Renal embryology, anatomy, physiology Flashcards
Describe the development (timetable/parts) of the kidney. What is derived from the ureteric bud? Frm the metanephric mesenchyme? What is the last portion to canalize? Clinical implications?
Pronephros: week 4, then degenerates
Mesonephros: interim kidney for 1st trimester, then contributes to male genitalia
Metanephros: permanent; first appears in 5th week of gestation, continues to develop through 32-36 weeks.
Ureteric bud (caudal end of mesonephric duct): ureter, pelvises, calyces, collecting ducts. Fully canalized by 10th week
Metenephric mesenchyme-interaction w/ bud leads to formation of glomerulus through the DCT
Ureteropelvic junction-last to canalize
Mmost common site of obstruction
Describe the pathophys and symptoms of potters sequence. Causes?
Oligohydramnios leads to compression of developing fetus leading to limb deformities and facial anomalies.
Chest is compressed and their is a lack of swallowing of amniotic fluid into lungs which leads to pulmonary hypoplasia (can cause death).
ARPKD, obstructive uropathy (posterior urethral valves), bilateral kidney agenesis
What is the pathophys of horseshoe kidney? Symptoms? Causes?
INferior poles of kidneys fuse. As they ascend, they get stuck under the IMA and remain low in abdomen.
Kidneys function normally.
Ureteropelvic junction obstruction, hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes.
What is multicystic dysplastic kidney pathophys? presentation? Diagnosis?
Abnormal interaction bw ureteric bud and metanephric mesenchyme
Nonfunctional kidney w/ cysts and CT
If unilateral, asymp w/ compensatory hypertrophy of CL kidney
Prenatal U/S
What is the pathophys of duplex collecting system? Associations? Risks?
Y shaped bifid ureter due to bifurcation of ureteric bud before it hits metanephric blastema or when two ureters hit blastema
Vesicoureteral reflux and/or ureteral obstruction
Incr. risk fr UTIs
Which kidney is taken during donor transplantation? Why?
Left, long renal vein
Describe the pathway of the ureters while entering bladder. Clinical implication?
Ureters pass under uterine artery and ductus deferens (retroperitoneal)
Water under the bridge
Gyn procedures must make sure not to obstruct/damage ureters when working w/ uterine artery.
What percent of body mass is water? What percent of body mass is ICF? What percent of body mass is ECF? What is a normal HCT? What percent of ECF is plasma? What is a normal blood volume? How is plasma volume mesaured? EC volume? What is a normal osmolality?
water=60% ICF=40% (2/3 of water) ECF=20% (1/3 of water) HCT=45% Plasma of ECF=25% Blood volume=6L Radiolabeled albumin Inulin Osmol=285-295 mOsm/kg H20
What is the function of the glomerular filtration barrier? 3 parts? Waht is lost in nephrotic syndrome?
filtration of plasma according to size and charge
Fenestrated capillary endothelium (size barrier)
Fused BM w/ heparan sulfate (neg. charge barrier)
epithelial layer consisting of podocyte foot processes
Charge barrier
How is renal clearance calculated? Waht does it mean if it’s less than GFR? Equal to? More?
Clearance of X=(Urine conc. of X) (Urine flow rate)/ (plasma concentration of X)
Cx < GFR: net tubular reabsorption of X
Equal to: no net secretion or absorption
More than: net tubular secretion
What is the equation for GFR? What is the best way to actually calculate GFR? Why? What is actually used to approximate GFR? How and why is it just an approx? What is a normal GFR?
Kf ((Pgc-Pbs) - (Pigc-Pibs))
Inulin=neither filtered nor secreted
Creatinine clearance=slightly overestimates it b/c it is moderately secreted
100 mL/min
How can effective renal plasma flow be estimated? Why? Why is it just an estimation? How is this then used to calculate RBF?
Para-aminohippuric acid (PAH)=both filtered and secreted in PCT (near 100% excretion)
eRPF Understimates true renal plasma flow by 10%
RBF=RPF/ (1-HCT)
What is the equal for filtration fraction ?Normal value? How is filtered load calculated? How do NSAIDS affect RPF, GFR, and FF? Mechanism? What might NSAID use result in? ACEIs?
