Renal Flashcards
Kidney embryology
P S T
Pronephros: week 4, then degenerates
Mesonephros: functions as interim kidney for 1st trimester, later contributes to male genital system system
Metanephros: permanent, first appears in 5th week, nephrogenesis continues though weeks 32-36 of gestation
Ureteric bud (Metenephric diverticulum)- derived from caudal end of mesonephric duct, gives rise to ureter, pelvis, calyces, collecting ducts, fully canalized by 10th week
Metenephric mesenchyme (Metenephric blastema)- ureteric bud interacts with this tissue interaction induces differentiation and formation of glomerulus through to distal convoluted tubule Aberrent interaction between these 2 tissues results in several kidney malformations-- renal agenensis, multicystic dysplastic kidney)
Ureteropelvic junction- last to canalize–> congenital obstruction. Most common cause of prenatal hydronephrosis (detected by prenatal ultrasound
Potter sequence/syndrom
Oligohydramnios–> compression of developing fetus–> limb deformities, facial anomalies (low set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs–>pulmonary hypoplasia (cause of death)
Causes include ARPKD, obstructive uropathy (posterior urethral valve), bilateral renal agenesis, chronic placental insufficiency
Babies who cant pee- Pulmonary hypoplasia, oligohydramnios, twisted face, twisted skin, extremity defects, renal failure (in utero)
Horseshoe kidney
Inferior poles of both kidneys fuse abnormally, as they ascend from pelivis during fetal development they get caught on the IMA and remain low in the abdomen, kidneys function normally, associated with hydronephrosis (ureteropelvic junction obstruction), renal stones, infection increased risk of renal cancer
Higher incidence in chromosomal aneuploidy (turner syndrome (turner, 13 18 21)
Congenital solitary functioning kidney
only one functional kidney, asymptomatic, with hypertrophy of functioning, can be seen in utero
Unilateral renal ageneisis- utereteric bud fails to develop and induce differentiation of metanephric mesenchyme–> complete absence of kidney and ureter
Multicystic dysplastic kidney- Ureteric bud fails to nduce differentiation of metanephric mesenchyme–> nonfunctional kidney consisiting of cysts and CT, usually nongenentic and unilateral–> biat will be potter
Duplex collecting system
Bifurcation of ureteric bud before it enters the metanephric blastema creates a Y shaped bifid ureter,
Can also be 2 ureteric buds reaching and interacting with metanephric blastema
vesicoureteral reflux and/or ureteral obstruction, increased risk of UTIs
Posterior urethral valves
membrane remnant in posterior urethra in males
Urethral obstruction- bilat hydronephrosis, dilated/thickwalled bladder on US
oligohydramnios in severe obstruction
Kidney structure
Left kidney gets cut out, longer renal vein (with left gonal vein, the arteries both com from the aorta)
Renal blood flow: renal artery-> segmental artery-> interlobar artery-> arcuate artery-> interlobular artery-> aferrent arteriole-> glomerulus-> efferent arteriole-> vasa recta/ peritubular capillaries-> venous outflow
Left renal vein receives left suprarenal and left gonadal vein
Despite high renal blood flow, renal medulla recieves less blood flow–> very sensitive to hypoxia
Glomerulus
Filtration barier- Endothelial cells, Basement membrane-Podocytes (touch urine)
The afferent has the Juxtaglomerular cells that are connected to the macula dena near the distal convoluted tubules
Juxtaglomerular cells secrete renin in response to B1 receptors, decreased perfusion pressure, decrease NaCL (aka water) sensed by macula densa
Course of ureters
Renal pelvis, travels under gonadal arteries-> over common iliac artery-> underuterine artery/vas deferens (reteroperitoneal
Gynecologic procedures (ligating the uterine or ovarian vessels can damage the ureterpp> ureteral obstruction or leak
Bladder contraction compresses the intravesical ureter, prevening urine reflux
Blood supply to ureter: Proximal (renal arteries), Middle (gonadal artery, aorta, common and internal iliacs) Distal (internal iliac and superior vesicle arteries)
