Renal pathophysiology Flashcards
(159 cards)
1
Q
What are the stages of embryologic kidney development?
A
pronephros - week 4 (degenerates)
mesonephros - interim kidney during 1st trimester, contributes to male GU
metanephros - permanent kidney, first appears 5th week
2
Q
What is the ureteric bud derived from and what does it give rise to?
A
derived from caudal end of mesonephric duct
gives rise to: ureter, pelvises, calyces, collecting duct; fully canalized by week 10
3
Q
The metanephric mesenchyme and ureteric bud interacts to form what?
A
forms glomerulus through DCT
4
Q
what can occur if there is poor interaction between metanephric mesenchyme and ureteric bud?
A
Multicystic dysplastic kidney
5
Q
What is the most common site of obstruction in the fetus and why?
A
Ureteropelvic junction, last to canalize
6
Q
What can cause Potter sequence (syndrome)?
A
Decreased ability of the fetus to produce urine:
ARPKD, obstructive uropathy (posterior urethral valves), bilateral renal agenesis
7
Q
What is the pathogenesis and symptoms of of Potter sequence?
A
Renal failure in utero -> decreased amniotic fluid -> oligohydramnios –> fetus is compressed by muscular wall of uterus -> limb deformities
- > facial anomalies (low-set ears and retrognathia)
- > compression of chest and lack of amniotic fluid in lungs –> pulmonary hypoplasia (cause of death)
8
Q
What causes horseshoe kidney?
A
inferior poles of both kidneys fuse together
9
Q
Where do horseshoe kidneys lie in the abdomen?
A
Trapped under the inferior mesenteric artery therefore remain lower in abdomen than normal (near superior mesenteric artery)
10
Q
What is horseshoe kidney associated with?
A
Kidneys function normally but associated with ureteropelvic junction obstruction, hydronephrosis, renal stones, infection
Chromosomal aneupolidy syndromes: Turner*, Edwards, Down, Patau
Rarely associated with renal cancer
11
Q
What are the characteristics of multicystic dysplastic kidney
A
Caused by abnormal interaction btwn ureteric bud and metanephric mesenchyme
Leads to NONFUNCTIONAL kidney consisting of cysts and connective tissue
-if unilateral other kidney compensates and hypertrophies; bilateral = death
12
Q
What is duplex collecting system?
A
Yshaped bifid ureter -> caused by either early bifurcation of ureteric bud before entering metanephric blastema or when 2 ureteric buds reach metanephric blastema
Associated with vesicoureteral reflux, ureteral obstruction, increase risk UTIs
13
Q
At what level are the kidneys located?
A
T12-L3
14
Q
Where does the kidney send sensory information to?
A
T10-T11 dermatomes –> CVA tenderness
15
Q
Which kidney is usually taken during donor transplantation and why?
A
Left kidney bc it has a longer renal vein
16
Q
What are the layers of the glomerular filtration barrier?
A
fenestrated capillary endothelium, basement membrane w/ heparan sulfate (neg charge barrier), podocytes
17
Q
Where are the ureters in relation to the uterine artery and vas deferens?
A
ureters pass under uterine artery and under vas deferens
18
Q
What are the % of body weight for total body water, intracellular fluid and extracellular fluid?
A
Total body water =60% body weight
ICF=40% body weight (2/3 of body water)
ECF=20% body weight (1/3 of body water)
19
Q
what molecule can be used to measure plasma volume?
A
albumin
20
Q
what molecule can be used to measure extracellular volume?
A
inulin
21
Q
How is renal clearance calculated?
A
Cx=UxV/Px
Cx=clearance (ml/min)
Ux=urine concentration of X (mg/ml)
Px=plasma concentration of X (mg/ml)
V= urine flow rate (ml/min)
22
Q
How is GFR calculated?
A
GFR=C inulin (approximated with creatine, but overestimates GFR)
GFR=Kf[(deltaP-deltaPoncotic)] delta=glomerular capillary - bowman space
23
Q
How is effective renal plasma flow (eRPF) and renal blood flow (RBF) calculated?
A
eRPF=Upah x V/Ppah= Cpah pah=PAH (para-aminohippuric acid: filtered and secreted in PCT)
RBF=RPF/(1-Hct)
24
Q
What is the filtration fraction (FF)?
A
FF=GFR/RPF = clearance of inulin (or creatine)/ clearance of PAH, normal FF =20%
25
How do NSAIDs affect the FF?
