Renal Flashcards
Prosnephros
Week 4, then degenerates
Mesonephros
- Functions as interim kidney for 1st trimester
- Later contributes to male genital system
Metanephros
- Permanent
- First appears in 5th week of gestation
- Nephrogenesis continues through 32-36 weeks of gestation
Ureteric bud
- Derived from caudal end of mesonephric duct
- Gives rise to ureter, pelvises, calyces, collecting ducts
- Fully canalized by 10th week
Metanephric mesenchyme/ blastema
- Ureteric bud interacts with this tissue
- Interaction induces differentiation and formation of glomerulus through to distal convoluted tubule (DCT)
- Aberrant interaction between these 2 tissues may result in several congenital malformations of the kidney
Uteropelvic junction
- Last to canalize
- Most common site of obstruction in fetus (hydronephrosis)
Horseshoe kidney associated with
- Hydronephrosis (eg uteropelvic junction obstruction)
- Renal stones
- Infection
- Chromosomal aneuploidy syndromes (eg Turner syndrome, trisomies 13, 18, 21)
- Renal cancer (rarely)
Compare unilateral renal agenesis and multicystic dysplastic kidney
Unilateral renal agenesis: ureteric bud fails to DEVELOP and induce differentiation of metanephric mesenchyme → complete absence of kidney and ureters; often diagnosed prenatally via ultrasound
Multicystic dysplastic kidney: ureteric bud fails to induce differentiation of metanephric mesenchyme → nonfunctional kidney consisting of cysts and connective tissue; often diagnosed prenatally via ultrasound
Duplex collecting system
- Bifurcation of ureteric bud before it enters the metanephric blastema creates a Y shaped bifid ureter
- Duplex collecting system can alternatively occur through ureteric buds reaching and interacting with metanephric blastema
- Strongly associated with vesicoureteral reflux and/or ureteral obstruction, ↑ risk for UTIs
Renal blood flow
Renal a. → segmental a. → interlobar a. → arcuate a. → interlobular a. → afferent arteriole → glomerulus → efferent arteriole → vasa recta/ peritubular capillaries → venous outflow
How to measure plasma volume
Radiolabeling albumin
How to measure extracellular volume
Inulin or mannitol
Filtration by fenestrated capillary endothelium
Size barrier
Filtration by fused basement membrane with heparan sulfate
Negative charge and size barrier
Filtration by epithelial layer consisting of podocyte foot processes
Negative charge barrier
What value can be used to calculate GFR
Inulin clearance, as it is freely filtered and is neither reabsorbed nor secreted.
Creatinine clearance is an approximate measure of GFR. Slightly overestimates GFR because creatinine is moderately secreted by renal tubules.
What value can be used to calculate effective renal plasma flow (eRPF)
Para-aminohippuric acid (PAH) clearance because between filtration and secretion there is nearly 100% excretion of all PAH that enters the kidney. eRPF underestimates true renal plasma flow (RPF) slightly.
