Renal week 3 Flashcards
(200 cards)
1
Q
Chronic kidney disease
A
permanent reduction in GFR that lasts more than 3 months
2
Q
Common causes of chronic kidney disease (6)
A
- Diabetic nephropathy (most common)
- Hypertensive nephrosclerosis and renal vascular disease
Glomerulonephritis
Polycystic kidney disease
Interstitial nephritis
Obstruction
3
Q
Stage 1 chronic kidney disease
A
some kidney damage, normal GFR
GFR>90
Action: diagnose and treat
- aggressively treat BP, lifestyle modifications
- diagnose cause of CKD
4
Q
Stage 2 chronic kidney disease
A
kidney damage, mild decrease in GFR
GFR = 60-89
Action: continue BP/lifestyle treatment, estimate progression
5
Q
Stage 3 CKD
A
moderate decrease in GFR
GFR = 30-59
Action:
- treat complications (give bicarb, restrict dietary phosphorous)
- select site for dialysis and preserve veins
- continue BP and lifestyle treatments
6
Q
Stage 4 CKD
A
severe decrease in GFR
GFR = 15-29
Action: prepare for renal replacement therapy (place and AVF)
7
Q
Stage 5 CKD
A
kidney failure
GFR
8
Q
How come you can lose 90% of your GFR before manifestations of uremic syndrome present?
A
- 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
9
Q
Intact nephron hypothesis
A
some nephrons damaged, but that are nephrons functioning in diseased kidneys maintain glomerulotubular balance comparable to all other nephrons
Filtration and excretion are coordinated
10
Q
Magnification phenomenon
A
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
11
Q
Individual solute control systems
A
each solute has specific control system geared to maintain external balance in CKD
Each solute system has individual tubular handling and hormonal influences
12
Q
Trade-off hypothesis
A
Mechanisms that are magnified to maintain individual solute control may have deleterious effects on other systems
13
Q
creatinine and urea handling in CKD
A
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
14
Q
water handling in CKD
A
Problems with concentration and dilution
–> Patients prone to hyponatremia (water excess) and hypernatremia (water deficiency)
15
Q
Sodium handling in CKD
A
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
16
Q
Potassium handling in CKD
A
-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
17
Q
H+ ion handling in CKD
A
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
18
Q
Calcium, phosphate, parathyroid hormone, and vitamin D loop in normal people
A
Calcium:
- 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
19
Q
Calcium, Phosphate, and Parathyroid hormone handling in CKD
A
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
20
Q
3 main impacts or uremic syndrome
A
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)
21
Q
Disorders commonly accompanying CKD (3)
A
1) Anemia
2) Hypertension
3) Mineral and bone disease
22
Q
Anemia occurs almost universally when GFR falls below ______ and in CKD is caused by…(4)
A
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
23
Q
Hypertension occurs in ______% of CKD patients and is caused by…(4)
A
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)
24
Q
What causes mineral and bone disease in CKD
A
-increase in phosphorous –> increase FGR-23 –> decreased 1,25 vitamin D –> decreased Ca2+ reabsorption –> increased PTH release –> mobilization of Ca2+ from bone
25
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
26
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
27
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
28
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
29
Hemodialysis
-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
30
Peritoneal dialysis
- much less common
- done by patient and/or caregiver
- continuous
- 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
31
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)
32
3 types of access ports used in hemodialysis
1) Arteriovenous fistula
2) Arteriovenous grafts
3) Dialysis catheter (dual lumen catheters)
33
```
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)
34
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
35
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
36
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
37
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
38
Complications of hemodialysis
*Infection (#1) (bloodstream infection with Staph. Aureus)
```
Hypotension
Muscle cramps
Angina
Myocardial ischemia
Disequilibrium syndrome: headache, somnolence, seizures coma
Air emboli (rare)
Anaphylaxis
```
39
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)
40
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
41
Warm ischemia
time from cardiac death to cold perfusion (max 60 min)
42
Cold ischemia
time from cold perfusion to recipient anastomosis (max 24-36 hours)
43
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
44
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
45
2 ways organ transplants can be rejected by T cells
1) direct activation
| 2) Indirect activation
46
Direct activation
recipient T cells recognize intact donor HLA antigens on donor APCs → early rejection
47
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
48
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)
49
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
50
3 layers of immunosuppression used in kidney transplantation
1) Calcineurin Inhibitor
2) Proliferation Signal Inhibitor
3) Prednisone
51
Calcineurin Inhibitor
cyclosporine
Side effects: **Highly nephrotoxic, HTN, diabetes
52
Proliferation Signal Inhibitor
2 different drugs
Mycophenolate Mofetil (MMF) - inhibits purine synthesis
mTOR Inhibitors - inhibit mTOR proliferation signaling
Side effects: cytopenias, GI toxicity
53
Prednisone side effects
Side effects: weight gain, HTN, diabetes, hyperlipidemia, bone loss, cataracts
54
Kidney transplant AKI
Can be just like normal AKI, but must consider transplant specific etiologies
Prerenal
Postrenal
Intrarenal
55
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
56
Causes of Post renal AKI in kidney transplant patients
Transplant ureter obstruction
57
Causes of Intrarenal AKI in kidney transplant patients (3)
Recurrence of primary renal disease
Infection: UTI, pyelonephritis, CMV virus, BK virus nephropathy
Rejection
58
Two types of nephrosis that commonly reoccur in a transplanted kidney
MPGN → 100% recurrence
| Primary FSGS → 20-50% recurrence
59
T cell vs. B cell rejection in kidney transplants
T cell → tubular and/or large vessel inflammation
| B cell → ab directed against HLA antigens
60
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
61
What drugs effectors cause efferent arteriolar dilation? (2)
effect on GFR and RBF?
