Renal Mod 2 Flashcards
what substances does the glomerulus filter in healthy indvls?
water electrolytes creatinine glucose nitrogenous wastes (urea & uric acid) small AA bicarbonates (HCO3-)
what substances are not normally filtered in glomerulus in healthy individuals?
blood cells
most proteins/peptides - some smaller sized proteins/AA do pass thru filter
3 layers of glomerular filtration
- fenestrated endothelium (pores)
- basement membrane (basal lamina)
- podocytes (epithelium)
size of pores in fenestrated endothelium
70-90nm
function of basement membrane (basal lamina)
no pores or slits
acts as a screen/physical barrier
size of slits of podocytes
filtration slits approx 25nm
how do RBCs/WBCs compare to glomerular pores
cell size:
RBCs approx 8 micrometers in diameter = 8000nm
WBCs approx 8-15 micrometeres = 8-15000nm
how does the endothelium filter?
pores of the endothelium allow small molecules to easily pass though and block blood cells
how does the basement membrane filter
- physically
2. membrane charge
how does the basement membrane filter physically?
membrane only permits very small molecules to pass thru into Bowman’s space (4-8nm easily pass, >8nm blocked)
how does the basement membrane filter based on membrane charge
membrane is negatively charged
therefore it repels small molecules that physically could pass thru but have a negative charge = proteins
example of albumin and membrane charge of basement membrane
lots of albumin in blood
easily passes thru endothelium
albumin is negatively charged tho - so not a lot should get thru into urine (only expect small amounts)
affects of pathology to the capillary membrane
a dz/damaged capillary allows :
- proteinuria
- hematuria
what is proteinuria and what does it indicate?
- proteinuria: excess levels of protein in urine - d/t loss of glomerular basement charge or size barrier, proximal tubule damage
what is hematuria and what does it indicate?
- hematuria - any condition in which blood is foun din the urine
- sign of glomerular capillary dz as well as other kidney pathologies (stones, tumor, infections)
- often associated with inflammatory condition of kindey
consistent finding in nephritic syndrome
hematuria
consistent finding in nephrotic syndrome
proteinuria
if proteinuria is present, what would other labs look like?
- hypoalbuminemia
- edema (result of altered albumin in blood)
- hyperlipidemia/-uria
if you have hematuria - what would other labs look like?
oliguria - low urine output/production
azotemia - elevated BUN and creatinine in blood
permeability of glomerular capillaries vs skeletal muscle
50x greater than capillaries of skeletal muscle
total surface area of glomerular capillary endothelium
0.8 m2
the surface area of capillary/mesangial cells can be functionally altered by what?
by the contraction of mesangial cells
whatwill the contraction of mesangial cells do?
effectively decreased the capillary surface area
less surface results in less filtration (decr GFR)
substances that sitmulate contraction of mesangial cells
- angiotensin II
- ADH
- NOrepinephrine
substances that stimulate relaxation of mesangial cells
ANP
dopamine
what is glomerular filtrate
solution that is filtered thru glomerular capillary
the sum of what four pressures will influence GFR?
- hydrostatic pressures of glomerulus and Bowman’s capsule
2. osmotic pressures in glomerulus and Bowman’s capsule
what is the glomerular capillary hydrostatic pressure
- major force in filtration, decreases at end of glomerular capillary
- opposed by hydrostatic pressure in Bowmna’s capsule
- clinical - extreme systolic BP changes will influence
what is Bowman’s capsule hydrostatic pressure
- small and fairly constant at beginning and end of glomerular capillary
- clinical - increased if obstructive pathology (stones), edema of kidney itself (renal capsule limited volume to allow swelling)
what is glomerular capillary colloidal osmotic pressure
- decreases at end of glomerular capillary which maximizes filtration at the end of capillary
- clinical - changes in plasma proteins (hypoproteinemia)
what is Bowman’s capsule colloidal osmotic pressure
NOT a factor unless diseased/damaged glomerular capillary
what is tubular reabsorption?
reabsorbs substances (filtrate) from the tubular portion of nephron back into capillary system (peritubular capillaries)
what is tubular secretion
secretes substances (filtrate) from the capillary system (peritubular capillaries) into the tubular portion of the nephron
what is the PCT
proximal convoluted tubule
15mm long, single layer of cells along wall with microvilli (brush border) along the lumen
what is the primary function of PCT?
resorption of sodium
-water, electrolytes and other substances are co-transported with sodium back into blood stream
what other substances are reabsorbed in the PCT?
