Case One PART ONE Flashcards
(61 cards)
1
Q
Nephrotic Syndrome s/s
A
Heavy proteinuria (>3g/24hrs) Edema Hypertension Minimal hematuria Hypoalbuminemia Hypercholesterolemia
**Nephrotic-range proteinuria - ONLY (+) large amts. pf protein but without CM
2
Q
Nephritic Syndrome s/s
A
Mild to mod proteinuria (1-2g/24 hrs) Hypertension Hematuria RBC casts Pyuria Fluid retention Rise in serum crea
3
Q
Kidneys - location
A
posterior wall of abdomen
4
Q
Kidneys - weight
A
150g; size of clenched fist
5
Q
Kidneys - medial side and surrounded by
A
Hilum (indented region)
Capsule (tough, fibrous)
6
Q
Hilum - passing structures
A
Renal artery and vein
Ureter
Nerve supply
Lymphatics
7
Q
Kidneys - 2 major regions
A
Cortex (outer)
Medulla (inner)
8
Q
Kidneys - MEDULLA is split into
A
Renal pyramids
9
Q
Renal pelvis
A
- multiple cone-shaped masses of tissue
- originates at the border bet cortex and medulla
- terminates in the MEDULLA
10
Q
Renal papilla
A
projects into the space of the RENAL PELVIS
11
Q
Renal pelvis
A
funnel-shaped
outer border is divided into open-ended pouches: MAJOR CALYCES —> MINOR CALYCES (collect urine from tubules of each papilla
12
Q
Renal blood flow
A
22% of CO or 1100ml/min
13
Q
Renal artery branches
A
Interlobar arteries
Arcuate arteries
Interlobular arteries (aka Radial arteries)
Afferent arterioles
14
Q
Glomerular capillaries
A
large amounts of fluids and solutes are filtered to begin urine formation (except PLASMA PROTEINS)
15
Q
distal ends of capillaries coalesce to form
A
Efferent arteriole
16
Q
Efferent arteriole leads to a SECOND capillary network
A
Peritubular capillaries (surrounds renal tubules)
17
Q
2 capillary beds of the renal circulation
A
Glomerular capillaries
Peritubular capillaries
18
Q
Glomerular capillaries and Peritubular capillaries are arranged in
A
SERIES
19
Q
Glomerular capillaries and Peritubular capillaries are separated by the
A
Efferent arterioles
20
Q
Efferent arterioles help
A
help regulate the hydrostatic pressure in both sets of capillaries
21
Q
High hydrostatic pressure in the glomerular capillaries
A
about 60 mm Hg
causes RAPID FLUID FILTRATION
22
Q
Loe hydrostatic pressure in the peritubular capillaries
A
about 13 mm Hg
allows RAPID FLUID REABSORPTION
23
Q
Peritubular capillaries empty into
A
Venous system vessels
- -which form the:
1. Interlobar vein
2. Arcuate vein
3. Interlobar vein
4. Renal vein
24
Q
Venous system vessels
A
- Interlobar vein
- Arcuate vein
- Interlobar vein
- Renal vein
25
Nephrons
- 1 million
- capable of forming URINE
- cannot be regenerated
26
DECREASE in nephrons seen in
Renal injury
Disease
Normal aging
27
After age 40, nephrons
| At age 80, nephrons
- 40: decreases about 10% every 10 years
| - 80: 40% fewer functioning nephrons than age 40 (but not life-threatening)
28
Nephrons contain
Glomerulus
| Tubule
29
Glomerulus
- tuft of glomerular capillaries
- large amounts of fluid are filtered from the blood
- have high hydrostatic pressure (about 60mmHg)
- covered by EPITHELIAL CELLS
- encased in BOWMAN'S CAPSULE
30
Tubule
filtered fluid is converted into urine
31
Fluid flow
Bowman's capsule
I
Prox. tubule (lies in the renal cortex)
I
Loop of Henle (dips into the renal medulla)
-Descending and Ascending Limb
*thin segment of LOH - walls of the descending limb
and lower end of ascending limb
*thick segment of ascending limb - at the end,
contains the MACULA DENSA (a
plaque in its wall)
I
Distal tubule (lies in the renal cortex)
I
Connecting tubule
I
Cortical collecting tubule
I
