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Urinary system
Ross 7th edition, pages 698-725
...
1
General structure of kidney
...
2
3) Kidney Lobes and Lobules:
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4
5) Tubules of Nephron:
...
6
7) Collecting tubules and ducts:
...
6
9) Mesangium
...
9
Kidney Tubule function:
...
19
1) Ureter:
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21
3) Urethra:
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Kidneys functions:
1) homeostasis maintenance
...

3) conservation of essential substances (as water and metabolites)
...

5) maintain composition and volume of E
...
F
...

6) Endocrine organ
...

o Blood is filtered at filtration apparatus in glomerulus, to form glomerular
ultrafiltrate and primary urine
...
that is delivered by ureter to urinary bladder, where
is it stored until discharge via urethra
...




As an endocrine organ:
1) produce erythropoietin (EPO)  regulates RBC formation when blood oxygen level decrease,
as it acts on erythrocyte progenitor (Er-P) cells in bone marrow
...

**Blue text: – form of erythropoietin is used to treat anemia in end-stage renal disease, and in case of
bone marrow suppression of AIDS patients
...
Renin is
produced by juxtaglomerular cells and convert angiotensinogen to angiotensin-1
...
D3
...

**Ultrafiltrate – urine fluid during its modification
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**hyperosmotic – the ultrafiltrate is more concentrated than the surrounding, the interstitial fluid and plasma
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Hilum – deep vertical fissure through which vessels and nerves pass/exit, including the ureter at
its origin, the renal pelvis
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Renal sinus is
filled with LCT and adipose tissue
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Location: at the sides of spine, retroperitoneal in the posterior abdominal cavity
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Right kidney is lower
...


Elements:
1) Capsule: CT that covers the kidney
...
has 2 layers:
I
...

II
...


2) Cortex and medulla:
the kidney’s outer portion can be divided into 2 parts: cortex (red-brown due
to blood vessels 90-95%) and medulla (lighter, fewer blood vessels 5-10%)
...
Nephron and its associated
structures are present in the cortex
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I
...

Lay between medullary rays
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II
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under the capsule there are no medullary rays but only labyrinth
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(**by woolf)
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IV
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Uriniferous tubule: nephron and its connecting tubule, that will connect to collecting duct, in
the medullary ray
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II
...


IV
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Collecting ducts: continue from cortex into the medulla
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Runs in parallel with various tubules
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The vessels
represent the vascular part of the countercurrent exchange
system that regulates the concentration of urine
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Form Pyramids – 8-18 conical structures (base-cortex &
apices-renal sinus)
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b
...
regarded as part of medulla
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Papilla – apical portion of the pyramid
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area cribrosa – Tip
of papilla, perforated by openings of collecting ducts
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2-3 Minor calyx become major calyces that empty into
renal pelvis
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Left side – A long-looped nephron Right side –
short-looped nephron
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juxtamedullary nephron – the lower nephron,
with long loop of Henle
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medullary ray – represented by the area of
Inverted cone in the picture
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Parts of the nephron:
1) renal corpuscle including the glomerulus and
Bowman’s capsule;
2) proximal convoluted tubule;
3) proximal straight tubule of henle loop;
4) descending thin limb of henle loop;
5) ascending thin limb of henle loop;
6) thick ascending limb (distal straight tubule);
7) macula densa located in the final portion of the
thick ascending limb (at the distal tubule);
8) distal convoluted tubule;
9) connecting tubule;
9*) connecting tubule of the juxtamedullary
nephron that forms an arch (arched connecting
tubule);
10) cortical collecting duct;
11) outer medullary collecting duct;
12) inner medullary collecting duct
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Lobes are clearly outlined in fetal kidney, yet disappears after birth
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8-18 lobes per human kidney
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Boundaries between lobules are not clear
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medullary
rays contain collecting ducts of few nephrons that drain urine to the papilla
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2 million nephrons per kidney
...
In addition, Collecting ducts are responsible for the final
concentration of urine, similar to modification in secretory glands
...


