Renal Pathology Puthoff Lecture Flashcards
(114 cards)
1
Q
What do kidneys do?
A
- Excrete certain waste products of metabolism
- Precisely regulate the body’s concentration of water, salt, calcium, phosphorus and other/cations/anions
- Serve as an endocrine organ–elaborating erythropoietin, renin, PGs, and regulating vitamin D metabolism
- Convert mor than 1700 L of blood prepay into the highly specialized, concentrated fluid known as urine
2
Q
The glomerulus is what kind of organ
A
microvascular
3
Q
The most common cause of end stage renal disease (ESRD) and second most cause? other causes?
A
- Diabetes is most common cause
- High BP is 2nd
- Other problems that cause kidney failure include: autoimmune diseases, such as Lupus and IgA nephropathy
4
Q
Are most people with ESRD old or young? What ethnic groups most affected?
A
- young–63% under age 65
- Hispanics and Asian Americans fastest growing ethnic groups newly diagnosed with ESRD
- Currently more than 20 million Americans have some level of chronic kidney disease related to diabetes; as diabetes increases, demand for dialysis will too
5
Q
CKD associated with what vitamin deficiency and what disease
A
- Folate
- which is associated with hyperhomocystenimia which is also associated with an increased risk for stroke/ASCVD
6
Q
What happens if you only have one kidney?
A
- the single nephron GFR goes up and over time will lead to glomerulosclerosis
- Also causes elaboration of renin that occurs from golblat phenomenon?
7
Q
The kidneys are what kind of organs? (intraperotineal or retroperitoneal?) at what level?
A
retroperitoneal
at the level of T12
8
Q
Why is right kidney lower than left?
A
because of its position under the liver on the right
9
Q
Where is the Renal angle?
A
Between lower border of 12th rib and lateral border of elector spinae muscle–Renal colic pain starts from this angle down and forwards to groin (CVA)–goes about to L2
10
Q
How common are renal cysts?
A
- Common–More than 50% of those over 50% have parenchymal kidney cysts
- Generally small, contain serous fluid, unremarkable dilations of proximal tubules
- Often small and asymptomatic and are generally incidental findings, but can become quite large
11
Q
Types of cysts (not all are small and unremarkable!!)
A
- simple cysts
- multilocular–subdivisions, some with smooth muscles in the wall
- dysplastic kidney–congenital anomalies
- adult and juvenile polycystic disease
- cystic tumor–some renal cell carcinomas can become cystic and have hemorrhagic areas
12
Q
How do most diseases/disroders of the kidney present?
A
-hematuria–SCHITTT: stones, congenital anomalies, hemologic abnormalities like coagulopathies, infection, trauma, tumor, tuberculosis
-proteinuria
-edema
-mass
-HTN
-oliguria
-anuria
-asymptomatic
increased serum/urine creatinine
-decreased creatinine clearance
-increased serum BUN
13
Q
By the time you palpate a mass for RCC what has happened?
A
the tumor has already metastasized if it is palpable
14
Q
Single most important question to ask patient suspected of having renal disease and why is this the most important question?
A
Have you had this before?
-Because distinct differences between acute and chronic kidney diseases
15
Q
Common imaging techniques of the kidney and associated GU organs
A
- US
- KUB–plain Ab film (not as common any more)
- Renal tomography
- IVP (not as common anymore bc associated with anaphylaxis and more invasive)
- Retrograde pyelography
Other techniques to evaluate the ureter, bladder or urethra
- Cystography
- Voiding urethrography
16
Q
Additional imaging techniques of the kidney
A
- CT scan
- MRI, MRA
- Rdionuclide imaging
- Renal angiography
17
Q
Techniques utilized on renal biopsy material
A
- light microscopy: standard stain (H&E), other (PAS, silver stains)
- Flouorescence microscopy (variety of targeted immunologic entities–glomerular diseases)
- Electron microscopy (transmission)
- *WITH URINALYSIS
- Other techniques: increasingly, molecular and genetic analyses
18
Q
Passage of materials through a membrane by a physical force
A
filtration
19
Q
Osmosis is the diffusion of water across what kind of membrane
A
semipermeable–necessary for osmosis bc it restricts the movement of certain solutes allowing solvent to pass through but water can pass freely
20
Q
Glomerulus is?
