Clinical Manifestations of Glomerular Disease (Brozna) 1 and 2 Flashcards
Kidney filters how much blood/ urine?
20% Cardiac Output Filters 1700 liters/day
1,000 mL urine/day
What part of the kidney is most susceptible to ischemic injury?
Since the arcuate arteries do not anastomose, the central portion of the renal lobe is most susceptible to ischemic injury
The two capillary beds
unique feature of renal circulation : two capillary beds arranged in series.
1. Afferent arteriole –> glomerulus (filtration of fluid and solutes).
- via the efferent arteriole–> the peritubular capillary network (fluid and solutes reabsorbed by the tubules are returned to the circulation.)
What is the final common pathway to end-stage renal failure?
Chronic hypoxia is the final common pathway to end-stage renal failure. Ischemia of the kidney is induced by the loss of peritubular capillaries in the tubulointerstitium in the late stage of renal disease
Glomerular filter consists of
fenestrated endothelium, basement membrane, and foot processes of epithelial cells. Note the filtration slits and diaphragm situated between the foot processes.
Note also that the basement membrane consists of a central lamina densa, sandwiched between two looser layers, the lamina rara interna and lamina rara externa
Assessment of renal function includes what?
Urine analysis
- Color, volume, cells, casts, pH, osmolality, protein, urea, creatinine, glucose
Blood examination
- Serum creatinine (used to estimate GFR, not specific)
- Blood urea (increased in many renal diseases with various glomerular, tubular or interstitial damage, not specific)
Glomerular function tests
- Glomerular filtration rate (GFR) is proportional to serum creatinine
Tubular function test
- Urine concentration test (requires water deprivation for 14 hours–> Specific gravity greater than 1.02 (normal)
- Vasopressin test
Urine sediment: dysmorphic RBC suggests what?
White blood cell cast are most typical for what?
dysmorphic RBC suggests glomerular disease (it squishes through the fenestration)
White blood cell cast are most typical for acute pyelonephritis
acute kidney injury
Increase in serum creatinine by ≥ 0.3mg/dLwithin 48 hours; or
Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days; or
Urine volume less than 0.5mL/kg/hfor six hours
Estimation of glomerular filtration rate through the calculation of creatinine clearance is mandatory
In most healthy people, the normal GFR is 90 mL/min/1.73 𝐦^𝟐 or higher.
A result of 60–89 mL/min/1.73 𝐦^𝟐 without kidney damage may be normal in some people (such as the elderly, infants).
A result of 60–89 mL/min/1.73 𝐦^(𝟐 )for three months or more, along with kidney damage (such as persistent protein in the urine), means the person has early kidney disease.
When GFR is less than 60 ml/min/1.73 m2 for 3 months or more, chronic kidney disease is present.
GFR must decline to approx half the normal level before the serum creatinine concentrtion rises above the upper limit of normal.
Chronic Kidney Disease
- Kidney damage > 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by either:
- pathological abnormalities; or
- Markers of kidney damage, including abnormalities in teh composition of the blood or urine, or abnormalities in imaging tests - GFR 3 months, with or without kidney damage
5 stages of chronic renal failure
- GFR 90+. Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease
- GFR 60-89. Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease
3a. GFR 45-59 Moderately reduced kidney function
3b. GFR 30-44 - GFR 15-29. Severely reduced kidney function
- GFR less than 15 or on dialysis.
Clinical Manifestations of Renal Diseases
hematuria proteinuria edema hypertension oliguria anuria increased serum creatinine increased serum BUN mass
Uroscopy
is the histologic medical practice of visually examining a patient’s urine for pus, blood or other symptoms of disease. It dates back to ancient Egypt Babylon and India
13th century description of symptoms of chronic nephritis
The signs of hardness in the kidneys are that the quantity of the urine is diminished, that there is heaviness of the kidneys, and of the spine with some pain: and the belly begins to swell up after a time and dropsy is produced the second day…
foamy urine is associated with
proteinuria
Bright Disease
= Glomerulonephritis
In 19th century Bright Disease became known as a chronic but incurable disorder… along with tuberculosis and cancer as diagnoses that could extinguish all hope and interest in life
Bright Disease was the FEARED disease of the 1800s
What the microscope and labs of late 1800s said about Bright disease
Acute form of Bright disease that made urine bloody as well as albuminuric, caused flank pain and was associated with blood engorged swollen kidneys –> Acute glomerulonephritis
Bright disease dominated by extreme albuminuria and stubborn dropsy, large pale kidneys –> Nephrotic syndrome
Bright disease arising from narrowing and hardening of the kidneys’ arterial network –> Vascular kidney diseases
4 groups of kidney pathology
Can divide kidney diseases into those that affect the basic morphologic components: Blood vessels Tubules Interstitium Glomeruli
Early manifestations of disease affecting each of these components tend to be distinct and some components seem to be more vulnerable to specific forms of renal injury
For example:
Most glomerular diseases are immunologically mediated.
