Urinary System & Kidney Function

• The function of the urinary system is to explain the lobes and lobules of the kidney, list the histological features of the uriniferous tubule structure and describe the structure of the excretory ducts

Functions of the Urinary System

• The urinary system has the essential functions of clearing nitrogenous and other waste metabolic products by filtration and excretion.
• It also balances the concentration of body fluids and electrolytes through filtration and excretion.
• Recovering small molecules, ions, and water by reabsorption helps to maintain blood homeostasis
• Blood pressure is regulated by producing the enzyme renin, which initiates the conversion of angiotensinogen to angiotensin II.
• Erythropoietin, the stimulant of red blood cell production in bone marrow, is produced
• This system activates 1,25-hydroxycholecalciferol, which is a vitamin D derivative involved in the control of calcium metabolism

Kidneys

• The kidneys are situated retroperitoneally on the posterior abdominal wall and are large, reddish, and bean-shaped
• The right kidney is approximately 1 to 2 cm lower than the left due to the position of the liver
• Kidneys measure ~11 cm long, 4 to 5 cm wide, and 2 to 3 cm thick
• The kidney's convex border lies laterally, and its concave hilum faces medially and is embedded in perirenal fat
• At the hilum, the renal artery, renal vein, lymph vessels, and ureter pierce the kidney
• A renal pelvis formation occurs where the ureter expands at the hilar region
• The renal sinus is a fat-filled extension of the hilum deeper into the kidney
• A thin, loosely adhering capsule invests the kidney, mainly consisting of dense, irregular collagenous connective tissue with some elastic fibers and smooth muscle cells

Anatomy of the Kidney

• It is made up of the capsule, cortex and medulla
• The cortex has an outer cortex and juxtamedullary cortex
• Conical masses called renal medullary pyramids form the medulla, and have bases are located at the corticomedullary junction
• A renal medullary pyramid and its associated covering cortical region defines the renal lobe
• Renal columns (of Bertin) are the lateral boundaries of each renal lobe and are residual structures that represent fusion of primitive lobes within the metanephric blastema
• The base of each pyramid is oriented toward the cortex, constituting the corticomedullary border, whereas its apex, the renal papilla, points toward the hilum
• The apex is perforated by ~20 openings of the papillary ducts, also known as ducts of Bellini
• This sieve-like region is known as the area cribrosa
• A cup-like minor calyx surrounds the apex, which, while joining two or three neighboring minor calyces, forms a major calyx
• The renal pelvis is the expanded continuation of the proximal portion of the ureter

Cortex Composition

• Three types of substances may be observed:
  • Red, dot-like granules, the renal corpuscles
  • Convoluted tubules, the cortical labyrinth
  • Longitudinal striations, medullary rays, which are cortical continuations of material located in the renal pyramids
• A renal pyramid, with its associated cortical arch and cortical columns, represents a lobe of the kidney
• The human kidney is a multilobar organ
• Each medullary ray with part of the cortical labyrinth around it is considered a kidney lobule, which continues into the medulla as a cone-shaped structure

Uriniferous Tubules

• The nephron (~1.3 million in each kidney) and the collecting tubule make up the consituents of the functional unit of the kidney, which is modifies bodily fluids to form urine
• The entire uriniferous tubule is epithelial tissue, separated from the connective tissue stroma by a basal lamina occupied by vasculature

Nephrons

• Shorter cortical nephrons are defined as superficial and midcortical, whereas longer juxtamedullary nephrons constitute only of all nephrons
• The structure that is oval to round, is about 200 to 250 μm in diameter, is only found in cortex and consists of a glomerulus and glomerular (Bowman’s) capsule, known as the Renal Corpuscle (Corpusculum Renalis Malpighi)

Glomerulus and Bowman's Capsule

• The visceral layer of Bowman's capsule is in intimate contact with the glomerulus, and is composed of modified epithelial cells called podocytes
• The parietal layer of Bowman's capsule is the outer wall surrounding Bowman’s space (urinary space), and is composed of simple squamous epithelial cells sitting on a thin basal lamina
• The vascular pole is the region where the vessels supplying (afferent glomerular arteriole) and draining (efferent glomerular arteriole) the glomerulus enter and exit Bowman’s capsule
• The urinary pole is the region between the renal corpuscle and the proximal tubule, which drains Bowman’s space
• The efferent glomerular arteriole presents greater resistance to blood flow, resulting in higher capillary pressures in the glomerulus than in other capillary beds
• Filtrate leaking from the glomerulus enters Bowman’s space through a filtration barrier, made up of the endothelial wall of the capillary, the basal lamina, and the visceral layer of Bowman’s capsule