A
capillary loops between afferent and efferent arterioles
21
Q
Most filtration occurs at which end of capillary bed? and osmosis/colloid osmotic pressure occurs at which end?
A
- filtration= arteriolar
- osmosis=venule via plasma proteins
22
Q
Osmotic vs oncotic pressure
A
- osmotic=pressure developed by solutes dissolved in water working across selectively permeable membrane
- oncotic=colloid osmotic pressure which is form of osmotic pressure exerted by proteins (albumin) in a blood vessel’s plasma that pulls water into circulatory system
23
Q
Typical normal pattern for serum protein electrophoresis
A
- positive pole=large quantities of albumin (small molecule) migrates fastest towards positive pole
- positive to negative pole order: albumin, alpha1, alpha2, beta, gamma
24
Q
Multiple myeloma serum protein electrophoresis findings
A
-IgG plasma cell malignancy dyscrasia with kappa light chains
25
Bence-Jones proteins effects on kidneys
-deposition of light chains in tubules which causes lots of tubular damage and can ultimately cause chronic renal failure
26
organs involved in causing edema in congestive heart failure
-kidney and liver
27
Nephrotic syndrome
-generalized edema
28
What can cause generalized edema
- kidney failure
- heart (congestive heart failure)
- Liver (not producing enough plasma proteins)
- GI proteins (caused by losing proteins--protein losing enteropathies)
- Lungs--because of its effect on the heart
29
What are the compartments or major morphologic components of the kidney?
- Glomeruli
- Tubules
- Interstitium
- Vessels
* Tubules and vessels are in interstitium)
30
Is diabetes primarily what kind of disease?
| What about hypertension?
- diabetes=GLOMERULAR disease (microvasculature) manifestations
- HTN=vascular (arteriolar) disease manifestations (TUBULOINTERSTITIAL DISEASE)
31
The general category of glomerular disorders is considered due to ____ disease
- immunologic (primary or secondary)
| - but diabetes effect on kidney is largely hemodynamic not immunologic in terms of diabetic nephropathy
32
is glomerulonephritis due to infection? Difference bw glomerulonephritis and glomerulopathy
- in most cases no! but may have inflammatory infiltrates
| - they are the same
33
How does the interstitium react to chronic kidney disease?
-by becoming fibrotic and may see some degree of inflammation and some edema of the interstitium as well
34
What diseases do you see nephrosclerosis?
- HTN
- diabetes
- other disorders that affect blood vessels
35
difference between azotemia and uremia?
-uremia is azotemia PLUS a constellation of clinical findings and biochemical abnormalities resulting from renal damage
36
Acute Kidney injury
- Rapid decline in GFR
- Most severe form exhibit oliguria or anuria
- May result from glomerular, interstitial, vascular or acute tubular injury (ATN)
- Can be reversible, or progress to CKD
37
CKD
- mild--clinically silent
- more severe--uremia
- defined with diminished GFR
38
ESRD
-GFR
39
Which disorders are characteristic of glomerular disease? And which disorders are characteristic of tubulointerstitial disease? Which are characteristic of both?
-Glomerular: nephritic syndrome, nephrotic syndrome, ASYMPTOMATIC hematuria or proteinuria
Tubulointerstitial: UTI, UT obstruction, renal tumors, nephrolithiasis
BOTH: renal tubular defects and acute renal failure
40
difference between neprholithiasis and nephrocalcinosis
- nephrolithiasis is kidney stones
| - nephrocalcinosis is dystrophic calcification of kidney parenchyma
41
Why do you see lipids in nephrotic syndrome?
