- 14&15

• URINARY SYSTEM


  ● consists of the paired kidneys and ureters, the bladder, and the urethra.

  ● Primary role is to ensure optimal properties of the blood
• GENERAL ROLE OF THE KIDNEYS


  ● Water and electrolyte regulation; acid-base balance ● Excretion of metabolic wastes, excess water, and electrolytes in urine ● Excretion of bioactive substances (e.g. drugs) ● Secretion of renin, a protease important for regulation of blood pressure ● Secretion of erythropoietin, stimulating RBC production in red marrow ● Conversion of vitamin D to the active form 1,25-dihydroxyvitamin D3 or calcitriol ● Gluconeogenesis during fasting state
• Anatomy of KIDNEY


  -bean shaped

  ● With thick outer cortex, surrounding a medulla that is divided into 8-12 renal pyramids; all of these comprise the renal lobe. ● The apical papilla of each renal pyramid inserts into a minor calyx, a subdivision of two or three major calyces extending from the renal pelvis. ● The ureter carries urine from the renal pelvis and exits the renal hilum, where the renal artery and vein are also located.
• NEPHRONS


  ● Functional units of the kidneys

  ● Around 4-5 million each kidney

  ● Major divisions (in order)

  ○ Renal corpuscle ○ Proximal convoluted tubule

  ○ Loop of Henle

  ■ Thin descending limb

  ■ Thin ascending limb

  ■ Thick ascending limb

  ○ Distal convoluted tubule

  ○ Collecting ducts
• Filtration (Renal function)


  water and solutes in the blood leave the vascular space and enter the lumen of the nephron
• Tubular reabsorption (Renal function)


  substances move from the tubular lumen across the epithelium into the interstitium and surrounding capillaries
• Tubular secretion (Renal function)


  substances move from epithelial cells of the tubules into the lumens, usually after uptake from the surrounding interstitium and capillaries
• Excretion (Renal function)


  - filtrate receives various secreted molecules and then enters the minor calyces as urine
• RENAL CORPUSCLE


  Comprises of glomerulus, a tuft of blood capillaries, surrounded by a double-walled epithelial capsule called the Bowman's capsule
• RENAL CORPUSCLE


  ● Inner visceral layer closely envelops the glomerular capillaries

  ● Outer parietal layer forms the surface of the capsule

  ○ Simple squamous epithelium
• Vascular pole


  where the afferent arteriole enters and the efferent arteriole leaves
• Tubular pole


  - where the proximal convoluted tubule (PCT) begins

  ○ Simple cuboidal epithelium
• Podocytes


  apparatus for renal filtration
• Pedicels


  interdigitating processes covering the capillary surface
• Filtration slits


  - spaces between pedicels
• Slit diaphragms


  - bridges of slit pores

  ○ modified and specialized occluding or tight junctions composed of nephrins and other proteins important for renal function
• -Fenestrated capillary endothelium

  -Glomerular basement membrane

  -Filtration slit diaphragms between pedicels


  What are the 3 layers of Glomerular filtration barrier?
• Fenestrated capillary endothelium


  - blocks blood cells and platelets
• Glomerular basement membrane


  - restricts large proteins and some organic anions
• Filtration slit diaphragms between pedicels

  - restrict some small proteins and organic anions
• Glomerular filtration barrier


  Formed by fusion of the basal laminae of a podocyte and a capillary endothelial cell
• Mesangial cells


  - tissue macrophage of the kidney

  ○ have contractile properties and produce components of an external lamina

  ○ Together with their surrounding matrix, comprise the mesangium
• Mesangium


  fills interstices between capillaries that lack podocytes
• Functions of the mesangium

  1.Physical support of capillaries within the glomerulus

  2. Adjusted contractions in response to blood pressure changes

  3. Phagocytosis of protein aggregates

  4. Secretion of several cytokines, prostaglandins, and other factors important for immune defense and repair in the glomerulus
• PROXIMAL CONVOLUTED TUBULE


  Location: Cortex Histological features:

  ● Simple cuboidal epithelium

  ● Cells well-stained, with numerous mitochondria

  Has numerous pits and vesicles near the bases of the microvilli, indicating active endocytosis and pinocytosis

  ● Prominent basal folds and lateral interdigitations

  ● Wth long microvilli that form a prominent brush border that facilitates reabsorption, giving the lumens a fuzz-filled appearance
• PROXIMAL CONVOLUTED TUBULE


