Renal Physiology Flashcards
Innervation
T10-L2 SNS
Hypo gastric Ganglion/Nerve–bladder relaxation, internal sphincter contraction
PNS (S2-S4)
Pelvic nerve
—bladder contraction
–internal sphincter relaxation
Voluntary–
Pudendal nerve
–external sphincter
Process of micturation
Bladder pressure stimulates afferent sensory nerves
Urethral sphincter relaxes
Pudendal nerve contraction to override parasympathetic micturation reflex
Filling of the bladder
Contraction of striated sphincter (somatic)
Contraction of smooth muscle (sympathetic)
Inhibition of destructor muscle (sympathetic
Emptying the bladder
Relaxation of striated spin her (somatic)
Relaxation of smooth muscle sphincter and opening of the bladder neck (sympathetic)
Detrusor muscle contraction (para)
Pressure
Stretch receptors–>SNS efferent–>pons–>SNS afferent–>NE–> B3
–>destrusor relaxation (inhibition of contraction)
NE–>alpha1–>contraction of internal urethral sphincter
SNS efferent and afferent so=hypo gastric
Pudendal–>ACh–>contract external urethral spinner
Pressure>10cmH20 (emptying phase)
> 10cmH2O–>pelvic PNS afferents–>pons–>pelvic PNS efferents–>ACh–>M3 receptors–>destrusor contraction
NO–>internal urethral sphincter relaxes
Pons–>pudendal–>ACh–>nicotinic–>contraction of external urethral sphincter until it is ready
Major functions of the Kidneys
Regulate body fluid osmolality and volumes, electrolyte balance, acid-base balance, excretion of metabolites and substances, production and secretion of hormones
Kidney Blood Flow
Renal artery, interlobar artery, arcuate artery, interlobular artery (comes second, longer name), afferent arteriole, glomerular capillaries, efferent arterioles, peritubular capillaries, interlobular vein, arcuate vein, interlobar vein, renal vein
Artery that enters the nephron
Afferent arteriole
Portion of the peritubular capillary that dives into the renal medulla
Vasa recta then back into an interlobular vein
Glomerulus vs peritubular capillary system
Glomerulus–high pressure, fluid out of capillaries
Peritubular–low pressure, filter fluid into capillaries
Two major divisions of peritublar capillary system
Cortical capillaries and deep medullary capillaries
3 layers of the barrier that any solute must pass from the glomerular capillary blood into bowman’s space
Capillary epithelium (Fenestrations) Combined basement membrane(most restrictive) Podocytes (filtration slits,structural integrity)
What does the nephron clear from blood plasma
Unwanted substances:
Urea, creatinine, Uris acid, unrated, Na+, K+, Cl-, H+, Drugs, organics
Blood supply to glomerular capillaries
Afferent arteriole
Blood supply to peritubular capillaries
Efferent arteriole
GFR values
100-140 ml/min (120 ml/min)
180 L/day
99% reabsorbed, 179 liters/day
Always permeable to H20
Proximal convoluted
Thick descending limb
Thin descending limb
Half of loop
Never permeable to H2O
Half of loop
Thin ascending limb
Thick ascending limb (distal straight tubule)
Distal convoluted tubule (early)
ADH permeable to H2O
Late distal convoluted tubule, cortical and medullary collecting tubule
GFR
Glomerular capillary permeability/surface area product (Kf)
Times the net hydrostatic pressure (glomerular capillary minus bowman’s) minus the PCOP (colloid pressure of glomerular capillary blood)
Kf
Permeability times surface area
Permeability: Fenestrations, basement membrane, filtration slits
Surface area:capillary size and number
Major Determinants of GFR
1) hydrostatic or blood pressure
2) permeability/cell-cell junctions
3) plasma components
Pt normal value
Normally 0 due to the drainage by the PCT
Blocking of a structure beyond the glomerulus will cause problems
Actual GF
Kf X ((Pc-Pt)-PIc)
Efferent Arteriole protein concentration
Higher on oncotic pressure, increased protein concentration
Even point where filtration=reabsorption is right before the efferent arteriole, therefor you are ALWAYS FILTERING
The high osmotic pressure will draw H2O back into the peritubular capillary from the PCT, more water into extracellular space
Why does reabsorption back into the capillary on the venular end occur?
