Functional Anatomy of the Urinary Tract

o During extreme conditions, it helps Glucagon, Cortisol,

Renal Physiology Epi/Norepinephrine, Catecholamines, Thyroid Hormone,
• The kidneys are part of the excretory system, but specifically and Growth Hormones (in children) to increase blood sugar
they are in the URINARY SYSTEM. levels
• Excretory System:
o Water-soluble wastes are through the sweat (minimal
amount) and the urinary system. Macroscopic Anatomy of the Kidney
o Lipid-soluble wastes excreted through the GIT.
o Gas (excess) are excreted through the Respiratory System.

• To form urine
• Excretion of Excessive Waste Products
o Urea – from amino acids
o Creatinine – from muscle creatine
o Uric Acid – from nucleic acid (purine)
o Bilirubin – from end product of hemoglobin breakdown
• Regulation of Water and Electrolyte
o Most of the water and electrolytes in the body are excreted
through the kidneys. This may be a basis for administration
of IV Fluid: 3L/day • There are 2 Kidneys in the body: Right and Left
• Regulation of body fluid osmolality and electrolyte • Located at the upper abdomen, posterior, and retroperitoneal
concentration • Approximately the size of a closed fist
o As it regulates the water and electrolyte balances, the • On the average:
plasma osmolality is also regulated o Length: 10cm
o Wide: 6cm
Starling’s Forces o Thick: 3cm
Inside the Capillary: o Weight: 115 – 170g (Average: 150g each kidney)
✓ Capillary Hydrostatic Pressure – drives away fluid • At the medial portion of the kidney, there is an indentation
✓ Capillary Osmotic (Oncotic/Colloid) Pressure of called the Renal Hilum
Plasma Protein – attracts fluid in o Very important because this is the area where you have the
Outside the Capillary: passage of the following structures:
✓ Interstitium or Tissue Hydrostatic Pressure
→ Renal Vein
✓ Interstitium or Tissue Oncotic Pressure of Plasma
Protein → Renal Artery
Filtration: Capillary Hydrostatic Pressure + Interstitial Osmotic → Renal Pelvis
Pressure → Renal Nerve
Reabsorption: Capillary Osmotic Pressure + Interstitial → Renal Lymphatic
Hydrostatic Pressure o If you have trauma in this area, chances are you will destroy
these 5 important structures
• Regulation of Arterial Pressure • Covered by a non-distensible structure called the Renal Capsule
o Plays a dominant role in long term regulation of arterial o Reason why in acute condition you don’t have enlargement
pressure by excreting variable amounts of Sodium and of the kidney
Water o In chronic conditions, there will be an enlargement of the
o Intermediate regulation of blood pressure: Renal-Fluid Shift kidney
→ ↑ BP = ↓ Urine Output
→ ↓ BP = ↑ Urine Output
o Short term regulation by secreting hormones and vasoactive
factors or substances (Renin) that lead to formation of
vasoactive products (Angiotensin II)
• Regulation of Acid-Base Balance
o 1st: Intra/Extracellular buffers (Ex. Bicarbonates,
Hemoglobin, Calcium, Phosphates, Phosphoric Acids)
o 2nd: Respiratory System
o 3rd: Recruit the Kidney
→ The kidney can only acidify up to the pH 5.0 and
alkalinize until pH 8.0 (Urine pH: 5.0 – 8.0)
• Regulation of Erythrocyte Production
o Erythropoietin – for erythropoiesis (primarily stimulated by
tissue hypoxia)
• Secretion, Metabolism, and Excretion of Hormones
o Renin, Erythropoietin, Vitamin D/1,25-dihydroxyvitamin • Renal Cortex – outer portion
D/Calcitriol (Final Activation) • Renal Medulla – inner portion
• Gluconeogenesis o Contains about 7 to 8 conical structure called the Renal
o Kidneys synthesize glucose from AA and other precursors in Papilla
cases of severe hypoglycemia
 o Hallmark of the Medulla: there is a triangular Renal Blood Flow
structure/pyramidal structure called “Renal Pyramids”, the
base is near the cortex. The apex towards the Renal pelvis. True Capillary is
o Apex of the renal pyramid is called “Renal Papilla” → drains between an arteriole
to the minor calyx. and venule →
o The boundaries of the Renal Cortex and Renal Medulla are Peritubular Capillary
the Bases of the Renal Pyramid
• Minor Calyces will join together to form Major Calyces. Special Circulation:
• Major Calyces will form the Renal Pelvis. Glomerular Capillary in
• Urine will now pass through the renal pelvis to the Ureters and between 2 arterioles
will be collected in the Urinary Bladder.

