glomerulonephritis /hsum
DESCRIPTION
Pathologic changes Pathogenesis Acute GN Subacute GN Chronic GN Treatment Diagnosis Prognosis Prevention ScreeningTRANSCRIPT
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
www.emedicine.medscape.com
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!