Renal 1 and 2 Flashcards
1
Q
A. Glomeruli –
A
Network of capillaries between afferent arteriole (bringing blood to the capillary bed) and efferent arteriole (drains blood away from capillary bed).
2
Q
Glomeruli: The capillary wall consists of
A
endothelium, basement membrane and epithelium (lining the urinary space).
3
Q
Glomeruli: The epithelial cells have many finger-like processes that come from the cell body and contact the
A
basement membrane.
4
Q
Glomeruli: A membrane connects adjacent processes (called the slit diaphragm) and is important in preventing
A
proteinuria.
5
Q
Glomeruli: The capillary wall is permeable to
A
water and small molecules and impermeable to albumin and larger proteins.
6
Q
Glomeruli capillaries are supported by connective tissue called the
A
mesangium.
7
Q
Kidney Tubules – The filtrate from the glomeruli travels through the system of
A
tubules. The tubular epithelium reabsorbs some substances and secretes other substances, eventually forming urine
8
Q
Kidney Interstitium – Formed by
A
collagen and blood vessels between the tubules and glomeruli.
9
Q
Kidney Vasculature – The efferent arterioles supply the
A
capillary bed around some of the tubules (vasa recta). Absence of blood flow through the glomeruli reduces oxygen delivery to the tubules.
10
Q
- Azotemia
Elevation of the
A
blood urea nitrogen (BUN) and creatinine levels, due to decreased filtration of blood through the glomeruli (decreased glomerular filtration rate).
11
Q
- Uremia
Association of azotemia with
A
clinical signs and symptoms, including gastroenteritis, peripheral neuropathy, pericarditis, dermatitis, hyperkalemia, and metabolic acidosis.
12
Q
- Acute nephritic syndrome: Results from
A
glomerular injury and is
characterized by acute onset of hematuria, mild to moderate
proteinuria, azotemia, and hypertension.
13
Q
- Nephrotic syndrome:
A
Glomerular syndrome characterized by heavy
proteinuria (> 3.5 grams per day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria.
14
Q
- Acute renal failure:
A
Acute onset of azotemia with oliguria (or anuria).
15
Q
Autosomal dominant (adult) polycystic kidney disease: 1. Clinical presentation:
A
seen in 1 out of every 500-1000 people,
characterized by multiple expanding cysts in both kidneys. Gradual onset of renal failure in adult, urinary tract hemorrhage (hematuria), pain, hypertension, urinary tract infection.
16
Q
Autosomal dominant (adult) polycystic kidney disease: 2. Etiology: defective gene is
A
PKD1 (in 90% of families) located on
chromosome 16. The gene encodes for polycystin-1
17
Q
Autosomal dominant (adult) polycystic kidney disease: 3. Extrarenal pathology:
A
1/3 of patients have cysts in liver; aneurysms
may develop in the circle of Willis (intracranial)
18
Q
Autosomal dominant (adult) polycystic kidney disease: 4. Pathology:
A
very large (up to 4 kg) kidneys with numerous cysts that arise in every part of the tubular system
19
Q
Autosomal dominant (adult) polycystic kidney disease: 5. Histopathology
A
Cysts arise from all levels of the nephron
20
Q
Autosomal dominant (adult) polycystic kidney disease: 6. Clinical:
A
flank pain around 4th decade, hematuria, hypertension and UTI, renal failure
21
Q
B. Autosomal recessive (childhood) polycystic kidney disease: 1. Clinical:
A
renal failure develops from infancy to several years of age –
rare; seen in 1 in 20,000 live births. Due to mutations in the PKHD1
gene
22
Q
B. Autosomal recessive (childhood) polycystic kidney disease: 2. Extrarenal pathology: almost all have
A
liver cysts and progressive liver fibrosis
23
Q
B. Autosomal recessive (childhood) polycystic kidney disease: 3. Pathology:
A
numerous small uniform-size cysts from collecting tubules
in cortex and medulla
24
Q
Mechanisms of glomerular injury
1. Immune complex deposits in
A
glomerular basement membrane (GBM)
or mesangium. These may result from circulating immune complexes that deposit in the glomerulus or circulating antibodies directed against glomerular components or non-glomerular antigens “planted” in the glomerulus.
25
Mechs of glomerular injury: 2. Epithelial and endothelial
cell injury.
26
B. Pathologic evaluation of kidney biopsies
| 1. Light microscopy -
In addition to H+E stain, PAS, trichrome and Jones stains are routinely done.
27
B. Pathologic evaluation of kidney biopsies: 2. Immunofluorescence -
Antibodies to immunoglobulin and complement, tagged with a fluorescent molecule, are used to identify immune complexes.
28
B. Pathologic evaluation of kidney biopsies: 3. Electron microscopy -
Identification of immune complexes, epithelial cell changes, basement membrane morphology and other changes.
