Renal pathology-Fung Flashcards
(124 cards)
1
Q
What are the three major things that the kidney does?
A
Metabolism
Endocrine Functions
BP regulation
2
Q
How does the kidney help with metabolism?
A
Excretion of H2O, Na+, Ca2+, P
Maintain acid-base balance
Excretion of toxic metabolite wast products
3
Q
How does the kidney help with endocrine function?
A
Secrete erythropoietin, prostaglandins
Regulate vitamin D metabolism (hydroxylation of vit D)
4
Q
How does the kidney regulate BP?
A
Renin secretion
5
Q
What all does the urinary system include?
A
the kidneys (in retroperitoneum), ureters, bladder, and the urethra
6
Q
What is the functional unit of the kidney? Where is it located?
What do you find in the medulla?
A
nephron-> cortex
medulla-> collecting tubules which empty ito the renal papila and into the calayx sytem.
7
Q
What does the hilum of the kidney contain?
A
renal sinus, renal vasculature, renal pelvis
8
Q
How does the blood flow from the aorta into the various parts of the kidney?
A
Aorta-> renal artery-> branch into the segmental artery-> interlobar artery-> arcuate artery-> Vasa recta + interlobuar artery-> afferent arterioles-> glomerulus-> efferent arteriole-> vasa recta artery to vasa recta vein-> interlobular vein-> arcuate vein-> interlobar vein->renal vein
9
Q
If you see glomeruli, what part of the kidney are you looking at?
A
cortex
10
Q
What is another name for the visceral layer of the glomerulus?
What does this blend into ?
A
podocyte layer
Blends into a layer of cuboidal cells that make the parietal layer of bowmen’s capsule
11
Q
What determines what molecules will be filtered?
What anatomically allows for filtration?
A
size, charge, and configuration
fenestrations of endothelial capilary membrane
12
Q
Podocytes have primary and secondary processes. Explain this
A
Primary process wrap around capillary and secondary processes create filtrations slits (foot processes)
13
Q
What is the endothelium like in the renal cortex? what does it lay adjacent to?
A
-fenestrated endothelial cells
(70-100 nm diameter)
-To the lamina rara interna of the GBM
14
Q
The visceral epithlium (podocytes) is located adjacent to the (blank). What does the visceral epithelium have that helps with filtration of WATER?
A
lamina rare externa of the GBM
-foot processes that are separated by filtration slits (20-30 nm))
15
Q
Filtration slits are more involved more in the filtration of (blank) and not so much proteins
A
water
16
Q
What are the three layers of the glomerular basement membrane (GBM)?
A
- lamina rara interna
- lamina densa
- lamina rara externa
17
Q
What makes up the GBM?
A
- type IV collagne
- laminin
- heparan sulfate
- fibronectin
- entactin
- glycoproteins
18
Q
What is super important about the fact that type IV collagen is involved in the GBM?
A
-in a lot of autoimmune diseases, they attack type IV collagen
19
Q
What does the mesangium do?
A
- it supports the glomerular tuft and lies b/w capillaries
- contract and are phagocytic
- secretes mediators and lays down a matrix similar in composition to the BM
20
Q
Blood filters into the glomerulus and the product of the filter will go into the (blank) which empties into the (blank)
A
bowman’s space
tubular system
21
Q
The bulk of the cortex is (blank).
The proximal convoluted tubules are going to have (blank). DCT will not have this, why?
A
tubules
microvilli (increases absorption surface area)
because most of the absorption occurs in the PCT
22
Q
(blank) will sense how much blood the kidney is getting – it is what releases renin based on this
A
Juxtoglomerulus apparatus
23
Q
Histologically where is the juxtoglomerulus apparatus located?
A
separates the DCT from the Bowman’s capsule
24
Q
What are the causes of renal disease?
A
- primary
- secondary
- infectious
- obstructive
- neoplastic
- glomerular
- tubular
- interstitial
- vascular
25
What are secondary causes of renal disease?
DM, HTN, Lupus
26
When glomeruli are injured, there are 4 basic patterns of reactions, what are they?
