostatic pressure (Pif); into cell
-osmotic force of [plasma protein]; into cell
-osmotic force of [interstitial fluid protein]; out of cell
what organs are associated with the kidneys?
ureter
bladder
urethra
what is micturition?
urination
what is the function of the ureter?
collects everything and sends it to the bladder
what is the function of the bladder?
holds and excretes urine; under ANS control
-para-sym and sym systems
what is the function of the urethra?
leads urine out of the body; autonomic control
what structures make up the kidney?
capsule, outer cortex, nephron-renal corpuscle and renal tube
what is the structures make up a nephron?
glomerulus-filters small solutes from the blood
bowman’s capsule-helps filter blood from glomerular capillaries
proximal tubule- reabsorbs ions, water and nutrients. removes toxins and adjusts filtrate pH
descending loop of henle- water passes from filtrate to IF
Ascending loop of henle- reabsorption of Na+ and Cl- from filtrate into IF
Distal tubule- selectively secretes and absorbs different ions to maintain blood pH and electrolyte balance
collecting duct-reabsorbs solutes and water from filtrate
what lines the tubule?
a single layer of epithelial cells
-cells in each segment vary in structure and function
what does the bowman’s space extend to?
It continues as the tubule
What do nephrons begin as in stage 1 of development?
They develop as blind-ended tubules composed of single layer epithelium
what occurs in stage 2 of renal corpuscle development?
the growing tuft of capillaries penetrate the expanded end of tubules
-basal lamina trapped between endothelial cells of capillaries and epithelial layer
-epithelial cell layer differentiates into parietal (outer) and visceral (inner) layer
what occurs in stage 3 of renal corpuscle development?
the parietal layer flattens to become the wall of the bowman’s capsule
-visceral layer becomes the podocyte cell layer
what structures make up the renal corpuscle?
inside to out
Glomerular capillary
Fenestrated endothelial layer
Basement membrane
Podocytes with filtration slits
where are renal corpuscles found in the kidney?
In the cortex
where are the loops of henle found within the kidney?
The medulla
what are the basic functions of the nephrons?
Filtration
reabsorption
secretion
What are the 2 types of nephrons?is their function?
cortical - 85%; basic functions (filtration,reabsorption,secretion)
juxtamedullary- 15%; basic functions + [urine] regulation
what is the renal fraction?
20%
what is the rate of flow of blood supply to kidneys?
1200 mL/min
what is cardiac output to kidneys?
5600mL/min - high blood flow
what are the 3 types of capillaries in the nephron?
Glomerular-inside corpuscle
Peritubular-around peritubular capillaries
vasa recta-parallel to the loop of henle
what are the 3 basic renal processes?
1-filtration
2-secretion
3-reabsorption
what processes enter into the lumen?
filtration and secretion
what processes exit from the lumen?
reabsorption and excretion of urine
what is the general formula for amount of substance excreted?
what 3 filtration layers are present in the glomerular capillary?
-fenestrated endothelial layer
-basement membrane (BM)
-Podocytes with filtration slits
what three reasons prevent large proteins (albumin) from crossing over the glomerular capillary?
1) pore size- too small for protein to pass through
2) Pores and basement membrane have a (-) charge, which repels (-) charge proteins
3) podocytes have slits that remain covered with fine semi porous membranes
what 2 proteins make up podocytes? what happens to the proteins with mutations of the podocyte membrane?
Nephrins and podocins
-mutations will cause the slit in podocytes to allow passage of these proteins
-the proteins will appear in the urine
what is filtered through the glomerulus?
small molecules, plasma, waste and water flow are filtered while large proteins and blood cells are held back
what is ultrafiltrate?
low molecular weight substances that have gone through the bowman’s space
what is prteinuria?
the passage of proteins through the bowman’s space into the urine
what forces are involved in glomerular filtration?
starling forces
-Glomerular capillary blood pressure (high)
-Fluid pressure in bowman’s space (low)
-Osmotic force due to protein in plasma (higher than fluid pressure lower than glomerular capillary pressure)
True or false: Net glomerular filtration pressure is always negative.
False. net glomerular filtration pressure is always positive in order to drive filtration and urine formation
what is the percentage of blood volume filtered each turn -filtration fraction?
20%
what is the percentage of fluid reabsorbed?
> 19%
what percentage of fluid volume is excreted into the external environment?
<1%
what percentage of the plasma entering the kidney will return back to systemic circulation?
> 99%
what is GFR? How much is it?
glomerular filtration rate is the volume of fluid filtered from the glomerulus into the bowman’s space per unit time
-1.8L/ day or 125mL / minute
-plasma filtration 60x per day
what factors influence GFR?
