Renal Pathology Flashcards
The kidney has a large functional reserve and as such there is typically damage >75% before impairment
True
The glomerulus is lined by 3 things namely
Fenestrated endothelium
Basement membrane
Pododcytes or foot processes
Gaps between endothelial cells are known as
Fenestrae measuring 70-100nm
The basement membrane of the glomerulus consists mainly of
Type IV collagen
Heparan sulphate
Laminin
Glycoprotein
With a thickness of 250-400nm
The visceral epithelia of the glomerulus is
Poeocytes or foot processes
Embedded into the bm and separated from adjacent ones by 20-30nm filtration skits bridged by thin diaphragm (nephrin that attaches to intracellular proteins known as podocin)
The parietal epithelium faces the bowman’s space and is not in contact with the BM. T/f
T
The functions of the mesangial cells of the glomerulus
Phagocytosis
Contractility
They lie between the capillaries
What are the layers of the glomerular basement membrane
Central lamina densa
Between a lamina rara interna and externa
Two types of azotemia include
Pre renal: reduced renal blood flow leading to hypoperfusion with or without parenchyma damage
Post renal: obstruction of urine flow beyond the level of the kidneys
Azotemia=asymptomatic
Uremia=symptomatic
T/f
Obviously
Are you dumb 😒
Nephritic syndrome
A clinical syndrome that presents as
P-proteinuria (mild-moderate)
H-hematuria (grossly visible or microscopic)
A-Anasarca (less than in nephritis syndrome tho)
R- red cell casts (from breakdown of red cells)
O- oliguria
A-azotemia
H-hypertensiom
Nephrotic syndrome
A clinical syndrome in which there is increased permeability of the glomerulus and thus presents as
H- hypoalbuminemia(<3g/dl)
H- hyperlipidemia/lipiduria
O-nephrotic
P- heavy proteinuria(>3.5g/day)
E- severe edema
Acute kidney injury
Characterised by a sudden and often reversible reduction in kidney function often denoted by
Rapid decline in GFR(within hours to days)
Concurrent dysregulation of fluid/electrolyte balance
Retention of metabolic waste(azotemia)
In severe cases, oliguria or anuria is present
The types of AKI and their causes include
Pre renal- reduced blood volume as a result of dehydration from vomiting, diarrhea etc
Hemorrhage
Shock, sepsis
Intrinsic renal…due to injury of the kidney in cases of acute tubular necrosis
Drugs, toxins, glomerulonephritis, lupus nephritis
Post renal- typically due to obstruction asin urethral stricture, bladder cancer,enlargement of the prostate
Chronic renal failure
Defined as presence of diminished GFR that is persistently less than 60ml/minute/1.73m² for at least 3 months from any cause and or persistent albuminuria
End result of all chronic renal parenchymal diseases.
End stage renal disease
occurs when the Gfr is <5% of normal . Terminal stage of uremia.
Secondary diseases with glomerular involvement
DM
SLE
Goodpastures disease
Wegener’s granulomatosis
Amyloidosis
Hence schnolein purpura
Pathologic responses of glomerulus to injury
Hate- hypercellularity( epithelia, mesengial cells or leukocyte infiltration, formation of crescents)
Sucking- sclerosis
Hate- hyalinosis
boobs-basement membrane thickening
Pathogenesis of glomerular injury
Disease caused by in situ formation of immune complexes
Diseases caused by deposition of circulating immune complexes
Due to antibodies directed against normal components of the glomerular basement membrane with crossreactivity asin good pastures disease
Cell mediated immunity in glomerulonephritis
Diffuse is to focal as global is to?
Segmental
Complications of nephritis syndrome
Infections especially staphylococcal and pneumococcal diseases probably due to loss of immunoglobulin in urine
Thrombosis(anticoagulation disorders) due in part to loss of antithrombin 3 in urine
Renal vein Thrombosis
Lipid based diseases
ESRD
Death
The most frequent Systemic causes of nephrotic syndrome
Das sad
DM
Amyloidosis
SLE
Uniform and diffuse effacement of podocytes is seen on light microscopy in minimal change disease
False, only seen on electron microscopy with no immunofluorescence
In which type of glomerulonephritis is there selective proteinuria typically to albumin
Minimal change
Prognosis of minimal change
Good to corticosteroid therapy especially children >90%
However proteinuria may recur and some patients may become steroid dependent or resistant although this typically resolves by puberty
Most common cause of nephrotic syndrome in adults
Membranous nephropathy
About membranous nephropathy
Chxd by diffuse thickening of glomerular capillary wall due to accumulation of deposits containing immunoglobulin along the subepithelial side of the BM
Approximately 75% of cases of membranous nephropathy are secondary whereas the rest are primary. T/f
False..other way round
Secondary causes of membranous nephropathy
Drugs like gold captopril gold NSAIDs
SLE,tumors, infections, AI disorders
Morphology of m.nephropathy
Light microscopy- uniform and diffuse thickening of the glomerular capillary wall
Electron microscopy- Effacement of podocytes with Irregular electron dense subepithial deposits
Immunofluorescence- granular deposits of IgG and complement
Prognosis of membranous nephropathy
Variable, could be spontaneous remission or renal failure within 10-15yrs
Better response to corticosteroid in children than adults
May progress to focal segmental glonerulosclerosis
Most common cause of nephrotic syndrome in adults in the U.S
Focal segmental
What is focal segmental glomerulosclerosis
Here, some glomeruli exhibit segmental sclerosis whereas others are normal
FSG occurs in the following setting
Primary: in which there’s no identifiable cause
Associated with other conditions: HIV, heroin Scd morbid obesity
Secondary: following igA nephropathy or m.nephropathy.