- hypercellularity
- basement membrane thickening
- hyalinosis
- sclerosis
27
What can cause deposition of plasma protein in a glomerulus?
hyalinosis (due to eosinophilic processes)
28
What is sclerosis of the glomerulus due to?
laying down of collagen
29
What is diffuse glomerular injury?
involving all glomeruli
30
What is focal glomerular injury?
involving only a proportion of the glomeruli
31
What is global glomerular injury?
involving the entire glomerulus
32
What is segmental glomerular injury?
affecting a part of the glomerulus
33
Most glomerular injury is due to (blank) causes
immunologic
34
What are the three ways that glomerular injury can be caused by immunologic causes?
- interaxns w/ intrinisic glomerular antigens or antigens implanted in the glomerulus
- circulating antibody deposits w/in the glomerulus
- cytotoxic antibody directed against glomerulus due to complement pathway
35
What is azotemia?
elevation of blood urea nitrogen (BUN) or creatinine (Cr)
36
What are the three types of azotemia?
prerenal
renal (intrinsic)
postrenal
37
What is the cause of prerenal azotemia?
volume status issues (hypovolemic), sepsis etc.
38
What is the cause of intrinsic azotemia?
tubular disease
39
What is the cause of postrenal azotemia?
obstruction
40
What is acute renal failure?
rapid (hours to days) decline in glomerular filtration rate (GFR)
41
What is acute renal failure characterized by?
```
azotemia
fluid and electrolyte imbalance
-hyponatremia
-hyperkalemia
-hyperphosphatemia and hypocalcemia
-metabolic acidosis
oliguria or anuria
```
42
What are the causes of acute renal failure?
- glomerular injury
- interstitial injury
- vascuar injury
- tubular injur
43
What are the symptoms of acute renal failure?
- decreased or absent urine output
- lethargy
- fatigue
- nausea
44
A FENa+ of less than 1% indicates (blank) while greater than 1% indicates (blank)/
prerenal failure
| renal failure
45
What does a BUN/Cr ratio of less than 20:1 indicate?
| What does a BUN/Cr ratio greater than 20:1 indicate?
renal failure
| prerenal failure
46
What does a urine Na+ of less than 20mEq/L indicate?
What does a urine Na+ of more than 20mEq/L indicate?
prerenal failure
| renal failure
47
What does a urine osmolality of less than 400 mOsm/kg indicate?
What does a urine osmolality of more than 500 mOsm/kg indicate?
Renal failure
| Prerenal failure
48
What does a specific gravity of less than 1.020 indicate?
| What does a specific gravity of more than 1.020 indicate?
renal failure
| prerenal failure
49
What does a diminished GFR (less than 60 mL) for at least 3 months indicate?
chronic renal failure
50
What is chronic renal failure characterized by?
azotemia
fluid and electrolyte imbalance
uremia
51
What is uremia?
syndrome associated with fluid, electrolyte, and hormonal imbalances and metabolic abnormalities
52
What are the symptoms of uremia?
- nausea, vomiting, fatigue, anorexia, weight loss, muscle cramps, pruiritis
- menta status change, visual disturbances, increased thirst
53
What are the causes of chronic renal failure?
- diabetes
- hypertension
- renal parenchymal disease
54
What is this:
GFR=50% of normal
BUN/Cr=normal
asymptomatic symptoms
Diminished renal reserve
55
What is this:
GFR=20-50%
BUN/Cr=azotemia
Symptoms=anemia, HTN, polyuria
Renal insufficiency
56
What is this:
GFR= less than 20-25%
BUN/Cr=azotemia
Symptoms=uremia
Chronic renal failure
57
What is this:
GFR=less than 5%
BUN/Cr=azotemia
Symptoms=uremia
End stage renal disease
58
In nephritic syndrome, what do patients present with?
| What is it characterized by?
- hematuria (red cell casts)
- azotemia
- oliguria
- slight proteinuria
inflammation of the glomeruli
59
Nephritic syndrome presents with (blank) in the urine while nephrotic syndrome present with (blank) in the urine
blood
| protein
60
What is this:
A 6 year old male presents to his pediatrician with his mom with complaints of dark discolored urine for 1 day duration. The boy has no significant past medical history but mom states that 3 weeks prior he missed 2 days of school due to a sore throat, cold and fever.