1) net glomerular filtration pressure
2) permeability of the corpuscular
3) SA available for filtration
4) neural and endocrine control
What is the role of mesangial cells on GFR?
they are not part of the filtration layers
-contraction of these cells reduces SA of the glomerular capillaries causing a decrease in GFR
what does resistance changes in renal arterials cause?
causes alteration to renal blood flow and GFR
what occurs when resistance in AFFERENT arterioles is increased?
increased resistance decreases blood flow to that area
—->decreases capillary blood pressure —> decreases GFR
what occurs when EFFERENT arteriole pressure is increased?
increased resistance decreases blood flow to capillary —> pressure is increased due to build up of RBC —> GFR increases
explain the effects of modulation of arteriolar resistance on GFR
what happens to GFR following large and sudden changes in arterial pressure/renal blood flow? How does this occur?
GFR remains fairly constant due to autoregulation and the adaptation of renal blood vessel resistance
-this allows for compensation in blood flow
what 2 ways do renal blood vessels change resistance?
Myogenic response -quick
Tubuloglomerular feedback effect
how do blood vessels respond to increased tubular flow through autoregulation on GFR?
causes constriction of afferent arterioles in order to reduce GFR
how does neuronal and hormonal control impact autoregulation of GFR?
there is no effect; it is independent of neuronal and hormonal control
what regulates auto regulation of GFR?
paracrine control and tubule factors of arterial resistance
what is a healthy range of MAP
80-180mmHg
what is the juxtaglomerular apparatus (JGA)
a structure involved in the feedback control of renal blood flow and glomerular filtration
what is the macula densa?
cells on the wall of the distal tubule that sense increased fluid flow (Na+/Cl-) and responds by secreting vasoactive compounds (adenosine)
-this changes afferent arterial resistance which sends signal to juxtaglomerular cells
what are juxtaglomerular cells?
also known as granular cells, these are located on the wall of the afferent arterial
-controls renin release based on [Na+]
explain the tubuloglomerular feedback
what is filter load?
the total amount of non-protein / non-protein bound substance filtered into Bowman’s space
filtered load = GFR x [substance in plasma]
what is the filtered load of glucose?
180g/day
what occurs when substance excreted in urine < filtered load?
reabsorption
what occurs in filtration and secretion?
complete secretion- no substances are needed by the body
what occurs in filtration and partial reabsabsorption?
majority of the substance is kept by the body; some filtration
what occurs in filtration and complete reabsorption?
all of the substance is taken back by the body- complete reabsorption
what type of substances go through filtration only?
inulin and creatinine
what substance goes through filtration and partial reabsorption?
electrolytes
what substances go through filtration and complete reabsorption?
glucose and amino acids
what substances go through filtration and complete secretion?
organic acids and bases (PAH, para-amino hippuric acid)
what 2 types of transport are reabsorption mediated by?
mediated transport (transepithelial) -major
diffusion across tight junctions (paracellular)- minor
what is the pathway of substances using transepithelial /mediated transport?
1) across luminal / apical membrane
2) across basolateral membrane
what side of the membrane does active transport occur?
active transport of Na+/K+ ATPase occurs on the basolateral membrane side
explain the process of reabsorption of Na+
1) Na+/K+ ATPase drives Na+ out of the cell creating a low [Na+] inside the cell
2) low [Na+] in the cell drives Na+ in though secondary active transport
-diffusion
what is the process of glucose reabsorption?
1) Na+/K+ ATPase created low [Na+] within the cell
2) This drived Na+ into the cell along with glucose through the SGLT carrier protein (secondary active transport)
3) glucose diffuses out of the basolateral side using the GLUT protein (facilitated diffusion)
what is transport maximum? what is the normal range?
the capacity of how much can be transported
-normal range 100-200 mg/100mL of plasma
what is renal threshold? what is its value for glucose?
the maximum at which the kidney tubular cells can’t do anymore reabsorption
-300mg
explain the steps in urea reabsorption
what is tubular secretion coupled with?
reabsorption of Na+
-involves active transport
what is the clearance of inulin?
inulin is only filtered so it’s filtered load = clearance
GFR = Uin V / Pin
what must occur if clearance of substance > GFR?
secretion
what must occur if clearance of substance < GFR?
reabsorption
what % of reabsorption occurs in distal tubules?
12-15%
what % of reabsorption occurs in proximal tubules?
80%
explain the process of water absorption in the proximal tubule
explain the process of water absorption in the loop of henle
water reabsorption in the descending loop and salt reabsorption in the ascending loop
what is the importance of countercurrent multiplication?
Countercurrent multiplication is the process of using energy to generate an osmotic gradient that enables you to reabsorb water from the tubular fluid and produce concentrated urine.
