Renal Tubular Diseases and Congenital Diseases

Question 1

definition of acute tubular necrosis (ATN)

Answer 1

destruction of tubular epithelial cells with suppression of kidney functions leading to acute renal failure (ARF)

the latter becomes clinically apparent when tubular insufficiency is reduced by 80%

a common cause of ARF

Question 2

types of ATN

Answer 2

ischemic and toxic

Question 3

ischemic ATN

Answer 3

usually pre-renal, characterized by pale kidneys, edema, pathcy necrosis of proximal tubule, rupture of TBMs

casts in the distal tubules and collecting ducts

Question 4

nephrotoxic ATN

Answer 4

antibiotics- or othe rtoxins-induced

characterized by diffuse necrosis of middle segment of the proximal tubule

histologic changes depend on the type of the agent

recovery phase is characterized by regenerating epithelium

Question 5

What is the primary event in ischemic injury?

Answer 5

marked reduction/cessation of aerobic respiration, impairment of oxidative phsophorylation by mitochondria and loss of ATP

activation of proteases, phospholipases and generation of O2 radicals that cause cell death

Question 6

What happens in reversible early injury of the tubules in ATN?

Answer 6

the cell polarity and redistribution of Na-K ATPase leads to increased concentration of sodium in the tubular lumen and constriction of afferent arteriole of the glomerulus

note that the proximal tubular cells are very much dependent upon aerobic respiration, while the distal tubular cells are capable of anaerobic glycolysis and thus can maintain cellular integrity and functions for a longer hypoxic period

Question 7

What happens in irreversible injury in ATN?

Answer 7

there is a loss of mitochondrial functions and cell membrane integrity that leads to cell death (necrosis or apoptosis)

Question 8

direct hemodynamic effects of ischemia

Answer 8

activation of RAS

increased endothelin expression

decreased NO and PGI2 production

Question 9

nephrotoxic injury ATN

Answer 9

critical event is the formation of free radicals that injure the cell membranes by lipid peroxidation and followed by cell death

these events are similar to reversible injury that is seen in irreversible injury due to ischemia

Question 10

phases of acute tubular necrosis

Answer 10

oliguric phase

early diuretic phase

late diuretic phase

Question 11

oliguric phase of ATN

Answer 11

characterized by loss of tubular functions, uremia, hyperkalemia, metabolic acidosis, and fluid overload

Question 12

early diuretic phase of ATN

Answer 12

characterized by progressive increase of urine output, howevve,r tubular functions remain impaired

as a result, there are massive losses of fluid and electrolytes, and hypokalemia rather thna hyperkalemia is observed

Question 13

late diuretic phase of ATN

Answer 13

characterized by progressive increase in the concentrating ability of tubules line with regenerating epithelia, and uremia subsides

renal functions return to level over a period of a couple months

Question 14

tubulointerstitial nephritis (TIN)

Answer 14

primary structural and functional alterations of tubules and interstitium

may be acute with interstitial edema, PMN infiltration, and focal tubular necrosis

may also be chronis with interstitial fibrosis and tubular atrophy

Question 15

causes of TIN in man

Answer 15

bacterial infection (pyelonephritis)

toxins

metabolic disorders

urinary stones and strictures

neoplasms

immunologic assault

vascular anomalies

polycystic disease

Question 16

general characteristics of acute pyelonephritis

Answer 16

characterized by acute suppurative bacterial infection of kidney and renal pelvis

second most common infectious disease in man

usually caused by organisms that include predominantly (85%) gram-negative bacilli, and serological studies point that the organisms are derived from patient’s own fecal flora

there are 2 major routes of infections to the kidneys

Question 17

What are the two major routes of infection to the kidneys for acute pyelonephritis?

Answer 17

hematogenous and ascending

Question 18

hematogenous route of infection for acute pyelonephritis

Answer 18

uncommon and caused by circulating Staphylococci or E. coli

normal kidney is highly resistant to blood-born infection, and obstruction dramatically enhances its susceptibility to UTIs

infected kidneys have multiple abcesses on its surface

Question 19

ascending route of infection for acute pyelonephritis

Answer 19

quite common

bacteria is commonly E. coli

ascends from the urethra and bladder

urinary tract obstruction greatly increases the risk of infection

with obstruction, bacteria multiple and colonization occurs

vesicoureteral reflux is the most important

Question 20

vesicoureteral reflux

Answer 20

major cause of urinary infections in children, and is due to the anomaly of the vesical segment of the ureter

infection is recurrent

condition is diagnosed by voiding cystourethrogram

surgically correctable

Question 21

pathology of acute pyelonephritis

Answer 21

characterized by patchy acute suppurative inflammation of interstitium and tubules with pus casts, tubular necrosis, and secondary involvement of glomeruli and blood vessels

the complications include perinephric abcesses, papillary necrosis (particularly in diabetics and urinary tract infections) and pyonephrosis

Question 22

characteristics of chronic pyelonephritis

Answer 22

characterized by chronic or recurrent infections of the kidney, renal pelvis, and calyces

usually bacterial in origin

usually associated with obstruction or vesicoureteral reflux, and resulting deformities of the pelvcalyceal systems distinguish it from other causes of tubulointerstitial diseases

Question 23

What are the types of chronic pyelonephritis?