Acute proliferative glomerulonephritis (Post-infectious glomerulonephritis-strep pyogenes)
61
What are the symptoms of acute proliferative glomerulonephritis (Post-infectious glomerulonephritis strep pyogenes)?
- URI or skin infection 1-6 weeks prior (like impetigo)
- Gross hematuria (cola-colored urine)
- Periorbital edema
- Oliguria
- RBC casts
- Peripheral edema
- HTN
- Azotemia
- Mild proteinuria
62
Acute proliferative glomerulonephritis is more commonly associated with strep infections of the skin like (blank)
impetigo
63
What is the pathogenesis of acute proliferative glomerulonephritis (Post-infectious glomerulonephritis strep pyogenes)?
Strep pyogenes (group A strep) produces a M type protein that causes immune complex deposition in glomerulus in the subepithelium
64
What will acute proliferative glomerulonephritis (post-infectious glomerulonephritis) present like on H and E? What will it look like on EM? What will it look like on IF?
- hypercellularity from inflammation
- subepithelial humps
- immune complex deposition (granular pattern)
65
Who typically gets acute proliferative glomerulonephritis (post-streptococcal glomerulonephritis)?
What is the treatment an prognosis like?
usually seen in children, but may occur in adults.
- tx is supportive
- 95% of children recover totally w/ therapy aimed at maintaining Na and water balance (1% progress to renal failure)
- In adults only 60% recover (25% develop rapidly progressive clomerulonephritis (RPGN)
66
(blank) is a syndrome associated with glomerular injury. What is it characterized by?
Rapidly progressive glomerulonephritis
- rapid and progressive loss of renal function
- oliguria
- nephritic syndrome symptoms (limited proteinuria less than 3.5g/day, oliguria and azotemia, salt retention w/ periorbital edema, htn, RBC casts, and dysmorphic RBCs in urine)
67
What is rapidly progressive glomerulonephritis characterized by in an H and E stain?
Characterized by cresecents in Bowman space (of glomeruli).
68
What are the crescents made up of in rapidly progressive glomerulonephritis?
fibrin and macrophages
69
What are the three types of rapidly progressive glomerulonephritis?
```
Type I (anti- GBM antibody)
Type II (immune complex)
Type III (Pauci-immune)
```
70
What is the immunofluorescence pattern like in type I Rapidly Progressive Glomerulonephritis (anti-GBM antibody)?
linear pattern caused by deposits of IgG/C3
| immune complex is formed against the glomerular BM
71
What disease will you see a type 1 rapidly progressive glomerulonephritis (anti basement membre)?
Goodpasture syndrome
72
What is the treatment for Anti-GBM antibody (type I rapidly progressive glomerulonephritis)?
Plasmapheresis
| Immunosuppression
73
What is the immunofluorescence patter of type II Rapidly Progressive Glomerulonephritis?
What are the diseases associated with this?
Immune complex deposition-> Granular
- PSGN (most common)
- Lupus nephritis (due to diffuse proliferative glomerulonephritis)
- IgA nephropathy
74
What is the treatment of rapidly progressive glomerulonephritis type II?
treat the underlying disease
| No plasmpheresis
75
Diffuse proliferative glomerulonephritis is due to diffuse antigen-antibody complex deposition, usually located (blanK); most common type of renal disease in (blank)
sub-endothelial
| SLE
76
What is the IF pattern of Pauci-immune (type III) Rapidly Progressive Glomerulonephritis?
It doesnt show anything
77
What are the diseases that cause Pauci-immune (type III) rapidly progressive glomerulonephritis?
What is the most common cause of Pauci-immune (type III) rapidly progressive glomerulonephritis?
```
Wegener granulomatosis (C-ANCA)
Microscopic polyangiitis (p-ANCA)
Churg-Strauss syndrome (p-ANCA)
```
Most common cause is idiopathic
78
How do you treat pauci-immune (type III) rapidly progressive glomerulonephritis?
therapy includes steroids and cytotoxic agents
79
What are the characteristics of nephrotic syndrome?