3 common points of ureteral obstruction: ureteropelvic junction, pelvic inlet, ureterovesicle junction
Fluid compartments
60-40-20 rule (percents of body weight)
60% total body water
40% Intracellular fluid, mainly composed of K, Mg, organic phosphates (ATP)
20% Extracellular fluid, mainly Na, CL, HCO3, albumin
Plasma volume 25% of ECG, 75% is interstitial fluid
Plasma can be measured by radiolabeling albumin
ECF volume can be measured by inulin or mannitol
Serum osmolality= 285-295 mOsm/kg of H20
Plasma volume= total blood volume x (1-Hct)
Total blood volume 6L
Glomerular filtration barrier
filters plasma
Fenestrated capillary endothelium
Basement membrane with type 4 collagen chains and heparanated sulfte
Visceral epithelial layer consisting of podocyte foot processes
All 3 layers contain negative charged glycoproteins that prevent entry of negative charged molecules (AKA Albumin)
Size barrier- fenestrated capillary endothelium (prevents entry of >100 nm molecules/ blood cells
Podocytes interpose with glomerular basement membrane: slit diaphragm (prevents entry of molecules > 50-60 nm)
Renal clearance
Cx= clearance (mL/min) Ux= Urine concentration of X (mg/mL) Px= Plasma concentration of X (mg/mL) V= urine flow (Vlow) rate (mL/Min)
Cx= (Ux *Vx)/ Px (volume of plasma that a substance is completely cleared in urine /time)
If Cx < GFR (net Reabsorption or not completely freely filtered)
if Cx> GFR (net tubular secretion of X
if Cx = GFR (no secretion or REAB)
GFR
Inulin can be used to estimate GFR cause not REAB or secreted
Cinulin= (Uinulin * V)/ Plamsa inulin
Normal GFR= 100 mL/min
Creatinine clearance is an approximate measure of GFR (overestimates cause creatinine is a litttle secreted in renal tubules)
Effective renal plasma flow
eRPF can be estimated using para Aminohippuric acid clearacen
it is filtered and secreated bu no REAB, so 100% of it goes in urine
eRPF = (Upah * V)/ Ppah
RBF= RPF/ (1-Hct)
usually 20-25% of Cardiac output
eRPF underestimates true renal plasma flow
Filtration
Filtration fraction= GFR/RPF ( how good is the glomerulus at fitering out the plasma)
proportion to GFR
normal 20%
filtered load (mg/min) = GFR x Plasma conentration
Ureter constriction does not change renal plasma flow
Dehydration - decreases RPF by a lot comared to gfR decrease so elevated FF
REabsorption and secretion rate calculation
Filtered load: GFR x Px
Excretion rate: V x Ux
Reabsorption = filtered - excreted
Secretion rate= excreted - filtered
FeNA = fractional excretion of sodium
amount excreted/amount filtered
Glucose Clearance
Glucose is normally completely reabsorbed in proximal convoluted tubule (PCT) by Na/glucose co transport
In adults 200 mg/dl glucosuria starts, at 375 all na glucose co transportes are fully saturated
pregants is associated with increased GFR (glucose gets in urine at normal leverls
SGLT 2 inhibitors (Flozins –> glucosuria
Proximal convoluted tubule
Early PCT contains brush border. reabsorbs all glucose and Amino acids and most HCO3-, Na, Cl, PO4-, K, H20 and uric acid
Isotonic absorption, generates and secretes ammonia (NH3) which enables the kidney to secrete more H+
SGLT2 inhibitors prevent Na/Glut co transporters
Angiotensin 2 increases the action of NA/H+ transporter
CO2 +H20 –> H2CO3 via carbonic anhydrase which then spontaneously turns into H+ and HcO3- (HCO3- gets reabsorbed and H+ gets secreted with Na being reabsorbed
Carbonic anhydrase ALSO can convert H2CO3 into CO2 and H2O from HCO3 and H+
Acetazolamide inhibits carbonic anhydrase
PTH inhibits Na/PO4 cotranssport–> PO4 excretion
Angiotensin 2 stimulates Na/H exchange–> increased Na and H20 and HCO3- reabsorption (permitting contraction alkalosis)
65-80% Na and H20 reabsorption
Thin descending loop of henly
Its thin because theres no water in it
passively reabsorbes H20, via medullary hypertonicity impermeable to Na, concentrating segment makes urine hypertonic
The medullary interstitium (extremely hypertonic) is highly permeable to water but not ions