29
Nephrotic syndrome
| symptoms:
• Heavy proteinuria, hypoalbuminemia, severe edema (most obvious clinical sign), hyperlipidemia and lipiduria
30
Nephrotic syndrome caused by
• Caused by increased glomerular capillary permeability to plasma proteins:
31
Nephrotic syndrome: 1. Minimal change disease a) most common cause of
nephrotic syndrome in children.
32
Minimal change disease: b) pathology -
normal-appearing glomeruli by light microscopy; no immune complexes; electron microscopy demonstrates effacement of epithelial cell foot processes
33
Minimal Change disease: c) good response to
treatment (especially in children)
34
2. Focal and segmental glomerulosclerosis: a) one of the most common causes of
nephrotic syndrome in adults.
35
2. Focal and segmental glomerulosclerosis: b) Causes
primary (idiopathic) or secondary to other glomerular diseases, loss or scarring of other glomeruli, or genetic.
36
2. Focal and segmental glomerulosclerosis: c) pathology
- partial (segmental) sclerosis of some (focal) glomeruli characterized by increased mesangial matrix collagen with obliteration of capillary loops. The idiopathic form has no immune complexes.
37
2. Focal and segmental glomerulosclerosis: d) poor response to
corticosteroid treatment – renal failure in 50% after 10 yrs.
38
```
Membranous nephropathy (glomerulonephritis)
a) most common in adults age
```
30-50
39
Membranous nephropathy (glomerulonephritis): b) Causes
primary (disease limited to the kidney) or secondary to infection, malignancy, SLE, or drugs.
40
Membranous nephropathy (glomerulonephritis): c) pathology -
immune complexes in the epithelial side (subepithelial) of the GBM demonstrable by immunofluorescence and electron microscopy
41
Membranous nephropathy (glomerulonephritis): d) poor response to
corticosteroid treatment, with 40% developing
| renal failure in 2-20 years
42
4. Glomerular disease in diabetes mellitus (see pp. 746-7): a) minimal proteinuria progresses, over
10-15 years, to severe proteinuria.
| •
43
4. Glomerular disease in diabetes mellitus (see pp. 746-7): b) thick glomerular basement membranes, diffuse increase in
mesangial matrix and formation of mesangial nodules (the latter is nodular glomerulosclerosis or Kimmelstiel-Wilson lesion). Other changes Hyaline arteriolosclerosis, Atherosclerosis, Nephrosclerosis
44
D. Nephritic Syndrome: • Characterized by acute onset of
1) hematuria, 2) oliguria & azotemia and 3) hypertension
45
Nephritic syndrome: • Proliferation of cells within the
glomeruli, accompanied by inflammatory cells
46
Nephritic syndrome: • Inflammation severely injures
capillary walls
| • Results in blood passing into the urine as well as reduced GFR
47
. Acute postinfectious (poststreptococcal) glomerulonephritis
a) most commonly occurs in
children 1-4 weeks after a bout of streptococcal pharyngitis (other infections as well)
48
. Acute postinfectious (poststreptococcal) glomerulonephritis: b) pathology -
proliferation of endothelial and mesangial cells; infiltration of neutrophils and monocytes; immune complexes in GBM and sometimes in the mesangium.
49
. Acute postinfectious (poststreptococcal) glomerulonephritis: c) progression to chronic renal disease is more likely in
adults.
50
IgA nephropathy
| a) usually occurs in
children and young adults
51
IgA nephropathy: b) hematuria is noted
1-2 days after non-specific upper respiratory
| tract viral infection.
52
IgA nephropathy: : c) pathogenesis may involve
increased IgA production
53
IgA nephropathy: d) when the glomerular disease is associated with systemic manifestations (purpuric skin rash and arthritis), this is called
Henoch-Schönlein purpura.
54
IgA nephropathy: e) pathology - mesangial deposition of immune complexes containing
IgA and variable proliferation of mesangial and endothelial cells. Occasionally there is epithelial cell proliferation with crescents.
55
E. Crescentic or Rapidly Progressive Glomerulonephritis: • Acute clinical syndrome, not a specific form of
glomerulonephritis
56
E. Crescentic or Rapidly Progressive Glomerulonephritis: • Progressive loss of
renal function; lab finding c/w nephritic syndrome; severe oligouria
57
E. Crescentic or Rapidly Progressive Glomerulonephritis: • Death from renal failure in
weeks to months if untreated
58
E. Crescentic or Rapidly Progressive Glomerulonephritis: • Characteristic finding is
crescentic glomerulonephritis due to proliferation of epithelial cells with infiltration of histiocytes
59
E. Crescentic or Rapidly Progressive Glomerulonephritis: • Several different disorders:
* Anti-GBM antibody disease (12% of cases)
* Immune complex disease (44% of cases)
* Pauci-immune, lack of anti-GBM or immune complexes (44% of cases)
60
Crescentic or Rapidly Progressive Glomerulonephritis
1. May be associated with
antibodies directed against a glomerular basement antigen, deposition of immune complexes, or lack of immune complex deposition (called pauci-immune glomerulonephritis).
