CHEGHE PEREZ

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Renal Physiology
Lecture Outline
• General Functions of the Urinary System
• Quick overview of the functional anatomy
of the urinary system
• How the nephron works & is controlled
• Micturition
• Disorders of the Urinary system
General Functions
• Produce & expel urine
• Regulate the volume and composition of the
extracellular fluid
– Control pH
– Control blood volume & blood pressure
– Controls osmolarity
– Controls ion balance
• Production of hormones
– Renin
– EPO
 Surface anatomy of the Kidney
• Hilum is located on
the medial surface

10 cm

3cm

5.5cm
4
Overview of Function Anatomy
The System

• Urinary system consists of:

Kidneys – The functional unit of the system

Ureters

Urinary Bladder Conducting & Storage

components

Urethra
Overview of Functional Anatomy
The Kidney

• Divided into an outer

cortex
• And an inner medulla

• The functional unit of

renal
pelvis this kidney is the
nephron
– Which is located in
both the cortex and
medullary areas
 External Anatomy of the Kidney
• Renal Capsule: Kidney
covered by fibrous layer of
connective tissue.
• Renal Hilum: Gives kidney
its shape.
• @ Hilum renal arteries
bring blood to kidneys to be
filtered and renal veins take
filtered blood away from
kidney.
• Ureter also attached at
hilum to transport urine
from kidney to bladder
 Internal Anatomy
of the Kidney
Kidney divided into 3 layers:
• Renal cortex: outer layer,
grainy in appearance, has little
obvious structure to naked eye;
where blood filtration occurs.
• Renal medulla: middle layer:
Transports urine to the renal
Path of Urine Production
pelvis via “pyramids.”
1. Renal Cortex
• Renal pelvis: inner layer. 2. Renal Medulla
Collects urine. 3. Renal Pelvis
 Renal Cortex
• Outer layer: grainy in appearance, has little
obvious structure to naked eye; where blood
filtration occurs.
Renal Medulla

• middle layer: Transports urine to the renal pelvis

via 7-18 “pyramids,” or collecting tubes.
• pyramids composed of collecting tubules for urine
that is formed in kidney.
 Renal Pelvis

• Inner layer: Collects, then empties urine into

proximal Ureter on way to bladder.
 Overview of Functional Anatomy
The Kidney

• The nephron consists of:

– Vascular components
• Afferent & efferent
arterioles
• Glomerulus
• Peritubular capillaries
• Vasa recta
– Tubular components
• Proximal convoluted
tubule
• Distal convoluted tubule
• Nephron loop (loop of
Henle)
• Collecting duct
– Tubovascular component
• Juxtaglomerular appartus
The Nephron
• Simplified view of its functions

• Glomerular
Filtration
• Tubular
Reabsorption
• Tubular
Secretion
• Excretion
The Nephron
• Locations for filtration, reabsorption,
secretion & excretion
Nephron
Filtration

• First step in urine formation

– No other urinary function would occur without
this aspect!
• Occurs in the glomerulus due to
– Filtration membrane &
• Capillary hydrostatic pressure
• Colloid osmotic pressure
• Capsular hydrostatic pressure
Nephron
Filtration Membrane
• Capillaries are fenestrated

• Overlying podocytes with pedicels form

filtration slits

• Basement membrane between the two

Nephron
Glomerular Filtration

• Barriers
– Mesanglial cells can alter blood flow through
capillaries
– Basal lamina alters filtration as well by
• Containing negatively charged glycoproteins
– Act to repel negatively charged plasma proteins
– Podocytes form the final barrier to filtration
by forming “filtration slits”
Nephron
Glomerular Filtration

• Forces
– Blood hydrostatic pressure (PH)
• Outward filtration pressure
of 55 mm Hg
– Constant across capillaries
due to restricted outflow
(efferent arteriole is smaller
in diameter than the afferent
arteriole)
– Colloid osmotic pressure (π)
• Opposes hydrostatic pressure
at 30 mm Hg
• Due to presence of proteins in
plasma, but not in glomerular
capsule (Bowman’s capsule)
– Capsular hydrostatic pressure
(Pfluid)
• Opposes hydrostatic pressure
at 15 mm Hg
Nephron
Glomerular Filtration

• 10 mm Hg of filtration pressure
– Not high, but has a large surface area and nature of
filtration membrane
– creates a glomerular filtration rate (GFR) of 125
ml/min which equates to a fluid volume of 180L/day
entering the glomerular capsule.
• Plasma volume is filtered 60 times/day or 2 ½ times per hour
• Requires that most of the filtrate must be reabsorbed, or we
would be out of plasma in 24 minutes!
– Still…. GFR must be under regulation to meet the
demands of the body.
Nephron
Glomerular Filtration