FF remains constant (prostaglandins preferentially dilate afferent arteriole so RPF and GFR both decrease with NSAIDs)
26
How do angiotensin II affect the FF?
FF increases since RPF decreases and GFR increases; AT II constricts efferent arteriole preferentially
27
Hartnup disease
AR, deficiency of neutral amino acid (like tryptophan) transporters in PCT cells and enterocytes -> decreased absorption from gut and increased secretion from kidneys -> low tryptophan for conversion to niacin --> pellagra
Treat with high protein diet and nicotinic acid
28
What is reabsorbed and secreted at the early PCT?
Reabsorbed: ALL glucose and amino acids, most HCO3-, Na+, Cl-, PO4-3, K+ and H2O
Secreted: NH3 and H+
29
What are the renal tubular defect syndromes?
FABulous Glittering LiquidS
```
FAnconi syndrome (PCT)
Bartter syndrome (thick ascending loop Henle)
Gitelman syndrome (DCT)
Liddle syndrome (collecting tubule)
Syndrome of apparent mineralocorticoid excess (collecting tubule)
```
30
Fanconi syndrome
Reabsorptive defect in PCT
Increased excretion of amino acids, glucose, bicarb and phosphate -> can cause metabolic acidosis (proximal renal tubular acidosis)
31
What can cause Fanconi syndrome?
hereditary defects (Wilson disease, tyrosinemia, GSD), ischemia, multiple myeloma, toxins/drugs (lead, expired teracyclines, tenofovir)
32
Bartter syndrome
AR reabsorptive defect in thick ascending loop of Henle, Defect of Na/K/2Cl co transporter
Causes hypokalemia and metabolic alkalosis with hypERcalciuria
33
What does Bartter syndrome mimic?
Loop diuretics
34
Gitelman syndrome
AR reabsorptive defect of NaCl in DCT
Less severe than Bartter syndrome; leads to hypokalemia, hypomagnesemia, metabolic alkalosis, hypOcalciuria
35
Liddle syndrome
AD, increased Na+ reabsorption in collecting tubules (Increased ENaC activity)
Causes HTN, hypokalemia, metabolic alkalosis, decreased aldosterone
Treatment: Amiloride (K+ sparring diuretic) Na+ channel blocker in collecting tubule
36
Syndrome of apparent mineralocorticoid excess
Increased Na+ reabsorption in collecting tubules
Deficiency of 11beta-hydroxysteroid dehydrogenase (converts cortisol to cortisone --> excess cortisol in cells -> increased mineralocorticoid receptor activity -> increased Na+ reabsorption -> HTN, hypokalemia, metabolic alkalosis, low aldosterone levels
37
How can syndrome of apparent mineralocorticoid excess be acquired?
glycyrrhetic acid (in licorice)
38
What does it mean if TF/P is >1, =1,
TF/P [tubular fluid]/[plasma]
TF/P>1 --> solute is reabsorbed less quickly than water (creatinine, Cl-, urea)
TF/P=1 --> solute is reabsorbed at the same rate as water (~Na+)
TF/P solute is reabsorbed more quickly than water (glucose, amino acids)
39
What stimulates renin release?
```
low BP (JG cells)
low Na+ delivery (macula densa)
increased sympathetic tone (Beta1-receptors)
```
40
What affects does ACE have?
released by the lungs and kidney to convert angiotensin I to angiotensin II and also breaks down bradykinin
41
What are the 6 effects of angiotensin II?
1. acts at angiotensin II receptor (AT1) on vascular smooth muscle -> vasoconstriction -> increase BP
2. Constricts efferent arteriole -> increase FF and GFR
3. stimulates release of Aldosterone from adrenals
4. stimulates release of ADH from posterior pituitary
5. increases PCT Na+/H+ activity to increase Na+, bicarb and water reabsorption
6. Stimulates hypothalamus for thirst sensation
42
What are the effects of aldosterone on the kidney?
Regulates ECF volume and Na+ content; responds to low blood volume
increases Na+ channel and Na+/K+ pump insertion in principal cells and enhances K+ and H+ excretion ---> Na+ and water reabsorption --> increased BP
43
What are the effects of ADH?
Regulates osmolarity
inserts aquaporin channels in principal cells -> increased water reabsorption -> increased BP
44
What are the effects of ANP and BNP
ANP released from atria and BNP released from ventricles in response to increased blood volume --> relaxes vascular smooth muscle via cGMP -> dilates afferent arteriole -> increases GFR and also decreases Renin
45
What releases EPO?
