PATHOLO GY

Renal Diseases
Remedios Adamos- Magkasi, MD, MHPEd, FPSP, FPSMID

Normal Kidney (please refer on separate sheet)

Renal Artery

Anterior branch

Posterior Branch

Interlobar Artery

Arcuate Arteries

Interlobular Arteries Afferent arterioles Glomerulus

Efferent arteriole
TUBULES 1. PROXIMAL CONVOLUTED TUBULE (PCT) Abundant long microvilli, which forms a brush border that partly obscures the lumen and increases surface area available for absorption. Increased Mitochondria, required for the energy-intensive abdorptive function interdigitate with basal membrane infoldings and make the lining cells acidophilic Apical Canaliculi Increased intercellular digitations Reabsorbs glucose, amino acids, vitamins, proteins, acetoacetate, 2/3 of water, 2/3 of sodium

1. JUXTAGLOMERULAR APPARATUS (refer on separate sheet)

2. ASCENDING AND DESCENDING LIMB, LOOP OF HENLE LOOP OF HENLE FUNCTION: A prerequisite for forming hypertonic urine, the loop acts as a countercurrent multiplier to establish an osmotic gradient in the interstitial fluid of the medulla. DESCENDING PART Plays a passive role in making the medullary interstitium hypertonic and helps maintain the gradient. Permeable to both water and salt, although it is more permeable to water. Loses water, may reabsorb some salt from interstitium ASCENDING PART More active role in setting up the gradient and, in particular, making the medullary interstitium hypertonic. Contains NA+/K+/Cl- pump (symporter) that constantly pums these ions (in a 1:1:2 ratio) from the filtrate into the interstitial fluid around the tubules. These symporter thes increases the salt concentration (and tonicity, or osmolarity) in the interstitium. Impermeable to water. Water in the filtrate cannot follow the salt into the interstitium and dilute it. 1. DISTAL COLLECTING TUBULES Acidification of urine (H+) PHYSIOLOGY (refer on separate sheet) FUNCTIONS OF THE RENAL SYSTEM

1. FILTER PLASMA modify filtrate urine

a. Excretes waste material Ex. Urea, creatinine, uric acid b. Control Fluid and electrolyte balance c. Contribute to Acid-Base Balance Controls the synthesis and excretion of bicarbonate and hydrogen ions 1. PRODUCE HORMONES a. RENIN regulates vascular tone increase in blood pressure b. ERYTHROPOIETIN synthesized in the renal cortex by interstitial cells in the peritubular capillary bed 1. MAINTAINS CALCIUM HOMEOSTASIS a. Second hydroxylation of Vitamin D 1-alpha- hydroxylase is synthesized in the proximal renal tubule cells Converts 25-hydroxycholecaliferol to 1,25- dihydroxycholecalciferol a. 1,25 DIHYDROXY VITAMIN D Increases gastrointestinal reabsorption of calcium and phosphorus Promotes bone mineralization; maintains serum calcium PATHOLOGY OF RENAL DISEASES Traditional approach: BASIS morphologic renal components (Glomerulus, tubules, Interstitium, Blood Vessels) Reason: 1. Useful in Diagnosis The kidneys have a large functional reserve and manifest when much damage has occurred

 Early signs and symptoms are important Later, damage to one almost always affect the others 1. Some components are more vulnerable to specific forms of injury Ex. Glomerulus Immune Injury Tubules, interstitium toxic, infectious 2. All forms of chronic diseases will destroy all 4 components End-Stage Chronic Renal Failure

GLOMERULAR DISEASES
GENERAL PATHOGENESIS: Immune Mechanisms 1. IN-SITU/ CIRCULATING ANTIBODY MEDIATED A. Anti-GBM Nephritis Linear Immunofluorescence

B. Heyman Nephritis Granular Immunofluorescence

C. Antibody against planted Antigen Ex. Viral, bacterial, parasitic, drugs

Antigen + Antibody

Antigen Antibody complex

Granular deposits

( by immunofluorescence stain) 1. CIRCULATING IMMUNE COMPLEX (IC) NEPHRITIS trapped in glomeruli a. Exogenous Bacterial products Viral antigen (HsB, HsC) Treponema Falciparum Malaria a. Endogenous auto

Localization a. Large removed by MPS b. Cationic croos GBM subepithelial c. Anionic do not cross GBM subendothelial d. Neutral in mesangium

Immune Complex digested

Subside (limited exposure)

Re-exposed

- show of Ag (SLE, viral hepatitis)

Cycles of IC deposits

Chronic membranous GN

Chronic mem-prolif. GN 1. CYTOTOXIC Ab Mesangial Cells Lysis

Endothelial Cells injury thrombosis Epithelial Cells injury Proteinuria (leakage) 1. CMI sensitized T-Lymphocytes Ex. Anti-GBM Ab initiate / facilitate glomerular injury by activated T cells = Exper. CRESCENTERIC GN 2. ALTERNATE C PATHWAY ACTIVATION MEMBRANO-PROLIFERATIVE GN TYPE II (Dense deposit disease)

Ab + Ag (epithelial cell)

Effaced foot processes Vacuolation detaches from PROTEINURIA

MEDIATORS OF GLOMERULAR INJURY (ACUTE/ CHRONIC INFLAMMATION) 1. CELLS a. PMN, monocytes

b. Macrophages, T-lyphocytes, NK cells c. Platelets d. Glomerular/ Mesangial Cells 1. Soluble Mediators a. Complement b. Cytokines c. Chemokines d. Eicosanoids, No angiotensin, endothelin e. Coagulation system OUTCOME OF RENAL DISEASES

DISEASE

Decreased GFR (30 to 50% of

Progress (constant rate) END-STAGE KIDNEY FAILURE (regardless of stimulus) DIALYSIS TRANSPLANTATIO NN

SECONDARY FACTORS LEADING TO PROGRESSION 1. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) 2. TUBULO-INTERSTITIAL FIBROSIS a. Prevented or delayed HISTOLOGIC CHARACTRISTICS OF RENAL DAMAGE 1. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
Diseased Kid

Affected

Unaffected

Endothelial injury Epithelial Injury (podocytes) Inc. permeability