Cortical collecting duct
-Initial parts of 8-10 collecting ducts joins to form a
single larger collecting duct -> which then
becomes the MEDULLAR COLLECTING DUCT
I
Ducts empty into the RENAL PELVIS through the RENAL PAPILLAE
**each kidney has about 250 very large collecting ducts; each of which collects urine from about 4000 nephrons
32
Macula densa
plays a role in controlling nephron function
33
2 types of nephron
Cortical (located outside the cortex)
| Juxtamedullary (deep in the cortex) -20-30%
34
Cortical nephrons
- have short LOH
| - entire tubular system is surrounded by extensive network of peritubular capillaries
35
Juxtamedullary nephrons
have long LOH
-long efferent arterioles extend from glomeruli down in the outer medulla then divide into VASA RECTA (specialized peritubular capillaries)
36
Vasa Recta
- specialized peritubular capillaries
- empty into the cortical veins
- plays an impt role in CONCENTRATED URINE formation
37
Glomerular disease - pathogenesis
| -linked to:
```
Hypertension
Atherosclerosis
Thrombosis
Emboli
DM
```
Genetic mutations
Autoimmunity
Infection
Toxin exposure
38
Glomerular disease - pathogenesis
| -cause and lesion
Cause: Unknown
Lesion: Idiopathic
39
Glomerular disease - pathogenesis
| Some glomerular diseases result from genetic mutations producing familial disease
1. Congenital Nephrotic Syndrome
- from mutations in NPHS1 (nephrin) and NPHS2 (podocin)
- affect the slit-pore membrane at birth
2. Focal Segmental Glomerulosclerosis (FSGS)
- adulthood
- TPRC6 cation channel mutations
- Polymorphisms in the gene coding apolipoprotein (APOL 1) - Major risk for 70% of African Americans with non-diabetic ESRD, esp. FSGS
Mutations in COMPLEMENT FACTOR H associate with:
* Membranoproliferative glomerulonephritis (MPGN)
* Atypical Hemolytic Uremic Syndrome (aHUS)
40
Alport's syndrome
- mutations in the genes encoding for the 3, 4, 5 chains of type IV collagen
- produces SPLIT-BASEMENT MEMBRANES with GLOMERULOSCLEROSIS
41
Lysosomal storage diseases
-such as Galactosidase A deficiency causing:
*FABRY'S DISEASE
*N-ACETYLNEURAMINIC ACID HYDROLASE
DEFICIENCY causing Nephrosialidosis
produce FSGS.
42
Mutations in COMPLEMENT FACTOR H associate with:
* Membranoproliferative glomerulonephritis (MPGN)
| * Atypical Hemolytic Uremic Syndrome (aHUS)
43
Focal Segmental Glomerulosclerosis (FSGS)
- adulthood
- TPRC6 cation channel mutations
- Polymorphisms in the gene coding apolipoprotein (APOL 1) - Major risk for 70% of African Americans with non-diabetic ESRD, esp. FSGS
44
Congenital Nephrotic Syndrome
- from mutations in NPHS1 (nephrin) and NPHS2 (podocin)
| - affect the slit-pore membrane at birth
45
Systemic HPN and atherosclerosis can produce
Pressure stress
Ischemia
Lipid oxidants
that lead to CHRONIC GLOMERULOSCLEROSIS
46
Malignant HPN complicates glomerulonecrosis with
Fibrinoid necrosis of arterioles and glomeruli
Thrombotic microangiopathy
Acute RF
47
Diabetic nephropathy
- acquired sclerotic injury
- assoc. with thickening of the GBM secondary to the long standing effects of hyperglycemia, advanced glycosylation end products, and reactive oxygen species
48
Glomerulonephritis
- Inflammation of the glomerular capillaries
- EARLY T-CELL ACTIVATION - plays an impt role in the mechanism
**Immune-mediated glomerulonephritis - antigens involved are UNKNOWN
49
Autoimmune diseases
Idiopathic membranous glomerulonephritis (MGN) - CONFINED to the kidney
50
Systemic Inflamm. Diseases
- 1. Lupus Nephritis
2. Granulomatosis with polyangitis (Wegener's)