Renal Cortex Renal Medulla

Composed of: Composed of:
✓ Glomerulus ✓ Loop and Henle
✓ Bowman’s Capsule ✓ Medullary Collecting
✓ PCT and DCT Duct
✓ Cortical Collecting
Duct
Concentration: Isotonic Concentration: Hypertonic • Blood supply of the kidneys comes from the renal arteries.
Renal artery is direct branch of aorta.
• Even though the kidneys are very small, they are receiving the
majority of the cardiac output.
Renal Renal o Each kidney weighs only 150 grams and yet they receive
Minor Calyx
Pyramid Papilla 20%-25% of the CO.
→ 1200-1250 mL/min
o Highest percentage of CO per 100 g of tissue = kidney (if you
consider the weight)
• Renal artery is a direct branch of the aorta so it means the
Ureter Renal Pelvis Major Calyx pressure is high in the renal artery.
o Normal hydrostatic pressure = 25-35 mmHg
o The pressure in the renal artery decreases as it bifurcates
into several branches.
o When the artery reaches the glomerular capillaries, the
Urinary pressure is 60 mmHg. It exceeds the normal hydrostatic
Urethra
Bladder pressure.
o When the blood passes through the efferent arteriole, from
60 mmHg it decreases to 18 mmHg because there is a high
Urethra resistance in the arterioles.
✓ Female: 5cm (2in) – more prone to UTI → Highest resistance is in the Efferent Arteriole followed
✓ Male: 20cm (10in) by the Afferent Arteriole and followed by the
→ 3 Sections: Prostatic (hidden), Membranous combination of the Interlobar, Arcuate and Interlobular
(hidden), Penile Urethra Arteries. *mostly Interlobular*
→ (+) Glands of Littre, releases antibacterial o High capillary hydrostatic blood pressure favors fluid
secretions = less prone to UTI filtration because it exceeds oncotic pressure but if the
Take Note: oncotic pressure exceeds CHP it will favor fluid reabsorption.
The right kidney has 3 Minor Calyces while in the left it only has
2 Minor Calyces Blood vessels in the kidneys are unique in that it has 2 Arteriolar
Systems and 2 Capillary Beds, such that the arterioles will
Micturition is the process by which the urinary bladder empties regulate the pressure of the 2 capillary beds
when it becomes filled.
✓ Both involuntary and voluntary Glomerular Capillaries Peritubular Capillaries
1st Voluntary: the bladder fills progressively until the tension in High Pressure Capillary Low Pressure Capillary
its wall rises above a threshold level 60 mmHg 18 mmHg
2nd Involuntary/Micturition Reflex: a nervous reflex that Favors Filtration Favors Reabsorption
empties the bladder
✓ Can be regulated on certain amounts/volume
Comparison of the Distribution of Blood Flow to the Different
→ Depending on the height, the capacity of the
Organs
urinary bladder is around 700 mL (<5ft); 1L
Kidney 4.0 mL/g/min
(>5ft)
Heart 0.9 mL/g/min
→ >700 mL or 1L = Reflex Micturition
Brain 0.6 mL/g/min
→ 150-300 mL → urge to urinate
Liver 0.2 mL/g/min
→
Resting Muscle 0.1 mL/g/min
 Nephron

• When the blood flow from one portion to another, the pressure
drops because it meets resistance
• The highest drop would be from the Efferent Arteriole

Vessel Pressure in % of Total Renal

Vessel (mmHg) Vascular Resistance
Start End • Characteristic cells of the Kidney
Renal Artery 100 100 0 • Basic unit of Renal Structure and Function
Interlobar, Arcuate, 100 85 16 o Building block of the Kidney
Interlobular Arteries • 1.2 million in each kidney
Afferent Arteriole 85 60 26 o You can actually survive with just 50%
Glomerular 60 59 1 o If you lose 50% of nephron, the other 50% will compensate
Capillaries o However, when you reach 40 y/o → ↓10% every 10 years
Efferent Arteriole 59 18 43 since the nephrons are postmitotic and therefore cannot
Peritubular 18 8 10 regenerate (on the average)
Capillaries
Interlobar, Arcuate, 4 4 0
Interlobular Veins • Glomerulus
• Renal Tubule