-bc when kidney is stressed it tries to make more proteins and the pathway it goes into makes lipoproteins that deposit primarily in proximal tubule
42
Glomerular disease characterized by severe proteinuria (albumin) (more than 3.5gm/day--less in children), severe edema, hyperlipidemia, and lipiduria
Nephrotic syndrome
43
Glomerular disease dominated by acute onset of grossly visible hematuria, mild to moderate proteinuria, and hypertension. Proteinuria and edema common but not as severe
-Nephritic syndrome
44
signs of nephritic syndrome with rapid decline (days-weeks) in glomerular filtration rate (GFR). Implies severe glomerular injury
- Rapidly progressive glomerulonephritis
- nephritic
- protein in urine but LESS than 3.5 gm/day;
- normal protein in urine is about UPTO 150mg/day
45
Isolated urinary abnormalities
-glomerular hematuria and/or subnephrotic range proteinuria
46
Where do you find endothelial cells?
-line ALL blood vessels
47
Where are podocyte foot processes located?
-directly on basement membrane which deep to the podocyte cells
48
Morphology of glomerulus
-initial nephron segment consists of a glomerulus and bowman's capsule (together make up the renal corpuscle) that captures and funnels the glomerular filtrate, the initial urinary stream into the tubular system
49
PAS stains what?
glycoproteins
50
Three layers of the basement membrane
- lamina densa
- lamina rara interna
- lamina rara externa
- within that are negatively charged anions--among those are HEPARIN which is how charge selectivity occurs
51
HEMATURIA, azotemia, oliguria, edema, HTN
Nephritic syndrome
52
Acute nephritic, proteinuria, and acute renal failure
RPGN
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>3.5 gm/day PROTEINURIA, hypoalbuminemia, hyperlipidemia, lipiduria
Nephritic syndrome
54
Azotemia-->uremia progressing for months to years
Chronic renal failure
55
Glomerular hematuria and/or subnephrotic proteinuria
Isolated urinary abnormalities
56
edema usually seen in nephritic or nephrotic syndrome?
-NEPHROTIC
57
Pathologic responses of the glomerulus to injury
- hypercellularity
- basement membrane
- Hyalinosis and sclerosis
58
Pathologic responses of the glomerulus to injury--hypercellularity
- proliferation of native cells (mesangial cells, endothelial cells and visceral epithelial cells) and infiltrates of inflammatory cells (neutrophils, macrophages, etc mononuclear cells, etc)
- crescents: occur in Bowman's space--both necrotizing elements and cellular elements
59
Pathologic responses of the glomerulus to injury----Basement membrane
- thickening (breaks, sclerotic regions)
- deposits (electron dense deposits)
- glomerulus BM is not the same as glomerular filtration membrane!!
- glomerulus BM is PART of glomerular filtration
60
Pathologic responses of the glomerulus to injury----Hyalinosis and sclerosis
- Hyaline change
| - sclerosis: acellular sclerotic pattern that involves small vessels of the microvasculature of glomerulus
61
Primary Glomerulonephropathies
- Acute Proliferative Glomerulonephritis (usually DIFFUSE)
- RPGN
- Membranous Glomerulopathy
- Minimal change disease (lipoid necrosis/ mills disease)
- Focal Segmental glomerulosclerosis
- Membranoproliferative Glomerulonephritis (mesangial-capillary GN)--Dense deposit disease
- IgA nephropathy (acute FOCAL GN)
- Chronic Glomerulonephritis--End stage
62
Systemic diseases with glomerular involvement
- Lupus
- Diabetes
Not as common:
- Amyloidosis
- Goodpasture
- Microscopic polyarteritis/angiitis
- Wegener granulomatosis
- Henoch-schonlein purpura (IgA systemic disease!)
- Bacterial endocarditis
63
Systemic diseases with glomerular involvement--Heriditary disorders
- Alport syndrome
- Thin Basement membrane disease
- Fabry disease
64
Immune complexes in the glomerulus Subepithelial humps
acute glomerulonephritis
65
Immune complexes in the glomerulus--epimembranous depostis
Membranous nephropathy
| Herman glomerulonephritis
66
Immune complexes in the glomerulus--SUBENDOTHELIAL DEPOSITS
Lupus nephritis
| Membranoproliferazive glomerulonephritis
67
Immune complexes in the glomerulus--Mesangial deposits
- -Acute focal proliferative GN!
| - IgA nephropathy!!