• 10 mm Hg of filtration pressure
– Not high, but has a large surface area and nature of filtration
membrane
– creates a glomerular filtration rate (GFR) of 125 ml/min which
equates to a fluid volume of 180L/day entering the glomerular
capsule.
• Plasma volume is filtered 60 times/day or 2 ½ times per hour
• Requires that most of the filtrate must be reabsorbed, or we would
be out of plasma in 24 minutes!
– GFR maintains itself at the
relatively stable rate of 180L/day
by
• Regulation of blood flow
through the arterioles
– Changing afferent and
efferent arterioles has
different effects on GFR
Nephron
Regulation of GFR

• How does GFR remain relatively constant

despite changing mean arterial pressure?
1. Myogenic response
• Typical response to stretch of arteriolar smooth muscle due
to increased blood pressure:
– increase stretch results in smooth muscle contraction and
decreased arteriole diameter
– Causes a reduction in GFR
• If arteriole blood pressure decreases slightly, GFR only
increases slightly as arterioles dilate
– Due to the fact that the arterioles are normally close to maximal
dilation
– Further drop in bp (below 80mmHg) reduced GFR and
conserves plasma volume
2. Tubulooglomerular feedback at the JGA
3. Hormones & ANS
Nephron
Autoregulation of GFR

2. Tubulooglomerular feedback at the JGA

– Fluid flow is monitored in the tubule where it
comes back between the afferent and efferent
arterioles
• Forms the juxtaglomerular apparatus
– Specialized tubular cells in the JGA form the macula
densa
– Specialized contractile cells in the afferent arteriole in the
JGA are called granular cells or juxtaglomerular cells
Juxtaglomerular Apparatus
 Nephron
Regulation of GFR

• The cells of the

macula densa
monitor NaCl
concentration in the
fluid moving into the
dital convoluted
tubule.
– If GFR increases,
then NaCl
movement also
increases as a
result
– Macula densa cells
send a paracrine
message (unknown
for certain) causing
the afferent
arteriole to
contract,
decreasing GFR
and NaCl movment
Nephron
Regulation of GFR
3. Hormones & ANS
– Autoregulation does a pretty good job, however
extrinsic control systems can affect a change by
overriding local autoregulation factors by
• Changing arteriole resistance
– Sympathetic innervation to both afferent and efferent
arterioles
» Acts on alpha receptors causing vasoconstriction
» Used when bp drops drastically to reduce GFR and
conserve fluid volume
• Changing the filtration coefficient
– Release of renin from the granular cells (JG cells) of the JGA
initiates the renin-angiotensin-aldosterone system (RAAS)
» Angiotensin II is a strong vasoconstrictor
– Prostaglandins
» Vasodilators
– These hormones may also change the configuration of the
mesanglial cells and the podocytes, altering the filtration
coefficient
Nephron
Regulation of GFR

• Renin-Angiotensin-Aldosterone System

(or low NaCl

flow in JGA)
Nephron
Tubular Reabsorption
• GFR = 180 L/day, >99% is reabsorbed
– Why so high on both ends?
• Allows material to be cleared from plasma quickly
and effectively if needed
• Allows for easy tuning of ion and water balance
– Reabsorption
• Passive and Active Transport Processes
• Most of the reabsorption takes place in the PCT
Movement may be
via epithelial
transport (through
the cells) or by
paracellular
pathways (between
the epithelial cells)
Nephron
Tubular Reabsorption
• Na+ reabsorption
– An active process
• Occurs on the basolateral membrane (Na+/K+ ATPase)
– Na+ is pumped into the interstitial fluid
– K+ is pumped into the tubular cell
• Creates a Na+ gradient that can be utilized for 2º active
transport
Nephron
Tubular Reabsorption

• Secondary Active Transport utilizing Na+

gradient (Sodium Symport)
– Used for transporting
• Glucose, amino acids, ions, metabolites
Nephron
Tubular Reabsorption

• The transport membrane proteins

– Will reach a saturation point
• They have a maximum transport rate = transport maximum
(Tm)
– The maximum number
of molecules that can be
transported per unit of
time
– Related to the plasma
concentration called the
renal threshold…
» The point at which
saturation occurs and
Tm is exceeded
 Nephron
Tubular Reabsorption

• Glucose Reabsorption
– Glucose is filtered and reabsorbed hopefully 100%
• Glucose excreted = glucose filtered – glucose reabsorbed

Implication of
no glucose
transports past
the PCT?
Nephron
Tubular Reabsorption

• Where does filtered material go?

