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Flashcards in Renal week 3 Deck (200):

Chronic kidney disease

permanent reduction in GFR that lasts more than 3 months


Common causes of chronic kidney disease (6)

*Diabetic nephropathy (most common)
*Hypertensive nephrosclerosis and renal vascular disease

Polycystic kidney disease
Interstitial nephritis


Stage 1 chronic kidney disease

some kidney damage, normal GFR


Action: diagnose and treat
-aggressively treat BP, lifestyle modifications
-diagnose cause of CKD


Stage 2 chronic kidney disease

kidney damage, mild decrease in GFR
GFR = 60-89

Action: continue BP/lifestyle treatment, estimate progression


Stage 3 CKD

moderate decrease in GFR
GFR = 30-59

-treat complications (give bicarb, restrict dietary phosphorous)
-select site for dialysis and preserve veins
-continue BP and lifestyle treatments


Stage 4 CKD

severe decrease in GFR
GFR = 15-29

Action: prepare for renal replacement therapy (place and AVF)


Stage 5 CKD

kidney failure


How come you can lose 90% of your GFR before manifestations of uremic syndrome present?

-Functioning nephrons compensate for damaged nephrons
-Magnify excretion of given solutes to maintain external balance (hormonal/tubular hadndling altered of individual solutes)
-Mechanisms that are magnified to maintain individual solute control may have deleterious effects on other systems


Intact nephron hypothesis

some nephrons damaged, but that are nephrons functioning in diseased kidneys maintain glomerulotubular balance comparable to all other nephrons

Filtration and excretion are coordinated


Magnification phenomenon

although nephrons in diseased kidneys function homogeneously, they alter their handling of given solutes as needed to maintain external balance of that solute if possible

Magnify excretion of a given solute


Individual solute control systems

each solute has specific control system geared to maintain external balance in CKD

Each solute system has individual tubular handling and hormonal influences


Trade-off hypothesis

Mechanisms that are magnified to maintain individual solute control may have deleterious effects on other systems


creatinine and urea handling in CKD

balance/rate of filtration maintained at expense of elevated plasma concentrations of these waste products

Excretion rates for urea and creatinine remain constant despite diminished clearance


water handling in CKD

Problems with concentration and dilution
--> Patients prone to hyponatremia (water excess) and hypernatremia (water deficiency)


Sodium handling in CKD

Kidneys no longer able to rapidly adjust sodium excretion in response to sudden changes in sodium intake or extrarenal losses

Increase sodium intake → edema, decrease sodium intake → volume depletion

Inability to adjust can result in:
→ volume expansion
--> increased tubular fluid flow rate and hyperfiltration at active nephrons


Potassium handling in CKD

-can't secrete K+ as well

-Increase tubular secretion of K+ by increasing Na+ delivery and aldosterone activity at cortical collecting duct
-Fecal excretion of K+ ramped up to compensate for reduced renal secretion

-Patient susceptible to hyperkalemia from sudden K+ loads


H+ ion handling in CKD

Functioning nephrons produce more NH4+ to compensate for loss of nephron mass (limited to 4x increase) → keep acid balance normal until GFR below 20-25 ml/min

Once GFR falls below that level, there is a retention of H+ ions → non-anion gap metabolic acidosis


Calcium, phosphate, parathyroid hormone, and vitamin D loop in normal people

-Ca2+ absorbed in kidneys --> inhibits production of PTH
-low Ca2+ stimulates PTH

Parathyroid hormone:
-stimulates Ca2+ kidney reabsorption
-stimulates Ca2+ mobilization from bone
-reduces phosphate reabsorption in kidney

Active Vitamin D (1,25 dihydroxyvitamin D):
-stimulates gut absorption of calcium and phosphate and stimulates PTH production


Calcium, Phosphate, and Parathyroid hormone handling in CKD

GFR falls → early increase in phosphate → promote FGF-23 release to maintain phosphate balance

FGF-23 suppresses 1,25 vitamin D production → decreases gut Ca2+ absorption → decreases serum Ca2+ → PTH increases → increase Ca2+ reabsorption and mobilize Ca2+ from bone

GFR falls more → cycle continues


3 main impacts or uremic syndrome

1) Retained metabolic products (urea, etc.)

2) Overproduction of counter-regulatory hormones (PTH in response to low Ca2+, ANP in response to volume overload)

3) Underproduction of renal hormones (EPO, 1-hydroxylation of vitamin D)


Disorders commonly accompanying CKD (3)

1) Anemia
2) Hypertension
3) Mineral and bone disease


Anemia occurs almost universally when GFR falls below ______ and in CKD is caused by...(4)

universal when GFR below 25

1) Decreased EPO production
2) Shortened red cell life span due to a “uremic” toxin
3) Blood loss (Secondary to abnormal coagulation/decreased platelet function)
4) Marrow space fibrosis due to secondary hyperparathyroidism


Hypertension occurs in ______% of CKD patients and is caused by...(4)

in 80-90% of CKD patients

1) Expansion of ECF volume due to reduced Na+ excretion ability

2) Increased RAAS activity

3) ANS dysfunction - insensitive baroreceptors, increased sympathetic tone

4) Diminished presence of vasodilators (prostaglandins)


What causes mineral and bone disease in CKD

-increase in phosphorous --> increase FGR-23 --> decreased 1,25 vitamin D --> decreased Ca2+ reabsorption --> increased PTH release --> mobilization of Ca2+ from bone


Why is renal disease progressive?

