Renal Physio Flashcards
Describe the endocrine functions of the kidney.
*stabilize volume & ion conc of ECF
EX: hemorrhage
-low blood flow/BP = renin released
-low oxygen = erythropoietin released
>new mature RBCs
Describe the RAAS system.
Describe calcitriol.
-stimulated by PTH in response to hypocalcemia -> absorption of Ca by intestinal epithelium = increasing conc of Ca in blood
*Calcitriol is active form of VitD
Skin->liver->kidney
Describe the structures of the nephron.
*cant be replaced
*functional unit of kidney
1. renal corpuscle = in renal cortex
-glomerulus surrounded by bowman’s capsule
2. proximal tubule = longest part
-proximal convoluted/straight
3. loop of henle = thick/thin descending & thick/thin ascending
4. distal tubule = convoluted & straight
5. Collecting ducts = thru cortex & medulla
*at renal papilla CD open in the renal pelvis via ureter -> bladder -> urethra -> exit
Describe cortical nephrons VS juxta nephrons.
- Cortical
-glomerulus far from cortex/medulla
-short loop of henle
-peritubular capillaries - Juxta
-glomerulus near cortex/medulla
-efferent arterioles give rise to long straight capillaries (vasa recta) that descend into renal medulla
-long loops of henle (for urine conc)
Describe the perfusion to the kidney.
*20-25% CO to kidney
Describe ischemia-reperfusion.
*Ischemia = interruption of blood supply to tissue
*Reperfusion = re-estab of blood flow to tissue
Ischemia-reperfusion = Issues medically
-organ transplant
-stroke
-myocardial infarction
-perinatal asphyxia
-acute renal failure
Describe glomerular filtration.
-filtrates fluid through the glomerular capillaries into Bowman’s capsule (99% reabsorbed, 1% excreted)
-glomerulus = capillaries & semipermeable membrane
>impermeable to lg protein
-glomerular filtrate = glomerulus makes fluid like plasma
-GRF depends on rate of kidney perfusion with blood = RPF (renal plasma flow)
-20% plasma filtered thru glomeruli
*protein free
Describe the structure of the glomerulus.
-capillaries covered by epithelial cells (podocytes) & encased in Bowman’s capsule
Describe bowman’s capsule.
-parietal epi
-bowman’s space = area between glomerular capillaries & bowmans capsule
Describe selective filtration.
-size (smaller are filtered freely ex; water, Na, glucose)
>filterability is inversely related to radius & MW
-electrical charge (cations more permeable bc glomerular BM is neg)
-capillary pressure
-plasma protein binding
>drugs retained in circulation for a time period before being eliminated
Describe the components of the filtration barrier.
- Capillary endothelial cells (fenestrated)
- Glomerular BM (glycoproteins)
- Visceral epi (podocytes)
Describe the glomerular BM.
*neg charge
1. Lamina rara interna
2. Lamina densa (electron dense)
>glycoproteins
3. Lamina rara externa
Describe glomerular capillary hydrostatic pressure.
-driving force for filtration is the glomerular capillary hydrostatic pressure
>forces opposing filtration = hydrostatic pressure in bowman’s space & oncotic pressure of plasma
*oncotic pressure of filtrate is nonexistent
Describe the pressures at the glomerular capillaries.
-hydrostatic pressure is constant
>fluid forced out with increased resistance in the efferent arteriole
-oncotic pressure of blood increases
>plasma proteins retained in capillaries
*oncotic pressure of blood opposes filtration = net filtration pressure is reduced along glomerular capillaries
Describe the glomerular filtration rate.
-total volume of fluid filtered by the glomerulus into bowmans space
-GFR is a product of:
1. Net filtration pressure
2. Permeability of filtration barrier
3. SA available for filtration
*99% of GFR returns to ECF by reabsorption
Describe the glomerular filtration indicator substances.
- Freely filterable
- Filtered amount can’t change due to reabsorption, secretion, metabolized in kidney
- Cant alter renal function
- not protein bound in plasma
- doesnt enter RBCs
- no other route of clearance from plasma
- doesnt alter GFR
*insulin & creatinine
Describe the GFR & renal clearance.