• The Glomerular Capillaries are enclosed by a Bowman’s

Capsule which forms the Glomerulus
• The Peritubular Capillaries surround the tubule
• Similarities:
o Both are capillaries • Formed by the Glomerular Capillaries enclosed by a Bowman’s
o Both present in any type of nephron Capsule
• Difference: • Primary Function:
Glomerular Capillaries Peritubular Capillaries o Fluid Filtration
High Pressure Capillary Low Pressure Capillary
In between and Afferent and In between and Efferent
Efferent Arteriole Arteriole and a Venule
Favors Filtration Favors Reabsorption and
Secretion
60 mmHg 18 mmHg
• Bowman’s Capsule (Parietal/Visceral Layers)
o Both layers are lined with Simple Squamous (podoctyes with
pedicel)
o Bowman’s Space – space between the Parietal and Visceral
Layer
• Glomerular Capillaries
o Fenestrated without diaphragm
o It has perforations; thus, podocytes have pedicel to make
the holes smaller
o Forms the Filtration Barrier – size, shape, and charge
selective
• Afferent Arteriole – thick
• Efferent Arteriole - thin • The cells are columnar with so many mitochondria
• Only portion with Brush Border
• Highly invaginated basolateral member
• This portion is the Major Reabsorptive Area
• The reabsorption in the Proximal Convoluted Tubule is said to
be obligatory – Obligatory Reabsorption
o Whether you need the substance or not, this area will
reabsorb it
• Most are non-hormonal dependent

• The cells are flat

• Proximal Convoluted Tubule (Pars Convoluta) • Few mitochondria
• Proximal Straight (Pars Recta) • Lesser reabsorptive capacity
• Thin Descending Loop of Henle • It only reabsorbs water
• Hairpin Loop • Thin Descending Loop of Henle
• Thin Ascending o The one involved in dilution and concentration of urine
• Thick Ascending
• Distal Tubule
o Early Distal Tubule
o Late
• Connecting Tubule
• Collecting Duct
o Cortical
o Medullary

All areas of the Renal Tubule can reabsorb, only that:

o Thin Descending, it least likely reabsorbs solute – it
mostly reabsorbs water.
→ Concentrating Segment
o The Thick Ascending Loop of Henle and Early Distal • Columnar
Tubule least likely reabsorb water – it mostly reabsorbs • Many mitochondria but less than Proximal Tubule
solutes. • No Brush Border
→ Diluting Segment • Not highly invaginated
• Contains the NKCC2 Transporter
Can all the areas of the Renal Tubule secrete? Yes, but least o Sodium Potassium 2 Chloride
likely are the Thin Descending and Thin Ascending → Very powerful transporter
→ Inhibited by loop diuretics
• Can only reabsorb solute and not water, even with ADH
• Unique Characteristic:
o Passes through the Afferent and Efferent Arteriole
o The cells become modified → becomes Granular
o Becomes Macula Densa
 • All epithelial cells contain a Primary Cilium except the
Intercalated Cells
• A single non-motile cilium found in the apical membrane
• Functions:
o Serves as mechanosensors
→ Detects the flow rate of fluid in the tubule
o Serves as chemosensors
→ Detects the chemical composition of the fluid flowing in
the tubule
o Initiate Calcium-Dependent Signaling Pathway (cell
function, proliferation, differentiation, and apoptosis)
→ Responsible of the Ca2+ influx which is very important
• More mitochondria in cell function, proliferation, differentiation, and
• Invaginated basolateral membrane apoptosis
• No Brush Border • Encoded by Polycystin 1 (PKD1) and 2 (PKD2)
• The one involved in reabsorption similar to the Collecting Duct

