Renal I(a) Flashcards by Elyaa Saleh

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.

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Clinical Manifestations of Nephritic vs Nephrotic Syndrome.

Note : there is proteinuria and oedema in Nephritic however it’s mild

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Primary Causes of Nephrotic Syndrome

Minimal Change Nephropathy (children)
Focal segmental Glomerulosclerosis
Membranous Nephropathy, etc.
Membrano-proliferative Glomerulonephritis

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secondary causes of Nephrotic Syndrome

Diabetes Mellitus
Lupus Erythematosus
Viral infections, etc.

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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

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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

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CM of Acute Kidney disease

1) Oliguria (low urine) or anuria (no urine)
2) Recent onset of azotaemia

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Causes of Chronic Kidney Disease (Chronic Renal Failure)

1) Diabetes Mellitus
2) Hypertension
3) Glomerulonephritis

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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

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CM of Urinary Tract Infection

Bacteriuria
Pyuria (puss in urine)
Pyelonephritis (kidney inflammation)
Cystitis (inflammation of the bladder)

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CM of Nephrolithiasis

Renal colic (obstruction of urine flow –>pain in the kidney area)
Haematuria, without RBC casts

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Causes of Podocyte injury

Abs against podocyte Ags
Toxins and Circulating factors
Mutations in structural components of slit diaphragm

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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

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CF of Podocyte Injury

Proteinuria

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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

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————- : thickening and sclerosis of arterial
walls and the renal changes associated with benign hypertension

Arterionephrosclerosis

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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

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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

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CF of Arterionephrosclerosis

Loss of concentrating ability or diminished GFR
Mild degree of proteinuria

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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’

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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

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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

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————– : 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**

1. Cellular Proliferation within the glomeruli 2. 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**