Answer 23

chronic obstructive and reflux type

Question 24

chronic obstructive pyelonephritis

Answer 24

characterized by recurrent bouts of renal inflammation

usually associated with congenital anomalies

ex. posterior uretheral valve or vessel compressing on the ureter

may be unilateral or bilateral

Question 25

reflux type chronic pyelonephritis

Answer 25

common in young people abnormal insertion of ureter into the urinary bladder recurrent bouts of infection ultimately leading ot chronic polar damage to the kidney

Question 26

pathology of chronic pyelonephritis

Answer 26

deep surface scars on the kidney along with dilatation and distortion of the pelvicalyceal system blunting of the papillae microscopicaly, interstitial chornic inflammation, scarring, tubular atrophy with thyroidization of tubules containing casts are seen glomeruli are relatively spared, except when focal segmental glomerulosclerosis sets in

Question 27

What are four factors that may be responsible for the susceptibility of the kidney to drug or toxins?

Answer 27

1) large blood supply 2) concentration of toxins in tubular fluid 3) secretion of certain toins by nephrons 4) concentration of toxins in medulla by the countercurrent mechanisms

Question 28

types of TIN

Answer 28

drug-induced TIN acute hypersensitivity TIN analgesic abuse TIN NSAID-induced TIN

Question 29

analgesic abuse TIN

Answer 29

chronif corm of TIN due to excessive intake of analgesic mixtures (aspirin, phenacetin, caffeine) papillary/medullary necrosis due to covalent binding, oxidative damage, and decreased prostaglandin synthesis locally imparied urine concentrating ability and renal tubular acidosis

Question 30

histological findings of analgesic nephropathy

Answer 30

necorsis of medullary papilla

Question 31

general characteristics of drug-induced tubulo-interstitial nephritis (DITIN)

Answer 31

antiboitics, diuretics, NSAIDs fever, rash, proteinuria, increased creatiinine type-I hypersensitivity, IgE-mediated reaction eosinophils - body tissue, blood, and urine

Question 32

histological findings of DITIN

Answer 32

interstitial edema and influx of eosinophils focus of tubulitis (invasion of tubules)

Question 33

types of congenital anomalies of the kidney

Answer 33

**agenesis** - bilateral incompatible, unilateral-associated with adaptive changes **hypoplasia** - developmental/acquired, unilateral-associated with adaptive changes **ectopic kidney** - abnormal location, susceptible to infection **horseshoe kidney** - 1:500 autopsies, 90% lower pole fusion

Question 34

thrombotic microangiopathies

Answer 34

conditions where the renal vasculature is involved secondarily due to systemic thrombosis two condition with overlapping features include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenia purpura (TTP) **pathology** - thrombi in the capillaries due to denuddation of endothelium and activation of platelets

Question 35

cystic kidney disease

Answer 35

ADPKD ARPKD medullary sponge kidney medullary cystic disease complex (recessive/dominant) simple cysts (mostly incidental finding) acquired renal cystic disease (hemodialysis)

Question 36

What are the clinico-pathologic characteristics of the autosomal recessive form of polycystic kidney disease (APRKD)?

Answer 36

large cystic kidneys at birth radial **fusiform cysts** hepatic fibrosis (_fibrocystin_) bile duct proliferation death in early childhood splenomegaly cysts appear as longitudinal cysts that are oriented at right angles to the cortical surface

Question 37

What are defining features of kidneys of patients with ARPKD?

Answer 37

fusiform cysts large kidneys and hepatic fibrosis bile duct proliferation

Question 38

What gene is responsible for ARPKD? What is its function?

Answer 38

fibrocystin transmembrane protein responsible for cell-cell signaling immunoglobulin type domain can interact with other proteins on other cells

Question 39

What are the clinico-pathologic characteristics of medullary sponge disease (MSD)?

Answer 39

bilateral medullary cysts - involves the collecting ducts hematuria, infections stones, gravel in urine sometimes asymptomatic benign course

Question 40

What are the clinico-pathologic characteristics of medullary cystic disease complex (MCDC)

Answer 40

cortico-medullary cysts recessive (juvenile) dominant (adult) salt wasting, polyuria nephronophthisis - wasting of the kidney (_nephrocystin_) uremia leads to chronic renal failure

Question 41

What is the gene responsible for MCDC? What is its function?

Answer 41

nephrocystin intracytoplasmic protein important SH3 domain for binding to other adhesion proteins

Question 42

What are the clinico-pathologic characteristics of autosomal dominant polycystic kidney disease (ADPKD)?

Answer 42

tubular disease, high penetrance, occurs in **any segment of the nephron** and kidneys, become **progressively larger** multiple genes (PKD1, PKD2, and PKD3) familial, disvered in 2nd or 4th/5th decade of life prevalence is 1:650 **hematuria in teenage yars if received injury to flank regions** complications include rupture of cysts, pain and recurrent UTIs liver or splenic cysts, colon diverticula, intracranial aneurysm

Question 43

pathogenesis of ADPKD

Answer 43

abnormal cell-matrix or cell-cell interactions cellular proliferation and polarity characteristics of the cells with aberrant fluid secretion and accumulation (cAMP)

Question 44

What do the kidneys look like in ADPKD?

Answer 44

large kidneys with a lot of fluid normal glomeruli bilateral cysts sometimes can see chocolate cysts - large cysts filled with blood clot

Question 45

What genes are affected in autosomal dominant polycystic kidney disease (ADPKD)?

Answer 45

85% PKD1 - chromosome 16 PKD2 - 15% of cases, chromosome 4 PKD3 - minority of cases homotypic and heterotypic interactions between C-termini of polycystin-1 and -2 mutations lead to tubular dysmorphogenesis and disease

Question 46

Polycystin-1

Answer 46

transmembrane protein with extracellular N-terminus and multiple complex domains extracellular lectin domain and Ig-like folds mediate cell-matrix interactions complex that it forms lacks focal adhesion kinase (FAK) when mutant

Question 47

Polycystin-2

Answer 47

Na+ channel transmembrane protein with coiled-coil domain and SH3 domains in the intracellular side that interacts with polycystin-1