Nephron structure –
I
...
It is spherical, 200 micrometers and Consist of
Glomerular capillary (visceral epithelial layer) and
Bowman’s capsule (parietal layers):
a) glomerulus – 10-20 capillary loops, surrounded
by bowman’s capsule
...
) & visceral layer
(simple cuboidal, podocytes)
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Blood flowing through, undergo filtration to
produce glomerular ultrafiltrate, not yet urine
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Urinary pole – opposite to vascular pole
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c) Course: Bowman’s capsule  proximal thick
segment of proximal convoluted tubule, cuboidal
epithelium, (pars convoluta)  proximal straight
tubule (pars recta)  thin segment of loop of Henle  distal thick segment of distal
straight tubule (pars recta) and distal convoluted tubule (pars convoluta)  connecting
tubule (sometimes)  cortical collecting duct  medullary collecting duct  papilla
...

**Blue text – 1) glomerulonephritis (glomerulus inflammation) is indicated by parietal
epithelium proliferation
...
The term collecting tubuleNot used
in this chapter
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From Bowman’s capsule, sequential parts of nephron:
Proximal convoluted tubule
...

Enters medullary ray to  proximal straight tubule
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Descends into medulla  thin descending limb
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Referred to as thick ascending limb of
loop of Henle
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epithelial cells
of the tubule adjacent to the afferent arteriole of
glomerulus are modified to form macula densa
...
less tortuous than PCT  arched connecting tubule (connecting
tubule) collecting duct
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Thin descending and ascending are always found in medulla
...
Than prox
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descending limb of the loop of Henle, pass from cortex to medulla)

*in the cortex
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Pass through both
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II
...


Subcapsular (cortical) nephrons: renal corpuscle in the outer part of cortex
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No thin ascending limb
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Juxtamedullary nephrons: 1/8 of nephrons
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Long loop of Henle with ascending thin segments in inner pyramid region –
essential for urine concentration mechanism
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Intermediate (midcortical) nephrons: renal corpuscles in midregion of cortex
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Similar in characteristics to cortical nephron
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Proceed to medullary ray and join cortical collecting ducts  travel to medulla, medullary
collecting duct  Travel to pyramid apex few of them merge into papillary ducts (ducts of
Bellini), which open through apex into minor calyx
...


8) Filtration apparatus of the Kidney:








Filtration apparatus – also glomerular filtration barrier
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Function: semipermeable barrier
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Despite the selective barrier, each day several
grams of proteins pass through the barrier
...

**Blue box: Albuminuria is the presence of a lot
of albumin in urine and hematuria, the presence
of a lot of RBCs in urine, can both indicate physical
or functional damage to GMB
...

The filtration apparatus is Enclosed by parietal
layer of Bowman’s capsule, and consists of
five different components:
**first 3 are the main ones

I
...

The fenestration is larger and more numerous than usual fenestrated capillaries
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o **Blue box: NO or PGE2 secreted by endothelial cells have main role in pathogenesis of
several thrombotic glomerular diseases
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o
o
o
o

o

III
...
(combination of the other layers – 1 and 3)
...
6 nm
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Good visualization with PAS stain because of thickness
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Composed of type IV and 18 collagen and other molecules: sialoglycoproteins
...

The components of the GBM are Divided between three portions:
1
...
Rich in polyanions (heparin
sulfate) – negative molecules that prevent passage of negatively charged molecules
...

2
...
Same molecules as in lamina rara
externa
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3
...
in the middle between them
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Type XVIII collagen perlecan, and agrin – anionic charges found in GBM
...

Extend processes around glomerular capillaries
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secondary processes, that interdigitate
Glomerular filtration barrier
with those of neighboring podocytes, forming filtration slits
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The outer layer of these cells, forms the
squamous cells of parietal layer of Bowman’s capsule
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Act as sizeselective filter
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Clogging of slits is prevented by
negative charges of GAGs in GBM, negative charges of podocyte cell
membrane, and phagocytic function of mesangial cells in renal
corpuscle
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the slip is the space in the middle, between
central density with pores on both sides
...

proteins: Neph-1, Neph-2, P-cadherin, FAT1, FAT2
...


IV
...




Endothelial surface layer of glomerular capillaries – meshwork of Carbohydrate attached to
luminal surface of glomerular endothelial cells
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Plasma proteins (albumins) adsorbed from blood coat the luminal surface of glycocalyx
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Cover 60% of entire surface area of
glomerular filtration barrier
...