4 compensatory changes

Glomerulus and tubule function as a unit but must make compensatory changes to keep up with increased load

Compensatory changes occur in functioning nephrons →
1) Glomeruli hypertrophy
2) Blood flow per nephron increases
3) Intra-glomerular pressure increases
4) Solute flow per tubule increases


Treatment of CKD (4)

**Delay progression:

1) Blood pressure control is MOST important (reduces risk of CVD, reduces proteinuria)
-3 drug combo: ACEI/ARB + 2 others
-CKD patients in highest risk group for CVD

2) Treat metabolic acidosis (oral NaHCO3-)

3) Treat vitamin D deficiency

4) Maintain serum phosphorus in a near normal range with dietary counseling and phosphate binders


Once uremic syndrome has developed in CKD patients...

--> dialysis or renal transplantation

Select site for dialysis access and preserve veins
Place an AVF around stage 4


Indications for starting dialysis (5)

1) Volume overload unresponsive to diuretics

2) Severe hyperkalemia

3) Uremic Pericarditis

4) Uremic symptoms (lethargy, difficulty concentrating, coma, seizures, nausea, uremic bleeding)

5) Other metabolic derangements - metabolic acidosis, hyperphosphatemia, calcium abnormalities

**Ideally begin dialysis prior to the development of life-threatening symptoms

No hard and fast BUN or eGFR that requires dialysis



-most common modality
-done by nurses/health techs
-requires vascular access (need good arteries/veins)
-lots of needle sticks
-usually done in dialysis unit
3x a week, each lasting 3-4 hours
-intermittent --> significant dietary and fluid restrictions

Semipermeable membrane → Rapid removal of small molecular weight solutes (urea), but not very effective at removing larger molecules or solutes that are protein bound


Peritoneal dialysis

-much less common
-done by patient and/or caregiver
-requires peritoneal catheter (no hernias or major abd surgeries), no vascular access
-no needles
-usually done at home
-may not need strict fluid restriction
-can be done during sleep


Process of hemodialysis (4)

1) Using specialized vascular access (a-v fistula, a-v graft, or catheter) blood is removed from body and enters hemodialysis filter

2) In dialysis filter, solutes are removed by diffusion into dialysate
-Countercurrent dialysate draws solutes from blood in by diffusion

3) Fluids can also be removed in filter by applying positive transmembrane pressure (ultrafiltration)

4) “Clean” blood is returned to body (via separate port)


3 types of access ports used in hemodialysis

1) Arteriovenous fistula
2) Arteriovenous grafts
3) Dialysis catheter (dual lumen catheters)


Arteriovenous fistula (AVF)
-pros and cons

Surgical anastamoses of native artery to vein
Preferable placed in non-dominant arm

Pros: lowest infection rate, longest lifespan, requires fewest procedures to maintain

Cons: takes months to mature, may never be usable, risk of steal syndrome (because diverting arterial blood flow to vein)


Arteriovenous grafts (AVGs)

-pros and cons

synthetic graft connecting artery and vein

Pros: can be used quicker than AVF, good blood flows, lower infection than catheters, but hight than AVFs

Cons: Fail quicker (stenosis) and require interventional procedures to maintain, steal syndrome


Dual lumen catheters (Dialysis Catheter)

-pros and cons

Placed in internal jugular vein and terminates in SVC

Pros: immediate use, no needles, does not require surgery

Cons: highest infection risk, high rate of dysfunction/low blood flows, requires insertion site care
Associated with high mortality


Process of peritoneal dialysis (3)

1) Catheter placed in peritoneal cavity that exits the abdominal wall

2) Sterile fluid with a high glucose concentration (high oncotic pressure) instilled in peritoneal cavity

3) Water pulled into dialysate and solutes with it

Patients perform at least 3-4 exchanges per day


Limitations of dialysis (3)

1) Uremic symptoms markedly improved, but some patients do not completely recover pre-illness health status

2) Difficulty achieving euvolemia → chronic heart failure because can’t remove enough volume

3) Abnormal bone and mineral disorders persist


Complications of hemodialysis

*Infection (#1) (bloodstream infection with Staph. Aureus)

Muscle cramps
Myocardial ischemia
Disequilibrium syndrome: headache, somnolence, seizures coma
Air emboli (rare)


Complications of peritoneal dialysis (4)

1) Increased intra-abdominal pressure → hernias

2) Infectious peritonitis

3) Catheter problems (kinking, malposition)

