Kidney and Collecting system

Question 1

68. End-stage kidney and renal failure:

KIDNEY FUNCTIONS

Answer 1

• excretion of waste products of metabolism
• regulate salt + H2O
• maintain acid balance
• secrete hormones + autacoids

Question 2

68. End-stage kidney and renal failure:

RENAL SYNDROMES

Answer 2

1. Nephritic syndrome⇒ glomerular injury
2. Nephrotic syndrome ⇒ glomerular disease
3. Asymptomatic hematuria ⇒ mild glomerular abnormalities
4. Rapidly progressive glomerulonepthiris ⇒ severe glomerular injury
5. Acute kidney injury ⇒ glomerular, vascular, intestinal or acute tubular injury
6. Chronic kidney injury ⇒ progressive scarring of the kidney
7. UTI ⇒ bacteremia and pyuria
8. Nephrolithiasis
9. Urinary tract obstruction
10. Renal tumors

Question 3

68. End-stage kidney and renal failure:

END STAGE KIDNEY

Answer 3

= complete failure of kidneys to function
- kidney function <20% of normal, GFR <15ml/min
- no longer removes waste products, concentrate urine, regulate endocrine functions
- CAUSES: DM, HT
MORPHOLOGY:
- kidneys skrink, red-brown color, granular
- sclerosis
- interstitial fibrosis
- lymphatic infiltration in interstitium
TREATMENT:
- dialysis
- transplant

Question 4

68. End-stage kidney and renal failure:

AZOTEMIA

Answer 4

= elevation of BUN (blood urea nitrogen) and serum creatinine due to renal failure

• BUN >9mM, Creatinine >120 microM
  1. PRERENAL AZOTEMIA:
  
  • decreases GFR in absence of parenchymal damage ⇒ hypo perfusion ⇒ hemorrhage
    2. RENAL AZOTEMIA:
  • renal parenchymal damage
    
    3. POSTRENAL AZOTEMIA:
  • urine flow obstructed

Question 5

68. End-stage kidney and renal failure:

UREMIA

Answer 5

= azotemia + biochemical abnormalities + clinical manifestations

Question 6

68. End-stage kidney and renal failure:

UREMIA clinical features

Answer 6

1. weakness, dyspnea, lethargy, edema, confusion
2. Electrolyte imbalance + Ca2+/PO4 imbalance
   ⇒ hyperkalemia, hyperphosphatemia, hypocalcemia
3. Cardio-pulmonary symptoms
   ⇒ HF, pulmonary edema, uremic fibrinous pericarditis, anemia, HT, arrhythmias
4. Hematopoietic symptoms
   ⇒ anemia (no EPO or tissue factor)
5. Neural
   ⇒ muscle twitch, weakness, headache, coma
6. Retinal
   ⇒ AS or HT retinopathy
7. Dermal
   ⇒ eyelid swelling, pruritus, purpura
8. Respiratory
   ⇒ Kussmaul breathing, urine smell, pleuritis, pneumonitis
9. GI
   ⇒ bleeding, anorexia, nausea, vomiting
10. Metabolic acidosis

Question 7

68. End-stage kidney and renal failure:

ACUTE RENAL FAILURE types

Answer 7

1. PRERENAL FAILURE:
   - reversible, function reduced by external factors
   - e.g. HT, salt depletion, dehydration
2. RENAL FAILURE;
   - malfunction of nephrons
   - e.g. acute GN, pyelonephritis
3. POSTRENAL FAILURE:
   - urinary tract obstruction

Question 8

68. End-stage kidney and renal failure:

ACUTE RENAL FAILURE morphology + clinical features

Answer 8

MORPHOLOGY:
- decreased cortical blood flow ⇒ ischemia
- large, pale pink kidney
- thick, pale cortex + dark, hyperemic pyramids
- Histo: glomeruli normal, distal tubules dilated with flattened epithelia
CLINICAL FEATURES:
- decreased urine output
- inquired azotemia, metabolic acidosis + serum potassium

Question 9

68. End-stage kidney and renal failure:

CHRONIC RENAL FAILURE

Answer 9

CAUSE:
- primary glomerular disease (acute GN)
- primary tubular disease (chronic hypercalcemia)
- vascular disease (nephrosclerosis)
- infections (tuberculosis)
- obstructive disease
- collagen disease (scleroderma)
- metabolic renal disease (amyloidosis)
- congenital anomalies of kidneys (polycystic kidney disease)
CLINICAL FEATURES:
- secondary hyperparathyroidism
- metabolic bone disease