*different transport capabilities on each side of the tubule
explain the process of countercurrent multiplication
https://youtu.be/cYyJF_aSC6o?si=1XibVO5kHaCADYLc
what is the gradient created between the descending limb and the interstitial space?
the interstitial osmolarity is initially the same as the descending limb osmolarity
what is the effect of a longer loop of henle on the [urine]?
as the length of the loop increases, there is a larger distance for water reabsorption to occur and the gradient is seen to be higher
-this creates a more concentrated urine
where in the loop of henle does fluid become concentrated?
The descending limb
-H2O is reabsorbed into the interstitial space
where in the loop of henle is fluid diluted?
up the descending into the distal tubule
where does fluid in the collecting duct become isoosmotic with?
fluid in the collecting duct becomes isoosmotic with the interstitial space
Where in the collecting duct is ADH activated?
cortical collecting duct
what is the importance of the vasa recta in the counter current exchange?
vasa recta form a parallel set of hairpin loops within the medulla; it is vital to prevent gradient from washing away
-MAINTAINS Na+ / Cl- concentration gradient by adding/removing solute and water from the medulla
how does the countercurrent exchange work in the vasa recta?
Nacl moves out of the ascending limb into the descending limb as blood enters the descending limb of the vasa recta
water diffuses out of the descending limb into the ascending limb
What 4 characteristics describ ADH or vasopressin?
1) fast acting peptide hormone
2) produced by cells of the SON of the hypothalamus
3) secreted from the posterior pituitary
4) osmoreceptors sense increases in plasma osmolarity
what regulates AQP2 insertion on the luminal side? and on the basolateral side?
ADH regulates the luminal side
- it does not regulate the basolateral side
what is diabetes insipidus?
central diabetes insipidus- failure to release ADH
nephrogenic diabetes insipidus- kidney resistance to ADH
what is the difference in gradients created between conditions of excess water vs water deprivation?
excess- smaller graident to decreases water absorption
deprived- larger gradient to increases absorption
explain how baroreceptors act when [Na+] is low
short term regulation
where is aldosterone secreted from?
adrenal cortex
what are the 3 actions of aldosterone?
1) induce synthesis of Na+ transport protein
2) stimulate Na+ reabsorption
3) reduce Na+ secretion
what are the steps in aldosterone Na+ regulation?
what does decreased [Na+] do to renin and angiotensin concentration?
increases renin secretion which increases angiotensin I, increasing angiotensin II
what directly increases aldosterone release?
increased anhgiotensin II concentration
what senses low [NaCl] in the renin-angiotensin system?
renin
what converts angiotensin I to angiotensin II?
ACE
-angiotensin converting enzyme
what is the affect of angiotensin II on blood vessels/ blood pressure?
causes vasoconstriction which increases blood pressure
what are juxtaglomeruar cells?
mechanoreceptors loctaed on the wall of afferent arterioles that sense plasma volume associated with low [sodium]
what are the macula densa?
chemoreceptors onthe wall of the convulated tubule that sense NaCl load of the filtrate
what 3 inputs do the juxtaglomerular cells recieve to promote renin release?
1) sympathetic input from extrenal baroreceptors
2) intrarenal baroreceptors
3) signals from the macula densa
explain the steps in barorecptor control for the renin-angiotensin system
what stimulates ANP secretion?
1) increased [Na+]
2) increased blood volume
3) atrial distension
where is ANP synthesized?
synthesized and secreted by the cardiac atria
where is ANP activated?
on cells in several tubular segments
-ANP inhibits aldosterone actions
-Inhibits Na+ reabsorption
-Increases GFR and Na+ excretion
where is majority of filtered K+ reabsorbed?
proximal tubule and loop of henle
where is [K+] in urine regulated?
cortical collecting duct
what occurs when extracellular [K+] is increased?
aldosterone is produced and more [K+] is excreted in urine
what are sources of H+ ion gain and loss in the body?
how do kidneys balance H+ changes in the body?
long term regulators that synthesize and excrete bicarbonate ions
decreased [H+] - excretion of HCO3-
increased [H+]- synthesis of HCO3-
how is HCO3- reabsorbed?
an active process that depends on H+ secretion
what is the repsonse mechanism to acidosis (NH4+)?
when excess H+ are in the lumen addition of HCO3- occurs by:
1) binding of H+ to HPO4 2-
2) HCO3- generation by tubular cells to diffuse into plasma
3) NET gain of HCO3- in plasma
what is the repsonse mechanism to acidosis (HPO4)?
1) only uses cells from proximal tubule
2) uptake of glutamine
3) NH4+ amd HCO3- formed inside the cells
4) NH4+ actively secreted via Na+/NH4+ counter transporter
5) HCO3- added to plasma
summarize the renal regulatoin of acids during acidosis and alkalosis