Interstitial cells (fibroblasts) in peritubular capillary bed
46
Where does the activation of vitamin D take place and what is the enzyme that does it?
PCT cells
25-OH D3 --> 1,25-(OH)2D3 via 1alpha-hydroxylase, stimulated by PTH
47
What are the effects of prostaglandins in the kidney?
paracrine secretion vasodilates the afferent arterioles to increase RBF
48
What are the effects of PTH?
increases Ca2+ reabsorption in the DCT
decreases phosphate reabsorption in the PCT
increases 1,25-(OH)2 vitamin D production in PCT by stimulating 1alpha-hydroxylase
49
What things cause K+ shift out of cells (hyperkalemia)?
```
Digitalis (blocks Na+/K+ ATPase)
Hyperosmolarity
lysis of cells
acidosis
beta-blocker
hyperglycemia (insulin deficiency)
```
50
What things cause K+ shift into cells (hypokalemia)?
Hypo-osmolarity
alkalosis (K+/H+ exchanger increases K+ into cell and H+ out of cell)
beta-adrenergic agonist (increase Na+/K+ ATPase)
insulin (increase Na+/K+ ATPase)
51
What are symptoms of low serum Na+?
Nausea, malaise, stupor, coma, seizures
52
What are symptoms of low serum K+?
U waves on ECG, flattened T waves, arrhythmias, muscle spasm
53
What are symptoms of low serum Ca2+?
Tetany, seizures, QT prolongation
54
What are symptoms of low serum Mg2+?
Tetany, torsades de pointes, hypokalemia
55
What are symptoms of low serum phosphate?
bone loss, osteomalacia (adults), rickets (kids); phosphate needed for hydroxyapetite formation
56
What are symptoms of high serum Na+?
irritability, stupor, coma
57
What are symptoms of high serum K+?
wide QRS and peaked T waves on ECG, arrhythmias, muscle weakness
58
What are symptoms of high serum Ca2+?
```
stones (renal)
bones (pain)
groans (abdominal pain)
thrones (increase urinary frequency)
psychiatric overtones (anxiety, AMS)
```
59
What are symptoms of high serum Mg2+?
decreased DTRs, lethargy, bradycardia, hypotension, cardiac arrest, hypocalcemia
60
What are symptoms of high serum phosphate?
renal stones, metastatic calcifications, hypocalcemia
61
Respiratory acidosis: what are the changes in pH, PCO2, bicarb and what are the causes?
```
pH 40mmHg
bicarb high (compensatory)
```
Causes: hypoventilation (opioids, chronic lung disease etc)
62
Respiratory alkylosis: what are the changes in pH, PCO2, bicarb and what are the causes?
pH > 7.45
| PCO2
63
Metabolic acidosis: what are the changes in pH, PCO2, bicarb?
pH
64
What is the equation for anion gap? What is considered normal?
Anion gap= Na+ -- (Cl- + HCO3-) = 8-12 normally
65
What are causes of increased anion gap metabolic acidosis?
MUDPILES
```
Methanol (formic acid)
Uremia
DKA
Propylene glycol
Iron/Isoniazid
Lactic acidosis
Etheylene glycol (oxalic acid)
Salicylates (late)
```
66
What are causes of normal anion gap metabolic acidosis?