-imp for renal function
-GFR measured by determining plasma clearance rate of a substance
-volume/conc of urine/plasma
Describe Inulin.
-ideal filtration marker
-urine flow, urine conc, & plasma conc = clearance
-exogenous substance
Define biomarker.
-biological molecule found in blood, or other body fluids/tissues thats a sign of normal/abnormal processes or condition/disease
Describe how creatinine acts as a renal biomarker.
-assess renal function
-byproduct of muscle metabolism
-fully filterable, not reabsorbed/secreted
LIMITATIONS:
-high variability w breeds
-nonlinear between creatinine & GFR
-creatinine doesnt rise until 75% nephrons are nonfunctional
-affected by extra renal factors like muscle mass & hydration = lacks specificity
Describe the relationship between blood creatinine conc & GFR.
-lg change in GFR + sm change in creatinine = early renal disease
-lg change in creatinine + little change in GFR = advanced renal failure
*normal creatinine doesnt mean normal renal func
Describe Iohexol as an indicator substance.
-nonionic, iodinated contrast agent
-fully filtered
-not reabsorbed/secreted
-determines GFR
-2-4 blood samples
*GFR = CLplasma = D/AUC
D -> dose
AUC -> area under curve (conc vs time)
[higher GFR = faster substance cleared]
Describe renal circulation & hydrostatic pressure.
-hydrostatic pressure differs in parts of renal circ
(renal artery has the highest & renal vein lowest)
renal artery -> afferent -> glomerulus -> efferent -> peritubular capillary -> intrarenal capillary -> renal vein
*changes in arteriolar resistance alters pressure in glomerular & peritubular capillaries
Describe the autoregulatory window.
-autoregulation = intrinsic ability of an organ to maintain blood flow at a constant rate despite changes in arterial pressure
-autoregulatory window = 80-180 mmHg
>short term change of blood in this range will alter GFR & RBF a little
[Q=P/R]
*higher RBF & GFR = more urine volume
Describe how renal blood flow & GFR change. (picture)
Describe GFR autoregulation.
GFR kept in range via:
-intrinsic control of renal blood flow
>control of glomerular capillary perfusion mediated by myogenic reflex & tubuloglomerular feedback
-extrinsic control via nervous & endocrine systems
>systemic BP & volume control via RAAS
Describe the myogenic reflex.
*detect change in glomerular perfusion
increased tension + increased blood flow, hydrostatic pressure -> depol of vascular smooth muscle -> Ca enter cell -> muscle contraction -> constrict afferent arteriole = decrease tension + decrease blood blow, GFR, hydrostatic pressure
*when arterial BP falls = dilation of afferent arteriole
Describe the tubuloglomerular feedback. (picture)
*detect change in tubule fluid delivery
*renin synthesized in afferent arteriole (juxta cells)
Describe how the sympathetic system is involved in BP regulation.
*B adrenergic = induce renin release
-intrarenal regulation of vascular tone & glomerular filtration via vasodilatory (ex. NO) & constriction factors (ex. endothelin)
*NSAIDS = reduce GFR
Describe primary urine VS tubular fluid.
- primary urine
-ultrafiltrate in bowmans space
-same conc of salt & glucose as plasma (no proteins)
-fractional excretion rate = net rate of reabsorption/secretion of filtered substance
>assess renal tubule function (creatinine used as reference & Na as solute) - tubular fluid
-filtrate inside tubular system
-fluid modified by tubular reabsorption = final urine
-reabsorption of filtered substances (100% glucose, 99% H2O, Ca, Na, Cl, HCO3)
Describe the functions of the nephron segments.
- glomerulus = filter blood (solutes, water, urea, creatinine) ‘primary urine’
- PCT = reabsorb filtered solutes (glucose, proteins, etc), water & excrete waste
- thin limbs of Henle = maintain medullary hypertonicity & reabsorb water, Na, Cl
- thick ascending of henle = reabsorb Na, K, Cl & dilute tubule fluid & maintain medulla hypertonicity
- DCT = reabsorb Na, Cl, Ca, Mg & connecting segment regulate acid, HCO, ammonia, Ca, Na, K & water excretion
- collecting ducts = regulate acid, HCO, ammonia, Na, K, & water excretion/reabsorption ‘final urine’
Describe how the PCT reabsorbs filtered solutes.
