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Summary PBC Part 2
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Summary from all the Chapters in Boron that needed to be read for the SSAs (Ch34-40) including useful illustrations.
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TEST BANK FOR MEDICAL PHYSIOLOGY, UPDATED, 2ND EDITION, WALTER F. BORON, ISBN-10: 1437717535, ISBN-13: 9781437717532
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PHYSIOLOGY BASIC CONCEPTS PART 2Theme A Kidney Anatomy
SSA 2.2 Microscopic anatomy of the kidney
The urinary system consist of the kidneys, the ureters (kidney to bladder), the bladder and
the urethra (from bladder to outside).
The kidneys play an important role in the maintenance of homeostasis by conserving water,
electrolytes and metabolites. This is also important to regulate the acid-base balance and
thus the pH. They regulate the composition and volume of the body fluids. Waste is removed
from the body by filtration and then excretion. They are very vascular and receive around
25% of the CO.
The excretion process begins in the filtration apparatus in the glomerulus. A glomerular
ultrafiltrate is then produced which is modified by selective resorption and specific secretion.
The final urine then consists of water, electrolytes, waste products (like urea, auric acid and
creatine).
Besides this, the kidney is also an endocrine organ. It can produce EPO, renin and convert
inactive vitamin D into its active 1,25-(OH)2 D3 form. This is regulated by PTH that stimulates
the activity of 1α hydroxylase.
General structure
The kidneys are around 10 cm long and 6.5 cm wide.
On the upper poles are the adrenal glands that are
embedded within renal fascia and a protective adipose
tissue layer. The medial border contains a deep
vertical fissure, the hilum, through which the vessels
and nerves run. Also the renal pelvis, which is an
expansion where the ureter origins. The renal sinus is
the space in which these lie. Moreover, it contains the
urine filled major and minor calyces and the renal
pelvis.
The kidneys' surface is covered by a connective tissue
capsule that consists of an outer fibroblast/collagen
layer and an inner layer with myofibroblasts. These are
contractile and may aid in the resistance of the volume and pressure variations. It also goes
into the hilum to cover the sinus and forms the walls of the calyces and the renal pelvis.
The kidney itself also consist of two layers the cortex and the medulla. 90-95% of the blood
goes to the cortex and 5-10% to the medulla. The cortex consists of corpuscles with the
convoluted and straight tubules of the nephron, connecting tubules and collecting ducts that
have extensive vascular supply. The nephron is the functional unit. The renal corpuscles are
the beginning of the nephron on contain a capillary network, the glomerulus. The cortex also
has medullary rays of Ferrein. Each medullary ray is an aggregation of straight tubules and
collecting ducts. The medulla mainly consists of the straight tubules, collecting ducts and the
vasa recta that accompanies them. This vasa recta is part of the countercurrent exchange
system that regulates the concentrations of urine. The tubules in the medulla sometimes also
, form pyramids. The apical portion is the papilla that
represents an extension of the renal pelvis. The tip, the
area cribrosa is perforated by the opening of the
collecting ducts. Each pyramid has an outer and inner
medulla. The outer medulla is divided into and inner and
outer stripe. Renal columns of Bertin is a cap of cortical
tissue that extends into the medulla.
1 - Renal corpuscle with glomerulus and Bowman's
capsule
2 - Proximal convoluted tubule
3 - Proximal straight tubule
4 - Descending thin limbs
5 - Ascending thin limb
6 - Thick ascending limb (distal straight tubule)
7 - Macula densa
8 - Distal convoluted tubule
9 - Connecting tubule
10 - Cortical collecting duct
11 - Medullary collecting duct
Each medullary pyramid and the cortical tissue surrounding it constitute a lobe. The lobes
are further divided into lobules that each have a central medullary ray. The borders between
the lobules are not clear. However, the concept is of physiological importance as the
medullar ray with its collecting duct forms a group of nephrons that drain in it. It is a renal
secretory nit.
The nephron
Nephrons are responsible for the production of urine. The collecting ducts are responsible for
the final concentration. The nephrons consist of a renal corpuscle and a tubule system. The
renal corpuscle is the beginning and has the glomerulus that is surrounded by Bowman's
capsule. Here, blood undergoes filtration to produce the glomerular ultrafiltrate. The
glomerular capillaries have an afferent and efferent arteriole. The site where these penetrate
the Bowman's capsule is the vascular
pole. The other site is the urinary pole
where the proximal convoluted tubule
begins.
The distal convoluted tubule connects
to a cortical collecting duct. These
continue into the medullary
connecting ducts that empty into the
papilla.
The proximal convoluted tubules
originates from the urinary pole of the
Bowman's capsule. It goes to the
medullary ray and continues as the
proximal straight tubule. The thin
descending limb is a continuation of
,this within the medulla. The thin ascending limb is after the hairpin. The distal straight tubule
ascends through the medulla and then enters the cortex in the medullary ray to make contact
with the vascular pole. At this point there is a macula densa. The distal convoluted tubule
forms the cortical labyrinth. At the termination it empties into the cortical collecting duct that
lies in the medullary ray via a connecting tubule. The loop of Henle is a U-shaped portion of
the nephron and consists of the thin descending and ascending segments.