HARD-ASS
Hyperalimentation
Addison disease
Renal tubular acidosis
Diarrhea (both sodium and bicarb lost in stool)
Acetazolamide (carbonic anhydrase inhibitor)
Spironolactone (aldosterone antagonist)
Saline infusion
67
What is the defect and urine pH in Distal (type 1) Renal Tubular Acidosis (RTA)
defect in secretion of H+ in alpha intercalated cells --> no bicarb generated --> acidosis
urine pH > 5.5
68
What are the associations and causes of Distal (type 1) Renal Tubular Acidosis (RTA)
HypOkalemia -> increased risk for calcium phosphate stones (increased urine pH and bone turnover)
Causes: amphotericin B toxicity, analgesic nephropathy, obstruction of urinary tract
69
What is the defect and urine pH in Proximal (type 2) Renal Tubular Acidosis (RTA)
defect in PCT bicarb reabsorption -> more bicarb excreted -> acidosis;
Urine becomes acidified in alpha-intercalated cells to compensate --> pH
70
What are the associations and causes of Proximal (type 2) Renal Tubular Acidosis (RTA)
Associated with hypOkalemia, increased risk for hypophosphatemic rickets
Causes: Fanconi syndrome, carbonic anhydrase inhibitors, lead, aminoglycosides
71
What is the defect and urine pH in Hyperkalemic (type 4) Renal Tubular Acidosis (RTA)
Defect: hypoaldosteronism -> hypERkalemia -> decreased NH3 synthesis in PCT -> decreased urea excretion
urine pH
72
What are the associations and causes of Hyperkalemic (type 4) Renal Tubular Acidosis (RTA)
Hyperkalemia and hyperuricemia
Causes:
decreased aldosterone production (ACE inhibitors, ARBs, NSAIDs, diabetic hyoreninism, cyclosporine, adrenal insufficiency)
increased aldosterone resistance (K+ sparring diuretics, TMP/SMX, obstructive neuropathy)
73
ADPKD
* Autosomal dominant, mutation in PKD1 (chromosome 16) or PKD2 (minority of cases, chromosome 4)
* Bilateral ENLARGED kidneys with numerous cysts in cortex and medulla
* presents in young ADULTS as HTN, hematuria, renal failure
* Associated with berry aneurysms, MVP, benign hepatic cysts
74
ARPKD
* Autosomal recessive, presents in INFANCY
* Bilateral ENLARGED kidneys with numerous cysts in cortex and medulla
* Significant renal failure in utero can cause Potter sequence
* Associated with congenital hepatic fibrosis -> portal HTN and hepatic cysts
75
Medullary cystic kidney disease
AD defect -> cysts in medullary collecting ducts
* medullary cysts usually NOT visualized
* tubulointerstitial fibrosis -> SHRUNKEN kidneys on US and progressive renal insufficiency
76
What is the difference between simple and complex renal cysts?
Simple cysts: filled with UF (anechoic/dark on US). Common and usually asymptomatic
Complex cysts: septated, enhanced or solid components on US -> risk of RCC
77
What are the types of acute renal failure?
prerenal azotemia, intrinsic renal failure (intrarenal azotemia), postrenal azotemia
78
What causes prerenal azotemia?
Due to low renal blood flow - hypotension -> decreased GFR -> azotemia and oliguria
79
What are the basic features of acute renal failure?
Severe decline in kidney function developing within days
| Azotemia -> increased BUN and Cr and oliguria
80
What are the clinical features of prerenal azotemia? - urine osmolarity, urine Na+, FENa, serum ratio BUN:Cr
urine osmolarity: >500 mOsm/kg (tubular fxn intact)
| urine Na+: 15 (reabsorption of BUN due to increased aldosterone)
81
What causes postrenal azotemia?
BILATERAL outflow obstructions -> stones, BPH, neoplasia, congenital anomalies
82
What are the clinical features of early stage postrenal azotemia? - urine osmolarity, urine Na+, FENa, serum ratio BUN:Cr
EARLY stages:
urine osmolarity: >500 mOsm/kg (tubular fxn intact)
urine Na+: 15 (increased tubular pressure forces BUN into blood)
83
What are the clinical features of late stage postrenal azotemia? - urine osmolarity, urine Na+, FENa, serum ratio BUN:Cr
LATE stages:
urine osmolarity: 40 (tubular fxn impaired)
FENa: >2% (tubular fxn impaired)
BUN:Cr decreased BUN reabsorbed)
84
What causes intrinsic renal failure (intrarenal azotemia)?
Acute tubular necrosis, acute interstitial nephritis -> necrosis -> debris obstructs tubule -> decreased GFR --> urine has brown granular casts of dead epithelial cells
85
What are the etiologies of acute tubular necrosis?
Ischemic -> decreased blood supply (HF, hypotension, sepsis, shock etc), preceded by prerenal azotemia
Nephrotoxic ->
drugs (aminoglycosides)
heavy metals (Pb)
myoglobinuria (muscle injury)
etheylene glycol (oxalate crystals in urine)
radiocontrast dye
urate (tumor lysis syndrome; avoid with hydration and allopurinol)
86
What are the clinical features of acute tubular necrosis?
Oliguria with brown granular casts
Elevated BUN and Cr
Hyperkalemia with metabolic acidosis with increased anion gap
87
What are the clinical features of intrinsic renal failure (intrarenal azotemia)? - urine osmolarity, urine Na+, FENa, serum ratio BUN:Cr
urine osmolarity: 40 (tubular fxn impaired)
FENa: >2% (tubular fxn impaired)
BUN:Cr decreased BUN reabsorbed
88
What are the consequences of renal failure
MAD HUNGER
```
Metabolic Acidosis
Dyslipidemia (especially increased TAG)
Hyperkalemia
Uremia
Na+/H2O retention (HF, pulm edema, HTN)
Growth retardation
Erythropoietin failure (anemia)
Renal osteodystropy
```
89
What is uremia?
