2. Renal Path 1 Flashcards
Most glomerular diseases are immunologically mediated whereas tubular and what disorders are frequently caused by toxic or infectious agents?
Tubular and interestitial disorders
What is a biochemical abnormality that refers to an elevation of blood urea nitrogen (BUN) and creatining levels, and is related largely to a decreased glomerular filtratation rate (GFR)?
Azotemia
Azotemia is a typical feature of both acute and chronic kidney injury. What type of azotemia is encountered when there is hypoperfusion of the kidneys that impairs renal function in the absence of parenchymal damage?
Pre-renal azotemia
What type of azotemia is seen whenever urine flow is obstructed distal to the kidney, with the relief of obstruction correcting the azotemia?
Post-renal azotemia
Azotemia leads to what, which is characterized not only by failure of renal excretory function (azotemia) but also by metabolic and endocrine alterations resulting from renal damage with secondary involvements of GI system, peripheral nerves and the heart?
Uremia (=azotemia + clinical signs and symptoms)
What syndrome is a clinical entity caused by glomerular disease and is dominated by the acute onset of grossly visible hematuria or microscopic hematuria with dysmorphic red cells and casts on urinalysis, diminished GFR, MILD to MOD proteinuria and HTN?
Nephritic Syndrome (i)
Nephritic Syndrome is the classic presentation of acute poststreptococcal glomerulonephritis. Rapidly progressive glomerulonephritis is characterized as nephritic syndrome withrapid decline in?
GFR
What syndrome is due to glomerular disease and characerized by heavy (more than 3.5G/day) proteinuria, hypoalbuminemia, severe edema, hyperlipidemia and lipiduria?
Nephrotic Syndrome (o)
What kidney injury is chracterized by rapid decline in GFR (hours to days) with concurrent dysregulation of fluid/electrolytes and retention of metabolic waste products normally excreted by the kidney including urea and creatinine? reversible
Acute kidney injury - severe can see oliguria or anuria (no urine)
What kidney disease is defined as presence of diminished GFR that is persistently less than 60mL/min for at least 3 months from any cause, and/or persistent albuminuria, sometimes clinically silent? irreversible
Chornic kidney disease- end result of all chronic renal parenchymal diseases
What occurs when the GFR is less than 5% of normal and is the terminal stage of uremia?
End stage renal disease (ESRD)
Renal tubular defects are dominated by polyuria, nocturia, and electrolyte disorders (metabolic acidosis). They are the result of diseases that directly affect tubular structures or cause defects in?
specific tuburlar functions
What is manifested by spasms of severe pain (renal colic) and hematuria, often with reccurent stone formation?
Nephrolithiasis
11% of the US older adults have chronic kidney dz, it is usually the end result of many renal diseases but most commonly what two factors are the major cause of death from renal disease?
Hypertension
Diabetes
Disorders in which the kidney is the only or predominant organ involved constitute the various types of primary glomerulonephritis/glomerulopathy, all other causes are termed?
Secondary glomerular diseases (SLE, hypertension, diabetes, amyloidosis)
Glomerulus consists of anastomosing of capillaries that are lined by what type of endothelium invested in two layers of epithelial cells?
Fenestrated endothelium
The visceral epithelial cells aka as what, are incorporated into and become intrinsic part of the capillary wall, separated from endothelial cells by a basement membrane?
Podocytes/Foot processes
What type of epithelium sits on the bowman capsule and lines the urinary space, the cavity in which the plasma filtrate first collects?
Parietal epithelium
The average size of the kidney is between 120-150 gms, average length is 10-12 centimeters, and the width is 6cm and thickness is ?
3cm
The kidneys are located retroperitoneally, and the right is lower than the left kidney due to the liver, they sit at about T12 and what is between the lower border of the 12th rib and lateral border of the erector spinae muscle?
renal angle (renal colic pain starts from this angle down and forwards into groin)
On electrophoresis, Gamma, Beta, and Alpha globulin will not travel as far as what, which is the smallest, most negatively charged serum protein (migrates fast)?