the PCT reabsorbs majority of the glomerular filtrate
- 60-70% of water and sodium
- 50% of urea is reabsorbed
- 90-100% of glucose, amino acids, bicarb and other electrolytes
two pathways sodium is reabsorbed from the PCT into PCT cell
- co-transport
2. active exchange
how is sodium reabsorbed from the PCT via co-transport into PCT cell
with glucose, AA, water, electrolytes and other substances
–gradient formed by active transport of sodium out of PCT cell drives this pathway
how is sodium reabsorbed from the PCT via active exchange into PCT cell
exchange of Na+/H= as part of mechanisms to reabsorb bicarb
- Na+ is transported from PCT lumen in to PCT cell in exchange for H+ ion
- H+ ion that is transported into the lumen combines with bicarb as part of pathway to reabsorb filtered bicarb into blood stream (does not contribute to increased blood or urinary acid levels - recycling)
what are carbonic anhydrase inhibitors?
inhibit this pathway to block Na+ absorption in the PCT
how is sodium transported from PCT cell into peritubular capillaries
active transport via sodium/potassium pump
-creates the sodium gradient eneded to facilitate flow of sodium and co-transporters from the PCT lumen into the PCT cell
steps for glucose resorption in the PCT?
- glucose is transported from PCT lumen into PCT cell
2. glucose transported from PCT cell into peritubular capillaries
how is glucose transported from PCT lumen into PCT cell
- glucose is co-transported with sodium via specialized carriers
- glucose and sodium are transported from PCT lumen to PCT cell
- co-transport is dependent of the sodium gradient formed by active transport of sodium out of PCT cell
how is glucose transported from PCT cell into peritubular capillaries?
passively diffuses into blood stream via glucose carriers (GLUT)
what is glucose transport limited by?
number of available carriers
if there is too much glucose in the filtratrate then what?
PCT can’t reabsorb all the glucose
what is transport maximum
Tm - max rarte a substance can be transported across a cell wall
what plasma glucose level corresponds with transport max of glucose in PCT
> 350 mg/dl
in diabetes, elevated plasma glucose will:
increase glucose filtered at the glomerulus
increased glucose of filtrate flowing thru PCT
if too much glucose in filtrate then transport max is reached and glucose is excreted in the urine
what is the glucose renal threshold
refers to plasma values at which glucose first appears in urine
plasma glucose levels greater than what correspond with glucose dumping into the urine
180-200mg/dl
normal (100mg/dl)
functions of the loop of Henle
- reabsorbs 25% of sodium filtered by glomerulus along with other glomerular filtrate that was not reabsorbed in PCT
- regulate the osmotic state of the medullary interstitial fluid and the filtrate leaving the loop of Henle - urine concentration
where in the loop of Henle is sodium reabsorbed?
occurs in ascending limb only
sodium transport from loop of Henle lumen into PCT cell
sodium is co-transported with both Cl and K
-transport of Na/Cl/K is dependent on gradient formed by active transport of sodium out of loop of Henle cell
sodium transport from loop of Henle cell into peritubular capillaries
active transport via sodium/potassium pump
-this pathway creates the sodium gradient needed to facilitate flow of sodium and co-transporters from loop of Henle lumen into loop of Henle cells
what happens in descending limb of loop of Henle
- a combo of water permeability out of loop and minimal sodium permeability out of loop creates a hyperosmotic filtrate as in descends in the loop of Henle
- this allows water to be reabsorbed and does not allow sodium to be reabsorbed
what happens to osmolarity of the tubular fluid as it descends to the bottom of the loop of Henle
increases
what happens in ascending limb of loop of Henle
aka diluting segment
-a combo of limited water permeability out of loop and increased sodium permeability out of loop creates a hypo-osmotic filtrate as in ascends in the loop of Henle
how does the thickness of the ascending loop of Henle change?
starts thin and becomes thick
purpose of thick ascending loop of Henle
impermeable to water so water stays inside the loop of Henle
-permeable to sodium - so sodium leaves the loop
the osmolarity of the tubular fluid leaving the loop of Henle is __________ than when it first entered the loop of henle
hypo-osmotic (more diluted)
what are loop diuretics
ex. furosemide - inhibit the Na/K/Cl co-transport mechanism
- increase osmotic concentration of tubular fluid as it leaves the loop of Henle and decreases the medullary interstitial fluid
- the change of these two concentration results in diuresis and massive natriuresis
additional effects of loop diuretics
inhibiting the Na+ resorption in the loop of Henle:
- resorption of K+ is also inhibitied and thus hypokalemia is a secondary effect
- resorption of Ca+ is also linked to Na+ resorption thus hypocalcemia
where does the DCT begin
macula densa
function of macula densa at beginning of DCT
sense NaCl levels as part of feedback
-if increase in NaCl then macula densa signals afferent arteriole to constrict and slow RBF and GFR which filters less sodium
function of DCT
- dilution/concetration of urine
- early DCT: continue to dilute tubular fluid
- late DCT: begin process of concentrating fluid for urine output - regulate sodium, potassium, and calcium homeostasis
- contribute to regulation of acid-base balance via absorption/secretion of ions
early DCT aka
cortical diluting segment
what does the early DCT do?
