Renal I(a) Flashcards
Causes of Nephritic Syndrome
- Children: IgA Nephropathy, Post-streptococcal GN, etc.
- Adults: Membrano-Proliferative GN-I and -II, Rapidly
Progressive (Crescentic) GN, SLE or Lupus Nephritis, etc.
Clinical Manifestations of Nephritic vs Nephrotic Syndrome.
Note : there is proteinuria and oedema in Nephritic however it’s mild
Primary Causes of Nephrotic Syndrome
- Minimal Change Nephropathy (children)
- Focal segmental Glomerulosclerosis
- Membranous Nephropathy, etc.
- Membrano-proliferative Glomerulonephritis
secondary causes of Nephrotic Syndrome
- Diabetes Mellitus
- Lupus Erythematosus
- Viral infections, etc.
Clinical manifestations of Rapidly Progressive Glomerulonephritis
* Type of Nephritic Syndrome
1) Microscopic haematuria &
2) dysmorphic (spiked shape) RBC and RBC casts
3) Mild to moderate proteinuria
Causes of Acute Kidney disease
- Glomerular injury (Rapidly Progressive GN)
- Vascular injury (Thrombotic Micro-Angiopathy)
- Interstitial injury
- Acute tubular injury
Thrmobotic micro-angio –> injury to the small vessles
CM of Acute Kidney disease
1) Oliguria (low urine) or anuria (no urine)
2) Recent onset of azotaemia
Causes of Chronic Kidney Disease (Chronic Renal Failure)
1) Diabetes Mellitus
2) Hypertension
3) Glomerulonephritis
CM of Chronic Kidney Disease (Chronic Renal Failure)
- High blood pressure –> CHF
- Prolonged symptoms and signs of uraemia (lethargy, pericarditis, encephalopathy)
- Hyperkalaemia –> Fatal cardiac arrhythmias
- Fluid volume overload –> Pulmonary oedema
chronic –> affects the heart
CM of Urinary Tract Infection
- Bacteriuria
- Pyuria (puss in urine)
- Pyelonephritis (kidney inflammation)
- Cystitis (inflammation of the bladder)
*
CM of Nephrolithiasis
- Renal colic (obstruction of urine flow –>pain in the kidney area)
- Haematuria, without RBC casts
Causes of Podocyte injury
- Abs against podocyte Ags
- Toxins and Circulating factors
- Mutations in structural components of slit diaphragm
Morphologic changes:
* Effacement (thinning) of foot processes
* Vacuolisation
* Retraction and detachment of cells from the GBM
of?
* Vacuolisation –> normally indicates exposure to pathogens
Podocyte Injury
CF of Podocyte Injury
Proteinuria
Compensatory mechanism of Nephron Loss?
* Nephron loss –> work overload on the remaining nephrons
Hypertrophy of the remaining glomeruli (not destroyed by the initial renal disease)
* cause? podocyte injury/ capillary obliteration
————- : thickening and sclerosis of arterial
walls and the renal changes associated with benign hypertension
Arterionephrosclerosis
patho of Arterionephrosclerosis
Two processes participate in the arterial lesions:
1) Medial and intimal thickening, as a response to haemodynamic changes, aging and genetic defects
2) Hyaline deposition in arterioles, caused by:
a. Extravasation of plasma proteins
b. Increased deposition of basement membrane matrix
Macroscopic Features:
* Symmetrical atrophy of the kidneys
* Diffuse fine granularity of the renal surface
Microscopic Findings:
* Hyaline Arteriolosclerosis
* Lumen narrowing of the affected vessels
* Ischaemic atrophy of all renal structures
Severe cases: tubular atrophy, scleroting glomerulus
Features of?
Arterionephroscleoris
CF of Arterionephrosclerosis
- Loss of concentrating ability or diminished GFR
- Mild degree of proteinuria
causes of MALIGNANT HYPERTENSION?
