Glomerulonephritis /HSUM

GLOMERULONEPHRITISMUNKHTULGA G.

CONTENTS Structure and functions of glomeruli Introduction of Glomerulonephritis /GN/ Prevalence Etiology and risk factor Classification and types Pathogenesis and pathologic changes Clinical features and symptoms Diagnosis Treatment Differential diagnosis Complications Screening Prevention Reference

Anatomy

Structure of glomerulus

Ultrafiltrate

Pressure Range /mmHg/

Hydrostatic 60-90

Oncotic 25-30

Glomerular capsules 10-20

JuxtaGlomerularApparatus - JGA

Lacis cells –Гурмагтиг

Introduction of Glomerulonephritis /GN/

GN is group disease of glomerulus, an inflammatory process that involves glomerular structures, caused by immune disruption, is the leading cause of renal interstitial tissue damage.

Prevalence 2-7% of internal patients have GN.

Etiology and risk factor

Exogenic Endogenic

- Infectious- Bacterial /β-streptococcal-

1, 4, 12, 18, 25, 55, 60; staphylacoccal, pneumococcal/

- Viral- Non-infectious /sulfanylamid,

penicillin, iodine, mercury, brome, aspirin . . ./

- HLA - A2, BW 35, B7, B8, B15- Cancer, tuberculosis …- Disturbance of T/B lymphocyte

ratio- Congenital deficiency of T

lymphocyte- Deficiency of complement

synthesize- Auto-antigen

“Бөөр судлал” Гэлэгжамц.Х нар

ClassificationBy clinical and disease progress Acute GN

o Nephrotic Acute GN /minimal GN/o Nephritic AGNo Classical type

Rapidly progressive GN /Crescentic GN/ Chronic GN

o Latent Chronic GNo With Hematuriao Nephrotic CGNo Hypertensive CGN

“Бөөр судлал” Гэлэгжамц.Х нар

Classification

Source: Robbins & Cotran Pathologic Basis of Diseases

Pathogenesis Auto-Antibody/autoimmune/ - In situ Immune complex

Pathogenesis

Immunofluorescence microscopy /in situ GN/

Granular, IC deposition Linear, IC deposition

Glomerular Filtration Rate (GFR)

Collect patients 24 hours urine Fasting blood test

Ucr – Urine creatinineV – Volume of urineScr – Serum creatinine

90-120 mls/min/1,73 m2

NEPHROTIC vs NEPHRITIC

Nephrotic syndrome Nephritic syndrome

Proteinuria >3,5 g/l Hematuria

Lipiduria, hyperlipidemia Cylinderuria

Hypoproteinemia, Hypoalbuminemia

Leucocyturia, Glucosuria, Ketonuria,

Edema Hypo-Hyperstenuria …

1. Minimal changes GN By far the most common cause of nephrotic syndrome in

adolescent Declining to about 25% of cases of nephrotic syndrome in

older adults

Lesion of podocytes constitution GBMs charge changed No depositions in GBM Present with nephrotic syndrome No RBC and WBC in urine

2. Mesangial proliferative GN

Most common glomerular disease worldwide, is IgA nephropathy (Berger’s disease)

Mesangial widened Mesangial cells proliferation Mesangial matrix concentration

Hematuria, some times flank pain, Hypertension is common Nephrotic syndrome is uncommon 30% progressive renal failure

2. Mesangial proliferative GN

IC accumulated in mesangiocyte & endothelium mesangium thickened

IgG, IgA, C3

Berger’s disease Etiology is unknown

3. Membranous GN Sub-epithelial immune deposits, thickened GBM Most common cause of nephrotic syndrome in

adults

Prognosis: 25% End stage renal disease over 25 years 25% spontaneous remission

4. Focal segmental GN Second most common cause of nephrotic

syndrome in adults

Prognosis: Up to 75% develop progressive renal failure over 20 years.

5. Membranoproliferative

GN

Prognosis: 50% End stage kidney failure over 20 yearsThere is no effective therapy

Difference

5. Membranoproliferative

GN

Type 1 Type 2

Conclusion of pathologic changes

1. Acute GN2. Membranous

GN3. Membrano-

proliferative GN

4. Mesangial GN or IgA GN

Acute GN Glomerulonephritis is an inflammatory

process affecting primarily the glomerulus, with infiltration and proliferation of acute inflammatory cells.

These are principally mononuclear cells and neutrophils in post-infectious glomerulonephritis.

Acute GN The inflammation is immunologically mediated

with immune deposits in the glomerulus. Onset of symptoms is usually acute.

Usually Acute GN occurs after upper respiratory tracts infection, 10-21 days.