• Are expressed in the membrane of Primary Cilia

• Mediates entry of Calcium into the cell:
o Cell Function
o Cell Proliferation
o Cell Differentiation
o Programmed cell death
Principal Cell Intercalated Cell • Encodes the proteins in the Primary Cilium
• More mitochondria
• Invaginated basolateral membrane
• No Brush Border • Genetic disease caused primarily by mutations in PKD1 (85
• Involved in final processing and final concentration and dilution to 90%) and PKD2 (10 to 15%)
of urine • Manifested by enlargement of the kidney due to formation
of hundreds to thousands renal cysts
The Late Distal Tubule and the Collecting Duct undergo • Most of the PKD patients will end up with Renal Failure
Facultative Reabsorption o It is the 3rd leading cause of renal failure
o This area will reabsorb if you need an excess substance • Cysts are also seen in the liver and other organs in this
o Needs ADH (Antidiuretic Hormone) for Water condition.
→ ADH is primarily located in the Collecting Duct • About 50% of patients with ADPKD progress to renal failure
o Needs Aldosterone for Sodium by the age of 60.
→ Aldosterone is primarily located in the Collecting • Although it is not clear how mutations in PKD1 and PKD2
Duct cause ADPKD, renal cyst formation may result from defects
o Needs PTH for Calcium in Ca++ uptake that alter Ca++-dependent signaling
pathways, including those controlling kidney cell
proliferation, differentiation, and apoptosis.
• The one responsible for water reabsorption, sodium
reabsorption, and potassium secretion
• The one affected by Aldosterone
• Lesser mitochondria

• Very much involved in Acid-Base Balance

• Cause bicarbonate reabsorption and hydrogen secretion
• 2 Types of Intercalated Cells
o Alpha
→ Reabsorbs bicarbonate and secretes hydrogen
o Beta
→ Secretes bicarbonate and reabsorbs hydrogen

• Cortical Nephron or Superficial Nephron

• Juxtamedullary Nephron

• They can both form urine

• Contains glomerulus, glomerular capillaries, and peritubular
capillaries
• Most abundant, for every 10 Cortical Nephrons, you only have • Continuous but also porous
1 Juxtamedullary Nephron (10:1) • Made up of Negatively Charged Proteins:
• Have a short Loop of Henle o Type IV Collagen – major component
• Almost all the parts are present in the Cortex except for the Thin o Laminin
Ascending o Proteoglycan Agrin
• Can form urine but cannot concentrate urine o Perlecan
o Fibronectin
• If a negatively charged protein will pass through this barrier it
• Least abundant will not get through
• Some parts are in the Cortex, some parts are in the Medulla • Major Electrostatic Barrier
• Long Loop of Henle
• Contains Thin Ascending
• Can concentrate and form Hypertonic Urine • Contains finger-like projections that are interdigitating
• Unique Characteristic: The Efferent Arteriole has a long branch • Contains slits called Filtration Slits that are covered by Slit
called the Vasa Recta Diaphragm
• The Slit Diaphragm have very small pores
• Major Size Selective Barrier
• In the medullary area, its function is to convey oxygen and • Major Proteins in the Podocytes:
important metabolic substrates to support nephron function o Podocin
• Delivering substances to the nephron for secretion o Nephrin
• Serving as a pathway for return of reabsorbed water and solutes o NEPH-1
to the circulatory system • There are some intracellular proteins present in the podocytes
o Slower return of reabsorbed water and solutes that associate these proteins in the food process:
o Primarily solutes o Alpha-Actinin-4
• Concentrating and diluting urine o CD2-AP Protein
o Goes with Loop of Henle