4) Metabolic complications (hyperglycemia, hypertriglyceridemia, hypokalemia)


Risks/Benefits if transplant over dialysis

Transplant improves long term patient survival vs. dialysis, but has a higher mortality in the peri- and immediate postoperative period (reduced risk after a few months)

-Improves quality of life
-Financial benefits

-Requires immunosuppression → infection, cancer, drug-specific side-effects


Warm ischemia

time from cardiac death to cold perfusion (max 60 min)


Cold ischemia

time from cold perfusion to recipient anastomosis (max 24-36 hours)


MHC and kidney transplant

MHC = genes that encode proteins that present antigens to T cells (HLA in humans)

-T cells don’t recognize free antigens, only recognizes when when presented on HLA

-highly variable throughout the population (very small chance of two people having the same HLA genotype) → REJECTION of non-self


Class I vs. Class II HLA

Class I: HLA A, B, C → all nucleated cells present intracellular antigens to CD8+ cytotoxic T cells

Class II: HLA DR, DP, DQ → only on antigen presenting cells → present extracellular proteins to CD4+ helper T cells


2 ways organ transplants can be rejected by T cells

1) direct activation
2) Indirect activation


Direct activation

recipient T cells recognize intact donor HLA antigens on donor APCs → early rejection


Indirect activation

recipient T cells recognize donor HLA antigen fragments presented by host APCs → “normal” mechanism of T cell activation, usually via class II MHC


B cells and organ transplant rejection

B cells also activated by T cells → production of IgG for foreign donor HLA molecule
B cell rejection (antibody mediated + complement)


HLA matching

Match for 3 antigens: A, B, and DR (1 from mom, 1 from dad = 6)

The better the match, the better the survival


3 layers of immunosuppression used in kidney transplantation

1) Calcineurin Inhibitor
2) Proliferation Signal Inhibitor
3) Prednisone


Calcineurin Inhibitor


Side effects: **Highly nephrotoxic, HTN, diabetes


Proliferation Signal Inhibitor

2 different drugs

Mycophenolate Mofetil (MMF) - inhibits purine synthesis

mTOR Inhibitors - inhibit mTOR proliferation signaling

Side effects: cytopenias, GI toxicity


Prednisone side effects

Side effects: weight gain, HTN, diabetes, hyperlipidemia, bone loss, cataracts


Kidney transplant AKI

Can be just like normal AKI, but must consider transplant specific etiologies



Causes of Prerenal AKI in kidney transplant patients

Volume depletion from post-op fluid shifts, blood loss

Thrombosis of transplanted renal artery or vein

Calcineurin inhibitor effects on afferent arteriole


Causes of Post renal AKI in kidney transplant patients

Transplant ureter obstruction


Causes of Intrarenal AKI in kidney transplant patients (3)

Recurrence of primary renal disease

Infection: UTI, pyelonephritis, CMV virus, BK virus nephropathy



Two types of nephrosis that commonly reoccur in a transplanted kidney

MPGN → 100% recurrence
Primary FSGS → 20-50% recurrence


T cell vs. B cell rejection in kidney transplants

T cell → tubular and/or large vessel inflammation
B cell → ab directed against HLA antigens


What drugs and endogenous effectors cause afferent arteriolar dilation? (4)

effect on GFR and RBF?

increase GFR, increase RBF

NO, Prostaglandins
Dopamine --> D1 agonist
Caffeine --> adenosine antagonist


What drugs effectors cause efferent arteriolar dilation? (2)

effect on GFR and RBF?

decrease GFR, increase RBF

ACEIs/ARBs --> decrease AngII


What drugs and endogenous effectors cause efferent arteriolar constriction? (2)

effect on GFR and RBF?

increase GFR, decrease RBF



What drugs and endogenous effectors cause afferent arteriolar constriction? (4)

effect on GFR and RBF?

decrease GFR, decrease RBF

AngII (sorta), NE, Adenosine

NSAIDs --> decrease PGs


______, _______, and ________ drugs can cause acute renal failure

ACEI/ARBs (if hypovolemic)


________ can be renal protective via increase in RBF



________ has a well-describe diuretic effect via increase in GFR



Treatment of CKD associated anemia?

recombinant EPO (Epoetin and Darbepoetin)

Iron supplements


Treatment of CKD associated renal osteodystrophy (3)

(caused by hyperphosphatemia)

1) Phosphate binding agents
2) Vitamin D compounds
3) Calcimimetics


Phosphate binding agents

bind dietary phosphate in GI tract to form insoluble phosphates which are excreted in feces

Prevents increases in phosphate and increase in FGF-23

-treatment for renal osteodystrophy


Vitamin D compounds

-treatment for renal osteodystrophy

suppress PTH secretion and synthesis by stimulating intestinal calcium absorption

-Calcitriol → hypercalcemia

-Paricalcitol acts selectively at D3 receptors on parathyroid gland NOT intestine → no hypercalcemia



-treatment for renal osteodystrophy

binds calcium-sensing receptors on parathyroid cells → reduce release of PTH directly