68
Immune mechanisms of glomerular injury
- Ab mediated (in situ immune complex deposition)--fixed, intrinsic tissue Ags OR planted Ags
- Circulating immune complex deposition (Endogenous or exogenous Ags)
- Cell mediate immune injury
- Activation of alternative complement pathway
69
Ab mediated Glomerular injury
- deposition, circulating immune complexes sub endothelial
- In situ deposition on BM
- In situ deposition on foot processes--Heymann
70
Difference between Diffuse, focal, segmental and global
- diffuse involves all glomeruli
- Focal involves only subset of glomeruli
- Segmental means only portions of the affected glomeruli involved
- global means it involves entire glomerulus
71
Once GFR is reduced to 30-50% what happens?
-regadless of the stimulus underlying disease it results in FSGS and tubulointerstitial fibrosis even though it may not start as such
72
Proteinuria in nephrotic syndrome vs FSGS
- nephrotic is selective proteinuria--mostly just albumin
| - FSGS is nonselective
73
Immune complex injury triggered by exogenous bacterial, viral or fungal Ag
Historically antecedent of Group A hemolytic stop; specific nephritogenic strains of Lacefield group A
Acute proliferative Glomerulonephritis
74
Diffuse proliferative glomerulonephritis characterized by
- marked hypercellularity: ranges from simple mesangial to complex endocapillary cell infiltrate
- Leukocyte infiltration: exudate within glomerular tuft
75
EM: sub epithelial hump of immune complex; neutrophil in lumen
Acute proliferative glomerulonephritis
76
Acute proliferative glomerulonephritis IF findings
Granular deposits of IgG, IgM, and C3 in mesangium and along the GBM corresponding to sub epithelial humps
77
Acute proliferative glomerulonephritis children clinical presentation
- ages 6-10
- typically 1-4 wks following pharyngitis or skin infection
- often but not invariably strep B
- often present with malaise, fever, nausea, oliguria, and hematuria 1-2 wks after recovery from sore throat; dysmorphic RBC cast, mild proteinuria (
78
Acute proliferative glomerulonephritis --adults clinical
- more typical and aggressive course
| - may see sudden HTN or edema with elevated BUN
79
Acute proliferative glomerulonephritis children vs adults clinical course
- Children clear in 6-8 wks--renal biopsy not indicated
| - 95% recover completely;
80
Acute proliferative glomerulonephritis associated with what infections besides strep B?
- other bacterial (immunoglobulin feature with some staph infections)
- viral
- sequel to parasitic infx
81
What do you see in nephritic syndrome
-MAY exhibit nephritic syndrome with systemic disorders but typically seen in setting of post infectious disease and exudative GN, and syndromic clinical features helpful in dx of crescentic GN
82
Where do crescent formations occur?
-Bowmans space bw parietal (modified squamous cells) and visceral epithelial cells
83
Crescentic GN characteristic of what disorder?
- RPGN
- crescent shaped mass of proliferating visceral and parietal epithelial cells
- Rather rapid obliteration of urinary space
- infiltrates of macrophages & leukocytes
- PAS stain
84
RPGN Type 1
ANTI-GBM Ab
- Renal limited
- Goodpastures syndrome (kidney and lung hemorrhage)
85
RPGN Type 2
IMMUNE COMPLEX
-Idiopathic
-postinfectious GN
-Lupus nephritis
-Henoch Schönlein Purpura (systemic IgA disease)
-IgA nephropathy (renal limited IgA disease)
other
**Not all of these start out as RPGN!! They may be acute and focal and progress to RPGN later
86
Type 3 RPGN
PAUCI IMMUNE
- ANCA associated (anti neutrophil cytoplasmic associated)
- Idiopathic
- Granulomatosis with polyangiitis--wegners associated with ANCA
- Microscopic polyangiitis
87
50% of PRIMARY renal diseases (so not lupus or Heoch schnolen bc these are systemic) associated with RPGN have what type of RPGN on IF
Type III (paci immune) on IF
88
Type I RPGN characterized by
-anti-GBM Ab-induced disease characterized by LINEAR deposits of IgG and many cases C3 in GBM
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What happens when anti GBM Abs cross react with lung alveolar BM?