– Into peritubular capillaries because in the
capillaries there exists
• Low hydrostatic pressure
• Higher colloid osmotic pressure
Nephron
Tubular Secretion

• Tubular secretion is the movement of material

from the peritubular capillaries and interstitial
space into the nephron tubules
– Depends mainly on transport systems
– Enables further removal of unwanted substances
– Occurs mostly by secondary active transport

– If something is filtered, not reabsorbed, and

secreted… the clearance rate from plasma is greater
than GFR!
• Ex. penicillin – filtered and secreted, not reabsorbed
– 80% of penicillin is gone within 4 hours after administration
Nephron
Excretion & Clearance

Filtration – reabsorption + secretion = Excretion

• The excretion rate then of a substance (x) depends on

– the filtration rate of x
– if x is reabsorbed, secreted or both
• This just tells us excretion, but not much about how the
nephron is working in someone
– This is done by testing a known substance that should be
filtered, but neither reabsorbed or secreted
• 100% of the filtered substance is excreted and by monitoring
plasma levels of the substance, a clearance rate can be determined
Nephron
Excretion & Clearance

• Inulin
– A plant
product that is
filtered but not
reabsorbed or
secreted
– Used to
determine
clearance rate
and therefore
nephron
function
Nephron
Excretion & Clearance

• The relationship between clearance and

excretion using a few examples
Nephron
Excretion & Clearance
Nephron
Urine Concentration & Dilution

• Urine normally exits the nephron in a dilute

state, however under hormonal controls, water
reabsorption occurs and can create an
extremely concentrated urine.
– Aldosterone & ADH are the two main hormones that
drive this water reabsorption
• Aldosterone creates an obligatory response
– Aldosterone increases Na+/K+ ATPase activity and therefore
reabsorption of Na+… where Na+ goes, water is obliged to
follow
• ADH creates a facultative response
– Opens up water channels in the collecting duct, allowing for the
reabsorption of water via osmosis
Micturition
• Once excreted, urine travels via the paired
ureters to the urinary bladder where it is
held (about ½ L)
• Sphincters control movement out of the
bladder
– Internal sphincter – smooth muscle (invol.)
– External sphincter – skeletal muscle (vol.)
Micturition
• Reflex Pathway
Disorders of Urinary System
ORGANS THAT CONSTITUTE
THE URINARY SYSTEM?????

Kidneys

Ureters

Urinary bladder

Urethra
 Cardinal signs of Urinary System
Disorders
► Abnormal constituents of urine
▪ Protein (Albumin), blood/ haemoglobin, cells & tissue casts,
pus, glucose, ketone bodies,etc

► Abnormal volume of urine

► Pain and dysuria

► Uraemia
 Nephritis
Etiology
•virus

•Bacteria- E.coli, Streptococci, C. renale,

Leptospira
•
•Parasites- Dirofilaria immitis, Dioctophima renale

•Toxins

•Autoimmune diseases
Clinical Signs
► Rise in body temperature

► Polydypsia and polyuria followed by anuria

► Rough and staring body coat

► Uraemia and vomiting

► Cloudy urine
Clinical Signs (contd.)

► Blood, haemoglobin, cells and tissue cast, pus in

urine

► Puffy eyelids in glomerular nephritis

► Stiff gait, arching of back and pain in the lumbar

region
Diagnosis
► From clinical signs
► Urine analysis
▪ Physical Examination: Volume, colour, transparency,
odour, foam, specific gravity.

► Chemical analysis: pH, proteins, glucose, ketone bodies,

bile, blood, etc.

▪ Microscopic analysis: cells, microorganisms, casts,

parasites, spermatozoa, sediments, etc.
Treatment
► Antibiotics - for 7-10 days

► Frusemide @ 4.4 mg/kg b.i.d

► Corticosteriods

► Vit B complex and proteins

► Dextrose normal saline- slow i/v

► Low sodium diet and plenty of water

Contraindications
Antibiotics Cephalosporins, isoniazid, macrolides,
sulfonamides, tetracycline, vancomycin,
gentamicin, neomycin

NSAIDs Almost all agents

Diuretics Furosemide, thiazides, triamterene

Miscellaneous Acyclovir, captopril, cocaine, famotidine,

ranitidine
 Cystitis

► More common in females due to the short urethra.

► Interference with the act of micturition- retention of

urine enhance bacterial multiplication.

