Renal Week 3 Flashcards
Chronic kidney disease: definition
Permanent reduction in GFR for at least 3 months
Stages of CKD
1: >90 GFR w/ evidence of kidney damage
2: 60-89 GFR w/ evidence of kidney damage
3: 30-59 GFR - mild CKD
4: 15-29 GFR - moderate CKD
5:
Common causes of CKD
Diabetic nephropathy HTN nephrosclerosis GN PKD Interstitial dz Obstruction
Clinical signs of CKD
Anemia (stage 2)
HTN (tx ASAP, stage 1)
Bone/mineral disorders
4 components of anemia in CKD
Decreased EPO
Decreased RBC survival
Increased bleeding risk
Bone marrow space fibrosis
3 reasons for HTN in CKD
Expansion of ECF volume
Increased RAS activation
Autonomic dysfunction
Water/sodium balance in CKD
Can concentrate/dilute urine
200-300 mOsm
Increase in intake = edema
Decrease in intake = volume depletion
Potassium balance in CKD
Decreased kidney excretion -> increased fecal excretion
Therefore hard to clear K+ quickly
How much acid is normally generated every day?
1 meq/day
3 forms acid is excreted
NaPO4 (titratable acids)
H+ (via Aldosterone)
NH4+ trapping
Which forms of acid excretion change with CKD?
H+
NH4+ -> less nephrons making NH3, acidosis seen with >25% decrease from normal (stage 3 ish)
Ca2+ and Pi
High Pi triggers FGF-23 -> inhibit 1,25 vit D
Low Ca triggers PTH release
Chronically elevating levels of PTH
Low Vit D (stage 2 ish)
Intact Nephron Hypothesis
Functioning nephrons maintain glomerulotubular balance
Magnification Phenomenon
Remaining nephrons magnify their excretion of a given solute
Trade-off Hypothesis
Increased PTH for normal Ca2+ levels
Creatinine balance in CKD
Excretion must remain constant
With decreasing GFR, elevation in serum Cr
Progressive disease characteristics in CKD
Glomeruli hypertrophy
Blood flow per nephron increases
Intra-glomerular pressure increases
Solute flow per tubule increases
Treatments for CKD
Eval cause/eval CVD risk
Control BP and reduce risk factors (stage 1)
Restrict diet phos, phos binders, Vit D (stage 2)
Select site for dialysis and preserve veins (stage 3)
Place AVF (stage 4)
Dialysis/transplant (stage 5)
Indications for dialysis
Volume overload while on diuretics
Hyperkalemia
Uremic pericarditis
Uremic symptoms
Uremic symptoms
Lethargy, difficultly concentrating (early)
Coma/seizures (late)
Nausea, decreased appetite
Uremic bleeding
Types of dialysis
Hemodialysis
Frequent/nocturnal dialysis (night, at home)
Peritoneal dialysis
Types of access for hemodialysis
AV fistula
AV graft
Double lumen catheter (tunnel cath in IJ to SVC)
Types of peritoneal dialysis
Continuous ambulatory PD - drain manually
Continuous cycling PD - machine at night, leave dialysate
Nocturnal intermittent PD - same, don’t leave dialysate
Complications of peritoneal dialysis
Infection, scarring, cath dysfunction
Hernias
Metabolic: hyperG, hyperL, hypokalemia
Warm vs. cold ischemia
Warm: death/clamp to cold perfusion (60 min)
Cold: Cold perfusion to @ (24-36 hours)
Direct vs indirect rejection
Direct: R Tcells to intact D HLA antigens (transplant only)
Indirect: R Tcells to fragments D HLA (normal)
Immune signals
Tcell CD3 R w/ MHC complex -> PLC -> Ca2+ release -> Calcineurin activity -> dephos NFAT -> enters nuc -> IL-2
(Co-stimulatory CD28 binding)
IL-2 proliferation of CD4 (Th1 and B cells) and CD8 (attack)
T and B cell rejection
T cell: tubulitis (Banff I) or vasculitis (Banff II)
B cell: antibody mediated, complement
Immunosuppression regimen in transplant
1st: calcineurin inhibitor (cyclosporine, tacrolimus) - SE nephrotox, HTN, diabetes
2nd: proliferation inhibitor (MMF, sirolimus)
3rd: prednisone
AKI eval in transplant
Pre-renal (volume down, renal artery thrombosis, calcineurin tox)
Renal (delayed graft/function, acute rejection, recurrent primary dz, infection)
Post-renal (obstruction)
Routes of infection for UTI
Ascending (more common, ex fecal flora E.coli)
Bloodborne (less common, often ureteral obstruction/immunosuppression)
Virulence factors in UTI
Bacterial adhesion O Antigens (hard to tx) Endotoxin (decrease ureteric peristalsis)
Host defense mechanisms against UTI
Mechanical (peristalsis, flow)
Chemical (prostatic secretions, pH, ammonia, P1 BG Ag)
Immune (IgA, complement)
Cellular (PMNs)
Complications of UTI
Acute pyelonephritis Perinephric abscesses Scarring Recurrence Stones
Vesico-ureteral reflux
No valve, but oblique course in wall
Reflux with perpendicular entry - backflow of urine
Primary (congenital) vs. secondary (neurogenic bladder)
Factors for stones
HyperCa Increased uric acid low pH low volume Bacteria
Acute pyelonephritis and consequences
PMNs in interstitium
WBC, WBC casts
microabcesses, perinephric abscess
Can lead to pap nec, urosepsis
Chronic pyelonephritis and consequences
ESKD
Irregularly scarred, atrophy, periglomerular bifrosis