Mesangial Cells

• Located within glomeruli are anastomosing fenestrated capillaries that arise from branches of the afferent glomerular arteriole.
• Mesangial cells replace normal connective tissue cells, and are a specialized cell type that does not enter Bowman's capsule
• There are two groups of mesangial cells
  • At the vascular pole: extraglomerular mesangial cells
  • Situated within the renal corpuscle: pericyte-like intraglomerular mesangial cells
• Intraglomerular mesangial cells are phagocytic and function in resorption of the basal lamina
• Angiotensin II receptors are present, therefore reduce blood flow through the glomerulus
• Along with podocytes and the glomerular basement membrane, they provide physical support to the capillaries of the glomerulus
• With large, ranging between 70 and 90 nm in diameter, and are not covered by a diaphragm, capillaries only act as a barrier to blood that is formed and to macromolecules whose diameter exceeds the size of the fenestrae

Basal Lamina of the Kidney

• The Glomerular Basal Lamina is ~300 nm thick, and consisting of three layers
• The middle dense layer, is about 100 nm in thickness, consists of type IV collagen and is called Lamina densa
• Laminae rarae are less electron-dense layers on either side of the lamina densa composed of laminin, fibronectin, and the highly hydrated polyanionic proteoglycans perlacan and agrin, and rich in heparan sulfate
• Fibronectin and laminin assist the pedicels and endothelial cells to maintain their attachment to the basal lamina

Visceral Layer of Bowmans Capsule

• The visceral layer is composed of large epithelial cells (podocytes), that are highly modified to perform a filtering function
• They house the irregularly shaped nucleus, rough endoplasmic reticulum (RER), Golgi apparatus, and free ribosomes
• There are numerous long cytoplasmic extensions that constitutes primary processes, that follow but usually do not come in close contact with the longitudinal axes of the glomerular capillaries
• Each primary process bears many secondary processes (pedicels), arranged in an orderly fashion, and envelop most of the glomerular capillaries by interdigitating with pedicels from neighboring major processes of different podocytes
• Pedicels have a well-developed glycocalyx composed of the negatively charged sialoproteins podocalyxin and podoendin
• They rest on the lamina rara externa of the basal lamina, though contain no organelles, they house microtubules and microfilaments
• Interdigitation occurs with created narrow clefts, 20 to 40 nm in width, known as filtration slits, remain, but are in such a fashion that between adjacent pedicels
• the slits are not completely open, they are not completely open, and are known as filtrate, which extends between the pedicels and acts as a diaphragm with as membrane

Kidney Filtration

• Fluid leaving the glomerular capillaries is filtered through the fenestrae by the basal lamina
• The lamina densa traps molecules >69,000 Da in size and the polyanions of the laminae rarae prevent the passage of negatively charged molecules hindering their deformation
• Fluid that penetrates the lamina densa must pass through the pores in the slit diaphragm of the filtration slits by way of small molecules, ions, and macromolecules
• If macromolecules are uncharged with a diamtere of ≤1.8 nm they can be filtered
• If uncharged macromolecules are >4 nm they cannot be filtered The fluid entering Bowman’s space is called the glomerular ultrafiltrate
• Mesangial cells trapped by basal lamina undergo continuous phagocytosis and visceral layer of Bowman’s capsule and endothelial cells are then replenished

Kidney Clinical Correlations

• Albuminuria is the result of increased permeability of the glomerular endothelium and is caused by vascular injury, hypertension, mercury poisoning, and exposure to bacterial toxins
• The adjacent pedicels appear to fuse with one another with Lipoid nephrosis, which is the most prevalent kidney disorders in children

Kidney Nephrons

• Bowman’s space drains into the proximal tubule at the urinary pole
• The cells found within have an epithelium and it is part of the cortex and it comes from the loop of henle
• The simple squamous epithelium of the parietal layer of Bowman’s capsule joins the simple cuboidal epithelium with striated border of the proximal tubule, and the tubule constituting much of the renal cortex, has a diameter of ~60 μm and is ~14 mm long
• The tubule has a highly tortuous region, located near renal corpuscles, called the proximal convoluted tubule/pars convoluta, the descending thick limb of Henle’s loop (pars recta), along with a straighter portion, which descends in medullary rays within the cortex, then in the medulla to become continuous with the loop of Henle
• The height of the cells fluctuates and is from a low cuboidal to a high cuboidal epithelium

Functions of the Proximal Tubule

• For the proximal tubule cells 67% to as much as 80% of sodium, chloride (Cl−), and water is resorbed from the glomerular ultrafiltrate and transported into the connective tissue stroma
• All of the glucose, amino acids, and protein in the glomerular ultrafiltrate are resorbed by the vacuolar endocytic apparatus
• Organic solutes, drugs, and toxins that must be rapidly excreted from the body are eliminated by the proximal tubule

Thin Limbs of Henle's Loop

• The thin limb continues as the pars recta of the proximal tubule continues and has a has overall diameter of 15 to 20 um, is composed of squamous epithelial cells that possess an average height of 1.5 to 2 um
• Thin segment length varies with its location in the nephron In cortical nephrons, the thin segment measures 1 to 2 mm long or may be absent

Thin Segments

• Length differs depending on location of the nephron
• In cortical nephrons, are extremely short with a length of 1 to 2mm or completely absent
• In juxtamedullary, have hairpin loops and have much longer thin segments, with 9 to 10 mm long, that extend deep into the medulla down to the renal papilla
• Descending thin limbs contain aquaporin water channels and is highly permeable to water, and is also permeable to urea, sodium, chloride, and other ions