Colloid osmotic pressure is much greater than tissue colloid pressure
Water in via osmosis
Equal point of filtration in skeletal muscle vs glomerular capillaries
Due to the high hydrostatic pressure in glomerular capillaries, the colloid osmotic pressure doesn’t reach or surpass it until the efferent capillary
The equal point is when hydrostatic pressure=colloid osmotic pressure
WHat can/cannot pass through glomerular capillary wall?
Water, urea, glucose, inulin, creatinine–Can
Myoglobin, Hb, serum albumin cannot
Renal blood flow effect on Glomerular filtration
Increase flow, increases GFR
Increasing Glomerular pressure
Decreasing osmolality of blood passing through glomerulus since there is less time for blood to lose fluid and increase osmolality
Arterial pressure effect on GFR
Increase arterial pressure, increase GFR by increase glomerular pressure
But–auto regulation makes this a disproportional increase
Afferent arteriole diameter on GFR
Constriction decreases RBF, decrease blood to glomerulus, decreasing glomerulus pressure, decreasing GFR
Dilation–>increase RBF–>increase GP—>increase GFR
Efferent Diameter effect on GFR
Small construction will decrease outflow, increase pressure, increase GFR
Moderate degree of constriction will decrease GFR because blood stays longer in the Glomerulus–>plasma osmolality increases–>filtration decreases
Sympathetic stimulation effect on GFR
Afferent arterioles constrict preferentially to decrease GFR
Could decrease GFR to small perfect, and urinary output could decrease to 0
Kidney stone blocking ureter
Increase hydrostatic pressure in bowman’s space, decreasing GFR, no change in RBF
Reabsorption
Transfer of solute so from tubular fluid (pre-urine) to blood
Solute are subtracted from the filtered amount of pre-urine
Can be passive but often requires ATP
Glucose filtered-glucose excreted
Ureters
Visceral smooth muscle tubes
More urine via peristalsis waves
30 cm long
Connects posterior base of the bladder neck
Clearance
Result of filtration to the tubules or secretion back into the tubule.
Dimensions are crucial
VOLUME/TIME
INPUT=OUT
Only input=arterialx=venousx+urinex
Renal Clearance of a Solute verbal equation
Plasma concentration of a solute times the renal plasma flow of the solute in the artery is equal to (plasma venous concentration of solute times renal plasma flow in veins) plus (urine concentration of X times urine flow rate)
But venous content of X should be 0 (since all is excreted)
Cx
Virtual input volume
Or
RPFa
Classic Clearance Equation
Cx= (Ux times V)/Pax (arterial plasma concentration)
Formula for RPF
Clearance of PAH
Cpah=(Upah times V)/Ppah
RBF equation
RPF/(1-Hct)
(Upah X V)/Ppah all divided by 1-Hct
Cpah/(1-Hct)
Normal value of GFR
120 ml/min
Cannot be considered a clearance because there’s no volume component
GFR conditions
Amount filtered=amount excreted
NO REABSORPTION OR SECRETION CAN TAKE PLACE
Two substances that can be used to measure GFR
Inulin, creatinine
Normal values for Creatinine in urine and plasma
Urine–125
Creatinine-1-2
If Ccr isn’t equals to Ci or GFR, you have renal disease
Filtration Fraction
Fraction of renal plasma flow that becomes glomerular filtrate
FF= GFR/RPF
GFR=120
RPF=600
Normal FF=0.2
On average, a person gets about 20% of their plasma filtered per minute by the kidneys
Cpah equals GFR, RPF, or RBF?
RPF
Changes in afferent arteriolar resistance to GFR
Decrease resistance (increase radius) increases GFR more blood flow
Increase resistance (decrease radius) decreases GFR
Changes in efferent arteriolar resistance to GFR
Decrease resistance (increase radius) decreases GFR
Increase resistance (decrease radius) increases GFR
Myogenic mechanism of GFR
Increase pressure, brief increase in flow until compensation takes place, decrease diameter increase resistance, back to normal flow
Resulting diameter is smaller than original via meter
Structures that make up the JGA
Macula densa cells of DCT at the transitions from the TAL
Extra glomerular mesangal cells
Renin producing JG cells
What if macula densa sees too much NaCl in tubule?