Albumin
The entire glomerular tuft is supported by what cells inbetween the capillaries, forming a meshwork with basement membrane, they are contractile, phagocytic and capable or proliferation, laying down matrix and collagen, and secreting biologically active mediators?
Mesangial cells
What is important for the maintenance of glomerular barrier function, which has slit diaphragm presents a size selective distal diffusion barrier to the filtration of proteins and it is the cell type that is largely responsible for synthesis of GBM components (glomerular basement membrane)?
Visceral epithelial cells (podocytes/foot processes)
*NOTE: loss of these are the key event in development of proteinuria
What bridges the filtration slit between two podocyte foot processes, making a slit diaphragm?
Nephrin Molecules
Diabetes is the MCC of ESRD while HTN is the second MCC. In diabetes, primarily it is associated with glomerular disease (microvasculature manifestations = NO tubulointerstitial features), however in systemic HTN it is primarily vascular dz (arteriolar) thus including?
tubulointerstitial dz
What is the normal glomerular filtration rate which decreases with age?
about 100mL/min
All of the following are more characteristic of what renal disease? Nephritic syndrome nephrotic syndrome asymptomatic hematuria or proteinuria chronic renal failure renal tubular defects acute renal failure
Glomerular dz
All of the following are more characteristic of what renal disease? UTI urinary tract obstruction renal tumors nephrolithiasis
Tubulointerstitial dz
All of the following are more characteristic of what renal disease?
Renal tuburlar defects
acute renal failure
BOTH - have characteristics of glomerular and tubulointerstitial diseases
Some inflammatory diseases of the glomerulus are characterized by an increase in the number of cells in the glomerular tuft, known as ? (pathologic response to GM inj)
hypercellularity
Where can the macula densa be found, and what does it consist of?
Found near the afferent arteriole, and contains juxtaglomerular granular cells = make EPO/Renin
Hypercellularity can be d/t proliferation of mesangial/endothelial cells, infiltration of leukocytes, and d/t formation of what, which are accumulations of cells composed of proliferating glomerular epithelial cells and infiltrating leukocytes following an immune/ inflammatory injury involving the capillary walls?
Formation of crescents
Another pathologic response to GM injury is what, which can be seen on LM thickening of cap wall with PAS staining, and on EM you can see deposition of material, increased synthesis of protein components, and formation of additional layers?
Basement membrane thickening
Two other pathologic changes due to injury of the GM is hyalinosis which is accumulation of pink homogenous material (usually end result of glomerular damage) and what, which is characterized by deposition of ECM collagen?
Sclerosis (beyond fibrosis -scarring)
Histologic changes seen in glomerulopathies can be subdivided by distribution, define each of the following. Diffuse Global Focal Segmental
Diffuse: involves all gomeruli
Global: involves entire individual glomeruli
Focal: involves fraction of glomeruli
Segmental: involves part of an individual glomeruli
What mechanisms underlie most forms of primary glomerulopathy and many of the secondary glomerular disorders?
Immune mechanisms
There are two types of immune mechanisms causing glomerular injury, one being abs reacting in situ within the glomerulus and they other GM injury via circulation?
immune complex deposition
What type of nephropathy is associated with injury by antibodies reacting with intrinsic tissue antigen or planted antigens in the glomerulus (major cause of glomerulonephritis)?
Membranous Nephropathy (classic example - nephrotic syndrome - proteinuria)
In membranous nephropathy (in situ immune complex formation), antibody binding to PLA2R in the glomerular epithelial cell membrane forms characteristic deposits of immune complexes along the?
subepithelial aspect of the basement membrane
The pattern seen in IF of membranous nephropathy is known as what rather than being linear as seen in goodpasture anti-GBM?
granular on immunofluoresence
On light microscopy what can be seen in membranous nephropathy ?
thickened basement membrane (hence the name)
Membranous nephropathy develops in some infants fed cow’s milk, have abs to bovine albumin and lesions contain bovine milk antigens, this is a case of abs reacting in situ with what?
planted antigens (such as the milk ags)
What disease is characterized by anti-GBM antibody induced glomerulonephritis, antibodies bind to intrinsic antigens homogeneously distributed along the entire length of the GBM, resulting in a diffuse LINEAR pattern of staining for the antibodies by IF technique?