Glucose clearance in a normal pregnancy
Normal pregnancy may decrease ability of PCT to reabsorb glucose and amino acids → glucosuria and aminoaciduria
Early PCT physiology
- Contains brush border
- Reabsorbs ALL glucose and AAs and MOST HCO3-, Na+, Cl-, PO43-, K+, H2O, and uric acid
- Isotonic absorption
- Generates and secretes NH3, which acts as a buffer for secreted H+
- PTH: inhibits Na+/PO43- cotransport → PO43- excretion
- ATII: stimulates Na+/H+ exchange → ↑ Na+, H2O, and HCO3- reabsorption (permitting contraction alkalosis)
- 65-80% Na+ absorbed
Thin descending loop of Henle physiology
- Passively reabsorbs H2O via medullary hypertonicity (impermeable to Na+)
- Concentrating segment
- Makes urine hypertonic
Thick ascending loop of Henle physiology
- Reabsorbs Na+, K+ and Cl-
- Indirectly induces paracellular reabsorption of Mg2+ and Ca2+ through + lumen potential generated by K+ backleak
- Impermeable to H2O
- Makes urine less concentrated as it ascends
- 10-20% Na+ reabsorbed
Early distal convoluted tubule physiology
- Reabsorbs Na+, Cl-
- Makes urine fully dilute (hypotonic)
- PTH: ↑ Ca2+/Na+ exchange → Ca2+ reabsorption
- 5-10% Na+ reabsorbed
Collecting tubule physiology
- Reabsorbs Na+ in exchange for secreting K+ and H+ (regulated by aldosterone)
- Aldosterone: acts on mineralocorticoid receptor → mRNA → protein synthesis
- Aldosterone and principal cells: ↑ apical K+ conduction, ↑ Na+/K+ pump, ↑ epithelial Na+ channel activity (ENaC) → lumen negativitiy → K+ secretion
- Aldosterone and α intercalated cells: lumen negativity → H+ ATPase activity → ↑ H+ secretion → ↑ HCO3-/Cl- exchanger activity
- ADH: acts at V2 receptor → insertion of aquaporin H2O channels on apical side
- 3-5% Na+ reabsorbed
How much Na+ is reabsorbed at various parts of the nephron
- PCT → 65-80%
- Thick ascending loop of Henle → 10-20%
- Early DCT → 5-10%
- Collecting tubule → 3-5%
Where is the urine most hypertonic and hypotonic
Hypertonic → thin descending loop of Henle
Hypotonic → distal convoluted tubule
Fanconi syndrome
- Generalized reabsorptive defect in PCT
- Associated with ↑ excretion of nearly all AAs, glucose, HCO3-, and PO43-
- May result in metabolic acidosis (proximal renal tubular acidosis)
- Causes include hereditary defects (eg Wilson disease, tyrosinemia, glycogen stoage disease, cystinosis), ischemia, multiple myeloma, nephrotoxins/drugs, (eg isofosfamide, cisplatin, tenofovir, expired tetracyclines), lead poisoning
Bartter syndrome
- Reabsorptive defect in thick ascending loop of Henle
- AR
- Affects Na+/K+/2Cl- cotransporter
- Presents similarly to chronic loop diuretic use
- Results in hypokalemia and metabolic alkalosis with hypercalciuria
Gitelman syndrome
- Reabsorptive defect of NaCl in DCT
- Similar to using lifelong thiazide diuretics
- AR
- Less severe than Bartter syndrome
- Leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
Liddle syndrome
- Gain of function mutation → ↑ Na+ reabsorption in collecting tubules (↑ activity of epithelial Na+ channel)
- Presents like hyperaldosteronism, but aldosterone is nearly undetectable
- AD
- Results in hypertension, hypokalemia, metabolic alkalosis, ↓ aldosterone
- Treat with amiloride
Syndrome of apparent mineralocorticoid excess (SAME)
- Hereditary deficiency of 11β - hydroxysteroid dehydrogenase, which normally converts cortisol → cortisone (cortisol can activate mineralocorticoid receptors whereas cortisone cannot)
- Excess cortisol in these cells from enzyme deficiency → ↑ mineralocorticoid receptor activity → hypertension, hypokalemmia, metabolic alkalosis
- Low serum aldosterone levels
- Can acquire disorder from glycrrhetinic acid (present in licorice) which blocks conversion to cortisone
- Treatment: corticosteroids (exogenous corticosteroids ↓ endogenous cortisol production → ↓ mineralocorticoid receptor activation)
Reabsorbed less quickly than water ([tubular fluid]/[plasma] >1) → solute secreted
- PAH
- Creatinine
- Inulin
- Urea
- Cl-
- K+
Reabsorbed at the same rate as water ([tubular fluid]/[plasma] = 1)
Na+
Reabsorbed more quickly than water ([tubular fluid]/[plasma]
- HCO3-
- AAs
- Glucose
Why does tubular inulin ↑ in concentration, but not amount, along the PCT
It is as a result of water reabsorption
Rates of Na+ and Cl- reabsorption
Cl- reabsorption occurs at a slower rate than Na+ in early PCT and then matches the rate of Na+ reabsorption more distally. Thus, its relative concentration ↑ before it plateaus.