Pulmonary hemorrhage occurs in addition to renal disease (Goodpassure's syndrome)
90
Good pasture Ag is a
| IF pattern
peptide within non collagenous regions of collagen type IV
| -Anti-IgG localized to glomerular BM with DIFFUSE LINEAR staining
91
Goodpastures and gene associations
- high prevalence with certain HLA subtypes and haplotypes (HLADRB1) in RPGN patients
- genetic predisposition to autoimmunity
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Tx for Goodpastures
-Plasmapheresis to remove pathogenic circulating Abs is part of Tx regimen which is effective in conjunction with immunosuppressive Tx
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Type II vs Type III RPGN
- Type II immune complex deposition RPGN associated with acute proliferative GN, lupus nephritis and IgA nephropathy
- -Type I=celluar proliferation within glomerular tufts occurs in addition to crescent formation; IF studies reveal GRANULAR pattern of immune complex deposition
- Type II pts DO NOT RESPOND to plasmapheresis
- Type III defined by lack of anti GBM Abs or immune complexes by IF or EM
- Most pts with type III (pauci immune) have circulating antineutrophil cytoplasmic Abs (ANCA)
94
Renal syndrome where basic defect is increased permeability of glomeruli to plasma proteins resulting in proteinuria
Nephrotic syndromes
95
Major clinical features of nephrotic syndrome
- Severe proteinuria (>3.5 gm/day)
- Hypoalbuminemia
- Edema; common to start with periorbital but becomes GENERALIZED
- Hyperlipiemia--elevated serum cholesterol & lipoproteins
96
Causes of Nephrotic syndrome in children vs adults
- Children usually Minimal change disease (children usually get it from PRIMARY glomerular disease 95% like minimal change disease)
- Adults usually FSGS and Membranous glomerulopathy (more often associated with systemic disease compared to children but 60% still from primary disease)
97
Massive increase in urinary protein in nephrotic syndrome is due to
diffuse changes in the majority of glomeruli
- GBM becomes diffusely leaky or porous to proteins especially albumin which is both a small protein and represents half the total protein in blood
- But in NS the generalized increase in GBM porosity to proteins does not allow RBCs to transmit into urinary space (size and charge selectivity)
98
Primary vs secondary renal disease in nephrotic syndrome
- Primary: only kidney is affected (renal etiology); MOST common cause of NEPHROTIC syndrome in children
- Secondary: systemic diseases causing nephrotic renal disease (DM, SLE) with alterations in renal histomorphology; more frequent in adults (40% of cases)
99
PURE protein disorders (rarely exhibit hematuria)
- Minimal Change disease
- Membranous Glomerulopathy
- Focal segmental Glomerulosclerosis (of the 3, this is most likely to have hematuria)
100
Acute Proliferative GN and RPGNs (I, II and III) are nephritic or nephrotic?
-Nephritic
101
Leading etiologies of Nephrotic syndrome
-DM, and SLE most common
-Infections (malaria, syphillis, Hep B and C, HIV)--typically membranous glomerulopathies
-Malignant disease (carcinoma, lymphoma)--also membranous
-Amyloidosis
Drugs (non steroidal anti-inflammatory, penicillamine)
-Miscallaneous (bee sting allergy, hereditary nephritis)
102
Membranous Glomerulopathy major characteristics
- 75% of cases are primary
- Autoimmune disease linked to HLA-DQA1 and Abs to renal auto antigen PLA2 receptor with pathophysiologic involvement of complement (primarily MAC) and IgG4
- Remainder due to drugs, underlying malignancies, SLE, infections, other AI disease
- 85% are NEPHROTIC! Hematuria and HTN CAN occur (15-35% of cases)
- NON-selective proteinuria!