Goodpasture Syndrome (abs against normal components of GBM)
Goodpasture often occurs in lungs and kidney and is rare, and attacks the noncollagenous part of type IV collagen, causing severe necrotizing and crescentic glomerular damage presenting with?
Hemoptysis / Pulmonary hemmorrhage
Note: auto antibodies on IF show linear pattern of deposition while immune complexes show a?
granular pattern of deposition
Circulating immune complexes get trapped in the GM and cause glomerulonephritis. The antigens trigger the formation of circulating immune complexes from a endogenous origin such as SLE or in IgA nephropathy or they may be exogenous as seen in glomerulonephritis following?
certain infections (mainly viral, some strep)
Whatever the antigen may be, antigen-antibody complexes formed or deposited in the glomeruli may elicit a local?
inflammatory reaction that produces injury
Localization of immune complexes is a key determinant of the injury response and histological features. Immune complexes in the subendothelial portions of capillaries and mesangial regions are accessible to circulation and are more likely to be involved in inflammatory processes that require interaction and activation of circulating?
leukocytes
Disease with immune complexes confined to the subepithelial locations and for which the capillary basement membranes may be a barrier to interation with circulation leukocytes (such as membranous nephropathy) there is typically no?
inflammatory pahology
Note: cationic ag-ab complexes cross GBM and stay in subepithelial areas
anionic ag-ab do NOT cross GBM and are trapped subendothelially = not nephritogenic and neutral charged molecules accumulate in?
mesangium
Podocyte injury is common to many forms of primary and secondary glomerular diseases, stereotypic morphological changes in the podocytes include effacement of foot processes, vacuolization, and retraction and detachment of cells from the GBM causing?
Proteinuria
Loss of podocytes which have only a very limited capacity for replication and repair, may be a feature of multiple types of glomerular injury including focal and segmental glomerulosclerosis and?
diabetic neuropathy (causes proteinuria*)
Once any renal disease destroys functioning nephrons and reduces the GFR to 30-50% of normal, progression to what proceeds at a steady rate, independent of the originial stimulus or activity of the underlying disease?
end stage renal disease (failure) ESRD
The two major histologic characteristics of such progressive renal damage are focal segmental glomerulosclerosis FSGS and ?
tubulointerstitial fibrosis
What is a progressive fibrosis involving portions of some glomeruli developing after many types of renal injury and leads to proteinuria and increasing functional impairment? (*most common cause of nephritic syndrome in adults)
Focal segmental glomerulosclerosis (FSGS)
in Focal segmental glomerulosclerosis (FSGS) there is progressive fibrosis leading to functional impairment, causing proteinuria and hematuria, stems from loss of renal mass and is a result of what changes?
Adaptive changes
Loss of renal mass in Focal segmental glomerulosclerosis (FSGS) results in hypertrophy of the remaining glomeruli (compensation). Podocytes cannot grow in the glomeruli-losing filtration barrier and resulting ultimately in?
Glomerular HTN (assoc w systemic HTN)
This cycle mentioned above in Focal segmental glomerulosclerosis (FSGS) repeats continuously and can be treated with ?
Renin Angiotensin System Inhibitors
Proteins and cells are allowed to leak out in Focal segmental glomerulosclerosis (FSGS), resulting in macrophage induced fibrosis, causing a reduction in?
renal mass
What is tubulointerstitial injury manifested by tubular damage and interstitial inflammation, is a component of many acute and chronic glomerulonephritides?
Tubulointerstitial Fibrosis