Question 10

69. Developmental abnormalities and cystic diseases of the kidney:
    COMPLETE OR BILATERAL RENAL AGENESIS

Answer 10

= failure to develop kidneys
CAUSE:
- Potter sequence: no kidneys ⇒ oligohydramnios
⇒ clubbed feet, flat nose, low-set ears, recessed chin

Question 11

69. Developmental abnormalities and cystic diseases of the kidney:
    UNILATERAL RENAL AGENESIS

Answer 11

= 1 kidney missing due to failure of development

• no major health consequences
• prone to HT

Question 12

69. Developmental abnormalities and cystic diseases of the kidney:
    RENAL ECTOPIA

Answer 12

= abnormal localization of kidneys

- found in pelvis

Question 13

69. Developmental abnormalities and cystic diseases of the kidney:
    HORSESHOE KIDNEY

Answer 13

= fusion of kidneys during development
- 1/400
CONSEQUENCES:
  - obstruction
  - infection
  - stones

Question 14

69. Developmental abnormalities and cystic diseases of the kidney:
    DUPLICATED URETER

Answer 14

= 2 ureters due to ureteric bud arises twice

- may present as UTI- due to vesicouteral reflux

Question 15

69. Developmental abnormalities and cystic diseases of the kidney:
    SIMPLE CYST

Answer 15

• single cyst lined by membrane and filled with fluid
• usually on cortical area/surface
• can cause hemorrhage + pain

Question 16

69. Developmental abnormalities and cystic diseases of the kidney:
    DIALYSIS AQUIRED CYSTIC DISEASE

Answer 16

• in patients with end-stage renal disease on dialysis
• fibrosis ⇒ distal area becomes dilated
• both cortex and medulla
• may cause bleeding, hematuria

Question 17

69. Developmental abnormalities and cystic diseases of the kidney:
    AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Answer 17

- 1/500-1000
= multiple expanding cysts on both kidneys that destroy the intervening parenchyma ⇒ chronic renal failure
PATHOGENESIS:
  - deletion in PKD1 gene ⇒ polycystin 1⇒ dysfunctional tubules ⇒ cyst formation
  - PKD2 gene ⇒ no dimerization of PKD1
CLINICAL FEATURES:
  - symptoms in 40s-50s⇒ huge kidneys
  - renal failure
  - pain (Hemorrhage, obstruction)
  - UTIs
  - hematuria
TREATMENT:
  - dialysis + transplantation

Question 18

69. Developmental abnormalities and cystic diseases of the kidney:
    AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE

Answer 18

• perinatal, neonatal, infantile and juvenile subgroups
  PATHOGENESIS:
  
  • mutation in PKHD1 gene ⇒ fibrocystin ⇒ dysgenesis of collecting tubules ⇒ cysts
    CLINICAL FEATURES:
  • liver, lung, spleen and pancreas affected
  • early RF + hepatic failure
    MORPHOLOGY:
  • small cysts in cortex + medulla (sponge kidney)
  • epithelium lined cysts in liver

Question 19

69. Developmental abnormalities and cystic diseases of the kidney:
    MEDULLARY CYSTIC DISEASE OF KIDNEY

Answer 19

- infantile, juvenile, adolescent and adult types
PATHOGENESIS:
  - AD or AR
  - mutation in NPHP1-NPHP5
MORPHOLOGY:
  - numerous small cysts in cortico-medullary junction
  - kidneys small + contracted
  - intestinal fibrosis + inflammation
  - tubular atrophy
CLINICAL FEATURES:
  - polyuria + polydipsia
  - end-stage kidney in 5-10 years

Question 20

70. Pathogenesis of glomerular diseases:

GLOMERULAR DISEASES groups

Answer 20

1. Groups based on clinical features:
   - acute nephritic syndrome
   - RPGN
   - nephrotic syndrome
   - asymptomatic hematuria
   - CGN
2. Groups based on morphology:
   - glomerular hypercellularity
   - basement membrane thickening
   - sclerosis + hyalinization
3. Groups based on immunological manifestations:
   - circularoty immune complex GN
   - in-situ immune complex GN
   - heymans GN

Question 21

70. Pathogenesis of glomerular diseases:

ACUTE NEPHRITIC SYNDROME/NEPHRITIS

Answer 21

• accompany immune-mediated GN
• symptoms develop suddenly
  CLINICAL FEATURES:
  