Clinical syndrome of increased BUN:
- nausea and anorexia
- pericarditis
- asterixis
- encephalopathy
- platelet dysfunction
90
What are the mechanisms of renal osteodystrophy?
failure of vitamin D hydroxylation
-> decreased intestinal Ca2+ absorption
hypocalcemia (cant reabsorb calcium)
hyperphosphatemia (can't excrete phosphate)
- -> leads to secondary hyperparathyroidism
- -> decreases serum Ca2+ by causing tissue calcifications
91
What are the features of renal osteodystrophy?
Osteomalacia - cant mineralize osteoid due to low vitamin D
Osteoporosis (metabolic acidosis causes bone to be reabsorbed as buffer)
Ostetitis fibrosis cystica (secondary to hyperparathyroidism)- resorption of calcium destroys bone and fibrosis and cysts form
92
What parts of the nephron are most susceptible to ischemic damage? nephrotoxic damage?
ischemic - PCT and loop of Henle
| nephrotoxic - PCT
93
What are the stages of ATN (acute tubular necrosis)?
1. inciting event
2. maintenance phase - oliguric; 1-3 weeks; risk of hypERkalemia, metabolic acidosis, uremia
3. recovery phase - polyuric, BUN and Cr fall, risk of hypOkalemia
94
Renal papillary necrosis - what does it cause and what is it associated with?
sloughing of necrotic renal papillae -> gross hematuria and proteinuria
```
Associated with:
Sickle cell disease/trait
Acute pyelonephritis
Analgesics (NSAIDs)
Diabetes mellitus
```
95
What can cause diffuse cortical necrosis of the kidneys?
Usually combo of vasospasm and DIC
Associated with obstetric problems (abruptio placentae), septic shock
96
What are the symptoms of acute bacterial cystitis?
suprapubic pain, dysuria, urinary frequency, urgency
*Systemic signs (fever, chills) usually ABSENT
97
What are the lab findings of acute bacterial cystitis?
```
Dipstick
+ leukocyte esterase
+ nitrites for gram(-) organisms
UA: cloudy urine w >10 WBCs/hpf
+ culture (>100k colony forming units)
```
98
What does a negative urine culture in suspected bacterial cystitis suggest?
Sterile pyuria and negative cultures suggest urethritis by N. gonorrhea or C. trachomatis
99
What are the most common causes of acute bacterial cystitis?
```
E. coli
Staph saprophyticus (sexually active young F)
Klebsiella
Proteus *urine has ammonia sent
Enterococcus faecalis
```
100
What are the common causes of acute pyelonephritis?
Ascending infection of:
E. coli (90%)
E. faecalis
Klebsiella
101
what are the clinical features of acute pyelonephritis?
Fevers, CVA tenderness
WBCs in urine +/- WBC casts
CT: striated parenchymal enhancement
102
What are risk factors for pyelonephritis?
indwelling urinary catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy
103
What are the features of chronic pyelonephritis?
*Thyroidization of kidney on H&E - tubules contain eosinophilic casts resembling thyroid tissue
asymmetric corticomedullary scarring, blunted calyx
104
What are the causes and symptoms of drug-induced interstitial nephritis (tubulointerstitial nephritis)?
Pyuria and azotemia after drugs due to hypersensitivity
1-2 weeks after: diuretics, penicillin derivatives, PPIs, sulfonamides, rifampin
months after starting NSAIDs
Symptoms: fever, rash, hematuria, CVA tenderness; can also be asymptomatic
105
What are the symptoms of kidney stones (nephrolithiasis)?
colicky pain with hematuria, CVA tenderness (unilateral)
106
What are general risk factors for kidney stones?
low urine volume
| high concentration of solute
107
Calcium stones - what are the x-ray findings, precipitation pH and crystal shape?