Parietal layer of Bowman’s capsule contains parietal epithelial cells – simple squamous
epithelium
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Urinary space – also Bowman’s space
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where glomerular ultrafiltration (primary urine) can be found
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Additional group of cells in renal
corpuscle
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Enclosed by GBM
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mesangial cell in the renal corpuscle
Functions of mesangial cells:
1
...
Also Endocytose and process plasma proteins and immune
complexes
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Structural support – Produce components of mesangial matrix which provides support
for podocytes where epithelial basement membrane is absent
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Secretion – Synthesize and secrete IL-1, PGE2, and platelet-derived growth factor (PDGF),
in respond to glomerular injury
...
Modulation of glomerular distention – by their Contractile properties, they Help in
regulation of glomerular distention in response to increase blood pressure
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The proliferation may indicate immunoglobulin A
nephropathy (Berger disease), membranoproliferative glomerulonephritis, lupus nephritis, and
diabetic nephropathy
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Location: This part of distal straight tubule passes very close to the
renal corpuscle
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Consists of 3 cell types – Macula densa, Juxtaglomerular cells and
extraglomerular mesangial cells
...
These cells monitor and
effect ion concentration in the tubule
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o Characteristics: spherical nuclei and secretory granules that contain renin (aspartyl
protease, enzyme that use H2O + asparate to catalyze peptide substrate)
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o Function: regulate blood pressure by activating renin-angiotensin-aldosterone system
(RAAS), which maintains sodium homeostasis and renal hemodynamics
...

 Angiotensin II stimulates synthesis and release of aldosterone hormone from zona
glomerulosa of adrenal gland
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In addition, it causes secretion of K > increase blood volume > increase blood pressure
...

Juxtaglomerular apparatus Function:

1
...
G
...

2
...

Macula densa cells monitor Na+ concentration in tubular
fluid and regulate glomerular filtration rate and renin
release
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An increase of
blood volume  stretch juxtaglomerular cells of afferent
arteriole  stop feedback loop of renin secretion
...

o pass in the tubules and collecting ducts of kidney
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o Countercurrent multiplier by produce hyperosmotic urine by 2 kinds of actions:
a) Secretion of substances from tubule cells to primary urine (as creatinine, organic acid
and bases)
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Can be partial (as water, Na+, bicarbonate) or complete
(as glucose)
...
The ducts reabsorb materials into vasa
recta and secrete substances from it
...

They receive the reabsorbed content from nephron tubular system
...
C
...
):






Initial and major site for reabsorption
...

Cuboidal cells designed for absorption and fluid
transport, with the following features:
a) brush border – long, packed, and straight microvilli
...

b) junction complex –
1
...

2
...

c) Plicae or folds – large flattened processes, on the
lateral surface of the cell
...

d) Interdigitation of basal processes of adjacent cells – contain bundles of 6 nm actin
microfilaments, that regulate fluid movement from out of the cell to adjacent capillary
...
Help to
distinguish from other cells
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Fluid reabsorption, 2
...
3
...

1
...
C
...
reabsorbs (65%), or 120L out of 180L/day of fluid from ultrafiltrate
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 Reabsorb Na, that cause reabsorption of water in the P
...
T
...
active transport of Na+ into the cell
...
Cl- follow by passive diffusion
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accumulation of NaCl in the cell
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osmotic gradient that draw water from lumen into the cell
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cell distends
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6
...

7
...

o

Aquaporin-1 (AQP-1) – small (30kDa) cell membrane water channel
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2
...
C
...
reabsorbs nearly all glucose, amino acids, and small polypeptides –
Cells have many microvilli – covered by glycocalyx, ATPases, peptidases, and
disaccharidases
...
T
...

o amino acids – 98% are reabsorbed, by amino acid transporters exchange Na, H, K (acidic
transporter) of Na, H (basic and neutral transporters)
...
A
...

 large peptides – endocytosed
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A
...
T
...
P
...
T
...


2) Proximal straight tubule (P
...
T
...

 Comparison of proximal convoluted tubule (PCT) and proximal straight tubule (PST)
1) not specialized for absorption, 2) shorter, 3) less developed brush border, 4) fewer processes,
5) smaller mitochondria, 6) less apical invagination of endocytosis, and less lysosomes
...
S
...
cells recover the remaining glucose by high-affinity Na+ - glucose cotransporters
(SGLT1) that absorb Na+ and glucose
...
C
...