What effect do ANP and BNP have on renal arterioles
Dilates afferent arteriole, constrict efferent arteriole and promotes natriuresis
Juxtaglomerular apparatus
- Consists of mesangial cells, JG cells (modified smooth muscle of afferent arteriole) and the macula densa (NaCl sensor, part of DCT)
- JG cells secrete renin in response to ↓ renal blood pressure and ↑ sympathetic tone (β1)
- Macula dense cells sense ↓ NaCl delivery to DCT → ↑ renin release → efferent arteriole vasoconstriction → ↑ GFR
- JGA maintains GFR via renin-angiotensin-aldosterone system
- β blockers can decrease BP by inhibiting β1 receptor of the JGA → ↓ renin release
Where is erythropoietin released from
Released by interstitial cells in peritubular capillary bed in response to hypoxia
What secretes dopamine in the kidney
- Secreted by PCT cells, promotes natriuresis
- At low doses, dilates interlobular arteries, afferent arterioles, efferent arterioles → ↑ RBF, little or no change in GFR
- At high doses, acts as vasoconstrictor
Shifts K+ out of cell, causing hyperkalemia
- Digitalis (blocks Na+/K+ ATPase)
- HyperOsmolarity
- Lysis of cells (eg crush injury, rhabdomyolysis, tumor lysis syndrome)
- Acidosis
- β blocker
- High blood Sugar (insulin deficiency)
“DO LAβS”
Hyponatremia
- Nausea
- Malaise
- Stupor
- Coma
- Seizures
Hypernatremia
- Irritability
- Stupor
- Coma
Hypokalemia
- U waves
- Flattened T waves
- Arrhythmias
- Muscle cramps
- Spasm
- Weakness
Hyperkalemia
- Wide QRS
- Peaked T waves
- Arrhythmias
- Muscle weakness
Hypocalcemia
- Tetany
- Seizures
- QT prolongation
- Twitching (Chvostek sign)
- Spasm (Trosseau sign)
Hypercalcemia
- Stones (renal)
- Bones (pain)
- Groans (abdominal pain)
- Thrones (↑ urinary frequency)
- Psychiatric overtones (anxiety, altered mental status)
- But no necessarily calciuria
Hypomagnesemia
- Tetany
- Torsades de pointes
- Hypokalemia
Hypermagnesemia
- ↓ deep tendon reflexes
- Lethargy
- Bradycardia
- Hypotension
- Cardiac arrest
- Hypocalcemia
Hypophosphatemia
- Bone loss
- Osteomalacia
- Rickets
Hyperphosphatemia
- Renal stones
- Metastatic calcifications
- Hypocalcemia
Lab values of Bartter syndrome
- Normal blood pressure
- ↑ renin
- ↑ aldosterone
- Normal Mg2+
- ↑ urine Ca2+
Lab values of Gitelman syndrome
- Normal blood pressure
- ↑ renin
- ↑ aldosterone
- ↓ Mg2+
- ↓ urine Ca2+
Lab values of Liddle syndrome
- ↑ blood pressure
- ↓ renin
- ↓ aldosterone
Lab values of SIADH
- ↑ blood pressure
- ↓ renin
- ↓ aldosterone
Lab values of primary hyperaldosteronism (Conn syndrome)
- ↑ blood pressure
- ↓ renin
- ↑ aldosterone
Lab values of renin secreting tumor
↑ blood pressure, renin, and aldosterone
RBC casts
- Glomerulonephritis
- Malignant hypertension
WBC casts
- Tubulointerstitial inflammation
- Acute pyelonephritis
- Transplant rejection
Fatty casts (“oval fat bodies”)
Nephrotic syndrome → associated with “Maltese cross” sign
Granular (“muddy brown”) casts
Acute tubular necrosis
Waxy casts
End stage renal disease/ chronic renal failure
Hyaline casts
Nonspecific, can be a normal finding, often seen in concentrated urine samples.