  • hematuria
  • proteinuria
  • HT

Question 22

70. Pathogenesis of glomerular diseases:

RAPID PROGRESSIVE GLOMERULOSNEPHRITIS

Answer 22

- characterized by rapid loss of renal function ⇒ acute RF + death
CLINICAL FEATURES:
  - oliguria/anuria
  - hematuria + proteinuria
  - HT
TYPES:
  1. Anti-glomerular BM nephritis
    - AB against BM  ⇒ fibrosis
    - eg. Goodpasture syndrome
    - plasmaphoresis may help
  2. Immune-complex mediated crescentic GN
    - hereditary, homogenous
    - prolif. of Bowmans capsule, subepithelial deposit in EM + necrosis of capillary ducts
  3. Pauci-Immune type 3 crescentic GN
     - ANCA
     - necrosis of segments
     - endothelia preserved, BM fragmented

Question 23

70. Pathogenesis of glomerular diseases:

NEPHROTIC SYNDROME

Answer 23

= glomeruli of kidney damaged ⇒ leak of large amounts of protein into urine
CLINCAL FEATURES:
  - proteinuria
  - edema + lipiduria
  - hyperlipoproteinemia

Question 24

70. Pathogenesis of glomerular diseases:

ASYMPTOMATIC HEMATURIA

Answer 24

• no clinical symptoms
• some protein/blood in urine
• mild disease

Question 25

70. Pathogenesis of glomerular diseases: | CHRONIC GLOMERULONEPHRITIS

Answer 25

- end-stage kidney + decreased renal function - barrier defect ⇒ leakage of proteins ⇒ mesangial cell prolif. ⇒ obliterates glomeruli ⇒ hyaline glomeruli ⇒ kidneys shrink + have irregular surface CLINICAL FEATURES: - HT - oliguria/ anuria - anemia

Question 26

70. Pathogenesis of glomerular diseases: | GLOMERULAR HYPERCELLULARITY

Answer 26

1. Cellular proliferation ⇒ endothelial, epithelial and mesangial cells 2. Infiltration ⇒ cells not part of glomeruli infiltrate capsule (leukocytes)

Question 27

70. Pathogenesis of glomerular diseases: | BASEMENT MEMBRANE THICKENING

Answer 27

- whole fibrinogenesis | - linear or granular

Question 28

70. Pathogenesis of glomerular diseases: | SCLEROSIS AND HYALINIZATION

Answer 28

- precipitation of proteins in an onion-skin-like fashion ⇒ sclerosis ⇒ hyaline like secretion - end-stage kidney - diffuse or focal - segmental or global

Question 29

70. Pathogenesis of glomerular diseases: | CIRCULATORY IMMUNE COMPLEX GN

Answer 29

- HR type 3 - endogenous or exogenous AG - AG-AB complex formed in circulation ⇒ deposited in glomeruli ⇒ activation of complement system + recruitment of leukocytes ⇒ GN LOCATIONS: - mesangium - sub endothelial area - sub epithelial area - demonstrated by immunofluorescence ⇒ granular deposit

Question 30

70. Pathogenesis of glomerular diseases: | IN-SITU IMMUNE COMPLEX GN

Answer 30

- Type 2 HR 1. Anti-BM AB GN - AB directed against fixed AG in GBM - immunofluorescence ⇒ linear deposit - sometimes cross react with BM in lung alveoli ⇒ Goodpasture syndrome 2. AB against GBM fixed AG - AB act with previously planted non-glomerular AG - e.g. DNA, bacterial product. large aggregated proteins - immunofluorescence ⇒ linera/granular deposit

Question 31

70. Pathogenesis of glomerular diseases: | HEYMANS GN

Answer 31

- experimental model of membranous GN - brush-border antigen of rabbit injected into rat ⇒ anti-brush border AB ⇒ reinfected into rabbit ⇒ cross react with podocyte antigens ⇒ membranous GN

Question 32

71. Nephritic syndrome: | NEPHRITIC SYNDROME general

Answer 32

``` = set of clinical signs and symptoms that accompany immune-mediated GN - acute onset - glomeruli cells proliferate accompanied by leukocytic infiltrate SYMPTOMS: - hematuria with dysmorphic RBCs - oliguria - azotemia - mild hypertension ```

Question 33

71. Nephritic syndrome: | NEPHRITIC SYNDROME causes

Answer 33

``` 1. Primary GN ⇒ IgA nephritis 2. Postinfectious GN ⇒ poststreptococcal GN ⇒ bacterial endocarditis associated GN 3. Secondary GN associated with systemic diseases ⇒ SLE ⇒ Wegener's granulomatosis ⇒ Goodpasture's syndrome ```