The collecting ducts begin in the cortex and then go to the medulla via the medullary rays.
They are then medullary connecting ducts. These travel to the apex of the pyramid to merge
into the papillary ducts of Bellini that open into the minor calyx. The area cribrosa the are on
the pillar containing the openings.
Superficial nephrons have short loops that extend to the boundary between the outer and
inner medulla. The juxtamedullary nephrons have long loops and play a role in the
production of the concentrated urine.
Filtration apparatus
The renal corpuscle contains the filtration
apparatus and it consists of the glomerular
endothelium, the underlying basement
membrane and the visceral layer of the
Bowman's capsule. The endothelium of the
glomerular capillaries have fenestrations
without diaphragm. They have a low ow
AQP-1 water channels that allow the fast
movement of water. The GBM. is thick and
stains good with PAS. It consists of type IV
collagen, laminin, nidogen and entactin
together with heparin sulfate proteoglycans
and multiadhesive glycoproteins. The visceral
layer of the Bowman's capsule has podocytes
(visceral epithelial cells). They have
processes that go around the capillaries.
They form foot processes. Between these
processes are filtration slits of around 40 nm.
They have a ultrathin filtration slit diaphragm.
An important structural protein in this is
nephrin.
The endothelial surface and the subpodocyte space make an important contribution to the
overall glomerular function as well. The endothelial surface layer has an extensive
glycocalyx. The subpodocyte space may play a role in the regulation oft eh glomerular fluid
flux.
The GBM is a physical barrier and an ion-selective filter. The GBM has different components:
− Lamina rara externa; adjacent to the podocyte processes. Impedes passage of
negatively charged molecules by the polyanions.
− Lamina rara interna; Adjacent to the capillary endothelium. Similar to externa.
− Lamina densa; Overlap of the two basal laminae. Has collagen IV as a physical filter
and type XVIII collagen, perlecan and agrin that gives an anioinic charge to the GBM.
, Because of all this, there is a restriction of proteins larger than 70,000 Da or 3,5 nm.
However, the strong negative charge of the GBM impede flux of smaller anionic molecules.
Still, some protein passes through but this is reabsorbed by endocytosis in the proximal
convoluted tubule.
The parietal layer of the Bowman's capsule has parietal epithelial cells (simple squamous).
At the urinary pole it is cuboidal as it is continuous with the proximal convoluted tubule. The
space between visceral and parietal is the urinary space/Bowman's space. It contains the
glomerular ultrafiltrate (primary urine).
Mesangium
Mesangial cells constitute a space enclosed by GBM. These cells with their ECM form the
mesangium. Some cells are outside the renal corpuscle and are then lacis cells that make
the juxtaglomerular apparatus. The mesangial cells have several functions:
− Phagocytosis and endocytosis to remove trapped residues and proteins from the
GBM and filtration slit diaphragm to keep the filter clean. It maintains the glomerular
filter barrier.
− It provides structural support for the podocytes where the GBM is incomplete.
− It secretes molecules like IL-1, PGE2 and PDGF which is an important response to
glomerular injury.
− It modulates the glomerular distension as they gave contractile properties. By this it
regulates the filtration pressure and thus the filtration rate.
Juxtaglomerular apparatus
It includes the macula densa, juxtaglomerular cells and the extraglomerular mesangial cells.
The macula densa is a group of cells at the vascular pole at the terminal portion of the distal
straight tubule. The macula densa cells are narrow and longer and the nuclei seems
crowded. In this same region are SMCs of the arterioles. They contain granules and a more
spherical. These juxtaglomerular cells are responsible for activation of RAAS that is
important for sodium homeostasis and renal hemodynamics. The granules contain renin.
This catalyzes the conversion of angiotensinogen into angiotensin I. This is again converted
by ACE into angiotensin II. This stimulates the synthesis and release of aldosterone from the
zona glomerulosa of the adrenal gland. Aldosterone then increases reabsorption of Na and
water and secretion of K. This raises blood volume and pressure. Angiotensin II is also a
vasoconstrictor.
The juxtaglomerular apparatus also monitors the Na concentration to regulate the filtration
rate and the release of renin. A decrease in Na in the tubules stimulates a ion transporting
molecule on the macula densa cells. There is then also signaling so that there is renin
release and VSMC contraction.
Kidney tubule function
The volume of the ultrafiltrate really reduces and its composition also changes so that urine
is hyperosmotic. This is due to the loop of Henle and the antiparallel arranged blood vessels.
The proximal convoluted tubule is the initial portion and it the major site of reabsorption. It
receives the ultrafiltrate. The cuboidal cells have a huge surface and specializations to
enhance absorption and fluid transport. It has a brush border, junctional complex, plicae,
interdigitation of basal processes and basal striations. Actin filaments in the interdigitating
processes may regulate movement of fluid. Important membrane proteins are the Na/K
ATPase pumps to reabsorb Na and excrete K. The active transport of Na is followed by
passive diffusion of Cl to keep it electrochemically neutral. Accumulation of NaCl creates an
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