GFR/RPF (20%)
GFR x plasma concentration
NSAIDS block production of prostaglandins
Prostagladins dilate afferent arteriole which incr. RPF and GFR equally, so FF is the same
By decr. GFR, NSAIDS may result in acute renal failure
ACEIs blck ATII which constricts the efferent arteriolre which decr. RPF and incr. GFR so FF increases
What decr. GFR, decr. RPF, and has no effect on FF? Incr, decr., incr? Decr., no effect, decr (2)? Incr, no effect, incr?
Aff. art constriction
effer art constr
incr plasma protein conc, constriction of ureter
decr. plasma portein conc.
How is filtered load calculated? Excretion rate? How is reabsorption calculated? Secretion?
FL=GFR x Px
Excr. rate=V (urine flow) x Ux (urine conc.)
reab=filtered-excreted
secr=excr-filtered
Describe glucose in PCT? At what plasma glucose does glucosuria being? At what point are all transporters fully saturated? What can happen in normal pregnancy?
glucose at a normal plasma level is completely reab in PCT by Na/Gluc cotransport
200 mg/dL
375 mg/dL
Decrease ability of PCT to reab glucose and AAs
What happens to AAs in PCT? What is the pathophys of hartnups disease? Symptoms? Treatment?
Na+ dependent transporters in PCT reabsorb all AAs
Deficiency of neutral AA (tryptophan) transporters in PCT and on enterocytes leading to neutral aminoaciduria and decr. absorption from the gut
Decr. tryptophan leads to decr. niacin leading to pellagra like symptoms (dementia, diarrhea, dermatitis)
High protein diet and nicotinic acid
Describe the physiology of the PCT. What does PTH do there? ATII? How much of Na is reabsorbed there? What is the function of acetazolamide?
Reabsorbs all glucose and AAs and most HCO3-
Reabsorbs 65-80% Na
Sodium/Glucose cotransporter (both enter cell)
Sodium/AA transporter (AA enters cell)
Na/H antiporter (Na enters cell, H to lumen)
In lumen, H binds with HCO3 and eventually forms H20 and C02 (CA) which are transported into cell and form H and HCO3 (CA). H is transported into lumen and HCO3 into blood
Cl/Base- antiporter (Cl to cell, base to lumen)
Na/K ATPase (Na to blood, K to cell)
PTH inhibits Na/PO4 cotransport which leads to PO4 excretion
ATII stimulates Na/H exchange leading to incr. Na, H20, and HCO3 reabsorption (contraction alkalosis)
Acetazolamide blocks luminal CA which prevents H2O and CO2 from entering the cell.
What are the renal tubular defects? pneumonic?
FABulous Glittering LiquidS
FAnconi (PCT) Bartter Syndrome (Thick ascending) Gitellman (DCT) Liddle (collecting) Syndrome of apparent mineralocorticoid excess (collecting)
What is the pathophys of fanconi syndrome? Possible result? Causes?
Generalized reab defect in PCT
Incr. excretion of nearly all AAs, glucose, HCO3, and PO4
Metabolic acidosis
Hereditary defects (wilsons, tyrosinemia, GSD), ischemia, MM, nephrotoxins/drugs, lead poisoning
Describe the phys of the thin descending loop of Henle. Overall function?
Passively reabsorbs H20 (imperm to Na). Concentrating segment. Makes urine hypertonic.
Describe the phys of the thick ascending loop of henle. What does it reab and how? Function? How much Na is absorbed? What effect do loop diuretics have?
Na/K/2Cl cotransporter (all from lumen into cell)
K+ backleak channel (from cell to lumen=creates + poten)
Mg/Ca reabsorbed paracellularly (due to backleak)
Na/K ATPase (Na to blood, K to cell)
K and Cl flow into blood down EC gradient
Loop diuretics block the Na/K/2Cl channel
Makes urine less concentrated as it ascends
10-20% Na
Describe the pathophys of Barter syndrome. Results?
Blocks Na/K/2Cl cotransporter
Hypokalemia and metabolic alkalosis (more K in lumen) and hypercalciuria (less K backleak)
Describe the phys of the early DCT? Function? What is the effect of PTH there? How much of total Na is reab? Effect of thiazides?
Na/Cl cotrans (both enter cell from lumen)
Ca enters cell from lumen
Na/K ATPase (na to blood, k to cell)
Na/Ca antiport (Na to cell, Ca to blood)
PTH incr. Ca/Na exchange leading to more Ca reab
Makes urine most dilute (hypotonic)
5/10% of Na reab
Thiazides block the Na/Cl cotrans
What is Gitelman syndrome? Results?