X-ray: radiopaque
pH: alkaline pH for calcium phosphate crystals
acidic pH for calcium oxalate crystals
crystal: envelope or dumbbell shaped
108
What causes calcium stones? What is the treatment?
usually idiopathic hypercalciuria (high calcium in urine but normal blood calcium levels)
Oxalate crystals can result from ethylene glycol ingestion, vitamin C abuse, hypocitraturia, malabsorption (Crohn disease)
Treatment: hydration, thiazides (ca2+ sparring diuretic), citrate (complexes with calcium)
109
What causes ammonium magnesium phosphate (struvite) stones? What is the treatment?
commonly form struvite crystals
Caused by urease (+) bugs (proteus, staph saprophyticus, klebsiella) that hydrolyze urea to ammonia -> increases urine pH
Treatment: treat infection and surgically remove stone
110
ammonium magnesium phosphate (struvite) stones - what are the x-ray findings, precipitation pH and crystal shape?
X-ray: radiopaque
pH: alkaline pH
crystal: coffin lid
111
uric acid stones - what are the x-ray findings, precipitation pH and crystal shape?
X-ray: radiolucent** visible on CT and US but NOT X-ray**
pH: acidic pH
crystal: rhomboid or rosettes
112
What causes uric acid stones? What is the treatment?
Risk factors: decreased urine volume, arid climates, ACIDIC pH
Most common stone in patients with gout, hyperuricemia (leukemia or myeloproliferative disorders)
Treatment: alkalinization of urine (potassium bicarb), allopurinol
113
cystine stones - what are the x-ray findings, precipitation pH and crystal shape?
X-ray: radiopaque
pH: acidic pH
crystal: Hexogonal "SIXtine" stones have SIX sides
114
What causes cystine stones? What is the treatment?
AR condition causing loss of fxn in cystine-reabsorbing PCT transporter --> cystinuria (cystine is poorly soluble)
*mostly seen in children*
Can form staghorn calculi
(+) Sodium cyanide nitroprusside test
Treatment: alkalinization (potassium bicarb) of urine and hydration
115
Hydronephrosis - pathophysiology and findings
Causes: urinary tract obstruction (stones, BPH, cancer, injury), retroperiotneal fibrosis, vesicoureteral reflux
Presents with CVA tenderness and palpable mass in R/L upper quadrant
Dilation/distention of renal pelvis and calyces occur proximal to site of pathology -> imaged on US or CT
Cr only rises if bilateral or patient only has 1 kidney
116
What are complications of hydronephrosis?
compression and possible atrophy of renal cortex and medulla
117
What is nephritic-nephrotic syndrome and with what conditions is it most commonly seen?
nephritic syndrome with GBM damage that damages glomerular filtration charge barrier -> nephrotic proteinuria
Can occur with any nephritic syndrome, most commonly in: Diffuse proliferative GN and membranoproliferative GN
118
What is nephritic syndrome? What are the common clinical features?
Glomerular inflammation and bleeding -> GBM disruption
Causes HTN, increased BUN and creatinine, oliguria, hematuria, RBC casts
proteinuria
119
What is nephrotic syndrome? What are the common clinical features?
Podocyte disruption -> charge barrier impaired
Massive proteinuria >3.5g/day
Hypoalbuminemia -> edema
Hyperlipidemia and hypercholesterolemia
(some) Hypogammaglobulinemia -> increased infection risk
(some) Hypercoagulable state from loss of antithrombin III
120
Acute poststreptococcal glomerulonephritis - What is the etiology and clinical features?
~2 wks post strep A infection of skin or pharynx; most frequently in children
Type III hypersensitivity reaction - M protein virulence factor causes immune complex deposition containing IgG, IgM and C3
Clinical features: Nephritic syndrome (urine protein
121
Acute poststreptococcal glomerulonephritis - What are the LM, IF and EM features?
LM - glomeruli enlarged and hypercellular (inflammation)
IF - "starry sky" granular appearance "lumpy bumpy" due to IgG, IgM and C3 deposition along GBM and mesangium
*EM - subEPIthelial immune complex humps
122
Rapid progressive glomerulonephritis (RPGN)- What is the etiology and LM features?
Nephritic syndrome that progresses to renal failure in weeks to months
H&E LM: crescents comprised of fibrin and plasma proteins (C3b) with glomerular parietal cells, monocytes and macrophages in Bowman space
```
Can be caused by several diseases:
Goodpasture syndrome
PSGN
diffuse proliferative glomerulonephritis
Wegener granulomatosis
microscopic polyangiitis
Churg-Strauss syndrome
```
123
What is the etiology of RPGN with linear immunofluorescent staining?