+ reflux = secondary FSGS, poor prognosis
Renal papillary necrosis
Gross hematuria and proteinuria
Sickle cell, Acute pyelonephritis, Analgesics, DM
Benign tumors of the kidney
Renal papillary adenoma(small, well circumscribed in cortex)
Angiomyolipoma (vessels, SM, fat, often w/ TS)
Oncocytoma (eosinophilic epithelial cells, lots of mito)
Malignant tumors of kidney
Renal cell carcinomas: Clear cell Papillary (chromophillic) Chromophobic Collecting (Bellini) duct Familial RCC
RCC Clear Cell
Most common (80%) Hematuria, ball like mass Can extend renal cortex -> vein -> heart Often single (unless familial) Spherical, focal hemorrhage Types on micro: clear, granular, spindle
Papillary Carcinoma
Often multifocal
Papillary growth pattern
Better prognosis than clear cell
Chromophobic Carcinoma
Prominent cell membranes
Halo around nucleus
Similar to oncocytoma (from intercalated cells)
Excellent prognosis
Familial RCC
VHL: often bilateral and multifocal, hemangioblastomas of cerebellum and retina
Hereditary CCC: confined to kidney, same genes as VHL
Hereditary papillary carcinoma: AD, multiple bilateral with papillary histology (MET mutation)
Familial vs. sporadic
Hereditary = multifocal Sporadic = single
Urothelial carcinomas
Renal pelvis to urethra
M>F, >50yrs
Schistosomiasis
Two functions of bladder and dysfunction symptoms
Storage phase (frequency, uregency, incontinence) Emptying phase (hesitancy, weak stream, incomplete emptying)
LUT Innervation
T10-L2 = sympathetic, hypogastric nerves S2-S4 = parasympathetic, pelvic nerves S2-S4 = somatic, pudendal nerves
Micturition cycle
- Increase in wall tension
- Afferent input to pontine micturition center/cortical egress
- Pudendal nerve activity ceases, relaxation and detrusor neurons freed
- Proximal urethra opens
Bladder immediately contracts
Types of incontinence
Stress: F (post child), alpha-agonists
Urgency: frequency/nocturia, anti-chol drugs
LUT obstruction in men
Most common: BPH
80% or 80 y/o have, 50% with symptoms
Tx: alpha-blocker
Younger men: urethral stricture (trauma)
3 parts of embryonic kidney and destiny
Nephrogenic cord (in urogenital ridge) gives rise to:
Pronephros - degenerates by 4 weeks
Mesonephros - uteric bud, ureters -> collecting tubules
Metanephros - blastemia, SVT to capillary
Two ducts and destiny
Mesonephric duct - Wolffian duct
Paramesonephric duct - Mullerian duct
Urogenital sinus
From caudal portion of endoderm = cloaca
Allantosis (part of sinus) becomes urachus
Sinus becomes bladder and urethra
Renal agenesis and hypoplasia
Failure of metanephric to develop or early degeneration
Unilateral more common (associated with 1 umbilical artery)
Renal dysplasia
Abnormal differentiation of metanephric tissue
Presents w/in first decade
Renal ectopia
Failure of kidney to rise or rotate
Can lead to uteral obstruction or discoid kidney
Horseshoe kidney
Failure to separate along midline (90% lower pole)
Ureters exit anterior, stones likely
3 classifications of pediatric cystic kidney disease
Acquired
Genetic (AD or AR PKD)
Developmental (MCDK)
ADPKD
PKD1 (16p13) - 90%: manifests earlier (Adult) PKD2 (4q21) - 10% (Adult) Cystic dilations in ALL parts of nephron Can be spontaneous, 100% penetrant HTN, CRF, ESKD (50%)
ARPKD
PKHD1 (6p21) - Infantile
Early onset HTN, can’t concentrate urine
Cysts are dilations in collecting tubules
ADPKD organs vs. ARPKD organs
ADPKD: Liver/pancreas cysts, cerebral aneurysms
ARPKD: Fibrous expansion of portal tracts, bile duct prolif
MCDK
Abnormal induction of metanephros
Ureteral or uteropelvic atresia
Non-function and involuted over time kidney
Congenital mesonephric blastoma
Prenatal sonogram = ring sign Fibrotic, firm mass Non-cellular = bengin Cellular = ETV6-NTRK3 fusion (kinda aggressive) Often with trisomy 11
Wilms tumor
Claw sign
Triphasic: blastemal, epithelial, stromal
Anaplasia present = unfavorable
Rarely bilateral - instant stage 5
Wilms genetics
WT-1 11p13: intralobar rests (WAGR)
WT-2 11p15: perilobar rests (BW syndrome)
Ureteral duplication
Both enter ipsilaterally
Reflux into lower pole
Obstruction in upper pole (ureterocele)
Megalocystis
Chronic abnormal distention of bladder due to obstruction
Posterior urethral valves
Obstruction of posterior male urethral valves (ab insertion of mesonephric duct on cloaca)
Epispadias and hypospadias
Meatus on dorsal or ventral side of penis
Chordee
Fibrous band causing curve of penis
Potter sequence (consequences of obstruction/agenesis)
Large flattened ears/nose
Infraorbital skin folds
Amnion nodosum (skin cells on placenta)
Pulmonary hypoplasia (less fluid in lungs to expand)
Prune belly (Eagle-Barrett)
Mostly males, atrophy of anterior abdominal muscles
Undescended testes
Develop megalocystis