decrease GFR, increase RBF
ACEIs/ARBs --> decrease AngII
62
What drugs and endogenous effectors cause efferent arteriolar constriction? (2)
effect on GFR and RBF?
increase GFR, decrease RBF
AngII, NE
63
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
64
______, _______, and ________ drugs can cause acute renal failure
ACEI/ARBs (if hypovolemic)
NE
NSAIDs
65
________ can be renal protective via increase in RBF
dopamine
66
________ has a well-describe diuretic effect via increase in GFR
caffeine
67
Treatment of CKD associated anemia?
recombinant EPO (Epoetin and Darbepoetin)
Iron supplements
68
Treatment of CKD associated renal osteodystrophy (3)
(caused by hyperphosphatemia)
1) Phosphate binding agents
2) Vitamin D compounds
3) Calcimimetics
69
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
70
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
71
Calcimimetics
-treatment for renal osteodystrophy
binds calcium-sensing receptors on parathyroid cells → reduce release of PTH directly
72
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
73
Effect of CKD on insulin
half life prolonged, dose must be reduced
74
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
75
Effect of CKD on ACEIs/ARBs
used through all CKD stages
- Causes dilation of efferent
- Monitor for hyperkalemia
- May cause ARF in hypovolemic patients
76
Effect of CKD on beta blockers
Atenolol: half life prolonged
| Metoprolol preferred
77
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)
NaHCO3 (IV)
3) Remove K+ from body (kayexalate) (1-2 hours for onset)
78
Patiromer
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)
79
Routes of Urinary tract infections (2)
Hematogenous:
a. Less common
b. Distant source - septicemia or infective endocarditis
c. Usually presence of ureteral obstruction, immunosuppressive therapy
d. Staphylococci, fungi, viruses
2. Ascending:
a. Most common
b. Fecal flora (E. Coli usually, also proteus, klebsiella, enterobacter)
80
Virulence factors UTI
1. Bacterial adhesion → Pili
2. O antigens (Certain strains more resistant)
3. Endotoxin → decreased ureteric peristalsis
81
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
82
Predisposing factors for UTI (8)
1. Females > Males (shorter urethra, lack of antibacterial factors like prostatic fluid and hormone affecting adherence)
2. Pregnancy
3. Instrumentation (catheter, cystoscopy)
4. Decreased urine flow/stasis
5. Immune compromise
6. Kidney/UT disease
7. Urinary tract obstruction
8. Vesicoureteral reflux (VUR)
83
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)
84
Comlications of UTI (3)
1. Acute pyelonephritis
2. Papillary necrosis
3. Pyonephrosis
85
Chronic pyelonephritis
involves upper GU tract
i. Important cause of end stage kidney disease
ii. Usually asymptomatic
iii. Can have dysuria, flank pain, HTN
86
Histology of chronic pyelonephritis
irregularly scarred, asymmetric, cortico medullary scars
1. Atrophy, “periglomerular fibrosis”
2. FSGS is a poor prognosis
87
Two major causes of chronic pyelonephritis
1. Urinary tract infection
| 2. Vesicoureteral reflux
88
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
89
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
90
Consequences of urinary tract infection
hydronephrosis, hydroureter, infection, chronic obstructive pyelonephritis, renal failure, HTN
91
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
92
Causes of vesicoureteral reflux
Primary: congenital abnormality, common in infants, spontaneous remission (usually mild)
Secondary: Neurogenic bladder (paraplegia, spina bifida), bladder atony
93
Benign renal tumors (4)
i. Papillary Adenoma:
1. Well circumscribed nodules within the cortex
2. “Early cancers” → surgically removed
ii. Angiomyolipoma:
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
94
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
95
Clear cell carcinoma:
- Incidence
- Clinical features (4)
Incidence/Relative frequency: most common type (70-80% of RCC)
Clinical features:
a. Hematuria
b. Renal mass (incidental finding on imaging)
c. Metastatic often to lungs
d. Regional lymph node enlargement
96
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
97
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
98
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
99
Prognosis of clear cell carcinoma
5 year survival of 45-70% without metastases
100
Papillary renal cell carcinoma:
- Incidence
- Pathology (3)
Incidence/Relative frequency: 10-15% of RCC
Pathology
a. Frequently multifocal (unlike clear cell RCC)
b. Cellularity indicates grade
c. Papillary growth pattern
101
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
102
Prognosis of papillary renal cell carcinoma
Better than clear cell
103