*structure of PCT & proximity to peritubular capillary
>high oncotic pressure & low hydrostatic pressure
1. transcellular pathway
2. paracellular pathway
Describe the structure of the PCT.
-polarized (apical towards tubule fluid & basolateral toward capillaries infoldings)
-brush border (microvilli) = increase SA on apical membrane
-tight junctions (zona occuldens - paracellular pathway EX. Cl)
-coated pits (contain binding site for substances reabsorbed by receptor-mediated endocytosis)
Describe primary active transport.
Na/K ATPase (basolateral) = pump Na out of cell & K into cell
-chemical Na gradient
-electrical gradient (intracellular neg charge)
-high to low
Describe reabsorption in the PCT.
-glucose (SGLT), amino acids = all reabsorbed via secondary transport (driven by active reabsorption of Na by Na/K ATPase)
-electrolytes & water around 65%
*at basolateral some substances transport by passive transport into interstitium (GLUT 1 & 2)
Describe bicarb reabsorption.
-indirectly driven by Na gradient
-Na/H countertransport across apical
>Na gradient drives Na/H antiporter
-H+ combines with HCO3 to make H2O & CO2
-in the cell H2O & CO2 make H & HCO3 before transport across basolateral
*carbonic anhydrase responsible for this reaction
Describe the reabsorption of glucose.
*sodium dependent glucose transporter on APICAL
1. SGLT2
-low affinity in pars convoluta (near S1, S2)
2. SGLT1
-high affinity in pars recta (near S3, by loop)
*glucose transporter 2 on BASOLATERAL
-GLUT2 (facilitated diffusion)
Describe saturation. (Michaelis-Menten)
Saturation of carriers -> less reabsorption -> excretion in urine
EX: hyperglycemia -> glucosuria (glucose in urine) if glu conc exceed renal threshold
*glu is osmotically active
Describe reabsorption of peptides.
-peptides degraded to amino acids in PCT brush border & reabsorbed by cotransport with Na
-H gradient enables transport of di- & tri- peptides in the PCT by tertiary active transport
Describe reabsorption of proteins.
-low MW proteins are reabsorbed by receptor mediated endocytosis
-receptors in PM of PCT
-after endocytosis -> fusion of lysosomes & degrade proteins into amino acids
Describe how the proximal tubule secretes organic anions.
*PT uses active transport (carriers)
1. OATs = organic anion transporters
2. MRP2 = multi drug resistance protein 2
Describe how the proximal tubule secretes organic cations.
- OCT (organic cation transporter)
- MDR1 (multi drug resistance 1)
Describe the loop of henle.
*thin segments = thin epi, no brush border, few mitochondria, low metabolic activity
>maintain medullary hypertonicity
1. Thick descending (not imp)
2. Thin descending
3. Thin ascending
4. Thick ascending (medullary thick ascending limb = mTAL)
Describe mTAL transport systems.
secondary active transport
1. NKCC = Na, K, Cl Cotransport
>inhibited by furosemide (diuretic)
2. ROMK = Cl & K channels
*paracellular = Ca, Mg, Na (pos charge of lumen relative to interstitial, forces cations to diffuse from lumen to interstitium)
*ADH stimulates NKCC
Describe the different exchange mechanisms.
-countercurrent = maintain medullary hypertonicity
1. Simple exchange system: 2 tubes in parallel fluid flow
2. Countercurrent exchange: fluids flow in opp direction
Describe the medullary segments & urine conc.
Describe the loop of henle & countercurrent multiplier.
-sharp turn
-fluid flowing in opp direction
-water pass thru thin descending
-solutes reabsorbed in ascending limbs without water generating a osmotic gradient of 200
-water in interstitium reabsorbed by vasa recta (avoiding dilution of medulla)
-high osmolality of interstital fluid in medulla (1200) maintained by balance inflow & outflow of solutes & water into medulla
Describe the DCT & CT osmol conc.