Defect in NaCl cotransporter in DCT
Hypokalemia, hypomagnesia, metabolic alkalosis, hypocalciuria
Describe the phys of the collecting tubule. What is reab/secreted and where and how? What is the function of aldosterone there? ADH? What percent of Na reab? What is the effect of amiloride/triamterene?
PRINCIPAL CELL
Na enters cell from lumen basically in exchange for K entering lumen from cell.
Na/K ATPase
ADH acts on V2 receptor leading to insertin of aquaporin H20 channels so H20 can enter cell from lumen.
ALPHA INTERCAL
H+ ATPase (acid enters lumen from cell)
K/H ATPase antiporter (K enters cell and H enters lumen)
HCO3/Cl antiport ( HCO3 enters blood, Cl enters cell)
BETA INTERCAL
Cl is exchanged for HCO3 (Cl into cell, HCO3 into lumen)
H+ ATPase (H into the blood)
Aldosterone binds to mineralocorticoid receptor causing protein synth.
Principal cells: Incr. apical K+ conductance, Incr. Na/K pump, incr. ENaC channels leads to incr. sodium reab and incr. K secretion.
Alpha inter: Incr. H+ ATPase activity leadint o incr. HCO3/Cl- activity (loss of acid)
3-5%
They block ENaC (sodium transporter) which allows potassium to be spared.
What is the pathophys of liddle syndrome? Results? Treatment?
Gain of function mutation leads to incr. Na reab in collecting tubules.
Hypertension, hypokalemia, metabolic alkalosis (incr. K+ in lumen leads to more exchange with H+ leading to incr. H+ in lumen), decr. aldosterone
amiloride
What is the pathophys of syndrome of apparent mineralocorticoid excess? Symptoms? How is this acquired?
Hereditary defic of 11 beta hydroxysteroid dehydrogenase which normally converts cortisl to cortisone in mineralocorticoid receptor containing cells before it can act on the MCR. Excess cortisol in cells leads to incr. MCR activity leading to:
Hypertension, hypokalemia, metabolic alk, low serum aldosterone
Glycyrhetic acid (licorice) which blocks 11 beta etc.
What causes renin to be released? Mechanism? What is the function of renin? Where is ACE released from? Angiotensinogen? What are the functions of ACE? How do beta blockers affect BP?
Decr. BP (JG cells)
Decr. NaCl delivery to DCT(macula densa cells—>adenosine release—>vasoconstriction)
Incr. symp tone (beta 1 receptors—>beta blockers inhibit renin release leading to decr. BP)
Convert angiotensinogen (liver) to AT1 which is converted to ATII by ACE (lungs/kidney) ACE also aids in bradykinin breakdown
What are the functions of ATII? Where and how does it exert these effects?
AT1 receptor on vasc. SM leading to vasoconstricion and incr BP.
Affects baroreceptor function to help limit reflex bradycardia
Constricts efferent arteriole of glomerulus (incr. FF to preserve reanl function (GFR) in low volume states)
Releases aldosterone from adrenal gland.
Incr. Na channel and Na/K pump insertion in principal cells. Enhances K and H excretion by way of principal K channels and alpha intercalated H atpases.
Na and H20 reabsorption
ADH release from post. pit. (incr. aquaporin in principal cells)
Incr. PCT Na/H activity leading to Na, HCO3, and H20 reab
Stimulates hypothalamus (thirst)
What causes EPO to be released? From where? How is vitamin D made active in kidney? What part? What enzyme? In response to what?
Interstitial cells in peritubular capillary bed in response to hypoxia
25-OH D3 to 1,25-OH D3 by 1alpha-hydroxylase in response to PTH. Occurs in PCT cells.
What is the overall effect of ATII, PTH, ANP, aldosterone, and ADH on the kidney?
ATII=Incr. GFR and FF but with compensatory Na reab in proximal and distal (aldo) nephron
Preservation of renal function in low volume state with simultaneous maintenance of circulating volume (Na)
ANP=Incr. GFR and incr. Na filtration leading to Na and volume loss
Aldo=Secreted in response to ATII and incr. plasma K. Incr. Na reab. Incr. K and H secretion
ADH=In response to incr. plasma osmol. and decr. blood volume. Aquaporins and H20 reab
PTH=In response to decr. plasma Ca, incr. plasma PO4, or decr. plasma vit. D. Incr. Ca reab (DCT), decr. PO4 reab (PCT), and inc.r vit D production (PCT).
Vit. D leads to incr. Ca and PO4 absorption from gut.