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)
Pathology
a. Cells with prominent cell membranes and pale eosinophilic cytoplasm with halo around nucleus
b. Grading done with iron staining
104
Genetics of chromophobe carcinoma
multiple chromosome losses and extreme hypodiploidy
a.Grow from intercalated cells of collecting ducts
105
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)
106
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
107
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
108
Imaging of transitional cell carcinoma
1. Appear as filling defects in urinary tract
| 2. CT, MRI, cystography, IVP
109
Pathology of transitional cell carcinoma
1. Invasive or noninvasive
| 2. Papillary or nodular or flat
110
Primary functions of the urinary bladder (2)
1) Storage
2) Emptying/Voiding/Micturition
- Micturition reflex must override storage activity
111
Male Intrinsic sphincter = _______ + _________ + ____________
failure in this sphincter causes what?
bladder neck circular muscle fibers + smooth muscle of prostate + membranous urethra
→ responsible for incontinence
112
Female Intrinsic Sphincter = __________ + _______
failure in this sphincter causes what?
bladder neck muscle fibers + mid-urethral complex
→ responsible for incontinence
113
Innervation of lower urinary tract:
Parasympathetic nerves cause contraction of _________ and inhibit _________ causing _________
contraction of detrusor muscle
inhibition of urethra sphincter (relax)
--> micurition
114
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
115
Parasympathetic nerve originates from what level of the spine?
Travels via what nerve?
S2-4 → via pelvic nerve
116
Sympathetic nerve originates from what level of the spine?
Travels via what nerve?
hypogastric nerves/inferior mesenteric ganglion (T10-L2)
117
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
118
Cortex predominantly has ________ control over sacral centers. Basically tells you what?
INHIBITORY
tells you not to pee by keeping pudendal nerve innervation of external sphincter active
119
Motor nerve originates from what level of the spine?
Travels via what nerve?
S2-4 → Pudendal nerves
120
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
121
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
122
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
123
Symptoms of STORAGE disturbances
frequency, urgency, and urge incontinence (OAB)
124
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
125
Symptoms of emptying disturbances
Emptying disturbances → hesitancy, weak stream, incomplete bladder emptying
126
3 types of urinary incontinence
1) Stress incontinence (SUI)
2) Urge incontinence (OAB)
3) Overflow incontinence
127
Stress incontinence (SUI)
involuntary, sudden loss of urine during increases in intra abdominal pressure (laughing, sneezing, coughing, exercising, etc.) → PHYSICAL STRESS
128
Treatment of stress incontinence (2)
1) A-agonists:
- phenylpropanolamine, pseudoephedrine, ephedrine
- Modest effect in minimal SUI
- Increases bladder outlet resistance
2) Estrogen
129
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
130
Behavioral Treatment of OAB (3)
Fluid and dietary modification
Bladder retraining
Pelvic floor reeducation (Kegels)
131
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)
132
Causes of stress urinary incontinence in men (3)
Prostatectomy
Radiation
Neurogenic (pelvic fracture, radical pelvic surgery, spina bifida)
133
Causes of stress urinary incontinence in women (4)
Pelvic muscle strain
Childbirth
Pelvic muscle tone loss
Estrogen loss/menopause
134
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
135
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)
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Stricture is common in who?
Typically in younger men due to trauma to bulbar urethra
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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)
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Pronephros
pronephric duct + pronephric tubules
Disappears
Doesn’t do any kidney function - only developmental in function
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Mesonephros
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)
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Metanephros
Some nephrons partially functional within 2.5-3 months, but most develop until birth and afterwards
Give rise to adult version of kidney
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Mesonephric Duct grows ______ to join with ______
Mesonephric tubules contact ___________
caudally to join with cloaca
tubules contact small vessels that branch from dorsal aorta
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Mesonephric duct --> what reproductive function?