Children and guys

Acute GN - Causes

1 Infectious

* Post streptococcal GN

* Non-streptococcal

GN

1. Bacterial: endocarditis, pneumococcal pneumonia, meningococcecemia

2. Viral: B, C hepatitis, салхин цэцэг, Коксаки

3. Parasite: mosquito, malaria, toxoplasmosis

2 Systemically disease: SLE, RA, Schonlein-Henoch vasculitis

3 Primary renal disease: Mesangial capillary GN, Berger’s disease, Mesangial proliferative GN

4 Холимог: serum disease, Гийен-Баррын хам шинж

A groups, 4, 19, 25, 49 β hemolytic streptococcal angina“Бөөр судлал” Гэлэгжамц.Х нар

Clinical features of Acute GN

Acute Nephritic syndromeo Hypertension /Hypervolemia, hyperhydration/o Hematuriao Swelling, urine volume ↓

Facies nephritica Dry skin /lose nutrient/ Striae distansae Fragile nail and hair Swelling weakness, anasarca Edema Face, back around, abdomen, genital

organ

Complains Tachypnea, Palpitation, Loss of appetite Tympanitis Thirst Oligo-anuria Weakness

Classification of Acute GN

Presented with nephritic syndrome Classical type of AGN Presented with nephrotic syndrome

1. Acute GN with nephritic syndrome

Slowly beginning Puffiness around the eyes and face Flank pain Usually no urine color changes Symptoms are Latent chronic nephritis Mild hypertension /70-80%/ Proteinuria less than 1 gr/l RBC, cylinder is seen in the urine Macrohematuria occurs in few cases

2. Classical type of AGN

Acute Nephritic syndrome is clear GFR ↓ Sodium reabsorption in tubule ↑

Nephritic edema Imbalance of water-salt exchange Nephritic edema level < Nephrotic edema level Arterial Hypertension 140/100 – 170/110 ↑ Palpitation, tachypnea, left ventricle failure Proteinuria 1-3 gr/l Urine volume ↓

Heavy condition: pre-eclampsia, eclampsia, acute kidney and heart failure

3. Acute GN with Nephrotic syndrome

Proteinuria >3gr/l per day Decreased protein in blood serum oncotic

pressure ↓ Edema Anasarca Foam in urine (slowly removed) Hyperlipidemia No hematuria Arterial hypertension is rare

Complications of Acute GN

Acute Heart failure Eclampsia Nephrotic crisis Acute renal failure

Diagnosis of AGN After 14-21 days of angina and other infections,

young people could have acute nephritic syndrome and backache.

Important things:o Never had renal diseaseo Never had changes in the urinalysis

In urinalysis:o Proteinuria 1-3 gr/l [in heavy case: 3-20gr/l]o Detected erythrocytes, few leucocytes/lymphocytes/ and

cylinderso Specific gravity is normal [during excess proteinuria

SG ↑]

Laboratory changes CBCC /Complete Blood Cell Count/

o Decreased hemoglobin /water accumulated in body then it leads dissolved blood/

o Lightly increased WBC, УЭТХ ↓ Blood Function Test

o During nephrotic syndrome, Serum protein and albumin ↓

o γ-globulin↑, disproteinemiao Lipid and cholesterol ↑o C3 ↓, after 6-8 weeks becomes normalo GFR slightly ↓ o During heavy acute nephritis, serum creatinine, urea,

leftover nitrogen ↑

Laboratory Scan tests: Fundus photography:

o Arterial hypertension arterioles constricted, bulbous n. opticus swollen and stroke

Ultrasound: o Renal size is normal or little enlarged.

Necessary tests Urinalysis, identify: protein in daily urine CBCC: Hgb Хоолойн арчдас авч, нян ургуулах BFT: total protein, protein group, total lipid,

cholesterol, leftover nitrogen, creatinine, K+ Na+ C-reactive protein

Coagulogram: protrombin, fibrinogen Immunology: ЦИК, IgA, M, G, complement, T, B

lymphocytes Renal ultrasound: Size, cortex thick Renal biopsy Fundus photography, chest x-ray, ECG

Differential diagnosis – Acute GN

Chronic GNo Whether patient had renal disease or urine changeso After grater influenced, GNs symptoms and edema increased

within short termo During Chronic GN, urine changes keeps for long termo Arterial hypertension increased, constantlyo GFR ↓ - constantly, irreversible o Ultrasound: Parenchymal dense ↑, kidney size normal or small

Pyelonephritiso Dysuria, чинэрч өвдөнө, шээлэйн дагуу дамжиж өвдөнөo Fever, loss of appetite, weaknesso Palpate or push to Angle cost-vertebral/Symptom Pasternatski/:

Clearo Urinalysis: Protein 0,5-1,0 gr/l, leucocyte and bacterium +

Treatment Administrate to hospital for 30 days Keep treatment for 3 months to 1 year In not heavy case: symptomatic therapy for 14

dayso Anti-infection treatment: if it caused by infectiono Immunosupressant: if immune activation is high or heavy

nephrotic syndrome

General principle of treatmento Regimeno Dieto Drugo Sanatorium care

Acute GN - Treatment Bed rest or decubitus for 14-21 daysDiet: First 1-2 days restraint food, only given apple,

fruit juice & rice glop Next 5-7 days, limited animal protein 0,5 gr/kg,

only use non-animal protein After 10 days, protein 1gr/kg Kcal – 2300-2800 kcal No salt /2-3 week/

Acute GN – Drug treatment

Post-streptococcal: o Хагас нийлэг penicillin oxicillin, amoxicillin – 1-2 mill

U/dayo Penicillin G 1-2 mill U/day by injectiono Vitamin C oral or inject

Keep symptomatic treatment for 2-6 months Immunosuppressant/if there is no result >2 months/:

o During nephrotic syndrome, prednisone 0,8-1,2 mg/day, slowly decrease dosage by clinical and laboratory changes

o Keep treatment for 6 months to 1 yearo If patient can’t use glucocorticoid, We can use cytostatic

drugs

Acute GN – Drug treatment

Improve renal blood supply:o Heparin 15000-20000 ED/dayo Anti-aggregant: Curantil 200-300 mg/day for 2-4 months

by slowly decrease dosageo Nicotine acid 1%

Anti-hypertensive and diureticso Anti-hypertensive drugs /6 groups/o Diuretics: Thiazides – furosemide 20-80 mg/day 2-3

times

Screening Under doctors control for 2 years Avoid manual labor about 1 year Second prevention!!! Urinalysis - every 3 months Blood function test – every 3months Zimnitskii, Reberg’s test and isotopic renogram -

every 1 year If there was no deterioration or were no changes

in analysis in 2 years we will suggest that the patient is recovered

Rapidly progressive GN Rapidly progressive glomerulonephritis (RPGN) is a

syndrome associated with severe glomerular injury and does not denote a specific etiologic form of glomerulonephritis. It is characterized clinically by rapid and progressive loss of renal function associated with severe oliguria and signs of nephritic syndrome; if untreated, death from renal failure occurs within weeks to months.[7]

The U.S – 7:1,000,000 The U.K – 2:100,000 Male : Female – 1:1 2-92 age

Classification of RPGN

Rapidly Progressive Glomerulonephritides

TYPE I (ANTI-GBM ANTIBODY)

Renal limitedGoodpasture syndrome

TYPE II (IMMUNE COMPLEX)

IdiopathicPost-infectious glomerulonephritisLupus nephritisHenoch-Schönlein purpura (IgA nephropathy)Others

TYPE III (PAUCI - IMMUNE)

ANCA-associatedIdiopathicWegener granulomatosisMicroscopic polyangiitisSource: Robbins & Cotran Pathologic Basis of Diseases

Pathologic change

Clinical signs & Diagnosis

Hematuria Edema acute Arterial hypertension

After 2-3 months:o Azotemiao Anemia

RENAL BIOPSY

Treatment of RPGN 4 complexes treatment:

o Hormoneo Cytostatico Plasmophoresiso Hemosorbtive

2nd combination treatment

Chronic GN Nearly all forms of acute glomerulonephritis have

a tendency to progress to chronic glomerulonephritis. The condition is characterized by irreversible and progressive glomerular and tubulo-interstitial fibrosis, ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy, the net results are chronic kidney disease(CKD), end-stage renal disease (ESRD), and cardiovascular disease.[10]

Etiology

Etiology Exogenic Endogenic

Immunogenic Non-Immunogenic

o Renal functiono Circulatoryo Coagulationo Metabolism

Pathologic change

Classification

By Clinical Latent CGN

o CGN with Proteinuriao CGN with Hematuria

Nephrotic CGN CGN with arterial hypertension CGN холимог хэлбэр

Nephritic syndrome

CGN with proteinuria Only Urine changes No complains, No urine color & volume changes In few case: swelling Urinalysis:

o Protein less than 3 gr/lo Erythrocytes and cylinder is seen

Renal functions measurements keep normal range foe 20-30 year

CGN with hematuria Usually occurs children, young people Hematuria Decreased blood in urine within few days Protein in urine: 1-2 gr/L Old erythrocytes and cylinder in urine No renal pain, no edema, no hypertension Disease progress: 30-40 years