Nephritic syndromes
- Acute PSGN
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger disease)
- Alport syndrome
- Membranoproliferative glomerulonephritis
Nephrotic syndromes
- Focal segmental glomerulosclerosis
- Minimal change disease
- Membranous nephropathy
- Amyloidosis
- Diabetic glomerulonephropathy
Nephritic-nephrotic syndromes
Can occur with any form of nephritic syndrome, but is most commonly seen with:
- Diffuse proliferative glomerulonephritis
- Membranoproliferative glomerulonephritis
Acute poststreptococcal glomerulonephritis
- LM → glomeruli enlarged and hypercellular
- IF → “starry sky” granular appearance (“lumpy-bumpy”) due to IgG, IgM and C3 deposition along GBM and mesangium
- EM → subepithelial immune complex (IC) humps
- Most frequently seen in children
- Occurs 2-4 weeks after GAS infection of pharynx or skin
- Resolves spontaneously
- Type III hypersensitivity reaction
- Presents with peripheral and periorbital edema, cola-colored urine, hypertension
- Positive strep titers/serologies, ↓ complement levels due to consumption
Rapidly progressive glomerulonephritis
- LM and IF → crescent moon shape
- Crescents consist of fibrin and plasma proteins (eg C3b) with glomerular parietal cells, monocytes, macrophages
- Several disease processes may result in this pattern, in particular: Goodpasture syndrome (type II hypersensitivity, antibodies to GBM and alveolar basement membrane → linear IF); granulomatosis with polyangiitis; microscopic polyangiitis
- Poor prognosis → rapidly deteriorating renal function (days to weeks)
Diffuse proliferative glomerulonephritis
- Due to SLE or membranoproliferative glomerulonephritis
- LM → “wire looping” of capillaries
- EM → subendothelial and sometimes intramembranous IgG based ICs often with C3 deposition
- IF → granular
- A common cause of death in SLE (think “WIRE LUPus”)
- DPGN and MPGN often present as nephrotic and nephritic syndromes concurrently
IgA nephropathy
- LM → mesangial proliferation
- EM → mesangial IC depositis
- IF → IgA based IC deposits in mesangium
- Renal pathology of Henoch-Schonlein purpura
- Episodic gross hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings)
Alport syndrome
- Mutuation in type IV collagen → thinning and splitting of glomerular basement membrane
- Most commonly X linked dominant
- Eye problems (eg retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness
- EM → “basket-weave” appearance
Membranoproliferative glomerulonephritis
- TYPE 1: subendothelial IC deposits with granular IF; “tram-track” appearance on PAS stain and H&E stain due to GBM splitting caused by mesangial ingrowth
- TYPE 2: also called dense deposit disease
- MPGN, like DPGN, is a nephritic syndrome that often copresents with nephrotic syndrome
- Type 1 may be secondary to hepatitis B or C infection and can also be idiopathic
- Type 2 is associated with nephritic factor (stabilizes C3 convertase → ↓ serum C3 levels)
Minimal change disease/ lipoid nephrosis
- LM → normal glomeruli (lipid may be seen in PCT cells)
- IF → negative
- EM → effacement of foot processes
- Most common cause of nephrotic syndrome in children
- Often primary (idiopathic) and may be triggered by recent infection, immunization or immune stimulus
- Rarely may be secondary to LYMPHOMA (eg cytokine mediated damage)
- Primary disease responds well to corticosteroids
Focal segmental glomerulosclerosis
- LM → segmental sclerosis and hyalinosis
- IF → often negative, but may be positive for nonspecific focal deposits of IgM, C3, C1
- EM → effacement of foot processes similar to minimal change disease
- Most common cause of nephrotic syndrome in African American and Hispanics
- Can be primary (idiopathic) or secondary to other conditions (eg HIV, massive obesity, interferon treatment, sickle cell disease, heroin abuse, chronic kidney disease due to congenital malformation)
- Primary disease has inconsistent response to corticosteroids