DCT = reabsorb ions (Na, K, Cl, Ca, Mg)
Describe DCT transport systems.
-NCC = Na/Cl cotransporter
>NCC inhibited by thiazide diuretics = Na increase in tubule
>secondary active
>apical membrane
Describe the CD principal cells transport system.
-NaCl reabsorption by ENaC & K secretion by ROMK
-control of net renal K+ excretion
-intracellular K+ leaves the cell apically (down chemical gradient [high to low]) through K+ channels (ROMK)
Reabsorption summary!
Describe urea recycling.
- Urea
-waste product of protein metabolism eliminated thru urinary system
>maintain medullary hypertonicity
>excreted in urine - PT
-reabsorption
-not regulated - Descending thin limb
-urea secreted into tubule
-down conc gradient
-vasa recta thru interstitium to thin descending limb - Inner medullary collecting duct
-urea reabsorption enhanced by ADH
-UT-A1 & UT-A3
>ADH upreg = increasing urea reabsorption
>accumulation of urea in medullary interstitium contributes to medullary interstitial osmotic pressure & promotes water reabsorption
Describe medullary hypertonicity & urine conc.
-Na, Cl, urea (solvent)
-reabsorption of water by vasa recta
-increase osmol in interstitum & tubule fluid from cortex to medulla
Describe medullary hypertonicity & urine conc in the PT, descending thin limbs, & ascending limbs (thin & thick)
PT:
-water & solutes reabsorbed
-osmol of tubular fluid same from BC to beginning of thin descending limb
Descending thin limbs:
-water reabsorbed into medulla
-low permeability to solutes (NaCl & urea) = osmol of tubular fluid increases until equal to interstitum
Ascending limbs (thin & thick:
-impermeable to water
-high NaCl reabsorption
-osmol of interstitium raises (medullary hypertonicity) & tubule fluid in thick ascending limb is dilute
Describe medullary hypertonicity & urine conc in the late DT + cortical DT & inner medullary CD.
Late DT & cortical CD:
-osmol of fluid depends on level of ADH
>if ADH high -> water permeability high
Inner medullary collecting duct: (IMCD)
-filtered urea reabsorbed in IMCD by carrier mediated facilitated transport (UT-A1, UT-A3)
-urea conc increases in interstitium = medullary hypertonicity
-before excretion urea goes from interstitum to vasa recta (UT-B) & to tubule lumen by transport into thin limbs (UT-A2) to CD urea recycling
Describe ADH mechanisms of actions in the kidneys.
-made in hypothalamus but released by posterior pituitary & into blood
-ADH stimulates NKCC in TAL (Na, Cl, K reabsorption)
-ADH upreg UT-A1 & UT-A3 = increasing urea reabsorption
-higher osmol = water follow electrolytes
-ADH stimulates CD to increase # of AQPs
Describe aldosterone mechanisms of actions in the kidneys.
-made by adrenal cortex
-part of RAAS
-location in principle cells
>stimulate Na reabsorption in CD thru increasing activity of ENaC & synthesis of NaK ATPase
>K secretion via BK & ROMK transporters
*goal = increase ECF volume
Describe Angiotensin II mechanisms of action in the kidneys.
-part of RAAS
-increases Na reabsorption in PT (Na/H exchange, Na/K ATPase), TAL (NKCC), DCT (NCC)
Describe diuretics & diuresis.
-diuresis = increased urine production
-inhibition of NaCl reabsorption & decrease water reabsorption -> decrease ECF volume
Describe calcium reabsorption.
*calcitonin inhibits tubular reabsorption of Ca & Phos = decrease rate of loss in urine
1. PT
-50-60% reabsorbed paracellularly
2. Thick ascending limb
-30-35% reabsorbed paracellularly & transcellularly
3. DCT
-10% reabsorbed transcellularly
hypocalcemia -> PTH -> stimulate apical uptake of Ca through Ca channels in TAL & DCT
Ca & Phos reabsorption summary!