Nephrotic CGN Dry skin Urine has foam Daily urine volume ↓ First, puffiness around the eyes and face, Then, anasarca Sometimes, fluid accumulated in organ that has

cavity Loss of appetite Sensitive to cold Proteinuria: 3,5-20 gr/l Anemia

Complications of Nephrotic CGN

Complication of infection /immune weakness/ Fluid accumulation in thorax leads wound(pus) Pneumonia Urinary tract infection Venous thrombosis Tingle around kidney Blood pressure ↓ Acute Renal failure Nephrotic crisis fever, nausea, vomiting, tingle

around abdomen, detected symptom of peritonitis

Hypertensive CGN High blood pressure Nephritic syndrome Initial phase – normal blood pressure Deterioration period – high blood pressure Headache, dizziness, worsen eyesight, pain

around the heart. 2nd sound loudly around the aorta and systolic

clamor Left ventricle hypertrophy, arhythmia/heavy case/ Urinalysis: 1-3 gr/l protein, few erythrocyte &

cylinder BFT: Lipid↑, cholesterol↑

Холимог CGN Hypertension + Nephrotic syndrome Swelling, hypertension Complication: After 3-5 years Renal failure

Pathophysiologic results

Decreased production of erythropoietin, thus resulting in anemia

Decreased production of vitamin D, resulting in hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, and renal osteodystrophy

Reduction in acid, potassium, salt, and water excretion, resulting in acidosis, hyperkalemia, hypertension, and edema

Platelet dysfunction, leading to increased bleeding tendencies

Diagnosis After deteriorate, suddenly swelling During deterioration: Urine changes ↑, long term Ultrasound: shallow parenchyma, kidney size ↓

Necessary test:o CBCC, Urinalysiso Identify protein in daily urineo Ничепоренко, Аддис-Каковскийн сорилo Зимницкийн сорилo Blood function test: Total protein, proteins group, lipid,

cholesterol, creatinine, BUN, leftover nitrogen, K, Na, Ca, P

Differential diagnosis Cystitis Renal tuberculosis Hereditary nephritis Chronic Pyelonephritis:

o Urine color and odor changes, smoky urineo Neutrophilic leucocyturia and microbe in urineo Fever, pain around kidneyo Scan test: Detected calyx and pelvis changes

Acute GN ??? Interstitial tissue and tubular nephritis/toxicosis/

Treatment During deterioration, administrate to hospital for 14-30 days

Regimen and nutrient therapy Pathophysiological treatment

o Glucocorticoid – Prednisone 1mg/kg for 2-9 weekso Cytostatic – Имуран/азатиоприн/ 100-150 мг,

циклофосфамид 2-3 мг/кг/өдөрo Anti-coagulant – Heparin 10,000-40,000 U/dayo Anti-aggregant – Дипиридамол/курантил/ 225-400

мг/өдөрo Anti-hypertensiveo Symptomatic

Specific therapy for each types of CGN

Regimen and nutrient Bed rest or decubitus for 2-3 weeks Nephrotic, Hypertensive GN:

o Protein 0,5 gr/kg, after 3rd week 1 gr/kgo Hyperproteinuria, hypoalbuminemia : add egg, fish,

chickeno 2800-3000 kcal/dayo Apple, banana, cream, honey, jam – allowo Parching, grilled, preserved products, spicy… - Not-

allowedo Salt decrease about 2-3 gr hypertension

Stages of Chronic kidney disease

Stage

GFR mL/min

The action plan

1 ≥90 Diagnosis and treatment, Treatment of comorbid conditions, Slowing of the progressing of kidney diseaseReduction of cardiovascular disease risks

2 60-90 Estimation of the progression of kidney disease

3 30-59 Evaluation and treatment of complications

4 15-29 Preparation for renal replacement therapy

5 - Kidney failure, Kidney replacement if the patient is uremic

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Screening & Prevention

Urinalysis – every 3 months BFT – every 6 months On time treatment:

o Respiratory tract infectiono Every deterioration of CGN

References1. Бөөр судлал, Гэлэгжамц.Х, Ариунаа.Т нар, 2010 он2. Color atlas of pathophysiology, Silbernagl et al. 20003. Color atlas of physiology, 5th edition Agamemnon

Despopoulos et al. 20034. Clinical nephrology, Woo Keng Thye, 19985. Fox: Human physiology, 8th edition, 20036. Harrison's Principles of Internal Medicine, 17th edition7. Pathologic Basis of Disease, Robbins & Cotran, 8th edition,

20098. Pathophysiology: Concepts of Altered Health States, Carol

Mattson Porth, 7th edition, 20049. Textbook of medical physiology, 11th edition Guyton & Hall,

200610. www.emedicine.medscape.com

Thanks for your attention!