Distal Tubules

• The distal tubule is subdivided into the pars recta,(the ascending thick limb of Henle’s loop), the pars convoluta (distal convoluted tubule), and a modified region of the distal tubule (macula densa), interspersed between the thick limb
• Epithelial cells of the ascending thick segment have a centrally placed, round/oval nuclei and a few club-shaped, short microvilli

Ascending Thick Limb

• Not permeable to water or urea
• Cells have chloride (and perhaps sodium) pumps that function in the active transport of chloride (and sodium) from the lumen of the tubule
• The kidney’s filtrate reaches the cortex within the lumen of the distal tubule, its salt concentration is low and its urea concentration remains high
• Manufacture Tamm-Horsfall protein: which is release into the lumen of the thick ascending limb is intended to prevent the formation of kidney stones.

Macula Densa Structure and Function

• As the distal tubule’s ascending part passes alongside the renal corpuscle is between the afferent and efferent glomerular arterioles
• The location of the macula densa, is composed of short, closely compacted cells
• It probably monitors the filtrate volume and sodium concentration. If the sodium is below a certain thershold, it will dilation of the afferent glomerular arterioles, thus increasing blood flow back into the glomerulus, and signal the juxtaglomerular cells to release th enzyme renin into circulation

Distal Tubules

• The lumina of distal tubules are wide-open: the granular cytoplasm of the low cuboidal lining epithelium is paler than that of proximal convoluted tubules
• Any section of the kidney cortex has presents >X cross sections of proximal convoluted tubules than X sections of distal convoluted tubules because distal convoluted tubules are shorter
• On each renal corpuscle the ratio of cross sections proximal to distal is usually 7:1

Distal convoluted tubule

• Similar to the thick ascending limbs, the distal convoluted tubule is impermeable to water and urea
• High Na+,K+-ATPase activity drives sodium-potassium exchange pumps
• The response to the hormone aldosterone helps resorb most of the remaining sodium and passively, chloride passively from the lumen of the tubule into the renal interstitium
• In addition, potassium and hydrogen ions are actively secreted into the lumen, thus controlling the body’s extracellular fluid potassium level and the acidity of urine

Juxtaglomerular Apparatus (JGA)

• Made up of the macula densa , juxtaglomerular cells of the adjacent afferent (and occasionally, efferent) glomerular arteriole and extraglomerular mesangial cells
• Juxtaglomerular: modified smooth and contains the proteolytic enzyme
• The cells have a special geographical relationship because of a basal lamina that allows close contact between the cells of the macula densa and the juxtaglomerular cells

Collecting Tubules

• Collecting tubules, composed of a simple cuboidal epithelium
• Convey and modify the ultrafiltrate from the nephron to the minor calyces of the kidney
• Do not constitutes a part of the nephron, and have different embryological origins
• Distal convoluted tubules of X nephrons join to form a short connecting tubules leading to each of the
• About 20 mm long and possess the following 3 regions: the corticol, medulla and papillary regions

Cortical Collecting Tubules

• These are found in medullary rays
• Consist of cuboidal cells and have two types of known cells: - Principal cells: consist of centrally located nuclei, a few small mitochondria, and short, sparse microvilli, and membranes that display numerous infolds, and ADH sensitive Aquaporin 2 - Intercalated cells: display numerous apical vesicles, abundance of mitochondria, and a nuclei that is round and centrally located -Two types of such exist: Type A (Luminal membrane possesses H+-ATPase that transports +H in the tubule and helps urine to become acidic ), and Type B (basolateral membrane that functions to resorbed and secreting HCO3-)

Tubular Confluence

• Medullary collecting tubules have a larger caliber because they are formed by the union of X cortical collecting tubules

Cortical Collecting tubules & Papillary Collecting tubules

• These contain two cell types known as the Prnciple, and Intecalated cells
• Consisting of principal cells the tubule cells can only be located in the medulla’s inner zone
• Confluence with medullary collecting tubs to form papillary collecting tibules (ducts of Bellini)
• Tubules have larger ducts, 200 to 300 um: open at the area cribrosa of the renal papilla to deliver X product into the minor calyx lined with tall columnar principal cells only
• Collecting tubules are known to be normally impermeable to water unless the presence of ADH makes them permeable to water and urea Therefoe urine tends to be abundant, and hypotonic while adH makes urine smaller and concentrated

Renal Interstitium

• Renal Interstitium has the following features: the dense but irregular capsule made out of collagenous fibres and with a lack of the attachment of blood vessels
• In the cortex most connective tissue has connective tissues and the basement membranes, with fibrocytes-cellular components
• In the medulla and with in the uriniferous tubules there are the 3 kinds of cells known as fibro blasts, Macrophages, and instestital cells.
  • Interstitial cells between the ducts of Bellini have elongated nuclei and numerous lipid droplets.