Adaptive
Although fgs is typically nephrotic, there’s a higher incidence of nephritic symptoms including
Haematuria
Reduced Gfr
Hypertension
Prognosis of fgs
Poor response to corticosteroids
Progression to Ckd with at least 50% and ESRD in 10yrs
Negative immunofluorescence
Membranoproliferative glomerulonephritis produces only nephritic syndrome…t/f
False…produces both nephrotic and nephritic
Membranoproliferative glomerulonephritis is histologically chxd by
Thickening of GBM , proliferation of endothelial and mesangial cells, leukocyte infiltration and presence of deposits in mesangial and capillary wall regions
MPG is sometimes referred to as
Mesangiocapillary glomerulonephritis because the proliferation typically occurs in both cells
“GBM is Thickened and often shows a double contour or a tram track appearance caused by duplication of the BM with accentuated lobular appearance”. This is characteristic of ?
Membranoproliferative glomerulonephritis
Type I membranoproliferative glomerulonephritis is chxd by
Presence of discrete subendothelial electron dense deposits consisting of IgG and complement.
Type II membranoproliferative glomerulonephritis
Now called dense deposit disease whereby there is excessive activation of alternative complement pathway with deposition of unknown material within the Bm associated with a circulating ab named C3 nephritic factor
Circulatory antibody associated with dense deposit disease is known as
C3 nephritic factor
Prognosis of membranoproliferative glomerulonephritis
Treatment not proven to be effective, about half of the patients develop ESRD Within 10yrs
Diabetic glomerulosclerosis is also known as
Kimmelstiel Wilson disease or nodular glomerulosclerosis
The earliest lesion in nodular glomerulosclerosis is
GBM thickening followed by glomerular enlargement
It’s highly specific for diabetes
CRAP helps you to remember that
Congo Red Amyloid Positive deposits mainly in mesangium and capillaries is a feature of amyloid nephropathy
Acute proliferative gn is also known as
Post streptococcal or post infectious GN
Usually follows an acute infection with group A beta hemolytic strep, most often pharyngitis( including scarlet fever). What are we talking about
Acute proliferative gn
Acute proliferative gn
Occurs at all ages, typically in children.
Develops 1-4 weeks after a strep infection which may have already resolved
Others S.aureus, S.pneumoniae etc
In children, good prognosis
In adults, bad significant proportion leads to CRF
Pathogenesis of acute proliferative gn
Strep infxn->1- 4 weeks after-> streptolysin O antigen left behind->serum antistreptolysin O antibody(ASO) formed-> ASO combines with SO ->immune complexes formed-> deposited in glomeruli->acute proliferative gn
Nephritogenic strains of acute proliferative gn
Griffiths types-12, 4,1,25 and 49
Rapidly progressive glomerulonephritis is also known as
Crescentic glomerulonephritis
Clinical features at first resemble acute proliferative but instead of regressing after a week or two , they become progressively worse leading to advanced renal failure after a period of days or weeks…what are we referring to
Rapidly progressive
Pathology of post infectious gn
Diffuse enlargement and increased cellularity of the glomeruli
Narrowing or obliteration of the Bowman’s capsular space with part of the glomerular tuft seen to have herniated into the lumen of the PT
Narrowing of glomerular capillary lumina
Histology of post infectious gn
Electron microscopy: shows the presence of subepithelial humps due to deposits of electron dense material indicative of immune complex formation
IF-shows granular deposition of Ig and complements
In which gn is there herniation of glomerular tuft into the lumen of the proximal tubule?
Acute proliferative
Aetiology of crescentic glomerulonephritis
Most common cause is Anti neutrophil cytoplasmic antibody(ANCA) associated vasculitis. E.g microscopic polyangitis and wegener’s granulomatosis
Also patients with anti GBM antibodies develop goodpasture’s syndrome
Rarely follows a strep infxn, represents a severe end of the spectrum of acute diffuse proliferative glomerulonephritis.
Pathology of rapidly progressive gn
Chxtic Histological feature-> proliferation of the parietal epithelium of Bowman’s capsule to form epithelial crescents which in time are replaced by fibrous tissue
Also proliferation of both endothelial and mesangial cells
Histology of rapid progressive gn
IF shows absence of Igs in crescents but rather deposits of fibrin are present which have been shown experimentally to stimulate formation
Chronic glomerulonephritis pathology
Gross
Both kidneys are uniformly shrunken in size
Thinningof cortex and medullary pyramids are also shrunken
Noteee…that the renal pelvis and calyces are not distorted.
Flea bitten appearance of kidney is seen in
In cases of chronic gn complicated by malignant htn where the cotical surface of the kidney shows molting and hemorrhage
Microscopy of Chronic gn
Sclerosis and complete hyalinisation of many glomeruli. Arteries show hypertensive changes