► Invasion of bladder lead to shedding of epithelium,

erosion and haemorrhage
Etiology

► Ascending infection

► Descending infection

► Bacteria – Corynebacterium renale, E. coli,

Pseudomonas, Streptococci, Staphylococci,
etc
Clinical findings
► Animal dull, depressed,
inappetance

► Frequent attempt to urinate with

small quantity of urine

► Dysuria and abdominal pain

▪ Male dogs adopt squatting posture
during urination

► Urine cloudy containing blood

(haematuria) and cells.

► Body coat appears rough and

starring.
Treatment

► Inj. Antibiotics: for 7-10 days

► Urine pH
▪ Urine of herbivores- alkaline
▪ Urine of carnivores- acidic

► Urinary antiseptics- Hexamine

► Urinary acidifier such as sodium acid

phosphate

► Inj. Corticosteriods
Treatment (contd.)

► Inj antihistamines

► Inj. Dextrose-i/v

► In case of haematuria-
▪ Inj. Vit C or vit K.
▪ Inj Iron
▪ Inj Vit B complex

► Give plenty of drinking water.

Drugs that work well in specific pH

Acidic pH Alkaine pH Both pH

Oxyteracycline Gentamicin Sulpha drugs
Tetracycline Streptomycin Streptopenicillin
Cephalosporines Erythromycin Ampicillin
Penicillin Trimethoprim Norfloxacin
Nalidixic acid
Cephalexin
Cephaloridine
 Kidney Stones (Renal Calculi)
► Etiology:
Calcium, phosphorus, & uric acid
crystals, & nephritis.
► S/S:
Hematuria, flank/abd/pelvic pain. Urgency, fever,
N/V. Mild to extreme pain 10/10!
► D/X;
History/Exam, UA, Ultrasound or CT, KUB, IVP
 RX for Kidney Stones (Renal Calculi)
Depends on size & location of stone
► Pain/Nausea medications, fluids, strain UA
► Extracoporal Lithotripsy: shock waves to break up
stone into smaller stones.
► Ureteroscopy: fiberoptic endoscope threaded up
urethra, through bladder, & into ureter; attached
instrument shatters stone & captures pieces.
► Percutaneous Nephro/ureterolithotomy: Surgical
removal of stone
Extracoporal Lithotripsy
Urinary Tract (Bladder) Infection (UTI)
► Etiology: fecal bacteria into urinary tract
► S/S: freq, dysuria, hematuria, turbid urine, & urine
with unusual odor, fever, hypogastric or LBP.
► Dx: UA, C&S, Pt. History
► Rx: Antibiotics, increase fluids
► Prognosis: Excellent
► Pts. Most @ Risk: Women, elderly, hospitalized with
or without catheters, men with BPH.
Polycystic Kidney Disease
► Etiology: Genetic
► S/S: enlarged, cystic kidneys, hypertension, UTI,
dilute urine, liver cysts, pain, hematuria, aneurysm
► Dx: CT, MRI, Genetic tests
► Rx: various meds and or Renal Transplant
► Prognosis: No cure without transplant
Ischemic Nephropathy
► Etiology: decrease blood flow to kidneys
► S/S: kidney failure, uremia, hypertension or
hypotension, oliguria, increase serum creatinine &
urea.
► Dx: UA, BUN & Creatinine
► Rx: treat underlying cause & symptoms, possible
renal transplantation.
► Prognosis: Poor without treating cause or
transplantation.
Diabetic Nephropathy
► Etiology: Diabetes Mellitus (type I or II)
► S/S: early stages: increased glomerular filtration,
protein in urine, later: uremia, HTN.
► Dx: BUN, Creatinine, UA, 24 hour UA
► Rx: tight glycemic control, blood anti-HTN Meds,
lipid control, diet, kidney replacement
► Prognosis: Poor without RX & Pt. life-style changes
Diabetic Nephropathy
Drug Induced Nephropathy
► Etiology: drugs toxic to kidney tissue, especially
contrast dye & NSAIDs.
► S/S: early stages: increased glomerular filtration,
protein in urine, later: uremia, hypertension
► Dx: BUN, Creatinine, UA, 24 hour UA
► Rx: : stop drugs, no contrast dyes for patients with
known risk factors, keep patients well hydrated
before contrast dye use.
► Prognosis: Poor without treating cause or
transplantation.
Glomerulonephritis
► Etiology: : inflammation & scarring of glomerulus
► S/S: early stages: increased glomerular filtration,
protein in urine, later: uremia, hypertension
► Dx: BUN, Creatinine, UA, 24 hour UA
► Rx: treating underlying cause may decrease
progression.
► Prognosis: Poor if cause not found, transplantation
Uremia
► Etiology: build up of organic waste products in
blood due to renal insufficiency.
► S/S: elevated BUN & Creatinine, fatigue,
neuropathy, seizures, lack of appetite, decreased
smell & taste, mental confusion, insulin resistance,
itching, inflammation, clotting problems.
► Dx: BUN, Creatinine, UA, 24 hour UA
► Rx: dialysis or renal transplantation
► Prognosis: poor without dialysis or transplantation
Diabetes Insipidus (Dull-lacking flavor)
► Etiology: ADH deficiency
1. Central (Brain) 2. Nephrogenic (Kidneys)
► S/S: polyuria, dilute urine, thirst, dehydration, low
K+, lethargy, muscle pain, irritability.
► Dx: UA, 24 UA, BUN, Creatinine, CT head &
abdomen
► Rx: Thiazide or Amiloride “Loop” Diuretics or
surgery.
► Prognosis: Varies
Renal Failure
► Etiology: acute or chronic decrease in glomerular
filtration rate.
► S/S: decrease urine output, uremia, edema, loss of
appetite, fatigue, hiccups, nausea, mental
confusion, clotting disorder, seizures, coma.
► Dx: UA, BUN & Creatinine, CT, IVP.
► Rx: BP meds, glucose & protein control, treatment
of underlying condition, prevention CVD, peritoneal
or hemodialysis, transplantation.
► Prognosis: Good with transplantion
 Common Disorders of the Urinary System
Bladder Cancer
► Etiology: Malignant tumor fm tobacco, radiation
► S/S: Hematuria, UTI’s, dysuria
► Dx: UA, cytology, cystoscopy, CT
► Rx: 1.Transurethral Resection BT (TUR-BT)
2. Chemotherapy 3. Radiation
► Prognosis: Very good if Dx early, poor if stage 3-4.
Bladder Cancer
 Staging Cancer