  Major Functions:

  ● Reabsorption of glucose, amino acids, most water and electrolytes

  ● Secretion of organic anions and cations, H+ , and NH4 in the peritubular capillaries

  ● Hydroxylation of vitamin D

  ● Production of erythropoietin
• LOOP OF HENLE


  Location: Medulla THIN ASCENDING AND THIN DESCENDING LIMBS

  ● Histological features:

  ○ Simple squamous epithelium

  ○ Few mitochondria

  ○ Lumen is prominent

  ● Main functions:

  ○ Passive reabsorption of Na+ and Cl-

  ● The countercurrent flow of the filtrate (descending, then immediately ascending) establishes a gradient of osmolarity, maintaining the hyperosmotic interstitium
• LOOP OF HENLE


  Location: Medulla

  THICK ASCENDING LIMBS

  ● Histological features:

  ○ Simple cuboidal epithelium

  ○ No microvilli, but many mitochondria ● Main functions:

  ○ Active reabsorption of various electrolytes
• DISTAL CONVOLUTED TUBULE


  Location: Cortex Histological features:

  ● Simple cuboidal epithelium

  ● Cells smaller than in PCT

  ● Short microvilli and basolateral folds

  ● More empty lumens

  ● Fewer mitochondria than PCT Major functions:

  ● Reabsorption of electrolytes

  ○ The rate of Na+ absorption is regulated by aldosterone
• JUXTAGLOMERULAR APPARATUS


  ● forms at the point of contact between the distal tubule and the vascular pole of its glomerulus

  ● Utilizes feedback mechanisms to regulate glomerular blood flow and keep the rate of glomerular filtration relatively constant

  ● JG cells produce renin
• Macula densa


  - thickened region where cells of the distal tubule become columnar
• Juxtaglomerular granular (JG) cells

  - region of cells adjacent to the macula densa where the tunica media of the afferent arteriole is modified to a secretory phenotype, including granules with the protease renin
• Lacis cells


  extraglomerular mesangial cells adjacent to the macula densa, afferent arteriole, and efferent arteriole
• COLLECTING DUCTS


  ● Final site of water reabsorption from the filtrate

  ● Connecting tubule extends from each nephron join together in the cortical medullary rays to form collecting ducts

  ●

  These ducts merge further, forming larger and straighter collecting ducts with increasingly columnar cells, and will form papillary ducts, which deliver urine directly into the minor calyx
• PRINCIPAL CELLS


  ● Histological features:

  ○ Most abundant, cuboidal to columnar

  ○ Pale-staining, distinct cell membranes

  ● Main functions:

  ○ Regulated reabsorption of water & electrolytes

  ○ Regulated secretion of K+

  ● Rich in aquaporins, the integral membrane pore proteins that function as specific channels for water molecules
• INTERCALATED CELLS


  Histological features:

  ● Few and scattered

  ● Slightly darker staining Main functions:

  ● Reabsorption of K+ (low-K+ diet)

  ● Help maintain acid-base balance by secreting either H+ (from type A or α intercalated cells) or HCO3 - (from type B or β intercalated cells)
• urine


  is transported by the ureters from the renal pelvis to the urinary bladder where it is stored until emptying by micturition via the urethra.
• urethra


  Lined by the uniquely stratified urothelium or transitional epithelium, organized as 3 layers:

  ○ A single layer of small basal cells resting on a very thin basement membrane

  ○ An intermediate region containing from one to several layers of cuboidal or low columnar cells

  ○ Dome-shaped umbrella cells - protect the underlying cells against the potentially cytotoxic effects of hypertonic urine
• URETERS


  Histological features: Longitudinally folded mucosa, surrounded by a thick muscularis that moves urine by regular waves of peristalsis. The lamina propria is lined by transitional epithelium or urothelium
• URINARY BLADDER


  Histological features:

  ● Umbrella cells are especially well developed

  ● The thickness of the full bladder's urothelium is half that of the empty bladder (5-7 cell layers vs. 2-3 layers)

  ● Urothelium is surrounded by a folded lamina propria and submucosa, followed by a dense sheath of interwoven smooth muscle layers and adventitia

  ● The muscularis consists of three poorly delineated layers, collectively called the detrusor muscle, which contract to empty the bladder