Thick ascending limb of henle
REABs NA, K 2 CL symporter
indirectly induces paracellular reabsorption of Mg2, Ca2 through + lumen generated by K+ in the urine, impermeable to H2O, makes urine less concentrated as it ascends
10-20% of Na reabsorption
Loop diuretics inhibit the Na K 2CL symporter
Early distal convoluted tubules
Reabsorbs Na CL, impermeable to H20 Makes urine fully dilute
PTH increases Ca and/Na exchange–> increased Ca reabsorption
5-10 % of NA reabsorbed
Contains Na/Cl symporter,
Ca sucker
Na/Caswitcher on basal side, CL diffusion
Thiazides inhibit the NA,CL cotransporter
collecting tubules
reabsorbs Na + in exchange for secreting K and H (regulated by aldosterone)
Aldosterone- acts on mineralocorticoid receptor–> mRNA–> protein synthesis
In principal cells increase in K conductance, Na/K pump, increase epithelial Na channels (ENaC) acitivity–> Lumen negativity–> K secretion
In alpHa intercalated cells- lumen negativity –>H + ATPase activity –> increased H secretion–> HCO3-/CL- exchanger activity
ADH acts at V2 receptors–> insertion of aquaporin H20 channels on apical side
3-5% Na reabsorbed
Renal tubular defects
Fanconis BaGeLS
Fanconi syndrome- PCT
Barter syndrom- ascending loop of henle
Giltelman syndrome- distal convoluted tubule
Liddle syndrome
Syndrome of Apperent mineralocorticoid excess
Fanconi Syndrome
Generalized reabsorption defect in PCT
Exctra excretion of amino acids, glucose, HCO3-, PO$- and all substances
May lead to metabolic acidosis (proximal RTA)
Hypophosphatemia, osteopenia
Hereditary defcts causes it, Wilson disease, tyrosinemia, glycogen storage disease, ischemia, multiple myeloma, nephrotoxins/ drugs (ifosfamide, cisplatin) lead poisoning
Barter syndrome
Reab defect in thick ascending loop of henle (affects NaK2CL)
Metabolic alkalosis, hypokalemia, hypercalciuria
Autosomal recessive, presents similarly yo chronic loop diuretic use
Gitelman syndrome
Reabsorption defect of NaCL in distal convoluted tubule
metabolic alkalosis, hypomagnesemis, hypokalemua, hypocalciuria
Autosoma recessive
Presents like lifelong thiazide diuretics, less severe than barterr syndrome
Liddle syndrome
Gain of function mutation–> decreased Na channel degradation –> Na reabsorption increased in convoluted tubules
Metabolic alkalosis, hypokalemia, hypertension, decreased aldosterone
Autosomal dominant
Presents similarly to hyperaldosteronism but NO aldosterone
Treat with amiloride
SAME (syndome of apparent mineralocorticoid excess
Cortisol activates mineralocorticoid receptors
11BHSD converts cortisol to cortisone (inactive on these receptors)
Hereditary 11B HSD deficiency-> increased cortisol –> increased cortisol leads to increased mineralocorticoid receptor activity
Metabolic alkalosis, hypokalemia, hypertension, decreased serum aldosterone level, cortisol tries to be the SAME as aldosterone
Autosomal recessive
Glycyrrhetinic acid (present in licorice) blocks 11BHSD
Treatment K-sparing diuretics (decreased mineralocorticoid effects) or Corticosteroids (exogenous corticosteroids decrease endogenous cortisol production–> decreased mineralocorticoid receptor activation
Relative concentrations along proximal convoluted tubules
Tubular fluid / Plasma ratio > 1 when solute is not as reabsorbed
PAH, Creatinine, inulin, urea, CL K, OSM/NA (=1), HCO#,AA, Glucose
RAAS Activators
Decreased BP (renal baroreceptors), decreased NaCl delivery (macula densa cells), increased sympathetic tone (B1 recptors)
Liver makes angiotensinogen, Renin Converts to Angiotensin 1 (aCe from lung converts Angiotensin 2) (bradykinin breakdown to increase pressure)
Ang2 –> hypothalamus ADH (renal cells) H20 reabsorption via aquaporins
Aldosterone secretion principle cells (Na REAB, K secretion, increased K conductance, Na/K ATPase, and Enac activity)
Alpha intercalated cells( H secretion increased H ATPase activity
Na/H activity PCT –> Alkalosis
Constricts effereent arteriole
Angiotensin 2 receptor type1 Vasoconstriction
Juxtaglomerular apparatus
mesangial cells, modified smooth muscle of afferent arterioles and the macula densa (NaCL sensor located at distal end of loop of Henle