Pathogenesis of Glomerular Injury
- Most forms of human glomerulonephritis result from immunologic mechanisms
- Most precipitating factors initiate similar immune responses that result in glomerulonephritis via shared common pathways
- Most human glomerular diseases are characterized by glomerular immunoglobulin deposition +/- complement
- Immune deposits form either actively (AbAg) or passively as exogenous antigens become trapped in glomerulus due to glomerular filtration
Two forms of antibody-associated injury have been established:
Injury byantibodies reacting in situ within the glomerulus,either binding to insoluble fixed (intrinsic) glomerular antigens or extrinsic molecules planted within the glomerulus.
Injury resulting from deposition of circulating antigen-antibody complexes in the glomerulus.
*** the major cause of glomerulonephritis resulting from formation of antigen-antibody complexes is in situ immune complex formation, and not deposition of circulating complexes.
Pathogenesis of Glomerular Injury
Cellular immunity can lead to the production of cytokines
Cause the glomerular basement membrane to lose its negative charge
Damage podocytes causing the process fusion
Mesangial cell proliferation and matrix formation
Podocytes, mesangial cells, endothelial cells interact with each other
Growth factors Cytokines Vasoactive agents Chemokines Complement receptors
Podocyte injury frequently results in mesangial cell proliferation, whereas mesangial cell injury leads to foot process fusion and proteinuria
Four Types of Immune Reactions
Type I immune reaction (anaphylactic)
Hypersensitivity reaction mediated by IgE which occurs relatively rapidly following exposure to previously encountered antigen
Type II immune reaction (antibody mediated)
Caused by antibodies which react with self-antigens
Type III immune reaction ( immune complex mediated)
Involve the deposition of preformed immune complex which result in complement activation
Type IV immune reaction (delayed hypersensitivity cell-mediated)
Mediated predominantly by T cells
In situ Formation of Immune Complexes in the Glomerulus
Intrinsic antigens in the glomerulus
Antibody to glomerular basement membrane –> Goodpasture disease
Antibody to phospholipase A2 receptor –> Membranous nephropathy
Extrinsic antigens trapped (planted) in the glomerulus
Cationic molecules
Nuclear proteins
Infectious agent antigens
Deposition of Circulating Immune Complexes
Glomerular injury can be caused by the trapping of circulating immune complex
Immune complex antigens may be of endogenous origin
DNA, tumor antigens
Immune complex antigen may be of exogenous origin Microbial antigens (streptococcal proteins) Viral antigens (hepatitis virus)
Immune Complex Localization
Several factors affect glomerular localization of antigen, antibody or complexes:
Molecular charge and size
Cationic molecules tend to cross glomerular basement membrane and deposit in sub-epithelial location
Anionic molecules are excluded from the basement membrane and localized in sub-endothelial locations
Neutral charge antigens or complexes tend to accumulate in the mesangium
Antibody mediated immune injury
Immune complex formation leads to complement activation and activation of leukocyte mediated injury pathways
Primary Renal Disease
Pathologic changes in the kidney in the absence of associated systemic disease
Only kidneys are affected
Secondary Renal Disease
Systemic disease causes the renal disease Diabetes mellitus Systemic lupus erythematosus Hypertension Amyloidosis
Terms used to Describe
Histologic Lesions in Glomeruli
Focal- Involving less than 50% of glomeruli
Diffuse- involving > 50% of glomeruli
Segmental- involving part of a glomerular tuft
Global- involving all of a glomerular tuft