Want to decrease GFR by constricting afferent and possibly dilating efferent
Purpos of NKCC2 in TAL
Transport NaCl into MDC via apical NKCC2
General mechanism of GFR tubuloglomerular feedback
in GFR, inc salt in tubular fluid of TAL, inc salt to MDC via NKCC1, inc Cl in intercellular, Cl transport across MDC basolateral membrane, activation of non-selective cation channel on basolateral membrane, inc Ca2+ in MDC, MDC secrete ATP increase, decrease PGE2 and JG release of renin, CONSTRICTION of afferent, decrease GFR
What two dilator mechanisms are decreased when Calcium moves into the MDC
Decrease of PGE2 and NO (while increase ATP)
What happens to the extracellular Cl- increase after MDC measures increase NaCl in tubular fluid?
Cl increases and inhibits the JG cell release of renin, decreasing circulating renin, decreasing AngII and aldosterone (entire systemic reduction in resistance, decrease of blood pressure, decreasing GFR
Regulation by SNS of GFR
Dehydration, low blood pressure, strong emotions fear and/or pain
NE to alpha 1 adrenocrecptors
Afferent constriction
Decrease RBF, decrease GFR
Low AGTII on GFR
Constricts both efferent and afferent, but preference for efferent due to the diameter of the afferent
Decrease RBF, increase GFR
NO released from afferent when AGTII stimulated (counteracting constrictor)
Decrease RBF, increase GFR due to the dissimilar affects on efferent and afferent
High levels of AGTII
Decrease both RBF GFR
ET1 on GFR
Similar to high AGTII
Renal blood vessels, mesagnium, distal tubule secretion
Or in response to ANGII, bradykinin, epi, or decreased shear stress
Adenosine effect of GFR
Produced by kidneys
A1-adensonsine constriction of afferent
Decrease RBF and GFR
Mechanisms that decrease both RBF and GFR
Adenosine, high concentrations of AGTII, ET1, sympathetically
Substances that decrease RBF but increase GFR
Small concentration of AGTII
Prostaglandins effect on GFR
Sympathetic escape to increase RBF to avoid ischemic damage. Dampens sympathetic constriction of the afferent arterioles and its consequences.
No real change in GFR
Nitric oxide on GFR
Increase RBF, increase GFR
Vasodilates both afferent and efferents
Stimulated by ACh, Histamine, Bradykinin, ATP and increased shear stress
Bradykinin effect on GFR
Increase RBF, increase GFR
Stimulates NO and PG release
Vasodilation
ANP and BNP on GFR
No change in RBF, increase in GFR
Released by increased in extracellular volume (more Na in the body) so you’d want to increase GFR, dilation of Afferent Arterioles, constriction of efferent
Ultimate goal–decrease blood volume
Histamine affect on GFR
Dilation of both afferent and efferent
Increase RBF and GFR
Substances that increase both RBF and GFR
Histamine, bradykinin, NO
Two outliers that only effect GFR OR RBF
Increase GFR only–Natriuretic peptide
Think, make up pee.
Increase RBF only–Prostaglandins (sympathetic escape)
Net Reabsorptoin
Filtered-excreted
In mg/min
Net secreted
Excreted-filtered
Reversal of net Reabsorptoin
relative U/P ratios
Positive value>1, you are secreting something back into the urine because it is greater than something that is being filtered completely, so something must have happened to add more of it back into the urine
Positive value
Relative U/P for something less than 1
Make sure to subtract the decimal you get from 1, so that you can calculate the amount that is reabsorbed. The decimal you get is the amount that is filtered
Na+/H+ exchanger and Na/K+ATPase
Na from tubular fluid into tubule cell, H+ into tubular fluid
ATPase– promotes reabsorption gradient
SGLT-2
Simport to bring Na+ and Glucose down their concentration gradient to promote reabsorption
Apical
High capacity but a low affinity for glucose because this is where the high concentration of glucose is. Can transport as much as possible. Will take in any glucose moiety
FIRST HALF
GLUT-2
Basolateral transport of glucose into peritubular capillary network
1st half proximal tubule
3 random transport proteins in first half proximal tubule
Na/Amino acids
Na/P
Na/Lactate
All symport
All can flow freely through into blood (reabsorbed)
Anions that can be reabsorbed in the 2nd half of proximal tubule cell
OH Formate Oxalate Bicarb Sulfate
This is an H+-anion exchanger that brings anions in, and then the H+ and anion leave to bring in Na and Cl.