JG cells secrete renin in response to decreased renal blood pressure and increased sympathetic tone (B1 in the heart cardiovascular)
B blockers can decrease BP by inhibiting B1 receptors of the JGA- decrease renin release
Kidney endocrine functions
EPO- Released by interstitial cells in peritubular capillary ben in response to hypoxia, Stimulates RBc proliferatoin in bone marrow, administered for anemia secondary to chronic kidney disease, increased risk of HTN
Calciferol (vitamin D)- PCT cells convert 25OH vit D3 to 1,25-Oh2D3 (calcitriol, active form)Calcidiol (250H D3–> 125OH2 D3 Calcitriol
via 1 alpha hydroxylase
PTH activates this 1 a hydroxylase ( stimulates Ca and Pho4 absorption
Prostaglandins: Paracrine secretion vasodilates the afferent arterioles to increase RBF
NSAIDs block renal- protective prostaglandins–> constriction of afferent artieriole and decreased GFR, leads to AKI in low renal blood flow states
Dopamine- secreted by PCT cells , promotes natriuresis, at low doses dilates interlobular arteries, afferent arterioles, efferent artiole–> increased RBF , at high doses is a vasoconstrictor
Acidosis
if due to High PCO2
Respiratory: Hypoventilation, Airway obstruction, Acute lung disease, chronic lung disease, Opioids, Sedatives, Weakening of Resp muscles
elevated bicarb causes the anion gap
if due to Low Bicarb: Check anion gap (Na- ( CL+HCO3)
if elevated anion gap- MUDPILES (methanol, uremia, DKA, Propylene glycol (antifreeze), Iron tablets, INH, Lactic acidosis, Ethylene glycol (oxalate), Salicylates Late)
If Normal (ie 8-12) HARDASS: Hyperchloremia, hyperalimentation, Addisons disease, Renl tubular acidosis, Diarrheam Acetazolamide, Spironolactone, Saline - you wouldnt give drugs that cause anion gap elevation
Alkalosis
If due to low PCO2
Respiratory: Hyperventilation, Anxiety, panic attack, hypoxia (high altitidue), Salicylates early on, Tumors, PE
If due to high bicarb
H+ Loss/ HCO3- excess: Loop diuretics, Vomiting, Antacid use, Hyperaldosteronism
Renal tubular Acidosis
Disorder of the renal Tubules that causes normal anion gap (hyperchloremic metabolic acidosis)
Distal renal tubular acidosis (type 1): inability of alpHa intercalated cells to secrete H+ –> no new HCO3- is generated metabolic acidosis (urine ph is high >5 decreased serum K, amphoteric, increased risk for calcium phosphate kidney stONEs due to increased urine pH and increased bone turnover related to buffereing
Casts in urine
Presence of casts indicates that hematuria/pyruia is of glomerular or renal tubular origin
Bladder cancer, kidney stones–> hematuria but no casts
Acute cystitis-> pyria, no casts
RBC casts- glomerulonephritis, hypertensive emergency
WBC casts- Tubulointerstitial infalmmation, acute pyelonephritis, transplant rejection
Granular casts: Acute Tubular necrosis (ATN, Can be muddy brown in appearance
Fatty casts, Oval fat bodies- Nephrotic syndrome, associated with maltese cross sign
Waxy casts- end stage renal disease, chronic kidney disease
Hyaline casts: non specific, can be a normal finding, form via solidification of Tamm-Horsfall mucoprotein (secreted by renal tubular cells)
Nomenclature of glomerular disorders
Focal<50% of glomeruli are involved
Diffuse >50% of glomeruli are involved
Proliferative: hypercellular glomeruli
Membranous: thickening of GBM
NephrOtic syndrome- proteins
Nephritic syndrome- blood
Nephritic syndrome
Glomerular inflammation-> GBM damage–> loss of RBC in urine–> hematuria
Hematuria, RBC casts in urine, decreased GFR–> oliguria azotemia, increased renin release, HTN, Proteinuria often in subnephrotic range but in severe can be in nephrotic range
Think inflammatory process–> hypercellularity and bleeding in glomerulus–> RBC casts in the little urine that is mage
Acute poststrep glomerulonephritis, Rapidly progressive glomerulonephritis, IgA nephropathy (Berger disease), Alport syndrome, Membranoproliferative glomerulonephritis
Nephrotic syndrome
Podocyte damage–> impaired charge barrier–> proteinuria