Why?
- massive proteinuria (>3.5 gm)
- Hypoalbunemia (<3 gm/dL)
- Generalized edema
- Hyperlipidemia/hyperlipiduria
-glomerular injury allows for loss of proteins including albumin which results in loss of oncotic pressure and thus edema
80
In nephrotic syndrome, proteinuria can be selective. What proteins are highly selective?
What proteins are poorly selective?
low molecular weight albumin
and transferrin
Higher molecular weight globulins and albumin
81
What are the primary glomerular diseases that cause nephrotic syndrome?
- membranous glomerulopathy
- minimal change disease
- focal segmental glomerulosclerosis
- membranoproliferative glomerulonephritis
- IgA nephropathy
82
What are the systemic diseases that cause nephrotic syndrome?
- Diabetes
- Amyloidosis
- Lupus
- Drugs (NSAIDs, Penicillamine)
- Infections (malaria, syphillis, Hep B/C, HIV)
- Carcinoma/lymphoma
83
What is the most common cause of nephrotic syndrome in children?
minimal change disease
84
What will MCD (minimal change disease) look like on H&E?
What is it characterized by EM?
How do you treat it and why does this work?
normal (normal on light microscopy too)
- diffuse effacement of podocyte foot processes
- steroids, because disease is due to cytokines
85
What causes minimal change disease?
-immune dysfunction leads to an elaboration of cytokines that damage visceral epithelial cells and cause proteinuria
86
What is MCD associated with?
- Respiratory illness
- post immunization
- increased incidence with Hodgkin lymphoma
- atopic disorders
- Presence of HLA haplotypes
87
What are the clinical features of MCD?
| Whats the treatment?
- highly selective proteinuria (albumin)
- No htn or hematuria
Corticosteroids
88
What is the most common case of nephrotic syndrome in caucasian adults and is immune complex mediated?
-Membranous nephropathy
89
What are the ways that you can get secondary immune complex mediated membranous nephropathy?
-SLE, Infections, Drugs, malignant tumors, Hep B, Hep C
90
What is membranous nephropathy characterized by?
| What will it look like on EM?
- diffuse thickening of the glomerular capillary wall by Ig deposition along the subepithelial side of the BM
- Spike and Dome appearance
91
Where does IgE deposit in membrnous nephropathy?
subepithelial deposis
92
What are the clinical features of membranous nephropathy?
- insidious onset of nephrotic syndrome (nonselective proteinuria)
- mild HTN and hematuria posible
93
What will progression of membranous nephropathy result in?
| How do you treat it?
sclerosis of glomeruli
- tx of the underlying condition (secondary)
- does not respond to steroids
94
What is this:
| characterized by focal and segmental sclerosis of the capillary tuft.
Focal segmental glomerulosclerosis
95
What are the causes of focal segmental glomerulosclerosis?
Idiopathic
Secondary (HIV, heroin, sickle-cell, obesity)
Complication of focal glomerulonephritis
Adaptive response to loss of renal tissue
96
What is the most common cause of nephrotic syndrome in hispanics and african americans? What will you see on EM? on IF?
Focal segmental glomerulosclerosis
EM: effacement of foot processes
IF: normal, no immune complex deposits
97
Focal segmental glomerulosclerosis is thought to possibly be a phase in the evolution of (blank). Whats this due to?
minimal change disease
- An accentuation of diffuse epithelial cell change of MCD
- cytokine mediated or defects of slit diaphragm proteins
98
Focal segmental glomerlosclerosis presents with (blank and blank) due to entrapment of plasma proteins
Hyalinosis
| Sclerosis
99
Focal segmental glomerulosclerosis is usually idiopathic, but may be associated with (blank x 3)
HIV
Heroin use
sickle cell disease
100
What are the clinical features of focal segmental glomerulosclerosis?
little tendency for spontaneous remission in idiopathic form, response to steroids is variable
101
In membranoproliferative glomerulonephritis, patients present with (blank) symptoms
nephritic/nephrotic or asymptomatic
102
What is membranoproiferative glomerulonephritis characterized by?
