GFR : filtration of the plasma per unit per time / perfusion

pressure in glomerural capillaries

Tekanan osmotic : onkotik & hidrostatik

Hidrostatik : dari intravascular ke interstitial.
Normal : protein di darah banyak. Air dikit
Protein di luar dikit, air banyak,
Protein ga bias lewat epitel.
Yang bias lewat Cuma
Colloid osmotic/Onkotik : dari interstitial ke intravascular
Edema is the excessive accumulation of fluid within the
interstitial spaces. Darah> Glomerular filtration > hasil filternya 125ml/menit.
Protein (albumin,dll) : menolak cairan, kalo banyak cairan ga Darah yang filter Cuma 20% doang dari protein darah. 1 hari
bakal datengin dia. Kalo dikit, bakal datengin dia totalnya 180liter. > masuk ke tubular rearbosion diserap lagi Na
Net filtration 􀀝 (Forces favoring filtration) 􀀍 (Forces opposing dll, hasli dari tubular arbosropsi, dia bias 178,5L perhari. Masuk
filtration) ke lengkung henle, akan rearbsopsi lagi akan ada pembentukan
urin yang lebih pekat. Dibagian asending henle, urea bakal
Unilateral : lymph obstruction (cth kaki gajah,ada infeksi, jadi masuk ke urin. > masuk ke tubuus distal, urea dikeluarin, obat2
tersumbat), reaksi alergi, inflmasi yang dieksresi di ginjal dikeluarin, arbsosinya masi ada tapi
Bilateral : hF, sirosis, malnutrisi, fluid water retention karna tinggal banyak . ADH perlu untuk menyerap air lagi > masuk ke
ginjal, lebih ke panyakit sistemik
collecing duct, udah siap di buang. Normal urin perhari 0,5-
1mm/kgbb/jam
Creatinine : fungsi ginjal
The GFR provides the best estimate of functioning renal tissue.
Loss or damage to nephrons leads to a corresponding
decrease in GFR.
The GFR provides the best estimate of functioning renal tissue.
Loss or damage to nephrons leads to a corresponding
decrease in GFR.
Renal Insuffiency : decline in renal function sampai dengan 25%
dari normal. GFR nya 25-30x per menit
Acute renal falilure : sudden decline in renal function with a
decrease in glomerular filtration and accumulation of waste
product in the blood. Ditandai dengan peningkatan plasma
kreatinin dan blood urea nitrogen
Acute kidney injury ada 5 kategori, RIVEL risk (kreatini naik 1,5x,
GF menurun 25%)injury(kreatinin2xnya, GFR menurun 25%)
failure (kreatinin x3 GFR turun 75%)lose (lebih dari 4 minggu)
end state kidney desease (kalo kejadian udah lebih dari 3 bulan)
Chronic kidney failure : progressive renal failure, ada
hubungannya sama systemic syndrome, cth DM , hipertensi,
GFR<60ml/menit selama 3 bulan atau lebih, ga ada penyebab
pastinya, disebut chronic kidney
Stage : kidney damage GFR masi baik2 aja, GFR lebih dari sama
dengan 90ml permenit
2 : penurunan gfr mild , 60-89ml/menit,
3 ; moderate, 30-59
4 severe : 15-29
5 end state : <15
Pathophysiology of proteinuria. Proteinuria is consequence of
two mechanisms: the abnormal transglomerular passage of
proteins due to increased permeability of glomerular capillary
wall and their subsequent impaired reabsorption by the of the indentation after applying pressure are good indications
epithelial cells of the proximal tubuli. of the severity of the pitting edema.