Massive proteinuria (>3.5) with hypoalbuminemia, edema Frothy urine with fatty casts (the liver senses the thin blood (from hypoalbumin) so tries to beef it up with throwing some fat in the blood-- then ends up in the glomerulus
Associates with hypercoagulable state (Antithrombin 3 is preferentially lost in urine) losing your anticoag
increased risk of infection (loss of IgG in urine and soft tissue compromise by edema)
May be 1’ (direct podocyte damage) 2’ (podocyte damage from systemic process) (focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, amyloidosis, Diabetic glomerulonephropathy
Nephritic-nephrotic syndrome
Severe glomerulobasment membrane–> loss of RBCs into urine, impaired charge barrier–> hematuria and proteinuria
Nephrotic- range proteinuria and nephrotic syndormes
Most common with diffuse proliferatice glomerulonephritis, membranouproliferatic glomerulonephritis
Acute poststreptococcal glomerulonephritis
Kids, a few weeks after strep pharyngitis or skin
Resolves spontaneosly but can progress to renal insuffiiciency in adults
type 3 HS (immune complex on EM). Cola colored ueine, HTN Periorpital edema
M protein in bacteria similar to basement membrane
Positive strep titers/ serologies
low complement leves (C3 due to consumptive
LM- glomeruli are enlarged and Hypercellular, Immunoflorescence is granular due to immune complex groups (lumpy bumpy), due to IgG, IgM and C3 deposition along GBM and mesangium
Rapidly progressive (crescentic) glomerulonephritis
nephritic syndrome that progresses to renal failure in weeks to months
Poor prognosis, rapid- crescents form in glomeruli formed by fibrin and macrophages (plasma proteins) C3b) with glomerular parietal cel monocytes and macrophages
LM crescentic moon shape
you look at immuno floresence to delineate
goodpasture- Linear (anti-basement membrane Ab)- Ab against type 4 collagen in glomerular and alveolar basememnt membrane, Hematuria, Hemoptysis, young adult men (type 2 HS)- Treat with plamapheresis
PSGN (advanced), diffuse proliferative– granular immunoflorescnece- diffuse proliferative glomerulonephritis due to diffuse Ag-Ab complex deposition (subendothelial) most common in SLE
Wegners (gpa), - cANCA. Eosinophilic granulomatosis with polyangiitis (Churg stause or Microscopic polyangiitis (MPO or p ANCA)
IgA nephropathy (berger disease)
Episodic hematuria that happens with resp or GIT infections
Think if a IgA is a cause it goes to kidney (HSP)
IgA deposits in mesangium, EM mesangial IC deposition
Alport syndrome
Mutation in type 4 collagen–> thinning and splitting of GBM, Most commonly X linked, Eye problems, Retinopathy, anterior lenticonus, glomerulonephritis
sensorineural deafness
Can see can pee cant heer a bee
Alfoort syndrome
Membranoproliferatic glomerulonephritis
Nephritic syndrome that often co-presents with nephrotic syndrome
Type 1 may be 2’ to Hep B or C infection, Subendothelial IC deposits with granular IF
Type 2 is associated with C3 nephritic factor (IgG autoantibody that stabilizes C3 convertase–> persistent complement activation –> decreased C 3 levels
Intramembranous deposits, dense depsotis
GBM spilts–> tram track on HE and PAS staits
Really thick GBM that splits (immune complexwith Hep B C, type 2- C3 nephritic factor)
Nephrotic syndrome
Protein urua >3.5 g a day
Minimal change disease
Lipoid nephrosis. Most common cause of nephrotic syndrome in kids
Often 1’ (idiopathic) may be trigered by recent infection, immunization, immune stimulus
Rarely may be 2’ to lymphoma (cytokine mediated damage)
1’ disease has response to corticosteroids
Normal glomeruli, lipid may be seen, negative immunoflorescences, effacement of podocyte foot processes
Focal segmental glomerulosclerosis
Most common cause of nephrotic syndrome in AF AM and hispanics,
Can be 1’ (idiopathic) or 2’ to other conditions (HIV infection, SCD, heroin, massive obesity, IFN treatment, or congenital malfomation)
LM- segment sclerosis and hyalinosis
difference between it and diffuse glomerulonephritis is blood
Membranous nephropathy
Thickineng GBM
Antibodies to PLA2, 2 drugs
NSAIDs