61
CHRONIC (END-STAGE) RENAL DISEASE
• A. Loss of glomeruli and tubules leads to
fibrosis.
62
CHRONIC (END-STAGE) RENAL DISEASE: Damaged glomeruli become completely
sclerotic (global sclerosis).
63
CHRONIC (END-STAGE) RENAL DISEASE: With advanced loss of tubules and glomeruli, the remaining glomeruli develop
adaptive changes. These changes eventually lead to further injury and progressive renal failure.
64
CHRONIC (END-STAGE) RENAL DISEASE: May be detected at routine exam with
proteinuria, hypertension or azotemia.
65
CHRONIC (END-STAGE) RENAL DISEASE: Without treatment, ------- prognosis. Renal dialysis and kidney transplantation------------- for patient survival
POOR, necessary
66
VI. ACUTE PYELONEPHRITIS
A. AKA:
tubulointerstitial nephritis.
67
Acute pyelonephritis
Suppurative inflammation of kidney and renal pelvis caused by bacterial infection.This is a renal disease affecting tubules, interstitium, and pelvis and is most often secondary to bacterial infection.
68
Acute pyelonephritis: The infection may spread from the
urinary bladder, up the ureters and into the renal pelvis and kidney (ascending).
69
Acute pyelonephritis: A second but much less common route in infection is through
hematogenous spread of bacteria.
70
ACUTE PYELONEPHRITIS:
1. Predisposing conditions :
Urinary tract obstruction,Instrumentation, Ureteral reflux,Pregnancy, Gender (female), Immunosuppression, Diabetes mellitus
71
ACUTE PYELONEPHRITIS: 2. Clinical:
Sudden onset with pain at the costovertebral angle and
systemic evidence of infection. Often there is accompanying dysuria,
frequency and urgency.
72
ACUTE PYELONEPHRITIS: 3. Pathology:
Patchy interstitial and tubular neutrophilic inflammation.
73
ACUTE PYELONEPHRITIS: 4. Etiology:
Predisposing conditions, include urinary tract obstruction, instrumentation, vesicoureteral reflux, pregnancy, gender and age, diabetes mellitus and immunosuppression.
74
ACUTE PYELONEPHRITIS: 5. Prognosis:
Repeated bouts of acute inflammation of continuous inflammation may lead to chronic pyelonephritis. This is characterized by mononuclear inflammatory infiltration and irregular scarring.
75
VII. Drug-Induced Interstitial Nephritis
| The etiology includes some
antibiotics, non-steroidal anti-inflammatory drugs and others.
76
Drug-Induced Interstitial Nephritis: The pathogenesis involves
hypersensitivity reaction to the drugs.
77
DRUG-induced interstitial nephritis: The pathology consists of
interstitial infiltration of mononuclear inflammatory cells, often with neutrophils and many eosinophils.
78
Drug-induced interstitial nephritis; Granulomas may be
present. The glomeruli are not involved in the inflammation.
79
Drug-induced interstitial nephritis: Large doses of analgesics may lead to
interstitial nephritis with papillary necrosis (necrosis of the tips of the medullary pyramids).
80
Drug-induced interstitial nephritis: Treatment: Withdrawal of
offending drug and corticosteroids.
81
Drug-induced interstitial nephritis: Prognosis:
Generally good with full recovery in 6-8 weeks
82
Acute Tubular Necrosis:
| A. Clinical: rapid onset of
renal failure, reduced urine output, electrolyte imbalances. The clinical manifestations are reversible over a period of weeks as the damaged tubular epithelium regenerates.
83
Acute Tubular Necrosis: B. Etiology: injury to tubular epithelial cells from
ischemia (ie. shock) or a toxin
84
Acute Tubular Necrosis: A. Pathology:
dilation of tubules, interstitial edema, necrosis of epithelium (often very focal and subtle with ischemic injury, more diffuse with injury from a toxin)
85
Acute Tubular Necrosis: B. Treatment:
Supportive care, dialysis
86
Acute Tubular Necrosis: C. Prognosis: In the absence of preexisting kidney disease, most patients fully recover
renal function
87
Arterionephrosclerosis
| 1. Clinical:
Contributing factors are hypertension and diabetes. May
lead to gradual onset of chronic renal failure.
88
Arterionephrosclerosis: 2. Pathology:
Gross – kidneys are symmetrically atrophic, with
moderate reduction in size. The kidney surface has an even fine
granularity and the cortex is thin.