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Wolffian duct (mesonephric duct)
→ male reproductive system (epididymis and ductus deferens)
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degenerates in females
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Mullerian duct --> what reproductive function?
(paramesonephric duct) → oviducts and uterus in females
degenerates in males
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Ureteric bud
tiny bud of epithelial cells that develops on CAUDAL end of mesonephric duct enveloped by metanephric blastema
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Ureteric bud gives rise to... (5)
ureter, renal pelvis, and major/minor calyces, collecting ducts, and collecting tubules
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Metanephric blastema interacts with ________ inducing differentiation and formation of _______ through _______
(aka metanephric mesenchyme)
→ interacts with ureteric bud
glomerulus through to distal convoluted tubule
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As ureteric bud elongates, kidney ascends from ______ region to ________
As ureteric bud elongates, kidney ascends from sacral region to retroperitoneal location
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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
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Metanephric spheroid
cluster of metanephric mesodermal cells at the tips of the newly formed collecting tubules that form metanephric vesicle
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Metanephric spheroid --> _________ --> __________ --> __________
metanephric vesicle
tubule elongates, folds → metanephric tubule
eventually forms epithelium of nephron
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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
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Cells of metanephric tubules that are in contact with the glomerulus become ______
podocytes
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How does the urogenital sinus develop
Cloaca (endoderm) joins mesonephric duct forming urogenital sinus
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The urogenital sinus develops into ________ and ______
bladder and urethra
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Allantoid degenerates and forms _______
urachus (fibrous cord)
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Hydronephrosis
dilation of renal pelvis by accumulated urine due to obstruction
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Hydroureter
dilation of ureter by accumulated urine due to obstruction
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Vesicoureteral Reflux
backflow of urine up the urinary tract upon contraction of the detrusor muscle during micturition
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Megalocystis
abnormal distention of the bladder by urine due to bladder outlet obstruction
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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
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Ureteropelvic junction (UPJ) obstruction
incidence
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
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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
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Ureteral duplication
clinical presentation and incidence
most common renal abnormality (girls>boys)
Clinical presentation: failure to toilet train, continuous drip incontinence
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Ureterocele
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
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Ureterocele clinical presentation
Diagnosed prenatally when associated with hydronephrosis or during UTI workup
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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
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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
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Posterior urethral valves
abnormal congenital obstructing membrane located in the posterior male urethra
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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
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Posterior urethral valves
clinical presentation
anuria, bladder distention, poor urine stream, UT, urinary incontinence - boys only
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Bladder diverticulum
outpouching of bladder mucosa through a weakness in muscular wall (opposite of ureterocele - pushes into bladder)
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Hypospadias
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)
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Chordee
fibrous band causing penis to curve towards location of band
Associated with hypospadius and epispadius
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Epispadias
location of urethral opening on dorsal aspect of penis
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Exstrophy
exposure of bladder mucosa due to absence of the abdominal wall
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Exstrophy-Epispadias complex
failure of separation by urorectal septum of primitive cloaca into urogenital sinus and anorectal canal at 6 wks gestation
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Potter syndrome
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Cause
Clinical features (3)
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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
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Prune Belly Syndrome (Eagle-Barrett)
more rare than Potter’s
Atrophy of anterior abdominal muscles due to megalocystitis
Undescended testes (cryptorchidism)
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Renal agenesis embryologic basis
Due to failure of metanephric diverticulum to develop or its early degeneration
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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
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Renal hypoplasia
Underdevelopment of a kidney with contralateral compensatory hypertrophy
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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
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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
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Acquired cystic conditions (3)
1) Simple cysts
2) Medullary sponge kidney
3) Acquired renal cystic disease (ARCD)
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Simple cysts
most common renal lesion (65-70% of renal masses)
- 25-33% incidence by age 50
- usually asymptomatic
- may be large
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Medullary sponge kidney
In 20% of patients with nephrolithiasis
Normal sized kidney with at least one pale renal pyramid
May contain calcifications
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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
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Genetic cystic conditions
1) AD PKD
2) AR PKD
3) Multicystic Dysplasia of the Kidney (MCD)
4) Nephronophthisis-Medullary Cystic Kidney Complex
5) VHL
6) Tuberous Sclerosis
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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
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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
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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
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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
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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
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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
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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)
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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
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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
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2 genetic syndromes associated with Wilms Tumors
1) Beckwith-Wiedemann syndrome
| 2) WAGR
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Beckwith-Wiedemann syndrome
WT-2 gene (chr11)
Gigantism: big tongue, omphaloceles, abdominal wall defect
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WAGR
Wilms tumor, Aniridia, Genitourinary malformation and mental Retardation → WT-1 gene (chr11)