Glomerular Membrane • Characterized by an increase in permeability of glomerular

membrane to proteins and by loss of normal podocyte
structure, including effacement (thinning) of the podocyte
processes
• Mutations of the genes that encode the slit diaphragm
proteins
• Podocin Gene
o Steroid-Resistant Nephrotic Syndrome
• Nephrin Gene
o Congenital Nephrotic Syndrome
• 3 Cardinal Symptoms:
o Proteinuria
o Hypoalbuminemia
→ ↓ in albumin due to proteinuria
o Generalized Edema
• 3 Components → ↓ in oncotic pressure → there will be no resistance
o Endothelial Cells to filtration → Edema
o Basement Membrane
o Podocytes
• Filtration Barrier • Caused by a defect in Type IV Collagen
• Due to mutations of COL4A5 gene (85% X-linked) and
When you filter the blood, you only filter the Plasma. mutations in Type IV Collagen (15%)
o Everything in the plasma can be filtered EXCEPT the • Irregular thickness of basement membrane (not effective as
proteins filtration barrier)
• Manifestations:
o Hematuria
• Endothelial Cells in the kidney are fenestrated o Progressive Glomerulonephritis
• Large fenestration, the gap is about 8nm
o Protein can enter but not RBCs
• Contains negatively charged Glycoproteins
o Repel the other proteins so only few proteins can get
through
• If the substance is neutrally charged and below 6nm they are
freely filtered
• Secrete Nitric Oxide - vasodilator
• Secrete Endothelin - vasoconstrictor
o These 2 substances are very important for the regulation of
renal blood flow and GFR
 → The specific granules represent renin or its precursor
Molecular Molecular [Filtrate] / → Effectors
Weight Radius (nm) [Water] o Extraglomerular Mesangial Cells (Lacis Cells)
Water 18 0.10 1.0 → May serve as the functional link between the Macula
Glucose 180 0.36 1.0 Densa and the Glomerular Arterioles
Inulin 5,000 1.4 1.0
Hemoglobin 17,000 2.0 0.03 Mesangium
Cationic Dextran 3.6 0.42
Anionic Dextran 3.6 0.15
Anionic Dextran 3.6 0.01
Serum Albumin 69,000 3.6 0.001

• First consideration would be the Size (Molecular Radius)

o Size and filterability have an inverse relationship
o The greater the size the lower the filterability

1. Size
o Substances with molecular weight up to app. 5000 whose
molecular radii are less than 15A (6nm) will have a
plasma:filtrate ratio of 1 (freely filtered)
o Beyond 8nm → no longer filterable
2. Shape • Components:
o For a given molecular weight, a slender and flexible o Mesangial Matrix
molecule will pass through the glomerular filtration o Mesangial Cells (Contract)
membrane more easily than a specific, nondeformable → Primary Function: Provide structural support for the
molecule Glomerular Capillaries
3. Electrical Charge → Secrete extracellular matrix
o The glomerular filtration membrane bears fixed (-) charges → Exhibit phagocytic activity
o These anionic sites consist of glycosaminoglycans rich in → Secretes prostaglandins and pro-inflammatory
heparan sulfate cytokines
→ Influence GFR (Glomerular Filtration Rate) and RBF
Juxtaglomerular Apparatus (Renal Blood Flow) by changing the surface area
→ Made up of Actin and Myosin

Immune Complex
Immune Complex Mesangial Area
Accumulation

Production of
Enhance
Proinflammatory Infiltration of
Inflammatory
Cytokines and Inflammatory Cells
Response Autocoids

• These are group of cells that is important in autoregulation

o Autoregulation – ability of an organ to regulate its own blood
flow
o Most well-developed autoregulation Obliterates
Glomerulus (Cell
• 2 Types of Autoregulation Scarring)
o Myogenic
→ Laplace Law
o Metabolic Because the glomerular basement membrane does not
→ Tubulo-glomerular Feedback Mechanism – role of completely surround all glomerular capillaries some immune
Juxtaglomerular Apparatus complexes can escape the blood and enter the mesangium
• Tubulo-Glomerular Feedback Mechanism without crossing the glomerular basement membrane.
o Macula Densa
→ Present in the Thick Ascending Loop of Henle that Accumulation of immune complexes induces mesangial
passes between the Afferent and Efferent Arterioles infiltration of inflammatory cells and promotes local
→ The Macula Densa acts as the sensor arm for renin proinflammatory cytokine and autocoid production.
release
→ Sensors These cytokines and autocoids enhance the immune complex–
o Juxtaglomerular Granular (JG) Cells initiated inflammatory response, which can ultimately lead to
→ Made up of smooth muscles that become granular mesangial expansion, scarring, and obliteration of the
glomerulus.
→ Located in the Tunica Media of Afferent Arteriole
(mostly) and Efferent Arteriole
 Intrarenal Distribution of Blood Flow If the Urine Flow (V) is not given in the exams, use the normal value
% of % of Blood Perfusion = 1.0 mL/min
Kidney Blood Volume Rate
Weight Flow mL/g mL . g-1 . Average PAH Extraction Ratio: 0.9 (90%)
tissue min-1
𝐸𝑅𝐹 630
Cortex 75 90 0.2 5.3 𝐴𝑐𝑡𝑢𝑎𝑙 𝑅𝑃𝐹 = = = 700 𝑚 𝐿/𝑚𝑖𝑛
Outer 20 7 0.2 1.4 𝐸𝑥𝑡𝑟𝑎𝑐𝑡𝑖𝑜𝑛 𝑅𝑎𝑡𝑖𝑜 0.9
Medulla
Hematocrit (Hct) = 45%
Papilla 10 1 0.2 0.4 1
𝑅𝐵𝐹 = 𝑅𝑃𝐹 𝑋
1 − 𝐻𝑐𝑡
• The Cortex receives the highest flow since it is the largest
• The Medulla will only receive about 8% 1
𝑅𝐵𝐹 = 700 𝑋 = 1273 𝑚𝐿/𝑚𝑖𝑛
1 − 0.55