The TNM System

► T: describes the size & whether it has invaded
nearby tissues.
► N: describes regional lymph nodes involved
► M: describes distant metastasis
 Staging Cancer
► 0: no cancer found
► 1: In-situ (Latin “in the place”) in the layer
of cells in which they developed.
► 2: Localized: Cancer limited to the organ in which
they developed.
► 3: Regional: Cancer spread to nearby lymph nodes
or organs.
► 4: Distant: Cancer spread to distant lymph nodes or
organs.
 Hemolytic Uremic Syndrome
➢ Etiology: bacterial infection with certain strains of
E. coli, toxins damage kidneys

➢ S/S: fever, abdominal pain, pallor, fatigue,

bruising, decreased urination, swelling

➢ Dx: blood tests, history

► Tx: blood transfusion, kidney dialysis

 Obstructive Urolithiasis
(urinary calculi or stone)

► Obstruction of the urinary tract by

urinary calculi.

► Common sites:
▪ bladder, kidney, urethra at the
ischial arch and the sigmoid
flexure.
Urethra in domestic animals
Etiology
► Feeding high concentrates

► Pasture containing high oxalate and silica

► Hypervitaminosis D

► Avitaminosis A

► High estrogen intake

► Less water intake

 Pathogenesis

Calcium Oxalate Kidney Stone with Uric Acid Nidus

Common calculi in different species

► Dogs: Calcium phosphate, calcium oxalate

► Cattle/horse: Calcium/ magnesium/

ammonium phosphate

► Pig: Calcium/ magnesium carbonate,

magnesium phosphate
Clinical signs

► Anorexia and lethargy

► Small amount of urine in partial obstruction to

anuria in complete obstruction.

► Repeated attempts to urinate but in vain.

► Abdominal pain

► Per rectal examination: distended /flattened UB

► Distended ventral abdomen if UB ruptured.

Treatment
► Location of the site of obstruction can be
done by passing a urinary catheter.

► Tab cystone - 3-4 tab daily x 15-20 days

► Allopurinol @ 10 mg/kg p.o. t.i.d x 4 wks

► Inj. Antibiotics

► Surgical intervention- urethrotomy and

removal of the calculi.
 Drugs safe for use

► Penicillin

► Ampicillin

► Erythromicin

► Chloramphenicol
 Urinary incontinence

Constant dribbling of urine due to loss of voluntary

control of micturation. This could be due to:

▪ Bladder paralysis- damage of nerve

▪ Abnormal disposition of urinary organs

▪ Oestrogen and testosterone responsive incontinence

▪ Obstruction of urethra
http://www.youtube.com/watch?v=kZ0o6ubcYEA
 Treatment

► Attempt should be made to control the primary cause

► Measures to prevent infection

► Empty distended bladder

► Neurovitamins to induce contraction power of urinary

bladder
THANKS FOR YOUR KIND
ATTENTION