103
Primary vs secondary membranous glomerulopathy response to steroid therapy
- primary responds POORLY to steroid therapy; high disease recurrence in transplant patients; in contrast Minimal change disease responds very well to steroids!
- some evidence that women may have more beingn course
104
Membranous glomerulopathy morphology
- Marked diffuse thickening of capillary walls without increase in cellularity; spikes of silver staining matrix project from basement membrane toward urinary space
- acellular sclerotic glomerulus
- Effaced Foot processes
- Thick basement membrane: 5-20 fold increased thickness
- subepithelial deposits: dense aggregates IgG (electron dense) along epithelial side of BM
- Obliterated foot processes overlying dark deposits
- SPIKE AND DOME!!
- Lumpy bumpy IgG deposits
105
The only disease where you see ONLY fusion of foot processes
Minimal Change disease
106
Membranous Glomerulopathy Clinical Course
- Proteinuria persists in 60% of patients
- 40% develop renal insufficiency
- 10% progress to end stage renal failure
- corticosteroids and immunosuppressive tx NOT efficacious (in contrast to Minimal change disease)
107
MCD clinical characterisitics
- NS presentation--Edema
- Biopsy--ONLY foot process fusion
- peak incidence bw 2-6 yrs
- MCC of NS in children and may follow a respiratory infection or immunization
- significant evidence that it has immunologic basis
- associated with Hodgkin lymphoma and other lymphoreticular diseases
- HTN is rare
- highly selective proteinuria (albumin mostly)
- Respond well to corticosteroids and no clinical recurrence--very good prognosis
108
Visceral Epithelial Cell (podocyte) injury
- Abs against epithelial cell Ags, certain toxins, cytokines or other factors cause injury, resulting in foot process effacement (fusion or simplification)
- can be Associated with detachment of epithelial cells and protein leakage through defective GBM and filtration slits
109
Nephritic or nephrotic
MPGN Type I
MPGN Type II (dense deposit)
IgA nephropathy
type 1: mixed
type 2: hematuria, renal failure
IgA nephropathy: recurrent hematuria
110
FSGS involves what part of kidney
not just bowman's capsule but has a sclerosing pattern that extends deep into the glomerular tufts as well
111
FSGS types/classifications
- idiopathic/primary
- other known conditions/associations
- often a secondary glomerular event!!
- adaptive response to loss of renal mass
- uncommon inherited forms/mutations in genes that encode proteins localized to podocyte slit diaphragms
- can be associated with HIV
- Often a SECONDARY event in contrast to membranous and minimal change disease
- adaptive response to glomerular injury--leads to FSGS
112
Idiopathic FSGS epidemiology and clinical course
- idiopathic accounts for 35% of adults with NS--10% NS in children
- Primary FSGS most common overall cause of NS syndrome now in US adults ; greater incidence among Hispanics and African Americans
- 5-10% of MCD in children that does NOT respond to steroid tx exhibit FSGS upon biopsy (but children overall have better prognosis than adults in this disorder)
- FSGS also occurs in other disease settings and is generally a Dx that implies poor prognosis, as progressive renal disease occurs over time
- 20% of pts follow unusually rapid course with massive proteinuria and renal failure within 2 years
113
FSGS different from MCD and other podocytopathies how?
- higher incidence of hematuria, reduced GFR, and HTN
- Proteinuria is nonselective (large serum proteins equally part of exhibited proteinuria, as well as smaller proteins, i.e. albumin)
- Poor response to steroids
- significant progression to CKD with at least 50% developing ESRD within 10 years
114
FSGS HIV associated Nephropathy
- HIV can directly and indirectly cause renal disease including acute renal failure and/or acute interstitial nephritis
- collapsing variant of FSGS
- occurs in 5-10% of pts, more frequently in African americans and caucasians