- May progress to chronic renal disease
Membranous nephropathy/ glomerulonephritis
- LM → diffuse capillary and GBM thickening
- IF → granular as a result of immune complex deposition
- EM → “spike and dome” appearance with subepithellial deposits
- NEPHROTIC PRESENTATION OF SLE
- Most common cause of primary nephrotic syndrome in Caucasian adults
- Can be primary (eg antibodies to phospholipase A2 receptor) or secondary to drugs (eg NSAIDs, penicillamine), infections (eg HBV, HCV), SLE or solid tumors
- Primary disease has a poor response to corticosteroids
- May progress to chronic renal disease
Amyloidosis
- LM → congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium
- Kidney is the most commonly involved organ (systemic amyloidosis)
- Associated with chronic conditions that predispose to amyloid deposition (eg AL amyloid, AA amyloid)
Diabetic glomerulonephropathy
- LM → mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
- Nonenzymatic glycosylation of GBM → ↑ permeablity, thickening
- Nonenzymatic glycosylation of efferent arterioles → ↑ GFR → mesangial expansion
- Most common cause of end-stage renal disease in US
Kidney stone shaped like envelope or dumbbell
Calcium
Kidney stone shaped like coffin lid
Ammonium magnesium phosphate
Kidney stone shaped rosettes or rhomboid
Uric acid
Kidney stone that is hexagonal
Cystine
Hydronephrosis only presents with elevated creatinine when
Serum creatinine becomes elevated only if obstruction is bilateral or if patient has one kidney
Where does renal cell carcinoma originate
Originates from PCT cells → polygonal clear cells filled with accumulated lipids and carbohydrates
Paraneoplastic syndromes associated with renal cell carcinoma
- EPO
- ACTH
- PTHrP
- Renin
Where does renal cell carcinoma often metastasize to
Lung and bone
Where does renal oncocytoma originate
Benign epithelial cell tumor arising from collecting ducts. Has large eosinophilic cells with abundant mitochondria without perinuclear clearning.
WAGR complex
- Wilms tumor
- Aniridia (absence of iris)
- Genitourinary malformations
- mental Retardation/ intellectual disability
- WT1 deletion
Denys-Drash
- Wilms tumor
- Early-onset nephrotic syndrome
- Male pseudohermaphroditism
- WT1 mutation
Beckwith-Wiedemann
- Wilms tumor
- Macroglossia
- Organomegaly
- Hemihypertrophy
- WT2 mutation
Transitional cell carcinoma
- Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters and bladder)
- Painless hematuria (no casts) suggests bladder cancer
- Associated with problems in your “Pee SAC” → Phenacetin, Smoking, Aniline dyes, Cyclophosphamide
Squamous cell carcinoma of the bladder
- Chronic irritation of urinary bladder → squamous metaplasia → dysplasia and squamous cell carcinoma
- Risk factors: Schistosoma haematobium infection, chronic cystitis, smoking, chronic nephrolithiasis
- Presents with painless hematuria
Types of urinary incontinence
- Stress
- Urgency
- Mixed
- Overflow
Stress incontinence
- Outlet incompetence (urethral hypermobility or intrinsic sphincteric deficiency) → lead with ↑ intra-abdominal pressure (eg sneezing, lifting)
- ↑ risk with obesity, vaginal delivery, prostate surgery
- bladder stress test (directly observed leakage from urethra upon coughing or valsalva maneuver)
- Treatment: pelvic floor muscle strengthening (Kegel exercises), weight loss, pessaries
Urgency incontinence
- Overactive bladder (detrusor instability) → lead with urge to void immediately
- Treatment: Kegel exercises, bladder training (timed voiding, distraction or relaxation techniques), antimuscarinics (eg oxybutynin)
Mixed incontinence
Features of both stress and urgency incontinence
Overflow incontinence
- Incomplete emptying (detrusor underactivity or outlet obstruction) → leak with overfiling
- ↑ post-void residual (urinary retention) on catheterization or ultrasound
- Treatment: catheterization, relieve obstruction (eg alpha blockers for BPH)