- Alterations of the GBM
- Tram-track appearance on H and E
- Proliferation of glomerular cells
- Immune complex deposition
- leukocyte proliferation
103
Membranoproliferative glomerulonephritis can be caused primarily, or secondarily by (blank, blank, blank)
chronic immune disorders
malignant disease
alpha-1 antitrypsin deficiency
104
What is type I Primary membranoproliferative glomerulonephritis?
immune complex deposition of C3 in the SUBENDOTHELIUM w activation of classical and alternative complement pathways
105
What can type I primary membranoproliferative glomerulonephritis be due to?
Planted exogenous antigens (Hep B/C)
| Circulating immune complexes
106
What is type II primary membranoproliferative glomerulonephritis due to?
AKA DENSE DEPOSIT DISEASE
- dysregulation of alternative complement pathway
- autoantibody to C3 convertase leading to persistent C3 activation and hypocomplementemia (low levels of C3)
107
Where do the immune complexes deposit in Type II membranoprliferative glomerulonephritis?
intramembranous (Basement membrane)
108
What are the clinical features of membraneoproliferative glomerulonephritis? How do you treat it?
few spontaneous remissions with a slowly progressive and unremitting course
-not one, steroids or immunosuppressives are not effective INSTEAD patients go into chronic renal failure
109
What is the most common type of glomerulonephritis worldwide?
What do patients present with?
IgA nephropathy
-recurrent gross or microscopic hematuria with RBC casts, usually following mucosal infections (gastroenteritis)
110
What is the systemic form of IgA nephropathy?
Henoch-schonlein purpura
111
IgA nephropathy is characterized by IgA deposits in the (blank) region of the glomerulus and increased levels of polymeric forms of (blanK)
mesangial region
| IgA1
112
IgA nephropathy is believed to be due to a genetic or acquired abnormality of immune regulation upon exposure to environmental agents in the (blank and blank). What are 2 examples of this?
Lungs and GI tract
Gluten enteropathy, Liver disease
113
What is the pathogenesis of IgA nephropathy?
IgA and IgA immune complexes are trapped in the mesangium and then activate the coplement pathway leading to glomerular injury
(IgA production is increased during infection)
114
What will you see on H&E and IF with IgA nephropathy?
thickening of the mesangium
115
What are the clinical features of IgA nephropathy?
- presents with gross hematuria after a respiratory or GI infection
- may present with microscopic hematuria with or w/out proteinuria or acute nephritic syndrome
- may retain renal function for decades
116
What is one of the leading causes of kidney failure and what three glomerular syndromes are associated with it?
diabetic nephropathy
- non-nephrotic proteinuria
- nephrotic syndrome
- chronic renal failure
117
Diabetic nephropathy also affects other portions of the kidney such as....?
Hyalinizing arteriolar sclerosis
Pyelonephritis
Tubular lesions
118
What causes the nephrotic changes in diabetic nephropathy?
high serum glucose and hemodynamic factors leads to nonenzymatic glycosylation of vascular BM resulting in hyaline sclerosis
119
In diabetic nephropathy, what part of the glomerulus is affected?
The efferent arteriole is more affects lead to high glomerular filtration pressure.
120
In diabetic nephropathy you will have high GFR which will result in what?
What can this eventually progress to?
hyperfiltration injury leading to microalbuminuria
| Nephrotic syndrome
121
What is diabetic nephropathy characterized by?
How can you treat this?
sclerosis of mesangium w/ formation of Kimmelstiel-Wilson nodules, thickening of glomerular BM and BM thickening of tubules
-ACE inhibitors slow progression of hyperfiltration-induced damage
122
What is Alport syndrome?
X-linked syndrome of defective collagen Type IV (thinning and splitting of the glomerular BM)
123
What is Alport syndrome characterized by?
Hematuria w/ progression to renal failure
Nerve deafness
Ocular disorders
124
What is thin basement membrane disease? What is its presentation?
Benign familial hematuria due to defects in a collagen Type IV.
- Normal renal function and excellent prognosis.
- asymptomatic hematuria
- mild proteinuria
- thin GBM