-SPREAD to the Kidney -> causing secondary glomerular damage
51
Antiglomerular basement membrane disease
- produce GOODPASTURE'S SYNDROME
- primarily injures BOTH LUNGS and KIDNEYS
- -because of the narrow distribution of the 3 NC1 domain of type IV collagen (target antigen)
52
Mononuclear cell infiltration is induced by
Local activation of toll-like receptors on glomerular cells
Deposition of immune complexes
Complement injury to glomerular structures
53
Neutrophils
Macrophages
T cells
```
-drawn by CHEMOKINES into the glomerular tuft
I
they react with antigens and epitopes
I
producing more cytokines and proteases
I
damage the mesangium, capillaries, GBM
```
54
What are assoc. with immune deposits along GBM
1. Poststreptococcal glomerulonephritis
2. Lupus Nephritis
3. Idiopathic membranous nephritis
55
Sub-endothelial side of the GBM
| Sup-eipithelial side of the GBM
Sub-endothelial side of the GBM
--preformed circulating immune complexes precipitate
Sup-eipithelial side of the GBM
--other immune deposits form in situ
-accumulate when circulating auto-AB find their antigen trapped along the sub-epithelial edge
**IMMUNE DEPOSITS - stimulate the release of local proteases and activate the complement cascade --> producing C5-9 attack complexes
56
Persistent glomerulonephritis that worsens renal function is always accompanied by
1. Tubular atrophy
2. Interstitial nephritis
3. Renal fibrosis
57
RF in glomerulonephritis best correlates histologically with
appearance of TUBULOINTERSTITIAL NEPHRITIS
- EARLY TUBULOINTERSTITIAL NEPHRITIS - recoverable
- CHRONIC TUBULOINTERSTITIAL NEPHRITIS - results to permanent loss
58
Loss of renal function d/t interstitial damage --MECHANISMS
1. Urine flow is impeded by tubular obstruction as a result of interstitial inflammation and fibrosis
- -tubular obstruction results in AGLOMERULAR NEPHRONS
2. Interstitial changes (interstitial edema or fibrosis) alter tubular and vascular architecture
- -leads to an INCREASE in solute and water content of the tubule fluid --> ISOSTHENURIA and POLYURIA
3. Changes in vascular resistance d/t damage of peritubular capillaries
- -affect renal function in 2 mechanisms:
(a) Tubular cells are very metabolically active - so decreased perfusion leads to ischemic injury
(b) Impairment of glomerular arteriolar outflow = INCREASED intraglomerular HPN in less involved glomeruli = aggravates and extends mesangial sclerosis and glomerulosclerosis to these glomeruli
59
Effect of proteinuria on the development of interstitial nephritis
increasingly severe proteinuria
I
carry activated cytokines and lipoproteins
producing reactive oxygen species
I
triggers downstream inflamm. cascade in and around epithelial cells lining tubular nephron
I
Induce T lymphocyte and macrophage infiltrates
60
Epithelial-mesenchymal transitions
- form more interstitial fibroblasts
- the ff become more active:
1. Transforming growth factorf (TGF)
2. Fibroblast growth factor 2 (FGF-2)
3. Hypoxemia-inducible factor 1 (HIF-1)
4. Platelet-derived growth factor (PDGF)
61
With persistent nephritis, fibroblasts multiply and lay down
Tenascin and fibronectin scaffold for the poymerization of new interstitial collagen types 1/3
This event form scar tissue through FIBROGENESIS
- Can REVERSE early fibrinogenesis:
1. Bone morphogenetic protein 7
2. Hepatocyte growth factor
-when fibroblasts outdistance their survival factors - apoptes occurs - permanent renal scar becomes acellular = Irreversible renal failure
