CASE CONFERENCE 1

RENAL PHYSIOLOGY
CASE:
 An 18 year old man presents with a 2-day history of
reddish-brown scanty urine. He was diagnosed with
streptococcal pharyngitis 2 weeks prior to consult
and was given Amoxicillin. Physical examination
showed bilateral edema (2+). Blood pressure was
160/100 mmHg. Other vital signs were
unremarkable. Urine dipstick detects 3+ blood, 1+
protein, and 2+ for glucose. Urine sediment reveals
12 RBCs/hpf, RBC cast, and dysmorphic RBCs, FBS-
230mg/dL

 DX: NEPHRITIC SYNDROME

OBJECTIVES:
 Discuss the blood supply of the kidney from the renal artery.
 Discuss the presence of glucose in the urine of the patient.
 Discuss the role of immune system in the development of nephritic syndrome
 Explain the occurrence of hypertension in the patient.
 Discuss the filtration barrier.
 Discuss the physiologic basis in the development of edema of the patient in
the case.
Filtration Barriers present in the Glomerulus
Discuss the role of the Immune System
in the development of
Nephritic Syndrome
 Immune System in the development of
Nephritic Syndrome
Patients usually present with a nephritic picture:

✓ Microscopic hematuria or full-blown acute nephritis

✓ Redcell casts
✓ Proteinuria
✓ Edema
✓ Hypertension
✓ Acute renal failure
 Immune System in the development of
Nephritic Syndrome
IN GENERAL
❑ Hypersensitivity disease
❑ Antigen – antibody complexes in the glomerular
basement membrane
❑ Presence of cell surface receptors in the matrix
i.e. nephritis-associated plasmin receptor
❑ Phagocytic property of mesangial cells:
➢ endocytosis of immune complexes
➢ production of reactive oxygen species which cause
injury to the glomerulus
 Immune System in the development of
Nephritic Syndrome secondary to Streptococcal
Pharyngitis
1. Secondary to – “Bacterial infection” with B- hemolytic group A
streptococci (specifically S. pyogenes)
2. Initiated by antigen-antibody complexes in the glomerular basement
membrane
3. SpeB antigen
4. Ska ( streptokinase)
5. Nephritis- associated plasmin receptor
 Immune System in the development of
Nephritic Syndrome secondary to
Streptococcal Pharyngitis
6. Microscopic hematuria/ full blown acute nephritis ( red cell casts,
proteinuria, edema, hypertension and acute renal failure) acute after 10 days
of having streptococcal pharyngitis or 21 days of having streptococcal skin
infections ( impetigo ).
7.Circulating immune complexes with hypocomplementemia
8. Immunofluorescence of kidney biopsy – granular deposition of complements
and IgG in the glomerular tuft.
9. These subendothelial deposits are responsible for complement activation
and influx of inflammatory cells.
 Prominent Protein Antigens

1. Ska ( streptokinase)

2. SpeB
(Ska)Streptokinase

 Cleaves cell – surface bound plasminogen to active

plasmin → plasmin cleaves fibrin to degradation products
(seen in inflammatory processes)
 Not inhibited by endogenous antiproteases: unopposed
formation of fibrin degradation products
 SpeB
 Found in mesangial matrix
 Behaves like cysteine protease – activate endothelial
metalloprotease → TISSUE DESTRUCTION in GBM
 Implicated in signal transduction mechanisms that promote
synthesis of various inflammatory cytokines, vasoactive
substances, and growth factors
 Also bind to plasmin → complex → activation of complement
system
 Attach to nephritis-associated plasmin receptor in GBM
 Superantigen : stimulate T-cell proliferation → excessive
production of cytokines → mediate inflammation and tissue
injury
 Occurrence of hypertension
Piling of inflammatory Decreases GFR
cells, antibodies in
the glomerulus
Reduced delivery of
Sodium to macula
Activating RAAS, densa stimulates
Angiotensin II will be renin secretion
produced causing
vasoconstriction, Sodium
and water retention
Increase in BP
(Hypertension)
What is the physiologic basis in the
development of edema of the
patient in the case?.
 STREPTOCOCCAL INFECTION

CELLULAR
PROLIFERATION IMMUNE COMPLEX FORMATION
ABSORBED IN GLOMERULAR BASEMENT
MEMBRANE
CAPILLARY LUMEN
NARROWS
COMPLEMENT SYSTEM ACTIVATED

GFR LOW
IMMUNE COMPLEXES

DISTAL Na+ GBM FRACTURE

OLIGURIA REABSORPTION

RETENTION OF H2O EDEMA

AND Na+
 Glucose in the Urine

 The amount of glucose reabsorbed by the proximal tubule

is determined by the body's need to maintain a sufficient
level of glucose in the blood.

 If the concentration of blood glucose becomes too high,

the tubules no longer reabsorb glucose, allowing it to pass
through into the urine.
Renal Glycosuria
 Rare condition in which the simple sugar glucose is
excreted in the urine despite normal or low blood
glucose levels.
CORRELATION
• Male/ 18 yr. old
DX: NEPHRITIC SYNDROME
• Dx: Streptoccocal
pharyngitis- Amoxicillin
• Urine Dipstick: 3+ blood
2wks prior check up
• Protein: 1+
• 2-day reddish-brown
• Glucose: 2+
scanty urine
• Urine sediment: 12
• Bilateral edema: 2+
RBC/hpf,
• Blood
• RBC cast
pressure:160/100mmHg
• Dysmorphic RBCs
• FBS-230mg/dL