Question 34

``` 71. Nephritic syndrome: IGA NEPHROPATHY (BERGER DISEASE) ```

Answer 34

- affects children and young adults PATHOGENESIS: - abnormality in IgA production and clearance - IgA is high in serum due to increased production in marrow - abnormality of IgA glycosylation - in mesangium trapped IgA activates alternative complement pathway ⇒ acute nephritic syndrome CLINICAL FEATURES: - slow progression to chronic renal failure⇒ 20 years

Question 35

71. Nephritic syndrome: | ACUTE POSTSTREPTOCOCCAL GN pathogenesis

Answer 35

- immune complexes between bacterial AG and AB deposit in glomeruli ⇒ activate complement system ⇒ GN + proliferation of mesangial cells - Tonsillitis (s.pyogenes) ⇒ rheumatic fever ⇒ humps deposits - also pneumococcus, s.aureus, common cold viruses

Question 36

71. Nephritic syndrome: | ACUTE POSTSTREPTOCOCCAL GN clinical features + diagnosis

Answer 36

``` CLINICAL FEATURES: - malaise, fever, nausea and nephritic syndrome - hematuria - oliguria - periorbital edema DIAGNOSIS: - microscope: light, electron, immunofluorescence - blood test ```

Question 37

72. The nephrotic syndrome: | NEPHROTIC SYNDROME

Answer 37

= diseases that cause increased permeability of the glomerular capillaries SYMPTOMS: - massive proteinuria - hypoalbuminemia - generalized edema - hyperlipidemia and lipiduria PATHOGENESIS: - derangement in capillary walls of glomeruli⇒ increased permeability ⇒ proteinuria ⇒ hypoalbuminemia ⇒ edema + increased synthesis of lipoproteins - in children ⇒ lesion primary to kidney - in adult ⇒ systemic disease

Question 38

72. The nephrotic syndrome: | MINIMAL- CHANGE DISEASE (LIPID NEPHROSIS)

Answer 38

- primary lesion of kidney ⇒ nephrotic syndrome in children - age: 1-7yrs (any ages) MORPHOLOGY: - glomeruli show diffuse thinning/ detachment of podocyte foot processes PATHOGENESIS: - T-cell derived factor ⇒ podocyte damage + thinning of foot processes ⇒ proteinuria CLINICAL FEATURES: - no HT + renal function preserved - slow development of nephrotic syndrome TREATMENT: - corticosteroid therapy

Question 39

72. The nephrotic syndrome: | FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS general + pathogenesis

Answer 39

CAN OCCUR: - in association with other known conditions - secondary to GN - maladaptation after nephron loss - inherited or congenital forms - primary disease UNLIKE MCD: - more hematuria + HT - hematuria is non-selective - poor response to corticosteroid therapy - 50% develop end-stage kidney within 10yrs PATHOGENESIS: - deposition of hyaline masses ⇒ entrapment of plasma proteins and lipids in foci of injury where sclerosis develops

Question 40

72. The nephrotic syndrome: | FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS morphology + clinical features

Answer 40

MORPHOLOGY: - focal: affects initially juxtamedullary glomeruli but progresses - segmental: only segments undergo sclerosis - increased mesangial matrix, obliterated capillary lumens + deposition of hyaline masses and lipid droplets - thinning + detachment of foot processes of podocytes

Question 41

72. The nephrotic syndrome: | MEMBRANOUS GN cause

Answer 41

- idiopathic in 85% - infections (hepatitis B, syphilis, malaria) - malignant tumors - exposure to inorganic salts - SLE or other autoimmune diseases - Drugs

Question 42

72. The nephrotic syndrome: | MEMBRANOUS GN pathogenesis

Answer 42

- slowly progressive - age: 30-50yrs - circulating immune complex ⇒ trigger MAC complex on podocytes ⇒ release of proteases and oxidants ⇒ damage capillary walls ⇒ leakage

Question 43

72. The nephrotic syndrome: | MEMBRANOUS GN morphology

Answer 43

- Spike and dome: * subepithelial IC deposits in BM * podocyte foot process flat - thick BM with holes - sclerotic glomeruli with hyaline

Question 44

72. The nephrotic syndrome: | MEMBRANOUS GN clinical features

Answer 44

- non-selective proteinuria - no response to corticoid therapy - renal failure after 2-20yrs