3) Thin Segment of Loop of Henle:



Length varies with the location of the nephron in the cortex
...
cortex nephrons – shortest limbs
...
The differences reflect specific active or
passive roles in the process of concentrating the renal tubular fluid
...
Don’t memorize the differences, it is not
important
...

Simple structure
Low, flattened
epithelium

-

Many small
microvilli
few

Few

Non

Interdigitation
between cells
Almost non

Varies by
species
No lateral
Interdigitation
-

Ultrafiltrate changes as it passes through the descending and ascending parts of loop pf henle:
isosmotic as it enters thin descending limb, and hypoosmotic (less concentrated) as it leaves the
thin ascending limb
...
Each part has different
functions:
o Thin descending limb:
a) highly permeable to water – due to aquaporins (AQP) – allow free passage of water
...
Little amount of Na enters
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interstitial fluid in the medulla is hyperosmotic > water exit thin descending limb by osmosis
> tubule lumen become more concentrated > tubule fluid osmolality increase =
hyperosmotic
...

o Thin ascending limb – Diluting segment of the nephron – makes filtrated fluid hypo-osmotic
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a) Highly permeable to NaCl, so allow passive diffusion
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c) highly permeable to ions due to ion transporters (Na/K/2CL) at apical layer
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In interstitium increase  interstitium is hyperosmotic 
tubule fluid is hypo-osmotic
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cell characteristics: large cuboidal, apical nucleus – forms bulge into lumen
...

function: transports ions from tubular lumen to interstitium
...
Then they leave the cell to interstitium
– Na+ by active transport, K+ and Cl- by diffusion
...
*no water movement
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protein produced by epithelial cells of thick ascending
limb
...

**Blue text – Uromodulin 1) modulates cell adhesion and signaling by cytokines
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3) defend from urinary infection
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5) Distal convoluted tubule:







Location: Cortical labyrinth, 1/3 of proximal convoluted tubule length, 5 mm
...

Cell characteristics: similar to cells of distal straight tubules, but taller and have no developed
brush borders
...

Cells of this tubule have highest Na/K ATPase activity to interstitium  increase ion transport 
most ions reabsorb to body
...

function:
a) regulate Ca reabsorption by signal of parathyroid hormone
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 urine acidification – by bicarbonate reabsorption and H secretion
...

 Ammonium Secretion – due to bicarbonate generation
...

Pathway: 1) in sub-capsular nephron it joins directly to cortical collecting duct
...

Cell Characteristics: simple epithelium, changes from Distal Convoluted Tubule epithelium to
collecting duct epithelium, and may include the 2 kinds
...
Secretion is regulated by mineralocorticoids from adrenal
cortex
...

2) Determine final urine osmolality by reabsorbing water
...

o cortical collecting ducts – flattened cells, Between squamous to cuboidal
...

Have prominent Cell boundaries that help to distinguish between Collecting ducts from proximal
and distal convoluted tubules
...

o Predominant cell type
...

ii) basal infoldings that interdigitate with adjacent cells
...

v) Aquaporin-2 (AQP-2) – water channels regulated by ADH > make the duct permeable
to water
...

vi) mineralocorticoid receptors (MR) – target to aldosterone (also effects connecting
ducts but doesn’t affect distal convoluted tubule – according to new researches)
...

Secreted by adrenal cortex by stimulation of angiotensin II or increase K+
concentration (hyperkalemia)  binds cytoplasmic mineralocorticoid receptor (MR)
 translocated into nucleus  express genes of proteins that cause Na
reabsorption and K+ secretion  increases the reabsorption of Na+ and secretion of
K+  increases blood serum Na+ concentration  increases blood volume and
pressure
...

b) Dark cells – Also intercalated (IC) cells
...
Number decrease toward renal papilla until there are
none
...

ii) cytoplasmic folds (Microplicae), and microvilli on apical surface
...

iv) many vesicles in the apical cytoplasm
...

i) Alpha cells: more abundant
...

ii) Beta cells – work the opposite way: secrete bicarbonate into lumen of the collecting
duct
...
)רקמה תפקודית של איבר (בשונה מרקמת חיבור‬
Location: surrounds the nephrons, ducts, and blood and lymphatic vessels
...