TUBULAR (masalah di tubule intestitinal, keluar dalam low
molecular protein, supaya bias direarbsopsi sama tubu hlagi,
kalua kurang dari 2gram)OVERFLOW(peningkatan produksi dari
low molecular weight protein, cth pada kasus multiple myeloma
dan rabdomyolisis, jumlah melebihih kapasitas proximal tubule,
jadi tetep kebuang, jadi bias toxic ke tubul, jadi Acute kidney
failure) DAN GLOMEROLAR endotelialnya ga bisa maintain
contraction barrier, dipengaruhi sama RAAS (ada demage
patologis di glomerulus, bias juga orang2 yg ga ada pathological
dibagi jadi 2 ortostatik (kalua pasien ga ditemukan proteinuria
pada pagi hari, dan ditemukan low grade protein uri, ditemukan
pada lordosis berat)& tersien(GFK normal, proein kurang dari 1
gram perhari, bias terjadi pada kasus demam tinggi atau
aktivitas yg berat)). Kalua ada pathological demage, ada
nefrotik range lebih dari 3 gram perhari & non nefrotik
(<3,5gram per 24 jam dan muncul terus di tes urin)
Therefore, pitting edemas are graded by this simple
examination. The table below explains the four grades of pitting
edema.
Assessment of Pitting Edema
Grade 1+ Edema: A pit of 2 mm or less; presents as
slight pitting with no distortion. Pitting disappears
immediately.
Grade 2+ Edema:  A deeper pit measuring between 2
mm and 4 mm. It will have no easily discernible
distortion and the pitting will disappear in 10 – 15
seconds.

Grade 3+ Edema: A noticeably deep pit measuring

between 4 mm and 6 mm. The area affected will look
distinctly fuller and swollen. The indentation will take
as long as 1 minute before it disappears.

Grade 4+ Edema: A very deep pit is seen which will last

between 2 to 5 minutes before it disappears. This
indentation will measure 6 – 8 mm in depth and the
body part affected by the edema will look gross and
distorted.

NON piting : limfatik obstruction/lymph edema

The osmotic pressure generated by the swollen lymph nodes

may be responsible for the constant internal pressure pushing
Nilai GFR normal adalah 90 – 120 mL/min/1.73 m2. the fluids against the skin even when pressure is applied on the
affected area.

Pitting edema is mainly caused by complications of vital organs

of the body, such as heart, liver, and kidneys.
Malfunctioning of these organs can cause
retention of fluid in the body.
Regulation of diet, taking prescribed diuretics,
avoiding foods in high sodium and doing
exercises might help reduce pitting edema.
Pitting edema is also observed in edema
patients with rheumatoid-like diseases such as
rheumatoid arthritis and systemic lupus
erythematous. It is also the kind of edema
present in patients receiving intravenous fluids.

The indentation made on the skin when

pressure is applied to a pitting edema is due to
the fluid leaking out of the capillaries into the
subcutaneous tissue. The extent and duration
Non-pitting edema usually affects the legs or arms. If the WHY?
pressure applied to the skin does not result in a persistent o Levels of factors V, VIII, a-macroglobulin,
indentation, this type of edema is referred to as non pitting fibrinogen increased.
edema.  o Levels of factors X, XI and XII, plasminogen
activator inhibitors (PAI), antithrombin III
Non-pitting edema may be caused by certain disorders of the are decreased.
lymphatic system such as lymphedema, a condition of the - Vitamin D Deficiency and Hypocalcemia.
lymphatic circulation which may occur after a congenitally, WHY?
mastectomy, or lymph node surgery.  o 25 – hydroxyvitamin D readily filtered and
lost in the urine.
WEEK 1 – GLOMERULONEPHRITIS - Infection
WHY?
GLOMERULAR DISEASE CAN BE DIVIDED INTO 3 MAJOR o Loss of immunoglobulin and impaired
SYNDROMES: NEPHROTIC SYNDROME, NEPHRITIC SYNDROME, complement cascade.
ASYMPTOMATIC RENAL DISEASE. - Malnutrition
WHY?
NEPHROTIC SYNDROME o Massive proteinuria.
- Anemia: Iron-resistant microcytic hypochromic
In normal condition, only 30 – 45 mg protein excreted anemia.
in urine per day. WHY?
Upper limit of protein excretion is 150 mg/day. o Urinary loss of erythropoietin and
transferrin.
Pathogenesis
- Reflects non-inflammatory damage to the 5 most common primary glomerular diseases with NEPHROTIC
glomerular capillary wall. SYNDROME are:
- Glomerular disease results in proteinuria, a. Membranous glomerulonephritis
alteration in charge or size selectivity of b. Minimal change disease
glomerular capillary wall. This increases c. Focal segmental glomerular sclerosis
glomerular permeability to plasma proteins such d. Membranoproliferative glomerulonephritis (MPGN)
as Albumin, e. Mesangial proliverative glomerulonephritis

