M2PAsysL21 Urinary SystemLect 1:

Review: SF Nephron Kidney

Congenital lesion Cysts Hypertension Infection

Section of Kidney, Calyces and Pelvis of Ureter

Kidney: 150-200g normally (constant regardless of body size) receives 25% of Cardiac Output Bean shaped Main function --- fluid, electrolyte, acid base balance ~ 2000l blood filtered / day ~ 1l urine excreted (1/2000 varies depending on fluid/ solute intake) pyramids (varies from kidney to kidney) medulla collecting ducts cortex PCT, DCT calyx pelvis ureter

Glomerulus Bowman’s capsule (pg 440—Mama) Urinary space continuous and constant distance Podocytes impt for urine formation Podocytes & parietal cells continuous in embryonic development Visceral epitheliation Parietal cells hardly seen in adults except in diseased states Modified capillary bed Supported by mesangial cell (matrix production, stimulated in infection) Ultrafiltration occurs thru BM of vessels & podocytes (+ laminar layer)

Ultrafiltration1) endothelial slits2) BM of endothelium – most impt in selection of leakage of solutes (due to the fact that it’s charged)3) Epithelial slits of podocytes

Diseased states – BM charges changes serum proteins leak out.

Congenital malformation of urinary system

Incidence: in 10% of population (in live births – not all are significant) Renal dysplasias/ hypoplasias account for 20% of chronic renal failure in children [dysplasia: abnormal development, abnormality of the urogenital ridge etc.]

[hypoplasias: -- smaller kidneys, can be unilateral / bilateral -- can be aplasia (absence of kidneys) -- can survive with only one kidney ]

Polycystic kidneys cause for 6% of chronic renal failure in man(dev from birth but manifests later in life)

Development defects: abnormalities in size/ number

Agenesis-- Lack of metanephric primodium ; failure of ureteral bud development ; failure of contact of ureteral bud & metanephros.

Bilateral -Rare. -Male: female = 2.5:1-Still born-Flat nose, wide set eyes, prominent epicanthal folds ; large flabby & low-set ears; receding chin

Unilateral -Male: Female = 2:1

Prune belly at birth (enlarged stomach) implies problem with kidneys

Renal hypoplasia-- Decreased number of lobules of calyces (<5 ; normal 10 or >). Small kidney.

Microscopic: primitive glomeruli & tubules in dense, fibrous / fatty interstitium.

Renal hypoplasia with oligomeganephronia: Kidney small, glimeruli hypertrophied (instead of increasing in number) Number of glomeruli few but large in size Exposed to hyperfiltration (high systemic pressure)

Abnormalites in position / shape

Displacement of kidneys Above pelvic brim junction / in the pelvis Complications : kinking /tortuosity of ureters obstruction with urinary retention Path of ureter altered Commonly seen in perinatal abnormality

Horseshoe kidney Fusation of upper / lower poles -- usually sit on top of pelvic brim Complication: renal calculi Not very common

Cystic disease of kidney

Types of cystic kidney disease Cystic renal dysplasia Polycystic kidney disease

1) Adult polycystic kidney disease --- autosomal dominant disease, manifest in adulthood.2) Infantile polycystic kidney disease --- more rare3) Medullary sponge kidney, nephronophthisis

medullary cystic disease complex4) cystic uremic kidney5) simple renal cysts – associated with some conditions (eg: HPT, in dialysis patients)

Adult polycystic kidney Autosomal dominant. Hereditary order with high rate of penetrance 1 in 400-1000 live births

bilateral renal failure in <2% below 40 years ; rises to 75% by 70 years

(occurs insidiously, with time, usually not before 20 years, can present in many ways) disease occurring at birth but manifests in later life

Genetics of autosomal dominant (adult) polycystic kidney PKD1 gene located on chr 16p 13.3 in >85% of cases, encodes polycystin 1, a cell

membrane associated protein involved in cell-cell & cell-matrix interaction PKD2 gene on chr 4q 13-23 ; encodes polycystin 2, in 10% of families PKD3 gene in minority of cases

Mechanism of cyst formation Non-proliferating cells in cysts in the simplified str. }common, but not usu cause liver Cysts detached from adjacent tubules enlarge by active fluid }failure. Usu benign in behaviour secretion from living cells – progressive esp in adult type. }in these organs. ECM production by cyst lining cells abnormal

Polycystic kidney disease & other congenital abnormalities 40% polycystic liver disease cysts in spleen, pancreas, lungs intracranial berry aneurysms 4-10% associated with adult cystic disease mitral valve prolapse 20-35%

Causes of death chronic renal failure – in adult cystic disease coronary & hypertensive heart disease (40%) due to renal failure

common in adult polycystic disease subarachnoid haemorrhage (15%)

Childhood / infantile polycystic kidney disease rare, autosomal recessive gene serious manifestations at birth infancy renal failure about 80% associated with liver manifestation (eg: congenital hepatic fibrosis)

liver failure, cirrhosis

Polycystic microscopy-- large spaces

Medullary sponge disease cysts located at junction rare disease, not usually asked.

Cystic dysplastic kidney not genetic, due to abnormal development, associated with other systemic symptoms often unilateral, rather than bilateral, involve only certain lobes of kidneys primitive glomeruli, abnormal mesenchyme tubules malformed

Hypertension

1) Essential (1o) HPT – no evident cause, cannot be corrected by surgery; secrete substance that cause fluid retention.

2) 2o HPT – may be due to renal disease, renal cortical and medullary tumours, aortic coarctation, steroid therapy (can be corrected by surgery)

Hypertension further classified dynamically into:1) Benign HPT, in which there is gradual organ damage2) Malignant HPT, in which there is severe and often acute renal, retinal & cerebral damage

vascular tonemacula densa feedback Angiotensinogensym. stimulation

JG cells renin

Angiotensinogen I Angiotensinogen II

aldosterone

BP Na retention

coarctation of aorta – abnormal feedback to kidney -- hypoperfusion

converting enzyme blockers. – used in the treatment of HPT

Effects of HPT

Benign HPT: Myocardial hypertrophy Myocardial dilatation