Drugs that can cause hyperkalemia

1) K+ Sparing diuretics

-Aldosterone antagonists - spironolactone, eplerenone

-Collecting duct ENaC channel blockers - triamterene, amiloride

2) ACEI and ARBs

3) Digoxin


Effect of CKD on insulin

half life prolonged, dose must be reduced


Effect of CKD on diuretics

1) Thiazides may lose effectiveness as renal function declines
-As GFR falls, less drug reaches site of action in nephron → diuretic efficacy decreases
-GFR less than 30 → use loop diuretic

2) Avoid using K+ sparing diuretics


Effect of CKD on ACEIs/ARBs

used through all CKD stages

-Causes dilation of efferent

-Monitor for hyperkalemia

-May cause ARF in hypovolemic patients


Effect of CKD on beta blockers

Atenolol: half life prolonged
Metoprolol preferred


Treatment of acute hyperkalemia (3 strategies)

1) Calcium gluconate or chloride (IV) → antagonize cardiac conduction abnormalities (immediate onset)

2) Shift K+ intracellularly
Insulin/Glucose (IV)
B2 agonist → albuterol (inhaled)

3) Remove K+ from body (kayexalate) (1-2 hours for onset)



exchanges Ca2+-sorbitol counterion for K+ in gut

Used in non-life threatening hyperkalemia

May allow patients with comorbid conditions (CKD, HF, diabetes) to continue taking K+ sparing agents (ACEI/ARB, spironolactone)


Routes of Urinary tract infections (2)

a.Less common
b.Distant source - septicemia or infective endocarditis
c.Usually presence of ureteral obstruction, immunosuppressive therapy
d.Staphylococci, fungi, viruses

a.Most common
b.Fecal flora (E. Coli usually, also proteus, klebsiella, enterobacter)


Virulence factors UTI

1. Bacterial adhesion → Pili
2.O antigens (Certain strains more resistant)
3.Endotoxin → decreased ureteric peristalsis


Host defense mechanisms against UTI (4)

1. Mechanical: bladder emptying, urine flow, ureteric peristalsis

2.Chemical (urine):
a.Prostatic secretions (antibacterial)
b.Urine osmolality, pH, Ammonia
c.Blood group antigens (P1 blood group → increased risk of UTI)

3.Immunological: IgA, complement

4.Cellular: PMNs, shedding of urothelial cells with bacteria trapped in lysosomes


Predisposing factors for UTI (8)

1. Females > Males (shorter urethra, lack of antibacterial factors like prostatic fluid and hormone affecting adherence)


3.Instrumentation (catheter, cystoscopy)

4.Decreased urine flow/stasis

5.Immune compromise

6.Kidney/UT disease

7.Urinary tract obstruction

8.Vesicoureteral reflux (VUR)


Clinical manifestations of UTI

1. Asymptomatic bacteriuria

2.Symptomatic UT: reflective of level of infection, recurrent infection in males indicates UT disease

3.In children, symptoms nonspecific (irritability)


Comlications of UTI (3)

1. Acute pyelonephritis

2.Papillary necrosis



Chronic pyelonephritis

involves upper GU tract

i.Important cause of end stage kidney disease

ii.Usually asymptomatic

iii.Can have dysuria, flank pain, HTN


Histology of chronic pyelonephritis

irregularly scarred, asymmetric, cortico medullary scars

1.Atrophy, “periglomerular fibrosis”

2.FSGS is a poor prognosis


Two major causes of chronic pyelonephritis

1. Urinary tract infection
2. Vesicoureteral reflux


Urinary tract obstruction and Chronis pyelonephritis

Predisposes to infection, interferes with eradication, predisposes to recurrence → chronic pyelonephritis

a.Increased pressure, inflammation, ischemia, and direct injury


Nephrolithiasis (4 types and contributing factors)

a. Calcium oxalate and phosphate (70%) - radio-opaque

b.Magnesium ammonium phosphate (15-20%) - semi-opaque

c.Uric acid, cystine, etc. - not radio-opaque

d.Contributing factors: hypercalcemia, increased uric acid, low pH, decreased volume, bacteria

i.M>F, 20-30 years


Consequences of urinary tract infection

hydronephrosis, hydroureter, infection, chronic obstructive pyelonephritis, renal failure, HTN


Vesicoureteral reflux

1. Oblique course of ureter forms valve with bladder → compressed when intravesical pressure increases

2.Can get retrograde flow of urine from bladder into ureter and renal pelvis when portion enters perpendicularly

a.Results in polar scars with blunted calyces at the poles


Causes of vesicoureteral reflux

Primary: congenital abnormality, common in infants, spontaneous remission (usually mild)

Secondary: Neurogenic bladder (paraplegia, spina bifida), bladder atony


Benign renal tumors (4)

i. Papillary Adenoma:
1.Well circumscribed nodules within the cortex
2.“Early cancers” → surgically removed