Cl will exit the cell though K+/Cl- symport to be reabsorbed
SGLT-1
Late proximal tubule cell
Na/Glucose symport
Higher affinity, low capacity for glucose
Catch anything SGLT2 missed,
Influence of GFR on reabsorption
As GFR increase, reabsorption of solute and H2O increases
More H2O is filtered into the tubule, and that makes the peritubular capillary blood (from efferent) have a higher concentration of protein=higher oncotic pressure, as the peritubular capillary surround PT, the blood osmotic forces draws H2O and solute out of the tubule and into the capillary
NaKCC location
Thick ascending limb (impermeable to H2O)
Furosemide blocks in loop of Henle, diuretic.
Ions come in, but water cannot follow
Transport in early distal tubule
Water impermeable, NaCl symport
Thiazide blockage, diuretic, excess sodium stays in tubule nephron, decreasing BV
Principle Cell
Late distal tubule or collecting duct
AQP2–apical
AQP 3 and 4, basolateral
Potassium flows into urine via concentration gradient. Sodium flows into blood
Alpha intercalated cells
Secrete acid for K+ and take in Cl- from blood to conserve bicarbonate
Impermeable to H2O
Late distal tubule or collecting duct
Beta intercalated cell
Late distal tubule or collecting duct
Secrete bicarb, save/reabsorb acid (to neutralize bicarb in blood)
CA
Impermeable to H2O
Transport Maximum
Co-transporters limited by Maximum rate and maximum activity
The plasma glucose concentration at which glucose begins to appear in the urine
Tm for glucose
375
Splay
Not all nephrons are identical, smaller (shorter) nephrons will have thier SGLT and/or Na+/K+ ATPases saturated before bigger ones
What does a low Tm show?
Failure of some nephron filter. Decrease in Tm represents dysfunction at the level of capillaries.
Excreted-filtered?
Secreted
Decrease of PAH Tm
The transporters for PAH are on the basolateral (peritubular side) of the proximal tubule eipthelium, meaning they are the ones not getting blood.
Limits for Tm for PAH and Glucose
PAH–peritubular basolateral membrane
Glucose–luminal membrane
ANGII
Released due to decrease blood volume
Effects proximal tubule to increase Na+ and H2O Reabsorptoin, to increase BV
Aldosterone
TAL, distal tubule, collecting duct
Stimulates Na+ reabsorption
Stimulates K+ secretion
Aldosterone effect on principle cells during acute phase
Increase activity of Na/K+-ATPase BLM
By stimulation of Mineralocorticoid Nuclear
Aldosterone effects on principle cells during chronic phase
Increase number of Na/K+ ATPase on basolateral membrane
Increase the expression of Na+ and K+ in apical membrane
Release of more K+ from the cell into the urine due to addition of K+ transporters in apical membrane
ADH
From posterior pituitary in response to low blood volume or decrease plasma osmolality
Add AQP2 to the apical membrane to increase blood volume
Antidiuretic
Vasoconstriction of systemic
Increases activity of NKCC in TAL
V2 transporter on basolateral membrane
Mechanism of ADH
Binds V2 on basolateral membrane, increasing GS, increasing ardently Cyclase activity, increase cAMP, stimulating more PKA that inserts AQP2 in apical membrane
ADH and urea in principal cell of medullary collecting duct
Draws urea into intersitial fluid of medulla, urea is osmotically active
Ureaporins (UTA1 and UTA3)
A1–apical
A3–basolateral
Summary of ADH
Inserts AQP2 into apical membrane of distal nephron
Stimulates thirst
Increases activity of NKCC in the TAL
Increases inner medullary collecting duct permeability to urea, increasing the osmolality of the interstitium
Vasoconstriction to decrease the tank
Juxtaglomerular regulation of blood pressure, volume, and GFR