What causes potassium to shift out of cells (hyperkalemia)? Mechanism? Into cells?
DO LABS
Digitalis (blocks Na/K ATPase) HyperOsmolarity Lysis of cells Acidosis (H/K exchange) Beta blocker (blocks Na/K ATPase) High blood sugar (insulin deficiency)
Hypoosmolarity
Alkalosis
B agonist (incr. Na/K ATPase)
Insulin (incr. Na/K ATP ase)
What will low serum result in? High? Na K Ca Mg PO4
LOW
Na: nausea, malaise, stupor, coma, seizures (edema)
K: U waves on ECG, flattened T waves, arrythmias, muscle spasm (poor repolarization)
Ca: Tetany (less calcium means less sodium is required for AP), seizures, QT prolongation (Slower entering of Ca into cell creates a slower repol process)
Mg: Tetany, Torsades, hypokalemia
PO4: Bone loss, osteomalacia, rickets
HIGH
Na: irritability, stupor, coma
K: Wide QRS and peaked T waves on ECG, arrhythmias, muscle weakness (Too much repol)
Ca: Stones, bones, groans, thrones, psychiatric overtones, but not necessarily calciuria
Mg: Decr. DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
PO4: Renal stones, metastatic calcifications, hypocalcemia
What is disrupted in met acid, met alk, resp acid, and resp alk and what is the compensatory response? What is the henderson hasselbach equation? What is the Winters formula and why is it used?
Met Acid: Decr. HCO3=hyperventilation to decr. PCO2
Met Alk: Incr. HCO3=hypoventilation to incr. PCO2
Resp. Acid: Incr. PCO2=Incr. renal HCO3 reab
Resp. Alk: Decr. PCO2=Decr. renal HCO3 reab
pH=6.1 + log (HCO3/.03PCO2)
To predict compensation:
PCO2=1.5 [HCO3] + 8 +/- 2
What is a logarithm to determine resp/met alk/acid? How is the anion gap determined?
pH< 7.35 =acidemia
PCO2>40=resp. acidosis
PCO27.45 =alkalemia
PCO240=met alk
Anion gap=Na - (Cl+HCO3)
8-12
What are some causes of resp. acidosis? Resp. Alkalosis?
Airway obstruction acute lung disease chronic lung disease opioids weakening of resp. muscles
TACHYPNEA hysteria Hypoxemia (high altitude) Salicylates (early) Tumor Pulmonary embolism
What are some causes of incr. anion gap met. acid? Normal anion gap?
MUDPILES
Methanol Uremia DKA Propylene glycol Iron tablets or isoniazid Lactic acidosis Ethylene glycol Salicylates (late)
HARD-ASS
Hyperalimentation Addisons Renal Tubular Acidosis Diarrhea Acetazolamide Spironolactone Saline infusion
What are some causes of metabolic alk w/ compensation?
Loop/thiazide diuretics
Vomiting
Antacid use
Hyperaldosteronism
What is renal tubular acidosis? What are the 3 main types? What is the urine pH like in each?
A disorder of the renal tubules that leads to normal anion gap (hyperchloremic=hypo HCO3) metabolic acidosis
Distal=urine pH > 5.5
Proximal=urine pH < 5.5
Hyperkalemic=urine pH < 5.5
Describe the pathophys of RTA type 1. Symptoms? Causes?
Defect in ability of alpha intercalated cells to secrete H+ leading to no new HCO3 generation leading to metabolic acidosis.
Hypokalemia
Incr. risk for calcium phosphate kidney stones (incr. urine pH and incr. bone turnover)
Ampho B toxicity, analgesic nephropathy, cong. anomalies (obstruction) of urinary tract
Describe the pathophys of RTA type 2. Symp? Causes?
Defect in PCT HCO3 reabsorption leads in incr. HCO3 excretion in urine and metabolic acidosis. Urine is still acidified by alpha intercal. in collecting tubule.
Hypokalemia, incr. risk for hypophosphatemic rickets
Fanconi syndrome and CA inhibitors
Describe the pathophys of RTA type 4. Symp? Causes?
Hypoaldosteronism leads to hyperkalemia leading to decr. NH3 synth in PCT leading to decr. NH4+ excretion.
Decr. aldo synth (diabetic hyporetinism, ACEIs, ARBs, NSAIDS, heparin, cyclosporine, adrenal insuff), or aldo resistance (K sparing diuretics, nephropathy due to obstruction, TMP/SMX)