Question 45

72. The nephrotic syndrome: | MEMBRANOPROLIFERATIVE GN pathogenesis

Answer 45

MPGN-1 (sub endothelial deposit disease): - circulating immune complexes ⇒ complement activation - association with hepatitis B and C antigens, SLE, infected AV shunts, extrarenal infections MPGN-2 (dense-deposit disease): - Autoantibodies against C3-convertase ⇒ uncontrolled cleavage of C3⇒ excessive complement activation - mutation in gene encoding Factor H ⇒ deficiency ⇒ excessive activation

Question 46

72. The nephrotic syndrome: | MEMBRANOPROLIFERATIVE GN morphology + clinical features

Answer 46

MORPHOLOGY: - glomeruli are large - proliferation of mesangial cells + endothelial cells + infiltrating leukocytes - GBM thickened ⇒splitting of GBM⇒ tram track appearance - MPGN1: sub endothelial electron-dense deposits - MPGN2: intramembranous deposits CLINICAL FEATURES: - progress to renal failure - nephrotic syndrome - poor prognosis

Question 47

73. Systemic diseases associated glomerular damage: | DIABETIC GLOMERULAR SCLEROSIS/ NEPHROPATHY

Answer 47

= BM thickening due to non-enzymatic glycosylation of proteins - diffuse GS ⇒ all glomeruli ⇒ hyaline deposit - nodular focal GS ⇒ Kimmelstiel Wilson - proteinuria ⇒ sclerosis ⇒ renal failure

Question 48

73. Systemic diseases associated glomerular damage: | AMYLOIDOSIS

Answer 48

= deposition of amyloids in sub endothelium of glomeruli ⇒ severe proteinuria ⇒ renal failure - corticosteroids make it worse

Question 49

73. Systemic diseases associated glomerular damage: | GOODPASTURE SYNDROME

Answer 49

- genetic autoimmune disease: GN + hemorrhage of lungs | - immune system attacks Goodpasture antigen in GBM (component of non-collagenous domain of alpha-3 chain of collagen 4)

Question 50

73. Systemic diseases associated glomerular damage: | POLYARTHRITIS NODOSA/ WEGENER GRANULOMATOSIS

Answer 50

- autoimmune vascular diseases * PN: granular deposits * WG: ANCA WG: ⇒ acute necrotizing granulomas of upper respiratory tract ⇒ necrotizing granulomastous vasculitis ⇒ necrotizing GN

Question 51

73. Systemic diseases associated glomerular damage: | SYSTEMIC LUPUS ERYTHEMATOSUS SLE

Answer 51

- deposition of DNA/anti-DNA complexes within glomeruli ⇒ inflam. ⇒ proliferations ⇒ necrosis CLASS 1: - <5%, normal by LM, EM, IF CLASS 2: (mesangial lupus GN) - 10-25%, mild clinical symptoms CLASS 3: (focal proliferative GN) - 25-30%, a few foci show swelling + prolif. + infiltrate - hematuria, proteinuria CLASS 4: (diffuse proliferative GN) - 35-60%, endothelial + mesangial prolif. ⇒ diffuse hypercellularity - glomerulosclerosis, hematuria, proteinuria, HT, renal insufficiency CLASS 5: (membranous GN) - 10-15% - widespread thickening of capillary wall - severe proteinuria

Question 52

74. Vascular diseases of the kidney: | BENIGN NEPHROSCLEROSIS

Answer 52

= renal changes in benign HT ⇒ hyaline arteriolosclerosis - causes: HT + DM MORPHOLOGY: - atrophic kidneys, granularity on surface - hyaline thickening of walls of small arteries + arterioles - narrow lumen ⇒ ischemia - severe: glomerular tufts globally sclerosed

Question 53

74. Vascular diseases of the kidney: | MALIGNANT NEPHROSCLEROSIS pathogenesis

Answer 53

- initial event: vascular damage ⇒ increased permeability to fibrinogen and plasma proteins + endothelial injury + platelet deposition ⇒ fibrinoid necrosis + intravascular thrombosis - PDGF + plasma ⇒ intimal smooth muscle hyperplasia ⇒ hyperplastic arteriolosclerosis ⇒ narrowing ⇒ ischemia - affected afferent arterioles ⇒ RAAS ⇒ HT