Increase GFR, increase NaCL in PCT, if NaCl greater than Tm Macula densa senses increase NaCl in urine, decrease secretion of NO, afferent arteriolar constriction, decrease blood flow to glomerulus, decreas GFR`
Two mechanisms of renin release
Stretch of Mechanoreceptors trigger JG cells to convert pro-renin to renin
Sympathetic stimulation to beta one adrenergic mechanism,
Renin release in response to low blood pressure/ low blood volume
decrease BP, decrease glomerulus pressure, Afferent arteriole mechanoreceptors stimulate, JCG cells convert pro-renin to renin, ANGII, constriction of peripheral arterioles (increasing TPR), aldosterone secretion, late DCT and CT H2O and Na+ secretion of K+
Stimulates release of ADH aquaporins,
PTH
Inhibits Na and H20 reabsorption in PCT secondary to phosphate reabsorption inhibition
Urodilatin
Secreted by the DT and CD, paracrine effects to inhibit Na+ reabsorption in collecting duct
Water loss
Countercurrent Exchange
Vasa recta capillaries lose water to the medullary intersitium due to the osmotic gradient created by the loop of henle’s counter current multiplier
Calcium homeostasis in kidney depends on
Total amount of body Ca2+
Distribution of Ca2+ between bone and ECF/Plasma
PCT and Calcium Homeostasis
70% (80 para, 20 trans via Ca2+-ATPase)
Keep proximal tubular Ca2+ small
Hypocalcemia
Low blood Ca2+
PTH secretion, increasing bone resorption, increase Ca2+ reabsorption by TAL and DT
Stimulates release of calcitrol (vit d3 metabolite produced by proximal tubule)
Calcitrol
Metabolite of Vit D3 produced by Proximal Tubule
Hypercalcemia
Calcitonin from thyroid
Bone formation
Decrease plasma Ca
PTH effects in Kidney Nephron
- Increased Ca Reabsorptoin in ascending loop and distal tuble
- Decrease PO4- reabsorption in proximal loop by decreasing Tm
- Activating renal 1-alpha hydroxylated in PT cells to activate vitd
Everything is proximal is normal
Ca-ATPase in basolateral is most effected in neprhon
Active form of Vit D
1,25
Without PTH there is no activated 1-alpha-hydroxylated. The enzyme 24-hydroxylase will from inactive VIt D (24,25)
2 actions of Vit D
Synthesis of calcium binding protein that is needed:
Kidney distal tubule epithelium to efficient reabsorb filtered calcium
In the intestinal epithelium to efficiently absorb calcium from the diet.—> increase calcium in the blood
Where is the majority of phosphate absorbed in the proximal tubule?
85% of phosphate is absorbed in the proximal tubule, larger loss here
15 is lost in the urine due to the distal sections of the nephron not reabsorbing phosphate.
PTH causes phosphaturia
Four main groups of diuretics
- Things that increase GFR (more across glomerulus)
- Substance that inhibit ADH cause increased urine output
- Excess osmotically active particles (exceeding Tm for most of them, you will urinate)
- Renal transport inhibiting substances (Furosemide)
Inhibition of ADH as a diuretic
Pituitary disease
Diabetes insipidus (lack of ADH from pituitary)
Alcohol (inhibits ADH release)
Narcotics (depress CNS, inhibit ADH)
Lack of adequate ADH or lack of receptor
Carbonic Anhydrase Inhbitors
PCT (Because there is not brush border in DCT)
Inhibits filtered bicarb from reabsorption (losing water with this), promoting H+ and bicarb secretion
Short term effect
Metabolic acidosis
Loop Diuretics
Furosemide
Apical NaK2Cl cotranpsorter in TAL
K_ wasting diuretic
Thiazide Diuretics
Cholorthiazide
Inhibit Na-Cl cotranpsorter in the DCT
Amiloride and Triamterene
K+ sparing diuretic
Inhibit the apical Na+ channels in the Collecting Ducts
Spironolactones
Interfere with the actions of aldosterone
Increase Na+ and K+