1.Vessels, smooth muscle, and fat
2.Common in patients with tuberous sclerosis
3.Can be malignant

iii.Oncocytoma: (oncocytic adenoma)
1.Eosinophilic cytoplasm, epithelial cells, numerous mitochondria

iv.Metanephric adenoma


4 types of renal cell carcinoma

1. Clear cell carcinoma
2. Papillary renal cell carcinoma
3. chromophobe carcinoma
4. carcinoma of the collecting ducts of Bellini


Clear cell carcinoma:
- Incidence
- Clinical features (4)

Incidence/Relative frequency: most common type (70-80% of RCC)

Clinical features:
b.Renal mass (incidental finding on imaging)
c.Metastatic often to lungs
d.Regional lymph node enlargement


Imaging features of clear cell carcinoma (3)

a. Ball-like mass of renal cortex

b.Engorged tumor-filled renal vein/IVC

c.Look for metastatic disease


Pathology of clear cell carcinoma (4)

a. Located in cortex, propensity to invade renal vein

b.Epithelial cell origin

c.Clear cells and granular cells (or mixed)

d.Uglier and more anaplastic means it’s higher grade - nuclear morphology related with clinical outcome


Genetics of clear cell carcinoma

a. VHL gene (Chr3) - deletion, transocation, hypermethylation or mutation

b.Sporadic (95%) or familial (4%)

i.Familial RCC (VHL) associated with:
1.Hemangioblastomas of cerebellum and retina
2.Bilateral renal cysts
3.Multiple RCCs in 50-70% of VHL patients

ii.Sporadic: typically only one RCC


Prognosis of clear cell carcinoma

5 year survival of 45-70% without metastases


Papillary renal cell carcinoma:
- Incidence
- Pathology (3)

Incidence/Relative frequency: 10-15% of RCC

a.Frequently multifocal (unlike clear cell RCC)
b.Cellularity indicates grade
c.Papillary growth pattern


Genetics of papillary renal cell carcinoma

familial and sporadic
a.NOT associated with chr3 deletions

b.Trisomies 7, 16, and 17, and loss of Y in male patients

c.Familial → multifocal, sporadic → one focus


Prognosis of papillary renal cell carcinoma

Better than clear cell


Chromophobe carcinoma:
- Incidence
- Pasthology (2)

Incidence/Relative frequency: 5% of renal cell cancers, much less aggressive than papillary or clear cell (low grade, low malignant potential)


a.Cells with prominent cell membranes and pale eosinophilic cytoplasm with halo around nucleus

b.Grading done with iron staining


Genetics of chromophobe carcinoma

multiple chromosome losses and extreme hypodiploidy

a.Grow from intercalated cells of collecting ducts


Carcinoma of the collecting ducts of Bellini:
- Incidence
- Pathology

Incidence: 1% or less of renal epithelial neoplasms

a.Arise from collecting duct cells in the medulla

Pathology: nests of malignant cells enmeshed within a prominent fibrotic stroma (typically medullary location)


Genetics and prognosis of carcinoma of the collecting ducts of Bellini

Genetics: no distinct pattern

Prognosis: aggressive, poor prognosis

a.Surgical treatment often not curative


Clinical features of transitional cell carcinoma (6)

1. 90% of tumors that arise from the urinary tract

2.Hematuria and irritative bladder (dysuria, frequency, urgency)

3.May arise from renal calyces, pelvis, ureters, bladder, urethra, and urothelium lined ducts in the prostate

4.Metastases to the lung

5.Smoking is highest risk factor

6.Can cause ureteral obstruction → hydronephrosis, unilateral or bilateral


Imaging of transitional cell carcinoma

1. Appear as filling defects in urinary tract

2.CT, MRI, cystography, IVP


Pathology of transitional cell carcinoma

1. Invasive or noninvasive

2.Papillary or nodular or flat


Primary functions of the urinary bladder (2)

1) Storage
2) Emptying/Voiding/Micturition
-Micturition reflex must override storage activity


Male Intrinsic sphincter = _______ + _________ + ____________

failure in this sphincter causes what?

bladder neck circular muscle fibers + smooth muscle of prostate + membranous urethra

→ responsible for incontinence


Female Intrinsic Sphincter = __________ + _______

failure in this sphincter causes what?

bladder neck muscle fibers + mid-urethral complex

→ responsible for incontinence


Innervation of lower urinary tract:

Parasympathetic nerves cause contraction of _________ and inhibit _________ causing _________

contraction of detrusor muscle

inhibition of urethra sphincter (relax)

--> micurition


Innervation of lower urinary tract:

Sympathetic nerves cause contraction of _________ and inhibit ________ causing __________

contraction of urethra sphincter (smooth muscle of bladder neck and proximal urethra)

inhibits detrusor muscle contraction

--> prevents micturition until parasympathetic stimulation occurs


Parasympathetic nerve originates from what level of the spine?

Travels via what nerve?

S2-4 → via pelvic nerve


Sympathetic nerve originates from what level of the spine?

