Renal

Question 1

Kidney embryology

Answer 1

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

Question 2

Potter sequence/syndrom

Answer 2

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)

Question 3

Horseshoe kidney

Answer 3

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)

Question 4

Congenital solitary functioning kidney

Answer 4

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

Question 5

Duplex collecting system

Answer 5

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

Question 6

Posterior urethral valves

Answer 6

membrane remnant in posterior urethra in males

Urethral obstruction- bilat hydronephrosis, dilated/thickwalled bladder on US

oligohydramnios in severe obstruction

Question 7

Kidney structure

Answer 7

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

Question 8

Glomerulus

Answer 8

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

Question 9

Course of ureters

Answer 9

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

Question 10

Fluid compartments

Answer 10

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

Question 11

Glomerular filtration barrier

Answer 11

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)

Question 12

Renal clearance

Answer 12

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)

Question 13

GFR

Answer 13

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)

Question 14

Effective renal plasma flow

Answer 14

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

Question 15

Filtration

Answer 15

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

Question 16

REabsorption and secretion rate calculation

Answer 16

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

Question 17

Glucose Clearance

Answer 17

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

Question 18

Proximal convoluted tubule

Answer 18

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

Question 19

Thin descending loop of henly

Answer 19

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

Question 20

Thick ascending limb of henle

Answer 20

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

Question 21

Early distal convoluted tubules

Answer 21

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

Question 22

collecting tubules

Answer 22

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

Question 23

Renal tubular defects

Answer 23

Fanconis BaGeLS

Fanconi syndrome- PCT
Barter syndrom- ascending loop of henle
Giltelman syndrome- distal convoluted tubule
Liddle syndrome
Syndrome of Apperent mineralocorticoid excess

Question 24

Fanconi Syndrome

Answer 24

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

Question 25

Barter syndrome

Answer 25

Reab defect in thick ascending loop of henle (affects NaK2CL) Metabolic alkalosis, hypokalemia, hypercalciuria Autosomal recessive, presents similarly yo chronic loop diuretic use

Question 26

Gitelman syndrome

Answer 26

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

Question 27

Liddle syndrome

Answer 27

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

Question 28

SAME (syndome of apparent mineralocorticoid excess

Answer 28

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

Question 29

Relative concentrations along proximal convoluted tubules

Answer 29

Tubular fluid / Plasma ratio > 1 when solute is not as reabsorbed PAH, Creatinine, inulin, urea, CL K, OSM/NA (=1), HCO#,AA, Glucose

Question 30

RAAS Activators

Answer 30

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

Question 31

Juxtaglomerular apparatus

Answer 31

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

Question 32

Kidney endocrine functions

Answer 32

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

Question 33

Acidosis

Answer 33

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

Question 34

Alkalosis

Answer 34

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

Question 35

Renal tubular Acidosis

Answer 35

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

Question 36

Casts in urine

Answer 36

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)

Question 37

Nomenclature of glomerular disorders

Answer 37

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

Question 38

Nephritic syndrome

Answer 38

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

Question 39

Nephrotic syndrome

Answer 39

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

Question 40

Nephritic-nephrotic syndrome

Answer 40

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

Question 41

Acute poststreptococcal glomerulonephritis

Answer 41

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

Question 42

Rapidly progressive (crescentic) glomerulonephritis

Answer 42

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)

Question 43

IgA nephropathy (berger disease)

Answer 43

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

Question 44

Alport syndrome

Answer 44

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

Question 45

Membranoproliferatic glomerulonephritis

Answer 45

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)

Question 46

Nephrotic syndrome

Answer 46

Protein urua >3.5 g a day

Question 47

Minimal change disease

Answer 47

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

Question 48

Focal segmental glomerulosclerosis

Answer 48

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

Question 49

Membranous nephropathy

Answer 49

Thickineng GBM Antibodies to PLA2, 2 drugs NSAIDs