Question 54

74. Vascular diseases of the kidney: | MALIGNANT NEPHROSCLEROSIS morphology + clinical features

Answer 54

``` MORPHOLOGY: - normal/shrunken size - pinpoint petechial hemorrhages on cortical surface - fibrinoid necrosis - hyperplastic arteriolosclerosis CLINICAL FEATURES: - increased BP ⇒ proteinuria + hematuria ⇒ renal failure - prognosis: 50% survive at least 5yrs ```

Question 55

74. Vascular diseases of the kidney: | THROMBOTIC MICROANGIOPATHIES pathogenesis

Answer 55

PATHOGENESIS OF HUS: - endothelial injury + activation ⇒ intravascular thrombosis + vasoconstriction ⇒ microangiopathy - E.coli O156:H7 ⇒ shiga toxin ⇒ carried by neutrophils ⇒ renal glomerular epithelial cells ⇒ increased adhesion of leukocytes ⇒ increased endothelia production ⇒ loss of endothelial NO ⇒ endothelial damage - toxin gains entry into cells ⇒ cell death PATHOGENESIS OF TTP ( thrombotic thrombocytopenic purpura): - aquired defect in proteolytic cleavage of vWF multimers (ADAMTS13)

Question 56

74. Vascular diseases of the kidney: | THROMBOTIC MICROANGIOPATHIES morphology + clinical features

Answer 56

MORPHOLOGY: - widespread thrombosis in microcirculation - microangiopathic hemolytic anemia + thromocytopenia CLINICAL FEATURES: - HUS: sudden onset, bleeding manifestations, oliguria, hematuria, hemolytic anemia, neurological changes

Question 57

75. Diabetic nephropathy: | DIABETIC NEPHROPATHY causes

Answer 57

= progressive kidney disease caused by angiopathy of capillaries + glomeruli - nephrotic syndrome + diffuse GN - result of DM CAUSES: - Non-enzymatic glycosylation: glucose ⇒ AAs ⇒ AGEs⇒ cross-links between polypeptides ⇒ net ⇒ entrap proteins ⇒ thick BM - Hypercalcemia: ⇒ hyperosmolarity ⇒ overload of filtration ⇒ destroy filtration capacity - increased synthesis of collagen 4 ⇒ increased BM

Question 58

75. Diabetic nephropathy: | GLOMERULAR LESIONS

Answer 58

1. Glomerular BM thickening: - thickened thought entire length, more porous ⇒ nephrotic syndrome 2. Diffuse mesengial sclerosis: - increased mesangial matrix + proliferation + GBM thickening ⇒ nephrotic syndrome - age: >10yrs 3. Nodular glomerulosclerosis: - ball like deposits in mesangium ⇒ Kimmelstriel-Wilson lesion - induce ischemia ⇒ granular cortical surface

Question 59

75. Diabetic nephropathy: | RENAL VASCULAR LESIONS

Answer 59

- renal atherosclerosis + arteriolosclerosis ⇒ macrovascular disease in diabetics - both afferent + efferent arterioles affected

Question 60

75. Diabetic nephropathy: | PYELONEPHRITIS

Answer 60

= aute/chronic inflammation of kidneys, begins in interstitial tissue ⇒ affected tubules - acute: necrotizing papillitis (more in diabetics) - symptoms: micro- and macroalbuminemia + HT - may progress to end-stage renal disease

Question 61

76. Acute tubular necrosis ATN: | CAUSES OF ACUTE RENAL FAILURE

Answer 61

1. ATN 2. glomerular disease + RPGN 3. diffuse renal vascular disease 4. acute drug induced interstitial nephritis 5. diffuse cortical necrosis

Question 62

76. Acute tubular necrosis ATN: | PATHOGENESIS

Answer 62

= damaged epithelial cells + acute suppression of kidney function - reversible renal lesion - causes: tubular injury or disturbance in blood flow - ischemia ⇒ structural change in epithelial cells ⇒ detach ⇒ loss of cell polarity ⇒ redistribution of membrane proteins ⇒ decreased Na+ reabsorption in proximal tubule ⇒ vasoconstriction through RAAS ⇒ further damage to tubules + debris ⇒ block urine outflow ⇒ increase pressure ⇒ decreased GFR ⇒ fluid can leak to interstitium ⇒ edema ⇒ compression ⇒ collapse of tubules ⇒ ATN

Question 63

76. Acute tubular necrosis ATN: | TYPES

Answer 63

1. Ischemic ATN: - shock ⇒ decreased O2 + substrate delivery to tubular cells 2. Nephrotoxic ATN: - poisons (heavy metals, drugs, organic solvents) ⇒ necrosis of tubular cells 3. Pigment ATN (crush syndrome): - pigment stuck in lumen ⇒ obstruction ⇒ increased pressure ⇒ leakage ⇒ collapse - pigments: hemoglobin and myoglobin

Question 64

76. Acute tubular necrosis ATN: | MORPHOLOGY

Answer 64

1. Ischemic + pigment: - segmental influence - damaged cells ⇒ fragmentation of BM 2. Nephrotoxic: - proximal tubule - prognosis good (preserve BM)

Question 65

76. Acute tubular necrosis ATN: | CLINICAL FEATURES

Answer 65

1. Initiation (36h): - drop of urine output - increase urine creatine 2. Maintenance (3-6d): - anuria - uremia + fluid overload 3. Recovery: - increase in urine volume - electrolyte-balance disturbance (deranged tubular function) - urine volume normalizes

Question 66

77. Tubulointerstitial nephritis: | TUBULOINTERSTITIAL NEPHRITIS

Answer 66

= group pf inflammatory diseases involving interstitium and tubules - usually caused bacterial infection ⇒ renal pelvis involved - non-bacterial TIN ⇒ interstitial nephritis * drugs * metabolic disorders * physical injury * viral infection * immune reaction

Question 67

77. Tubulointerstitial nephritis: | ACUTE PYELONEPHRITIS pathogenesis + predisposing factors

Answer 67

= inflammation of lower and upper urinary tract due to bacterial infection PATHOGENESIS: - causative agents: E.coli, Klebsiella, Proteus, Enterobacter, Pseudomonas etc. - hematogenous spread by septicemia or infective endocarditis embolism - ascending infection from lower urinary tract PREDISPOSING FACTORS: - obstruction (e.g. stones, prostate hyperplasia) - vesicouteral reflux - catheters - females more prone - immunosuppression

Question 68

77. Tubulointerstitial nephritis: | ACUTE PYELONEPHRITIS morphology + clinical features

Answer 68

MORPHOLOGY: - yellow raised abscesses on renal surface ⇒ heals ⇒ fibrosis ⇒ flowerbed scar - HISTO: suppurative necrosis/ abscess formation in parenchyma ⇒ rupture into tubules CLINICAL FEATURES: - sudden onset pain at costovertebral angle + infection symptoms - pyuria, bacteruria - bladder + urethral irritation - benign + self-limiting ⇒ risk for chronic PN DIAGNOSIS: - leukocytes in urine by urine analysis + culture

Question 69

77. Tubulointerstitial nephritis: | CHRONIC PYELONEPHRITIS

Answer 69

= end-stage kidney after several APN infections TYPES: 1. Chronic obstructive PN - obstruction ⇒ recurrent infection ⇒ scarring 2. Chronic reflux PN - superimposition of UTI on congenital vesicoureteral reflux - more in children MORPHOLOGY: - scar formation ⇒ contraction of parenchyma ⇒ flowerbed scar on surface

Question 70

77. Tubulointerstitial nephritis: | ACUTE DRUG-INDUCED INTERSTITIAL NEPHRITIS

Answer 70