Cortex has 2 types of interstitial cells:
a) Cells that resemble fibroblasts – between the tubules basement membrane and the adjacent
peritubular capillaries
...

o Synthesize and secrete collagen and glycosaminoglycans of extracellular matrix of
interstitium
...

In the Medulla the main interstitial cell resembles myofibroblasts –
o Positioned along tubular structures and compress it by contraction
...

o Contain: many bundles of actin filaments and many rER, Golgi and lysosomes
...
During kidney injury or inflammation fibroblast are formed and
secrete E
...
M
...

2) Renal fibrosis – is caused by fibroblasts
...
Possible new treatment – reversing cytokine action
...
מסובך ויותר רלוונטי לפיזיולוגיה‬


countercurrent – fluid flow between 2 adjacent structures in opposite directions
...

o Creates and maintains ion concentration gradient in the medullary interstitium that
increases from upper to lower direction
...

2) thin ascending limb of the loop of Henle is impermeable to water (water cannot leave)
and it adds Na+ and Cl- to the interstitium  interstitium becomes hyperosmotic relative
to lumen  water are drawn out from descending limb
...


b) blood vessels surrounding the nephron
...

o Function: Help to maintain the osmotic gradient of the medulla
...

o Make loops in medulla that parallel the loop of Henle, to ensures that the vessels provide
nutrients to medulla without disturbing the osmotic gradient, that is established by
transport of Cl- at the ascending limb of the loop of Henle
...
that network surrounds the renal tubules in cortex to absorb water
...

course: efferent arterioles > unbranched arterioles that descend into the medullary
pyramid > arteriolae rectae (descending arterioles) arrive to medullary pyramid and turn
back up > become venulae rectae (ascending venules)
...

o

Mechanism: vasa recta (and also peritubular capillary network I think) form a
countercurrent exchange system
...
This mechanism is passive for endothelial cell, as all energy
is spent by renal tubules that secrete ions and water
...

2) As the arterial vessels descend in medulla, blood loses water to the interstitium and
gains salt > at the tip of the loop, in the medulla, the blood is essentially in equilibrium
with the hyperosmotic interstitial fluid
...


c) Collecting duct – acts as an osmotic equilibrating device
...

o Mechanism: Interaction between collecting ducts, loops of Henle, and vasa recta form the
countercurrent exchange mechanism that make the urine concentrated
...

2) Collecting duct descend in medulla through increasingly hyperosmotic interstitium >
increasing amounts of water leaving the tubule
...
In cortex – cause distal convoluted tubules and collecting ducts to be
highly permeable to water > ultrafiltrate in distal convoluted tubule (which is in cortex,
that is isosmotic with the blood) becomes isosmotic, by loss of water to the interstitium,
and by addition of ions other than Na+ and Cl- to the ultrafiltrate
...
Ultrafiltrate becomes hyperosmotic
...
Aspects of vessels that are part of
filtration mechanisms are described above
...

interlobular arteries terminate near the periphery of
the cortex, or enter the kidney capsule to provide it
...

2 kinds of peritubular capillaries:
a) Cortical glomeruli – Efferent arterioles form peritubular capillary network that surrounds the
local uriniferous tubules
...

Vasa recta is involved in the countercurrent exchange system
...

Peritubular cortical capillaries and (capsule capillaries through stellate veins) drain into
interlobular veins
...


Lymphatic vessels:
 2 major networks of lymphatic vessels that anastomose with each other, usually not visible
...

b) located more deeply in the kidney > drains into large lymphatic vessels in the renal sinus
...

 function: regulate urine production by contraction of vascular smooth muscle > vasoconstriction
...

b) Constriction of efferent arterioles > increases the filtration rate and urine production
...
However, kidney may have normal
renal function without innervation
...

Pathway: Collecting ducts leave at area cribrosa  minor calyx  major calyx  renal pelvis 
leaves kidney through the ureter  stored in urinary bladder  excreted through urethra
...