Appearance either de novo or with a sudden onset in patients with pre-existing mild hypertension
* de novo –> ‘from the beginning’
patho of MALIGNANT HYPERTENSION:
* Long-standing hypertension –> Injury to the arteriolar walls –> i. ——-,———-,———–> Fibrinoid necrosis of vessels —> (————) -> Increased narrowing of the arteriolar lumen –> Marked —— changes of the kidneys
* Renal ischaemia –> Further, Renin secretion (“———-”) -> Elevated ——— levels –> Salt retention -> Aggravation of blood pressure
- Long-standing hypertension –> Injury to the arteriolar walls –> i. increased permeabilty, endothelial injury and platelet deposition–> Fibrinoid necrosis of vessels —> (Hyperplastic Arteriolosclerosis) -> Increased narrowing of the arteriolar lumen –> Marked ischaemic changes of the kidneys
- Renal ischaemia –> Further, Renin secretion (“vicious cycle”) -> Elevated Aldosterone levels –> Salt retention -> Aggravation of blood pressure
Macroscopic features:
- Multiple small, pin-point petechial haemorrhages (on the kidneys)
- Flea-bitten Kidney
Microscopic features:
- Hyperplastic Arteriolosclerosis (Onion skin lesions)
- Fibrinoid Necrosis of Afferent Arteriole
Malignant HTN
————– : Disorders characterised by fibrin thrombi in glomeruli and small vessels, resulting in acute renal injury
Thrombotic Microangiopathies
causes of Thrombotic Microangiopathies
- Childhood Haemolytic Uraemic Syndrome: Intestinal infection with Shiga toxin-producing E. coli; 75% of cases
- Adult Haemolytic Uraemic Syndrome:
- Typical form (epidemic with diarrhoea) -> Shiga-like toxin
- Atypical forms <> Excessive, inappropriate activation of complement by the alternative pathway
- Thrombotic Thrombocytopenic Purpura: Defects in vWF <> Pathogenic auto-Abs directed against ADAMTS 13 (acquired) or mutations in the ADAMTS 13 gene (inherited)
* vWF (von Willebrand factor) -> clotting protein
Light Microscopy:
* Fibrin thrombi in the glomeruli, arterioles and larger arteries
* Possible, presence of cortical necrosis
Electron Microscopy:
* Widening of the sub-endothelial space, in glomerular capillaries
* Duplication or splitting of GBMs
* Lysis of mesangial cells -> Mesangial break-down
Features of?
Thrombotic Microangiopathies
CF of Thrombotic Microangiopathies
Sudden onset, after a GI or Flu-like prodromal episode, of:
* Haematemesis
* Melena
* Severe Oliguria
* Haematuria
* Micro-Angiopathic Haemolytic Anaemia
Thrombotic Microangiopathies progresses into ———— , in children
Acute Kidney Injury
prognosis of thrombotic Microangiopathies
25% of children –> Development of renal
insufficiency, as a consequence of the secondary scarring
Macroscopic Features:
* Symmetrical contraction of the kidneys
* Red-brown and diffusely granular surfaces
Microscopic Findings:
* Advanced scarring and sclerosis of the glomeruli
* Marked interstitial fibrosis
* Atrophy and loss of renal tubules
* Thick-walled and stenosed small- and medium-sized arteries
* Lymphocytic infiltrates
Features of?
Chronic kidney disease
progression of Chronic Kidney disease
End-stage Kidney Disease (sclerosing of all renal structures)
Prognosis of Chronic kidney disease:
If not treated, either with dialysis or transplantation –>
Death from Uraemia (accumulation of toxins in the blood)
Patho of Nephrotic Syndrome
* physicochemical alterations in capillary walls of the glomeruli –> ———-
* Long-standing proteinuria –>———- -> Sever ———
* Hypo-Albuminaemia –> Increased synthesis of lipoproteins and Impairment of peripheral break-down of lipoproteins. -> —–
* Increased permeability of GBM to lipoproteins –> ———
- physicochemical alterations in capillary walls of the glomeruli –> Proteinurea (Severe)
- Long-standing proteinuria –>Hypoalbunaemia -> Sever Oedema
- Hypo-Albuminaemia –> Increased synthesis of lipoproteins and Impairment of peripheral break-down of lipoproteins. -> Hyperlipidaemia
- Increased permeability of GBM to lipoproteins –> Lipiduria
Epi of Minimal-Change disease
* Type of Nephrotic Syndrome
Most common cause of Nephrotic
Syndrome in children (1-7 years)
Light microscopy
* Normal appearance of the glomeruli
* Protein droplets and lipids within the PCT -proximal convoluted tubules
Electron microscopy (Masson’s trichrome dye)
* Flattening of podocytes’ cytoplasm -> effacement (d.t cytokine damage)
* Epithelial cell vacuolisation
* Microvillus formation
* Focal detachments
Features of?
Minimal change disease
CF of Minimal change disease
* Type of Nephrotic syndrome
1) Insidious (slow) onset of Nephrotic Syndrome
2) Albumin selective proteinuria
Macroscopic Features:
* Involvement of some of the glomeruli (focal); initially only the juxta-medullary glomeruli -> With disease progress, all cortical levels
Microscopic Findings:
* segmental glomerular lesions
* Increased mesangial matrix
* Obliterated capillary lumina
* Deposition of hyaline (hyalinosis)
* Foamy (lipid-laden) macrophages
* IF: Non-specific trapping of IgM and complement (C1,C3)
* EM: Effacement of podocytes’ foot processes; similar to Minimal Change Disease
Features of?
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
* ass. w/ HIV and sickle cell disease
Association of FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
- In association with HIV, sickle cell disease
- Secondary event in other forms of GN (e.g. IgA Nephropathy)
- Inherited or congenital forms; Association of
autosomal dominant forms with mutations in
cytoskeletal proteins and podocin
CF of focal segmental Glomerulosclerosis
- Hypertension and haematuria (FSGS>MCD)
- Non-selective proteinuria
progression/ prognosis of Focal Segmental Glomerulosclerosis
Development in 50% of patients –> End-Stage Renal Disease
Children better prognosis than adults
Primary/ secondary Causes of Mebranous Nephropathy
*Type of Nephrotic syndrome
Primary: Auto-Abs that cross-react with
Ags on podocytes (80% of cases)
Secondary to other disorders, such as:
- Infections (Chronic Hepatitis B and C, Syphilis, etc.)