``` = adverse reaction to drugs (e.g. diuretics, antibiotics, NSAIDS) - HR type 1 or 4 - infiltration of interstitium with eosinophils, lymphocytes, macrophages etc. ⇒ tubular necrosis SYMPTOMS: - hematuria - leukouria - renal failure - increased size of kidneys TREATMENT: withdraw drug ```

Question 71

77. Tubulointerstitial nephritis: | ANALGESIC ABUSE NEPHRITIS

Answer 71

- large amount of analgesics (painkillers) ⇒ chronic interstitial nephritis + renal papillary necrosis SYMPTOMS: - hematuria - chronic renal failure

Question 72

78. Urinary outflow obstruction: | RENAL STONES consequenses + pathogenesis

Answer 72

= calculus formation at any level in urinary system - familial predisposing factors CONSEQUENCES: - pyelonephritis due to stasis - hydronephrosis PATHOGENESIS: - increased urine concentration ⇒ exceeds solubility in urine ⇒ precipitation - lack of Tamm-Horsfall protein, nephrocalcin - obstruction ⇒ intense pain, hematuria

Question 73

78. Urinary outflow obstruction: | RENAL STONES types

Answer 73

1. Calcium stone (Ca-oxalate, Ca-phosphate) 80% - hypercalcemia, hypercalcuria, hyperoxalemia 2. Struvite stone (Mg-NH4-PO4) 10% ⇒ alkaline urine - UTIs 3. Uric acid stone 6-7% ⇒ acidic urine - leukemia, gout 4. Cysteine stone 1-2% ⇒ acidic urine