Layers
A) Mucosa: * NO muscularis mucosae, NO submucosa
...
epithelium: lines calyces, ureters, bladder, and initial segment of urethra
...

has at least three layers: starts at 2 layers in minor calyces, increases
to 5 layers in ureter, and 6 or more layers to empty the bladder
...

o Called umbrella, dome-shape, cells because of curvature of
apical surface
...

o cell shape depends on the filling state of the excretory
passage:
cuboidal in an empty urinary bladder, squamous when
bladder is filled
...
contribute to the resistance of paracellular barrier that reinforces tight
junctions
...
thickness of this layer varies may reach up to 5 layers thick
...

c) Basal cell layer – contain urothelium stem cells
...


Characteristics:
a) accommodate distension – the epithelium begins in the minor calyces as 2 cell layers, increases
to 4-5 layers in the ureter and 6 or more layers in empty bladder
...
when the bladder is distended 3 layers are seen
...

o fusiform vesicles – vesicles in apical membrane of Dome-shaped cells, that forms
asymmetric unit membranes (AUM) on the inner side of the membrane
...
As
urothelium gets back to original state the process is reversed > vesicles are endocytosed
...

These proteins make the outer leaflet of membrane lipid
bilayer twice as thick as the inner leaflet > form
asymmetrical appearance named asymmetric unit
membrane (AUM)
...

contain all other non-plaque proteins
...

**Blue text: uropathogenic Escherichia coli bacteria cause
85% of urinary tract infections
...

 Permeability barrier is maintained despite dynamic changes
of stretching
...
lamina propria: – with Dense collagen fibers, many cells
and lymphocytes
...

B) Muscolaris layer:





In the tubular portions – ureters and urethra – usually 2
layers of smooth muscle beneath the lamina propria:
a) Longitudinal layer – inner layer that has loose spiral pattern
...

(*opposite to that of the muscularis externa of the intestinal tract)
...

Peristaltic contractions move urine from minor calyces through ureter to the bladder
...

Shape: 24-34 cm long
...
Usually the
ureter is embedded in the retroperitoneal adipose tissue
...

smooth muscle layer: 2 main layers and 2 additional layers
...

Adventitia layer: contain adipose tissue, vessels, nerves
...

Infections in bladder are common mostly in female
...

Location: pelvis, posterior to pubic symphysis
...
Formed by 3 openings – 2 for the ureters –
ureteric orifices, and one for the urethra – internal urethral orifice
...

Embryological: different origin results in the difference of the 2 parts:
a) trigone – derived from the embryonic mesonephric ducts,
b) the rest – originates from the cloaca
...
less arranged than in the tubular
portions of excretory passages – mixed muscle and collagen
...

Internal urethral sphincter – involuntary, formed by the Detrusor muscle
...

Innervation:
a) sympathetic – plexus of adventitia of bladder wall
...

b) parasympathetic – efferent fibers of micturition reflex
...
travel with pelvic splanchnic
nerves into the bladder
...

c) Sensory fibers – from bladder to sacral spinal cord
...


3) Urethra:


Function: fibromuscular tube, conveys urine from the urinary bladder to the exterior through
external urethral orifice
...

1) Male: urethra is the terminal duct for both the urinary and genital systems
...

Structure – 3 distinct segments:
a) Prostatic urethra – 3-4 cm, from the neck of the bladder through the prostate gland
...

ejaculatory ducts of the genital system enter the posterior wall of this segment,
and many small prostatic ducts also empty into this segment
...

passes through the deep perineal pouch of the pelvic floor as it enters the perineum
...

Covered by stratified or pseudostratified columnar epithelium as in the genital duct system
...

c) Penile (spongy) urethra:
o 15 cm through the length of the penis and opens on the body surface at the glans penis
o Surrounded by the corpus spongiosum
...


o
o

Pseudostratified columnar epithelium except at its distal end – stratified squamous
epithelium continuous with the skin of the penis
...


2) Female:
o urethra is shorter, 3-5 cm, from the bladder to the vestibule of the vagina, where it
terminates just posterior to clitoris
...

o Transitional epithelium – continuation of the bladder epithelium
...

o Mid-portion might have stratified columnar and pseudostratified columnar epithelium
...

Numerous small urethral glands, particularly in the proximal part of urethra, open
into the urethral lumen
...

Paraurethral glands - homologous to prostate gland in male
...

o lamina propria – highly-vascularized CT, similar to corpus spongiosum in male
...




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