• 20 to 25% of the Cardiac Output (1000 – 1250 mL/min)

• Can be determined by applying Fick’s Principle
Cardiac Output = 5,000 mL or 5L
Renal Blood Flow = 1,000 mL (1L) – 1,250 mL (1.25L)
= 20 – 25% of CO
Renal Plasma Flow = 550 mL – 600 mL (55 – 60% of whole
blood)
• Renal Blood Flow cannot be measured directly
o You need to use an indirect method in order to measure RBF
→ Using the indirect method, you will yield the value for
Renal Plasma Flow
Renal Innervation
• Exclusively innervated by Sympathetic Nervous System (Celiac
Plexus)
• Action of NE or β1 Adrenergic Receptors on JG cells and Renal
Tubular Cells
• Help regulate the renal blood flow
• Help regulate the GFR
• Help regulate Na and H2O reabsorption
REMEMBER:
All odd numbers are usually excitatory
All even numbers are usually inhibitory

• The Renal Clearance (C) of a substance (s) is the volume of

plasma required to supply the amount of substance excreted in (+) Sympathetic
Nerves
the urine during a given period of time

[𝑈𝑠 ] 𝑥 𝑉
𝐶𝑠 =
[𝑃𝑠 ] Increase NE and Increases NE and
S = any substance Dopamine release Increasing strength Dopamine Release
in the Renal Nerves in the Renal Nerves
C = Clearance, mL/min
Us = Urine Concentration, mg/mL
Ps = Plasma Concentration, mg/mL
V = Urine Flow Rate, mL/min (+) β1 adrenergic
Renal Directly stimulate
receptors in the JG
Vasoconstriction Renal Tubular Cells
Cells
• Paraaminohippuric (PAH) Acid
o Freely filtered
o Secreted
o Not reabsorbed Increases Renin Decreases GFR and Increases Na and
o Not metabolized secretion RBF H2O Reabsorption
o Not stored
o Not synthesized
• Administer PAH → circulate in the blood → some will be filtered Functions of the Kidney
→ go to the urine (Us) 1. Excretion of metabolic waste products and foreign
• Measure the urine formed per minute (V) chemicals
• Measure the concentration in the plasma (Ps) 2. Regulation of water, plasma volume, and osmolarity
3. Regulation of electrolyte balance and other organic
As the urine concentration increases, the clearance also substances
increases. 4. Regulation of acid-base balance
o If you form a lot of urine per minute, then your clearance 5. Endocrine function and Gluconeogenesis
is good 6. Regulation of arterial blood pressure
o If you check and there is still a lot of the substance left in
the blood then your clearance is low Note: According to Starling and Smith, the kidney is more of a
REGULATORY organ rather than an excretory organ.
EXAMPLE: Effective Renal Plasma Flow (ERPF)
Concentration of PAH in Urine = 14 mg/mL
Urine Flow (V) = 0.9 mL/min
Concentration of PAH in Plasma = 0.02 mg/mL

14 𝑥 0.9
𝐸𝑅𝑃𝐹 = = 630 𝑚𝐿/𝑚𝑖𝑛
0.02