Travels via what nerve?

hypogastric nerves/inferior mesenteric ganglion (T10-L2)


Motor (somatic) nerves sense _________

Motor (somatic) nerves innervate _________ and cause __________

sense fullness or stretch (send info to pons)

innervate muscles of pelvic floor and external urethral sphincter


Cortex predominantly has ________ control over sacral centers. Basically tells you what?


tells you not to pee by keeping pudendal nerve innervation of external sphincter active


Motor nerve originates from what level of the spine?

Travels via what nerve?

S2-4 → Pudendal nerves


Storage phase of bladder

Bladder adapts to increasing volume with little change in pressure

-Detrusor smooth muscle bundles stretch to maintain low pressure as bladder fills with urine → maintains constant intravesical pressure


Afferent information of bladder storage:

filling of bladder --> ?

Filling of bladder → sensory fibers enter dorsal root ganglion via pelvic nerve at S2-4 tell you that your bladder is filling


Efferent information of bladder

Response to bladder filling -->?

Response to bladder filling →

activation of motor neurons of pudendal nerve from S2-4 → inhibit detrusor muscle motor neuron and maintain sphincter contraction


Symptoms of STORAGE disturbances

frequency, urgency, and urge incontinence (OAB)


Micturition Cycle (5 steps)

1) Increase in wall tension in bladder

2) Afferent input from pelvic nerves S2-S4 overcomes pontine micturition center threshold and cortical egress micturition begins (brain says ok, yes time to pee)

3) Pudendal nerve (somatic) activity ceases, external sphincter/pelvic floor relaxes, detrusor neurons are freed and discharge

4) Proximal urethra opens

5) Bladder immediately contracts


Symptoms of emptying disturbances

Emptying disturbances → hesitancy, weak stream, incomplete bladder emptying


3 types of urinary incontinence

1) Stress incontinence (SUI)

2) Urge incontinence (OAB)

3) Overflow incontinence


Stress incontinence (SUI)

involuntary, sudden loss of urine during increases in intra abdominal pressure (laughing, sneezing, coughing, exercising, etc.) → PHYSICAL STRESS


Treatment of stress incontinence (2)

1) A-agonists:
-phenylpropanolamine, pseudoephedrine, ephedrine
-Modest effect in minimal SUI
-Increases bladder outlet resistance

2) Estrogen


Urge incontinence

urgency with or without incontinence usually with frequency and nocturia

Large amount of patients who have episodes of incontinence, unable to reach the toilet in time after an urge to void


Behavioral Treatment of OAB (3)

Fluid and dietary modification

Bladder retraining

Pelvic floor reeducation (Kegels)


Antimuscarinic agents

used to treat ?
mechanism of action?
side effects?

Used to treat OAB

(atropine, oxybutynin, tolterodine)

→ inhibit involuntary bladder contractions, increased bladder capacity (M2 and M3 receptors on detrusor muscle)

Relaxes SMOOTH MUSCLE of bladder by blocking efferent parasympathetic signal from S2-S4

Can have anticholinergic side effects (dry mouth, dry eyes, constipation, CNS effects)


Causes of stress urinary incontinence in men (3)

Neurogenic (pelvic fracture, radical pelvic surgery, spina bifida)


Causes of stress urinary incontinence in women (4)

Pelvic muscle strain
Pelvic muscle tone loss
Estrogen loss/menopause


Common causes of urinary tract obstruction in men

**1) BPH
2) Prostate or bladder cancer
3) Stricture following surgery, trauma, XRT
**4) Stricture
5) Urethral cancer
6) Diverticulum


BPH is common in who?

what are the symptoms?

80% of 80 year olds have BPH, but only 50% of this group show symptoms

Symptoms = OBSTRUCTIVE (hesitancy, straining, decreased stream dysuria, and dribbling)


Stricture is common in who?

Typically in younger men due to trauma to bulbar urethra


3 stages of kidney development and weeks they are present

1) Pronephros (2-4 weeks)
2) Mesonephros (4 weeks - 2 months)
3) Metanephros (5 weeks - maturity)



pronephric duct + pronephric tubules


Doesn’t do any kidney function - only developmental in function



Pronephric duct continues to grow and attaches to cloaca forming mesonephric duct and tubules

-Does primitive function of kidney

-Helps form metanephros and gives rise to testes (wolffian duct)



Some nephrons partially functional within 2.5-3 months, but most develop until birth and afterwards

Give rise to adult version of kidney


Mesonephric Duct grows ______ to join with ______

Mesonephric tubules contact ___________

caudally to join with cloaca

tubules contact small vessels that branch from dorsal aorta


Mesonephric duct --> what reproductive function?

Wolffian duct (mesonephric duct)
→ male reproductive system (epididymis and ductus deferens)

degenerates in females


Mullerian duct --> what reproductive function?