reabsorbs sodium and impermeable to water further diluting the tubular fluid
how does early DCT reabsorb sodium?
- reabsorbs 5% of sodium filtered in the glomerulus
- sodium transport from early DCT lumen to early DCT cell
- –transport of NaCl is dependent on gradient formed by active transport of sodium out of early DCT cell
how is sodium transported from early DCT cell into peritubular capillaries?
active transport via sodium/potassium pump (same as PCT/ascending loop of Henle)
this creates the sodium gradient needed to facilitate flow of sodium and co transporters from early DCT lumen into early DCT cell
how do thiazide diuretics work
inhibit Na/Cl co transporter which inhibits Na/Cl reabsorption in early DCT
secondary effect of thiazide diuretics
- has opposite effect on Ca+ = reabsorption is increased and may result in hypercalcemia
- calcium is normally reabsorbed into bloodstream from DCT cell as a sodium/potassium exchange
- also hypokalemia and metabolic alkalosis
two cell types located in both late DCT and collecting duct
- principle cell: reabsorb sodium and water, secrete potassium
- alpha - intercalated cells: secrete H+ ions
function of late DCT
regulate final urine concentration
maintain acid base homeostasis
how does the late DCT and collecting duct reabsorb sodium?
- reabsorption of sodium occurs in principle cells
- transport of sodium from late DCT lumen to late DCT cells
- transport of sodium from late DCT/collecting duct cells to peritubular capillaries
how is sodium transported from late DCT lumen to late DCT cells?
- aldosterone stimulates sodium reabsorption and potassium secretion
- aldosterone stimulates increased sodium uptake into late DCT cell which in turn stimulates sodium/potassium pump to transport sodium into peritubular capillary
- increased activity of the sodium/potassium pump will promote potassium secretion from late DCT into the late DCT lumen
how do K sparing diuretics work
- K sparing diuretics inhibit K secretion from principle cells in late DCT/collecting duct
- antagonizes aldosterone influence on principle cells and blunts sodium reabsorption
how does the late DCT and collecting duct reabsorb water?
if ADH is present then principle cells of late DCT increase permeability to water
how do intercalated cells of the late DCT and collecting duct reabsorb K?
only occurs if significantly low dietary intake of K
how does the late DCT and collecting duct contribute to acid-base regulation
- H+ is secreted into late DCT lumen from intercalated cells
- in the DCT lumen, the H+ combines with non-bicarb buffers in two pathways
- this creates a new bicarb which is reabsorbed from the intercalated cells into the peritubular capillaries
what are the two pathways that H+ combines with non bicarb buffers
- H+ combines with ammonia to form ammonium and is then excreted in the urine
- H+ combines with a dibasic phosphate to form monobasic phosphate and then excreted in the urine
how does the body attempt to compensate for an acidic environment in the blood stream?
excretion of H+ in the urine and adding bicarb to the blood stream
collecting duct function
-ultimately determines the final concentration of urine to be excreted by increasing the concentration of the tubular fluid as it passes thru the collecting duct
how does the collecting duct determine the final concentration of urine
- tubular fluid entering the distal DCT and collecting duct is hypotonic
- collecting duct reabsorbs Na+ and H2O to increase concentration of urine as in late DCT
what 2 things stimulate reabsorption of Na+ and H2O
aldosterone and ADH
fluid concentration in PCT
300 mOSM
Loop of Henle fluid concetration
start: 300mOsm
descending: gradual increase to 1200 mOsm
ascending: gradual decrease
finish: 100 mOsm
fluid concentration of DCT
early: continues to dilute 100 mOsm
late: begins to concentrate
finish: 150 mOsm
collecting duct fluid concentrations
start: 150mOsm
finish: 1200mOsm (depending on body’s needs and circumstances)
healthy kidney approximately how much water is reabsorbed
98-99%
how much water is filtered in glomeruli vs how much urine output on average
180L filtered vs 1L output