- Malignancies (e.g. Carcinoma of the Lung and Colon, Melanoma, etc.)
- SLE and other Autoimmune Diseases (e.g.Thyroiditis)
Patho of Membranous Nephropathy:
diffuse thickening of the —– and —- caused by subepithelial immune deposits -> Activation of the Complement –> ———— –> Damage of the mesangial cells and ——- –> Loss of slit filter integrity -> ——-
diffuse thickening of the glomerular capillary wall and GBM caused by subepithelial immune deposits -> Activation of the Complement –> C5b-C9 Membrane Attack Complex (MAC) –> Damage of the mesangial cells and podocytes –> Loss of slit filter integrity -> Proteinuria
**
Microscopic Findings:
Light microscopy: Uniform, diffuse thickening of the glomerular capillary wall and BM
IF: Granular deposits of IgG and complement (C5b-C9 -MAC) along the GBM
Electron microscopy:
* Characteristic “spike and dome” appearnace of sub-epithelial deposits
* Irregular dense deposits of immune complexes , deposition between the BM and the overlying epithelial cells
* Effacement of podocytes’ foot processes
MEMBRANOUS NEPHROPATHY
CF of Membranous Nephropathy
- Insidious onset of Nephrotic Syndrome (most cases)
- Non-selective proteinuria
- Haematuria and mild hypertension (15-35% of cases)
Progression and Prognosis of Membranous Nephropathy
- Persistent proteinuria (>60% of cases)
- Progressive disease leading to Renal Failure, after 2 to 20 years (40% of cases)
- Partial or complete remission (disappearnace) of proteinuria (10-30% of cases)
**
MPGN-1 vs Dense Deposit disease
Microscopic features:
Light microscopy:
* “Double-contour” or “Tram-track” appearance of the glomerular capillary wall.
* “Splitting” of GBM
IF: IgG and early complement components.
EM: Discrete sub-endothelial electron-dense deposits.
features of?
Membrano-Proliferative GN type 1
Microscopic Findings (Electron & Fluorescence Microscopy):
* Deposition of dense material of unknown composition (EM)
* Presence of C3 in irregular granular or linear foci in the BM and as mesangial rings in the mesangium (IF)
* Absence of IgG and early complement components (IF)
Features of?
Dense Deposit disease
Common Histopathological Findings among disorders associated with the development of Nephritic syndrome
- Cellular Proliferation within the glomeruli
- Leukocytic inflammatory cell infiltrates –> Damage of the capillary walls–> Passage of blood into the urine (Haematurea) –> Haemo-dynamic changes –> Reduction in the GFR -> Oliguria and Azotaemia, as well as fluid retention (mild oedema) –> increased BP (HTN)
Cause Post-Streptococcal GN
* type of Nephritic Syndrome
~ 2-4 weeks after infection w/ certain “Nephritogeninc” strains of group Α,β-heam. Streptoc.
(infection of pharynx or skin)
* most common in children
**
Microscopic Findings:
-
LM:Glomeruli enlarged and Hypercellular
(in a diffuse pattern : Leukocytic infiltration [neutrophils and monocytes, Proliferation of endothelial and mesangial cells, Crescent formation (severe cases)] - EM: Subepithelial IC “humps”
- IF: Scattered granular appearance “lumpy hump” due to IgG, IgM, and C3 deposits within GBM walls and mesangium
Features of?
Acute Post-streptococal Glomerulonephritis
CF of Acute Post-Infectious Streptococcal GN
Abrupt onset of:
* Malaise
* Slight Fever
* Nausea
* Oliguria and Haematuria (smoky or cola-coloured urine)
* HTN
* Peripheral and periorbital oedema
* Mild Proteinuria
Lab findings of ACUTE POST-INFECTIOUS
(POST-STREPTOCOCCAL) GN
- +ve strep titers (Elevated anti-Streptolysin O Ab-titers)
- ↓ complement levels (C3) due to consumption (during the active phase)
prognosis and progression of Acute post-strep GN
-
>95% of children –> Total recovery, with
conservative treatment - <1% of children –> Development of Rapidly
Progressive Glomerulonephritis -
15-50% of adults –> Development of End-Stage
Renal Disease in the next years
The localisation of Ag, Ab or immune complexes
determines the glomerular injury response:
* Deposits in endothelium or sub-endothelium –> [Inflammatory/ non-inflammatory reaction]?
Inflammatory rxn in the glomerulus with leukocyte infiltrates and proliferation of glomerular resident cells
The localisation of Ag, Ab or immune complexes
determines the glomerular injury response:
* Abs directed to sub-epithelial region of glomerular capillaries [Inflammatory/Non-inflammatory reaction]
Non-inflammatory rxn