Question 74

78. Urinary outflow obstruction: | HYDRONEPHROSIS general + pathogenesis

Answer 74

= dilation of renal pelvis and calyces + atrophy of parenchyma - caused by obstruction to outflow of urine * congenital * aquired: foreign body, tumor, inflammation, neurogenic, pregnancy PATHOGENESIS: - obstruction ⇒ still filtration ⇒ renal interstitial ⇒ lymph + veins - leads to dilation ⇒ increased pressure ⇒ compression of vasculature - obstruction ⇒ inflammation ⇒ fibrosis

Question 75

78. Urinary outflow obstruction: | HYDRONEPHROSIS morphology + clinical features

Answer 75

MORPHOLOGY: - obstruction below ureters: bilateral ⇒ renal failure - obstruction above ureters: unilateral * subtotal: enlarged kidney, atrophy of parenchyma * complete: decreased renal function - hydroureter CLINICAL FEATURES: - bilateral complete: anuria - bilateral incomplete: polyuria - unilateral: silent - with time irreversible

Question 76

79. Tumors of kidney: | RENAL CELL CARCINOMA

Answer 76

``` - derived from renal tubular epithelium ⇒ located in cortex RISK FACTORS: - age (60-70yrs) - sex (men) - smoking - HT + obesity - hypercholesterolemia - polycystic disease due to chronic dialysis MORPHOLOGY: - yellowish color, necrosis, hemorrhage, cystic degeneration CLINICAL FEATURES: - painless hematuria - palpable abdominal mass - dull flank pain - paraneoplastic syndromes METASTASIS: - renal vein ⇒ IVC ⇒ right heart - vertebrae, lung, bone, liver, brain ```

Question 77

79. Tumors of kidney: | CLEAR CELL RENAL CARCINOMA

Answer 77

- most common type - histo: cells with clear or granular cytoplasm - sporadic or familial ⇒ von Hippel-Lindau disease VHL: - AD disease - hemangioblastomas of cerebellum + retina - mutation in VHL gene on chr. 3p25

Question 78

79. Tumors of kidney: | PAPILLARY RENAL CELL CARCINOMA

Answer 78

- papillary growth pattern ⇒ multifocal and bilateral - familial or sporadic forms ⇒ MET proto-oncogene on chromosome 7

Question 79

79. Tumors of kidney: | CHROMOPHOBE RENAL CARCINOMA

Answer 79

- arise from intercalated cells of collecting ducts - cancer cells stain dark ⇒ blue cytoplasm + clear halo around nuclei - have loss in entire chromosome ⇒ chr. 1, 2, 6, 10, 13, 17, 21 ⇒ extreme hypodiploidy - good prognosis

Question 80

79. Tumors of kidney: | WILMS TUMOR

Answer 80

- children 2-5yrs - derived from mesoderm - 2 forms: 1. epithelial cell differentiation 2. stromal cell differentiation PATHOGENESIS: 1. WAGR syndrome ⇒ WT1 2. Denys-Drash syndrome ⇒ WT1 3. Backwith-Wiedemann syndrome ⇒ WT2 MORPHOLOGY: - large, solitary, well-circumscribed mass - soft, homogenous, tan-grey color - foci of hemorrhage, cystic degeneration, necrosis CLINICAL FEATURES: - palpable abdominal mass - fever, abdominal pain, hematuria, intestinal obstruction

Question 81

80. Tumors of the urinary bladder and collecting system: | PREDISPOSING FACTORS

Answer 81

- sex (men 3:1) - age (50-70yrs) - exposure to beta-naphtylamine - cigarette smoking - chronic cystitis - drugs - genetics (p16, p53, FGFR3)

Question 82

80. Tumors of the urinary bladder and collecting system: | TUMOR CLASSIFICATION

Answer 82

- rare benign papilloma - urothelial carcinoma - a group of papillary urothelial neoplasms of low malignant potential - in-situ stage of bladder carcinoma

Question 83

80. Tumors of the urinary bladder and collecting system: | MORPHOLOGY

Answer 83

1. Benign papilloma: - 0,2-1cm frond-like structures with delicate fibrovascular core covered by multilayered well-differentiated transitional epithelium 2. Urothelial carcinomas: - papillary to flat - noninvasive to invasive - lowgrade to high grade 3. In-situ stage of bladder carcinoma

Question 84

80. Tumors of the urinary bladder and collecting system: | CLINICAL FEATURES

Answer 84

- painless hematuria - usually arise in urinary bladder - tend to recur after surgical removal - cause urinary tract obstruction - low-grade shallow lesion has good prognosis - deep penetration 5yr survival: <20%