(paramesonephric duct) → oviducts and uterus in females

degenerates in males


Ureteric bud

tiny bud of epithelial cells that develops on CAUDAL end of mesonephric duct enveloped by metanephric blastema


Ureteric bud gives rise to... (5)

ureter, renal pelvis, and major/minor calyces, collecting ducts, and collecting tubules


Metanephric blastema interacts with ________ inducing differentiation and formation of _______ through _______

(aka metanephric mesenchyme)

→ interacts with ureteric bud

glomerulus through to distal convoluted tubule


As ureteric bud elongates, kidney ascends from ______ region to ________

As ureteric bud elongates, kidney ascends from sacral region to retroperitoneal location


Malpighian pyramids

part of ureteric bud

series of epithelial lined tubules that run from medulla into cortical regions of kidney

Become the collecting ducts of the kidney and give rise to short branching tubule that will become collecting tubules


Metanephric spheroid

cluster of metanephric mesodermal cells at the tips of the newly formed collecting tubules that form metanephric vesicle


Metanephric spheroid --> _________ --> __________ --> __________

metanephric vesicle

tubule elongates, folds → metanephric tubule

eventually forms epithelium of nephron


Metanephric tubules attach to what 2 things at their ends?

1) Fuse with collecting tubules to form single elongated epithelial tubule at one end (differentiates into different cell types of tubules)

2) Reaches glomerulus and envelops glomerular capillary at other end


Cells of metanephric tubules that are in contact with the glomerulus become ______



How does the urogenital sinus develop

Cloaca (endoderm) joins mesonephric duct forming urogenital sinus


The urogenital sinus develops into ________ and ______

bladder and urethra


Allantoid degenerates and forms _______

urachus (fibrous cord)



dilation of renal pelvis by accumulated urine due to obstruction



dilation of ureter by accumulated urine due to obstruction


Vesicoureteral Reflux

backflow of urine up the urinary tract upon contraction of the detrusor muscle during micturition



abnormal distention of the bladder by urine due to bladder outlet obstruction


Ureteropelvic junction (UPJ) obstruction

caused by...

Result of incomplete canalization of ureteric bud at 12wks gestation and/or local abnormality of smooth muscle fibers with increased fibrosis impeding peristalsis


Ureteropelvic junction (UPJ) obstruction

clinical presentation

most common cause of pediatric hydronephrosis (boys>girls, L>R)

Clinical presentation: abdominal mass, pain, UTI

Other congenital abnormalities in 50% of patients

Can be detected in prenatal ultrasound


Ureteral duplication

Complete ureteral duplication = 2 ureters ipsilaterally enter bladder

→ propensity for vesicoureteral reflux of lower pole and obstruction of upper pole

May insert ectopically into bladder and end in a ureterocele


Ureteral duplication

clinical presentation and incidence

most common renal abnormality (girls>boys)

Clinical presentation: failure to toilet train, continuous drip incontinence



cystic dilation of terminal intravesical ureter --> bulge into bladder

Can be obstructive if orifice is stenotic or cause reflux

May prolapse through urethra causing bladder outlet obstruction


Ureterocele clinical presentation

Diagnosed prenatally when associated with hydronephrosis or during UTI workup


what normally happens to the urachus during fetal development?

Urachus connects dome of fetal bladder to allantois in umbilical cord and then urachus involutes to form median umbilical ligament


Urachal remnant

what it is
clinical presentation

pain and retraction of umbilicus during micturition

Cysts can form causing a painful midline mass, sinus or fistula leads to drainage of clear or purulent urine at umbilicus and sometimes UTI

Clinical presentation: clear fluid accumulating in umbilicus with micturition


Posterior urethral valves

abnormal congenital obstructing membrane located in the posterior male urethra


Posterior urethral valves embryologic cause

Caused by abnormal insertion of mesonephric duct on the cloaca prior to dividing into urogenital sinus and anorectal canal → abnormal development of all upstream structures due to increased intraluminal pressure


Posterior urethral valves

clinical presentation

anuria, bladder distention, poor urine stream, UT, urinary incontinence - boys only


Bladder diverticulum

outpouching of bladder mucosa through a weakness in muscular wall (opposite of ureterocele - pushes into bladder)



orifice of penile urethra on ventral aspect of penis rather than tip of glans

Caused by abnormal fusion of urogenital folds in males (Androgen insufficiency)



fibrous band causing penis to curve towards location of band

Associated with hypospadius and epispadius



location of urethral opening on dorsal aspect of penis



exposure of bladder mucosa due to absence of the abdominal wall


Exstrophy-Epispadias complex

failure of separation by urorectal septum of primitive cloaca into urogenital sinus and anorectal canal at 6 wks gestation


Potter syndrome

Clinical features (3)

Don’t have kidneys or have obstruction of urine outflow tract → reduced amniotic fluid = oligohydramnios → less room in womb for fetus to move

1) Potter’s facies: large flattened ears, flattened nose, infraorbital skin folds, rocker bottom feet, contracted limbs

2) Amnion nodosum: nodules of squamous cells on amniotic membrane

3) Diminished volume of amniotic fluid leads to underdeveloped lungs → respiratory insufficiency → cause of death