89
Arterionephrosclerosis: 3. Histopathology: Narrowing of the lumens of arterioles and arteries
caused by
hyaline type of arteriolosclerosis and fibroelastic hyperplasia of muscular arteries. In addition, there is (1) tubular atrophy and interstitial fibrosis and (2) global sclerosis of glomeruli.
90
Arterionephrosclerosis associated with malignant hypertension:
1. Hypertension greater than
200/120 mm Hg – occurs in about 5% of
| patients with essential hypertension.
91
Arterionephrosclerosis associated with malignant hypertension: 2. Clinical:
Relatively rapid onset of renal failure with increased
intracranial pressure leading to headache, nausea, vomiting, and
visual impairment.
92
Arterionephrosclerosis associated with malignant hypertension: 3. Pathology: Arterioles show
hyperplastic arteriolosclerosis, reducing
| blood flow and causing necrosis of glomeruli.
93
Thrombotic Microangiopathies:
| 1. Thrombotic thrombocytopenia purpura (TTP) -
acquired defect in ADAMTS 13, a plasma protease that degrades vWF multimers. The large von Willebrand factor components activate platelets under certain conditions.
94
Thrombotic Microangiopathies: 2. Hemolytic-uremic syndrome (HUS) -
endothelial cell injury which, in most cases, is due to a Shiga-toxin from E. coli (reason for ground beef recalls in the news) or Shigella. The injury leads to platelet activation.
95
Thrombotic Microangiopathies: 3. The pathology is similar in both disorders with
microthrombus formation in capillaries.
96
In HUS, renal involvement predominates and the disorder most often occurs in
children.
97
There is more widespread involvement of other organs in
TTP (Thrombotic thrombocytopenia purpura)
98
Urolithiasis (Renal Stones): • By age 70, affects
11% men, 6% women
99
Urolithiasis (Renal Stones): • Clinical: May be
asymptomatic, obstruction, intense pain, infection, hematuria
• Types of stones
• Calcium (80%); increased Ca2+ in the urine
• Magnesium ammonium phosphate; alkaline urine, Proteus or staph infection
• Uric acid
100
Urolithiasis (Renal Stones): 1. Clinical: Stones result in
urinary tract obstruction, ulceration of the urothelial lining and bleeding.
101
Urolithiasis (Renal Stones): 2. Pathology: Stones are unilateral in
80% of patients and most
102
Urolithiasis (Renal Stones): 3. Types of stones
calcium
magnesium ammonium phosphate
Uric acid - occur in patients with gout, leukemia (high cell turnover) or
persistently acid urine.
103
Urolithiasis (Renal Stones): 4. Other causes of hydronephrosis -
congenital urinary tract
obstructions, enlarged prostate, neoplasms, neurogenic bladder,
pregnancy.
104
Small stones may migrate into the
ureters and produce intense flank pain
105
Large stones remain in the
pelvis and may be manifested by hematuria and superimposed infection.
106
Stones
| may also develop in the
bladder.
107
Large stones are referred to as
"staghorn calculi".
108
These large stones form a
cast of the pelvis and calyceal system.
109
frequent site for stone formation is within the
calyces and pelvis
110
Stone types: calcium -
patients have increased concentration of calcium in the urine
111
magnesium ammonium phosphate - patients have
persistently alkaline
| urine. Infection with Proteus predisposes to these stones.
112
• Uric acid;
gout, acid urine, high cell turnover
113
A. Renal Cell Carcinoma
| 1. Clinical:
2:1 male:female ratio. Hematuria, mass, pain, fever,
| polycythemia, paraneoplastic syndromes
114
A. Renal Cell Carcinoma: 2. Etiology: Risk factors include
smoking, hypertension, obesity,
| cadmium exposure and von Hippel-Lindau syndrome.
115
A. Renal Cell Carcinoma: 3. Pathology: Arise from
tubular epithelium, often reach a large size
| prior to diagnosis, often invade the renal vein.
116
A. Renal Cell Carcinoma: Most common
| histologic subtype has cells with very
pale or clear cytoplasm (clear cell
| carcinoma)
117
A. Renal Cell Carcinoma: 4. Treatment:
Surgery +/- radiation
118
A. Renal Cell Carcinoma: 5. Prognosis:
Stage dependent 5-yr survival
Stage 1: 81%
Stage 4: 8%
119
A. Renal Cell Carcinoma: 5. Prognosis:
Stage dependent 5-yr survival
Stage 1: 81%
Stage 4: 8%
120
B. Wilm’s Tumor
| 1. Clinical:
Abdominal mass, risk is greatly increased in some inherited
| syndromes, occurs in children ages 2 to 5 years
121
B. Wilm’s Tumor: 2. Pathology: Triphasic pattern with
epithelial structures resembling
primitive tubules or glomeruli, stroma (mesenchymal component) and
blastema which recapitulates early nephron formation.
122
Wilm's tumor; the tumor
illustrates --------- formation of renal structures in various stages of
renal development.
abortive