IF pattern: linear -> Goodpasture syndrome (anti-basement membrane antibody) Type II hypersensitivity rxn
Antibody also against alveolar basement membrane --> presents as hematuria and hemoptysis in young adult male
124
What are the etiologies of RPGN with granular immunofluorescent staining? How can they be differentiated?
granular IF: immune complex deposition
Etiology: PSGN (sub-EPIthelial deposition, MOST COMMON type of granular IF RPGN) or diffuse proliferative glomerulonephritis (sub-ENDOthelial deposition)
125
What are the etiologies of RPGN with negative immunofluorescent staining? How can they be differentiated?
Wegener granulomatosis: PR3-ANCA/c-ANCA; affects lung, kidney and nasalpharynx
microscopic polyangiitis: MPO-ANCA/p-ANCA
Churg-Strauss syndrome: p-ANCA; differentiate from microscopic polyangiitis b/c also granulomatous inflammation, eosinophilia and asthma symptoms
126
Diffuse proliferative glomerulonephritis (DPGN) - what is the etiology?
SLE or membranoproliferative glomerulonephritis --> nephritic syndrome
Most common type of renal disease in SLE and most common cause of death
DPGN and MPGN both present as nephrotic and nephritic syndromes concurrently
127
Diffuse proliferative glomerulonephritis (DPGN)- What are the LM, IF and EM features?
LM: "wire looping" of capillaries
EM: subendothelial and sometimes intramembranous IgG-based immune complexes with C3 deposition
IF: granular
128
What is the etiology and clinical features of IgA nephropathy (Berger disease)?
IgA immune complex deposition in mesangium -> nephritic syndrome
Presents in childhood as episodic gross or microscopic hematuria with RBC casts usually following mucosal infections (increased IgA produced)
Renal pathology of Henoch-Schonlein purpura
129
IgA nephropathy (Berger disease)- What are the LM, IF and EM features?
LM: mesangial proliferation
EM; mesangial immune complex deposits
IM: IgA based immune complex deposits
130
Alport syndrome - what is the etiology and clinical features?
X linked recessive mutation in type IV collagen -> thinning and splitting of GBM -> nephritic syndrome
Presents as hematuria, sensor hearing loss and ocular disturbances
"basket-weave" appearance on EM
131
Membranoproliferative glomerulonephritis - Type I
Nephritic syndrome often copresenting with nephrotic syndrome
*Associated with hep B and C*
sub-endothelial immune complex deposits with granular IF
Thick basement membrane with 'tram track' appearance from GBM splitting by mesangial ingrowth
132
Membranoproliferative glomerulonephritis - Type II
Nephritic syndrome often copresenting with nephrotic syndrome
*Associated with C3 nephritic factor (stabilizes C3 convertase -> overactivation of complement and decreased serum C3 levels*
intramembranous immune complex 'dense' deposits with granular IF
133
Minimal change disease - etiology, epidemiology and treatment
Most common cause of nephrotic syndrome in CHILDREN
-usually idiopathic, associated with Hodgkin lymphoma (cytokine-mediated damage to podocytes -> disrupts filtration charge barrier)
Treatment: excellent response to steroids!
134
Minimal change disease - LM, IF and EM characteristics
LM- NORMAL glomeruli, lipid may be seen in PCT cells
IF: negative
EM: effacement (fusion) of foot processes
135
Focal segmental glomerulosclerosis - etiology, epidemiology and treatment
Most common cause of nephrotic syndrome in African Americans and Hispanics.
Idiopathic or secondary to other conditions: HIV, heroin use, sickle cell, interferon treatment, obesity, congenital CKD
Treatment: primary disease has inconsistent response to steroids
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Focal segmental glomerulosclerosis - LM, IF and EM characteristics
LM- Segmental (only part of glomerulus) sclerosis and hyalinosis
IF- nonspecific for focal deposits of IgM, C3, C1
EM- effacement of foot processes
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Membranous nephropathy- etiology, epidemiology and treatment
Most common cause of primary nephrotic syndrome in Caucasian adults
Idiopathic or secondary to other conditions:
- antibodies to phospholipase A2 receptor
- drugs: NSAIDs, penicillamine
- infections: HBV, HCV
- SLE (most common is diffuse proliferative GN)
- solid tumors
Treatment: poor response to steroids
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Membranous nephropathy- LM, IF and EM characteristics
LM: diffuse capillary and GBM thickening
IF: granular due to immune complex deposits
EM: "spike and dome" appearance with subepithelial deposits
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Amyloidosis - nephrotic syndrome
Kidney is most commonly involved organ in systemic amyloidosis
Amyloid deposits in mesangium -> nephrotic syndrome
LM- congo red stain shows apple-red birefringence
Associated with chronic conditions like multiple myeloma, TB, RA
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Diabetic glomerulonephropathy
Nonenzymatic glycosylation of GBM -> lose charge barrier -> increase permeability, thickening
Nonenzymatic glycosylation of efferent arterioles -> increased GFR -> mesangial expansion
LM- mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
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Renal angiomyolipoma is associated with what condition?