Essential Diagnosis: 5 most common secondary glomerular diseases with

- Proteinuria >3.5 g/1.73 m2/24 hours (40 – 50 mg NEPHROTIC SYNDROME are:
mg/kg/day) a. Type 1 and type 2 diabetes
- Hypoalbuminemia b. Systemic myloidosis
- Edema c. Monoclonal immunoglobulin deposition diseases
- Hyperlipidemia d. Systemic Lupus Erythematous (SLE)
- Lipiduria e. Leukimia

Signs and Symptoms: PRIMARY CAUSE OF NEPHROTIC SYNDROME

- Edema occurs initially especially feet and ankles (high
intravascular hydrostatic pressure); periorbital and A. MEMBRANOUS GLOMERULONEPHRITIS
scrotal areas (low intravascular hydrostatic pressure). (MEMBRANOUS NEPHROPATHY)
MAY RESULTS IN SEVERE GENERALIZED EDEMA =
ANASARCA. - Primary MN is immune mediated glomerular disease,
WHY? usually IDIOPATHIC.
o Albumin in tubular lumen increase activity - Secondary MN caused by:
of the Na+ - H+ exchanger in the proximal o Autoimmune disease (SLE)
tubule resulting in increased sodium o Infections (Hepatitis B and C)
absorption -> EDEMA. o Medications (NSAIDs, D – Penicillamine)
o Neoplasias (Colon cancer, kidney cancer)
- Elevated hyperlipidemia and lipiduria.
WHY? PATHOGENESIS OF MN
o Increase synthesis of hepatic proteins in
response to hypoalbuminemia. Immune deposits of Immunoglobulin G and complement to
localizes on the sub - epithelial surface of the glomerular base
- Coagulation abnormalities: Hypercoagulable, causes membrane (GBM).
artery and vein thrombi.
WHY?
Megalin and RAP (Receptor – associated protein). Binding of
both causes activation of the compliment with insertion of C5b
– 9 (Membrane attack complex) to podocyte membrane.

This reaction located on GBM, causes podocyte activation and

signal transduction resulting in increase production of
cytotoxic molecules (cytokines, toxic oxygen, proteases,
vasoactive substances). This results in:
- Excessive synthesis of GBM, progressive tubular
sclerosis -> Reduction of GFR.
- Increases glomerular permeability, causes proteinuria.

NO SYSTEMIC INFLAMMATION REACTION on light microscopy

BECAUSE NO VASCULARIZATION.

MN PATHOLOGY

- IF Microscopy shows IgG and C3 granular pattern along

the epithelial side of GBM (In Idiopathic MN). CLINICAL FINDINGS
- IF Microscopy shows IgG, IgA, IgM. - Men and Women = 3:1
- Idiopathic MN are usually in MIDDLE AGED PERSON
EARLY STAGES (Fourth and fifth decade of life).
- Glomeruli appear normal by light microscopy. - Showing nephrotic syndrome:
- Capillary loops are widely patent.  Edema
- Glomeruli has no increase in cellularity and there is no  Non-selective proteinuria
cellular crowding.  Tendency to thromboembolic
- Proximal tubules remarkable for lipid vacuoles in the disease
cytoplasm and protein casts.  Normal or elevated BP
 Benign urinary sediment
LATE STAGES
- GBM develops a diffuse and uniform thickening on light
microscopy. DIFFERENTIAL DIAGNOSIS:
- Spike pattern on epithelial of GBM. - Minimal change disease
- Focal segmental glomerulosclerosis
LATER STAGES - Membranoproliverative glomerulonephritis type 1 and
- Progressing, capillary lumen narrows. 2
- Glomerulus sclerosis and hyalinization. - Amyloidosis
- Fibrosis and lymphocytes infiltrate are present in - Light chain deposition disease
interstitium. - Diabetic nephropathy
STAGING OF MEMBRANOUS GLOMERULONEPHRITIS
B. MINIMAL CHANGE DISEASE
Nil disease or lipoid nephrosis

PATHOLOGY
- Tubule become vacuolated with lipids because of
lipiduria
- IF (-)
- EM podocytes epithelial foot processes are fused.
- Mesangial deposits of IgG and C3.
Associated with:
- Hodgkin disease
- NSAIDs
- Treatment of melanoma with interferon

PATHOGENESIS
- May result from production of lymphokine that is
toxic for glomerular epithelial cell.