Robbins Chapter 20 - The Kidney Flashcards
Azotemia
Elevation in BUN (urea in blood) Elevation in creatinine Decreased GFR Both AKI and CKD Consequence of several renal disorders as well as extrarenal disorders
Prerenal azotemia
Results from hypoperfusion of the kidneys
Impairs renal function in absence of parenchymal damage
Postrenal azotemia
Urine flow is obstructed distal to the kidney
Uremia
Azotemia + other signs/symptoms/abnormalities
Failed excretory function + metabolic and endocrine alterations
Common systems effected by uremia
GI, peripheral nerves (neuropathy,) heart (pericarditis)
Nephritic syndrome
Glomerular disease Hematuria (gross or microscopic) Decreased GFR Proteinuria HTN
Ex. acute poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
Rapidly declining GFR (hours to days)
Nephrotic syndrome
Glomerular disease **Proteinuria (greater than 3.5 gm/day) Hypoalbuminemia Edema Hyperlipidemia and lipiduria
Asymptomatic hematuria or proteinuria
Mild glomerular abnormalities
AKI
Glomerular, interstitial, vascular or tubular injury Rapid GFR decrease Dysregulation of fluid and electrolytes Retention of metabolic waste **Could have oliguria or anuria
CKD
Any cause, glomerulonephritis one of most common
GFR less than 60mL/min/1.73m^2 for 3 mo
Persistant albuminuria
Mild - unnoticed decline in excretory function
Severe - signs of uremia
End result of all chronic renal parenchymal diseases
ESRD
GFR less than 5%
Terminal uremia
Renal tubular defects
**polyuria, nocturia, electrolyte disorders
Structural or function defect
Function defect can be inherited or acquired
Renal tumors and urinary tract obstruction
Depends on location and nature of lesion
UTI
Bacteruria and pyuria
Nephrolithiasis
Spasms of severe pain and hematuria
High recurrence
Most common cause of CKD
Diabetes and HTN
Major cause of death from renal disease
CKD
Tracking CKD
Creatinine levels
Systemic manifestations of uremia and CKD
Table 20-1
Secondary glomerular diseases
Systemic disease injuring glomeruli
SLE, HTN, DM, amyloidosis, Fabry disease
Primary glomerularnephritis
Only kidney involved
Glomerulopathy
No inflammatory component
General Glomerulus structure
Capillary network
Fenestrated endothelium, BM separating endothelium from visceral podocytes, and parietal layer lining Bowman capsule
GBM
Lamina densa - thick central layer
Lamina rara externa and interna - thin peripheral layers
Type IV collagen
Proteoglycan content of GBM
Permeability characteristics
NC1 domain of GBM
Important for collagen structure
Target for antibodies
Alpha-chains of GBM
Underlie some forms of hereditary nephritis
Podocytes
Interdigitate and are separated by filtration slits bridged by thin diaphragm
Mesangial cells
Supporting cells (can contract, proliferate and secrete necessary material) Form matrix surrounding capillary
Glomerulus permeability
Highly permeable to water and small solutes
Impermeable to proteins (depending on charge and size)
Visceral layer - size restriction
Exclusion of albumin
Charge dependent restriction of anion
Nephrin
Bridges filtration slit
Anchored by CD2 attached to actin
Defects can lead to defects in permeability
Hypercellularity
Inflammatory diseases increase number of cells in glomerular tufts
Caused by:
Proliferation of mesangial or endothelial
Leukocyte infiltration
Endocapillary proliferation
Swelling of cells and infiltration of leukocytes
Formation of crescents
Accumulations of cells (including epithelial proliferation) with deposition of fibrin
Follows immune/inflammatory injury to capillary walls
Basement membrane thickening
Deposition of increasingly dense material
Increased synthesis of proteins
Adding additional layers
Hyalinosis
Accumulation of material that is homogenous and eosinophilic
May obliterate capillary lumens
Result of endothelial or capillary wall injury
Sclerosis
Deposition of extracellular collagenous matrix
*Diabetic glomerulosclerosis
May obliterate capillary lumens
Chronic glomerular injury response
BM thickening, hyalinosis and sclerosis
Acute glomerular injury response
Hypercellularity
Severe injury - formation of crescents
Immune mechanisms
Most forms of primary glomerulopathy and many forms of secondary glomerular disorders
Two forms of antibody related injury
1) Antibodies reacting directly to glomerulus
2) Antigen-antibody complexes from circulation depositing in glomerulus
**Major cause - in situ complex formation
In situ formation of immune complexes
Antibodies react with intrinsic tissue or extrinsic antigens “planted” in the glomerulus from circulation
Granular immune deposition
Very localized antigen-antibody interaction
**Most cases
Primary membranous nephropathy
Autoantibodies to endogenous material in tissue
Secondary membranous nephropathy
Drug induced
Graft-versus-host disease
Possible uncontrolled B cell activation
Linear immune deposition
Classic anti-GBM disease
Planted antigens
Antigens that have landed in the glomerulus by interacting with intrinsic components and can have antibodies react to them and injure kidney
Cations, DNA nucleosomes, bacterial products, large aggregated proteins, immune complexes, drugs
Complex deposition appears no different from intrinsic antigens
Anti-GBM disease
Antibodies homogenously distribute along entire length of GBM
These antigens are fixed and cannot be mobilized
Antibodies may cross react with different tissue
Very severe
Goodpasture syndrome
Circulating immune complexes
No specificity for glomerulus
Physiochemical properties and hemodynamics of glomerulus bring them there
Exogenous or endogenous antigens
**In situ formation still more probable
Microbial antigens leading to glomerulonephritis
Bacterial products (strep) SA of Hep B SA of Hep C Treponema pallidum, plasmodium falciparum and several others Tumor
Cationic antigens
Cross GBM
Complexes reside subepithelially
Anionic antigens
Don’t cross GBM
Subendothelial or not nephrogenic
Neutral antigens
Tend to accumulate in mesangium
Large complexes
Not as nephritogenic
Pattern of localization influenced by
Charge, size, hemodynamics, mesangial function, charge barrier integrity
Subepithelial
Less likely to involve inflammatory processes
Acute glomerulonephritis
Epimembranous deposits
Membranous nephropathy
Heymann nephritis
Subendothelial deposits
More likely to involve inflammatory processes
Lupus nephritis
Membranoproliferative glomerulonephritis
Mesangial deposits
IgA nephropathy
Cell-Mediated immunity and glomerulonephritis
Sensitized T cells can propagate inflammatory response
Alternative complement pathway activation
Dense-deposit disease or membranoproliferative glomerulonephitis (MPGN Type II) or C3 glomerulopathies
Neutrophils and monocytes
Result from complement activation (5a) and Fc activation
GBM degradation, ROS damage cells, arachidonic acid metabolites reduce GFR
Macrophages and T cells
Release biologically active molecules
Platelets
Vascular injury and proliferation of glomerular cells
Resident cells
**Mesangial cells
Produce inflammatory mediators
Even in absence if leukocytic infiltration
Complement activation
Induce leukocyte influx
MAC complex: cell lysis and stimulate mesangial cells
**Can produce proteinuria without neutrophils
Hemodynamic changes
Eicosanoids, NO, angiotensin, endothelin
IL-1 and TNF
Produced by infiltrating leukocytes and resident cells
Leukocyte adhesion and other effects
Growth factors
Mesangial proliferation and hyalinization
VEGF
Maintain endothelial integrity and may help regulate capillary permeability
Coagulation system
Deposition of fibrin
Crescent formation
Podocytopathy
Principle manifestation is injury to podocytes
Effacement, vacuolization, retraction and detachment
Key event in developing proteinuria