Prune Belly Syndrome (Eagle-Barrett)

more rare than Potter’s

Atrophy of anterior abdominal muscles due to megalocystitis

Undescended testes (cryptorchidism)


Renal agenesis embryologic basis

Due to failure of metanephric diverticulum to develop or its early degeneration


Renal agenesis clinical presentation

-Opposite kidney hypertrophies to compensate

-May be associated with single umbilical artery

-1/1000 incidence, L kidney agenesis more common

-Complete renal agenesis is lethal


Renal hypoplasia

Underdevelopment of a kidney with contralateral compensatory hypertrophy


Renal Ectopia

Embryologic basis

Clinical features

kidney in the wrong place, malposition

Embryologic basis:
-Failure of kidney to rise out of pelvis or rotate medially

Clinical features:
-May result in ureteral obstruction
-Kidneys may be discoid in shape


Horseshoe kidney

fusion of kidneys, typically at lower pole

Anlage of kidneys is fused (90% of the time at lower pole)
→ linked together → ectopic also, fail to rotate medially

Increased incidence of urolithiasis
1/5000 incidence


Acquired cystic conditions (3)

1) Simple cysts
2) Medullary sponge kidney
3) Acquired renal cystic disease (ARCD)


Simple cysts

most common renal lesion (65-70% of renal masses)

-25-33% incidence by age 50

-usually asymptomatic

-may be large


Medullary sponge kidney

In 20% of patients with nephrolithiasis
Normal sized kidney with at least one pale renal pyramid
May contain calcifications


Acquired renal cystic disease

Occurs in patients with ESRD, especially dialysis dependent
-More cysts with more dialysis

Usually asymptomatic - can have hematuria, flank pain, renal colic, palpable renal mass, and even renal cell carcinoma


Genetic cystic conditions

3) Multicystic Dysplasia of the Kidney (MCD)
4) Nephronophthisis-Medullary Cystic Kidney Complex
5) VHL
6) Tuberous Sclerosis


Autosomal dominant polycystic kidney disease (ADPKD)

-presents later in life (40s)
-progress to HTN (age 50) and ESRD (age 60)

-100% penetrance
-PKD1 (90%) and PKD2 encode POLYCYSTIN

*associated with hepatic cysts, mitral valve prolapse, diverticulosis, cerebral aneurysms (berry aneurysms), and pancreatic cysts


Autosomal recessive polycystic kidney disease (ARPKD)

-Onset in infants

-cysts are dilated collecting tubules

-PKHD1 mutation encodes FIBROCYSTIN

-Associated with congenital hepatic fibrosis

-can cause HTN, ESRD


Von Hippel Lindau Disease

Mutation in VHL gene 3p25

Retinal and cerebellar hemangioblastomas, pheochromocytomas, and renal cell carcinoma in 40% of patients

May also have renal cysts, pancreatic, hepatic, and epididymal cysts


Tuberous Sclerosis

Mutation in TSC1 and TSC2

Facial nevi, cardiac rhabdomyomas, epilepsy, angiofibromas, mental retardation, multiple renal angiomyolipomas

-Diffuse renal cystic disease is rare - renal cysts in 20-25% of patients

-Cyst lined by large eosinophilic cells with enlarged hyperchromatic nuclei


Multicystic dysplasia of the kidney (MCKD)

Most common cause of abdominal mass in newborn period

-Affected kidney is nonfunctional, will involute over time (looks like a bunch of grapes)

-Can be asymptomatic


MCKD embryological origins

abnormal induction of metanephric blastema by ureteral bud due to 3 possible things:

1) malformation of ureteral bud
2) problem with formation of mesonephric duct
3) early degeneration of ureteral bud


Congenital mesoblastic nephroma

-Most common kidney tumor at birth to 6 months of age

-Can be detected on prenatal sonogram (“ring” sign)

-Solitary firm round infiltrating fibrous mass composed of bland spindle cells → benign if completely resected

-Cellular variant (worse prognosis)


Wilms Tumor

-Most common malignant kidney tumor of childhood (80%)
-Presents between 4-6 yrs
-“Claw” sign on imaging
-Treat with resection and chemo - DONT biopsy first! Puncturing capsule can upstage the tumor
Bilateral → genetic syndrome


Histology of Wilms Tumor

Solitary tumor with triphasic histology (STROMAL = fibroblastic, BLASTEMAL = small round blue cells, EPITHELIAL = tubules)

Anaplasia → unfavorable prognosis (less chemo sensitive)
-Large, hyperchromatic cells and bizarre mitoses


2 genetic syndromes associated with Wilms Tumors

1) Beckwith-Wiedemann syndrome


Beckwith-Wiedemann syndrome

WT-2 gene (chr11)

Gigantism: big tongue, omphaloceles, abdominal wall defect



Wilms tumor, Aniridia, Genitourinary malformation and mental Retardation → WT-1 gene (chr11)