benign, hamartoma made up of blood vessels, smooth muscle and adipose tissue
*Increased frequencyin tuberous sclerosis
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Where does renal cell carcinoma arise from?
malignant epithelial tumor arising from kidney tubules
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How does renal cell carcinoma present clinically?
hematuria, palpable mass, CVA tenderness, secondary polycythemia (paraneoplastic syndrome increased EPO, renin, PTHrP or ACTH), fever, weight loss
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Who typically gets renal cell carcinoma?
Sporadic: adult men 50-70 years old, single tumor in upper pole of kidney; smoking and obesity
Hereditary: younger adults, bilateral tumors; increased risk with Von Hippel-Lindau disease (AD, inactivation of VHL -> risk of cerebellar hemangioblastoma and RCC)
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What is the pathogenesis of renal cell carcinoma? Where does it metastasize?
loss of VHL (3p) tumor suppressor gene -> increased IGF-1 (promotes growth) and increased HIF transcription factor (increases VEGF and PDGF -> angiogenesis)
Invades renal vein -> IVC -> metastasizes to lung and bone; can spread to retroperitoneal lymph nodes
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What are the gross and microscopic features of renal cell carcinoma?
Gross: yellow mass
Micro: polygonal clear cells
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What is the most common primary renal malignancy?
Renal cell carcinoma
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Renal oncocytoma
benign epithelial tumor
large eosinophilic cells with abundant mitochondria without perinuclear clearing (contrast to RCC)
presents with painless hematuria, flank pain and abdominal mass
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Wilms tumor (nephroblastoma) - what is it and who gets it?
malignant tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells
Most common malignant renal tumor in children (avg age 3yo)
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Wilms tumor pathogenesis
loss of function mutations of tumor suppressor genes WT1 or WT2 on chromosome 11
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Beckwith-Wiedemann syndrome
Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly and macroglossia
Associated with mutations in WT2 (chromosome 11) gene cluster, especially IGF-2
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WAGR syndrome
Wilms tumor, Aniridia (absence of iris), Genitourinary malformation, mental Retardation
Associated with DELETION of WT1 tumor suppressor gene (11p13)
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Denys-Drash syndrome
Wilms tumor, progressive renal (glomerular) disease and male pseudohermaphroditism
associated with mutations of WT1
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Urothelial (transitional cell) carcinoma
Most common tumor of urinary tract system
Arises from urothelial lining and can occur in renal calyces, renal pelvis, ureters and bladder
--> usually the bladder
Major risk factors: smoking, azo/analine dyes, long-term cyclophosphamide or phenacetin use
Generally seen in older adults, presents with painless hematuria
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What are the 2 pathways of urothelial (transitional cell) carcinoma?
1. flat, associated with early p53 mutations -> develops as high-grade flat tumor and then invades
2. papillary (NOT associated with early p53 mutations) -> develops as low-grad papillary tumor-> progresses to high-grade -> invades
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Squamous cell carcinoma of the bladder - pathogenesis and risk factors
chronic irritation of bladder -> squamous metaplasia -> dysplasia -> squamous cell carcinoma
*presents as painless hematuria
Risk factors: chronic cystitis (older women), smoking, Schistosoma hematobium infection (Middle eastern men), chronic nephrolithiasis
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Adenocarcinoma of the bladder
arises from:
- urachal remnant (tumor at dome of bladder, urachus connects fetal bladder to drain waste into yolk sac)
- cystitis glandularis
- exstrophy (congenital failure to form caudal portion of anterior abdominal and bladder walls)
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How is predicted respiratory compensation for a metabolic acidosis calculated?
Winter's forumla:
| PCO2 = 1.5[HCO3-] + 8 +/- 2
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Causes of increased K+ excretion
1. High extracellular K+
2. Increased aldosterone -> Na+ retained at expense of K+ loss
3. Alkalosis (promotes K+ shift into cells for H+ exchange)
4. Increased fluid flow through distal tubule-> quickly flushes away secreted K+