Acute pyelonephritis pathology
- Neutrophils infiltrate renal interstitum
- Affects cortex with relative sparing of glomeruli/ vessels
- CT would show striated parenchymal enhancement
Does acute pyelonephritis always present with WBC casts
Can present with or without WBC casts
Complications of acute pyelonephritis
- Chronic pyelonephritis
- Renal papillary necrosis
- Perinephric abscess
- Urosepsis
What results in chronic pyelonephritis
Typically requires predisposition to infection such as vesicouretral reflux or chronically obstructing kidney stones
Xanthgranulomatous pyelonephritis
- Rare
- Characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages
- Granulomatous abscess formation
- Type of chronic pyelonephritis
Diffuse cortical necrosis
- Acute generalized cortical infarction of BOTH kidneys
- Likely due to a combination of vasospasm and DIC
- Associated with obstetric catastrophes (eg abruptio placentae), septic shock
Renal osteodystrophy
- Hypocalcemia
- Hyperphosphatemia (this is because kidneys aren’t functioning)
- Failure of vitamin D hydroxylation
- Associated with chronic renal disease → secondary hyperparathyroidism
- Hyperphosphatemia also independently ↓ serum Ca2+ by causing tissue calcifications
- ↓ 1,25-(OH)2D3 → ↓ intestinal absorption
- Subperiosteal thinning of bones
Consequences of renal failure
- Metabolic Acidosis
- Dyslipidemia (especially ↑ triglycerides)
- Hyperkalemia
- Uremia → clinical syndrome marked by ↑ BUN → nausea and anorexia, pericarditis, asterixis, encephalopathy, platelet dysfunction
- Na+/H2O retention → HF, pulmonary edema, hypertension
- Growth retardation and developmental delay
- Erythropoietin failure (anemia)
- Renal osteodystrophy
“MAD HUNGER”
Signs of uremia
- ↑ BUN
- Nausea
- Anorexia
- Pericarditis
- Asterixis
- Encephalopathy
- Platelet dysfunction
Acute interstitial nephritis (tubulointerstitial nephritis)
- Acute interstitial renal inflammation
- Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity (eg diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin, NSAIDs)
- Less commonly may be secondary to other processes such as systemic infections (eg mycoplasma) or autoimmune disease (eg Sjogren syndrome, SLE, sarcoidosis)
- Associated with fever, RASH, hematuria, and costovertebral angle tenderness, but can be asymptomatic
- Pee (diuretics)
- Pain-free (NSAIDs)
- Penicillins and cephalosporins
- Proton pump inhibitors
- RifamPin
Stages of acute tubular necrosis
- Inciting event
- Maintenance phase - oliguric; lasts 1-3 weeks; risk of hyperkalemia, metabolic acidosis; uremia
- Recovery phase - polyuric; BUN and serum creatinine fall; risk of hypokalemia
Nephrotoxic acute tubular necrosis results from
- Toxic sustances (eg aminoglycosides, radiocontrast agents, lead, cisplatin)
- Crush injury (myoglobinuria)
- Hemoglobinuria
Renal papillary necrosis
Sloughing of necrotic renal papillae → gross hematuria and proteinuria. May be triggered by recent infection or immune stimulus.
Where are cysts of AD polycystic kidney disease located
Cortex and medulla
Mutations associated with AD polycystic kidney disease
- PKD1 (85% of cases, chromosome 16)
- PKD2 (15% of cases, chromosome 4)
Where are cysts of AR polycystic kidney disease located
Collecting ducts
AR polycystic kidney disease is associated with what liver condition
Congenital hepatic fibrosis
Medullary cystic disease
- Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine
- Medullary cysts usually NOT visualized
- Shrunken kidneys on ultrasound
- Poor prognosis
Simple vs complex renal cysts
SIMPLE CYSTS:
- Simple cysts are filled with ultrafiltrate (anechoic on ultrasound)
- Very common and account for majority of all renal masses
- Found incidentally and typically asymptomatic
COMPLEX CYSTS:
- Includes those that are septated, enhanced, or have solid components on imaging
- Require follow-up or removal due to risk of renal cell carcinoma
