Aubf Lec Prelims

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[TRANS] LECTURE UNIT 01: RENAL FUNCTIONS

INTRODUCTION o Right kidneys are located


slightly lower than the left
• Functions of the Kidney:
because there is a liver (a
o (1) Elimination of waste products (metabolic by- very large organ) on the
products formed in the body) and conservation of right portion
important substances
• By location, kidneys are
▪ Kidney filters the blood so that blood will be termed “retroperitoneal”
cleansed and recirculated which means behind the
▪ The formed waste products will be eliminated in peritoneum.
the form of urine o Physicians pound this area (flank) to know if a
▪ Sometimes, substances are filtered out even if person has kidney infection, pyelonephritis, or UTI.
they are still usable. For the substances that o Retroperitoneum – likod
have been filtered but the body can still make
Physiologic Anatomy of the Kidney
use of it, the kidneys can conserve it.
o (2) Regulation of body fluids • Kidneys are part of the urinary system which mainly
o (3) Acid–base balance functions to filter the blood to produce urine
• Above the kidneys are adrenal glands (suprarenal
▪ Kidneys and lungs regulate this glands) which are part of the endocrine system.
o (4) Electrolyte balance o Suprarenal glands – above the kidneys
o (5) Maintenance of blood pressure
o (6) Erythropoiesis ▪ supra = above
▪ produces erythropoietin in response to hypoxia ▪ renal = kidney
or low blood supply to the tissues • 4 main components of urinary system:
 Hypoxia will trigger the kidneys to release o Kidneys – where urine production happens
erythropoietin → erythropoietin will stimulate o Ureters – where the produced urine travels
the bone marrow to produce RBCs to o Urinary bladder – where the ureters transport the
increase oxygenation rate urine for temporary storage
• Despite their relatively small size, the kidneys receive o Urethra – where the urine will be voided out to the
approximately 25% of the cardiac output external world through urination or micturition
o Cardiac output – blood being pumped by the heart • Hilus
o Kidneys need stable blood supply. If these run
o Where renal artery enters
out of blood supply, they cannot filter anymore.
o Cardiac output: renal artery delivers blood to the
o When there is no delivery of blood to the kidneys,
kidneys
the kidneys will shut down, and the person will die.
o Blood exits the kidney after being filtered via the
Gross Anatomy renal vein
o Renal vein exits via the hilus together with the ureter
Figure 1. Anatomy of Male (left) and Female (right) Figure 2. Urinary system
Urinary Tract

• 2 pair of kidneys (left and right) located at each side of


the vertebral column

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 1
LECTURE UNIT I: RENAL FUNCTIONS

Kidney Anatomy • Cortical nephrons

Figure 3. Physiologic Anatomy of the Kidney o Functions: (RR)


▪ Removal of waste product from the blood
▪ Reabsorption of nutrients
• Juxtamedullary nephron
o Final concentration of urine
o Final adjustment of urine composition before it is
voided out

Figure 3. Types of Nephrons

• Renal capsule – outer covering of kidneys


• Internal Structures: Cortex, Medulla, and the Renal
Pelvis
o Cortex – below the renal capsule; outer layer of the
kidneys
▪ Cortex may invaginate down to the medulla
o Medulla – middle layer; below the renal cortex
o Renal pelvis – expansion of the upper ureter
Renal Papillae

• Cortical Nephrons – Short Loops of Henle.


Renal Column

o Called cortical because most parts are found in the


renal cortex.

• Juxtamedullary nephrons – Long Loops of Henle.


o Called juxtamedullary because its parts extend
down to the renal medulla.

Figure 4. The Human Kidney & Nephron


• Renal column – extension of the renal cortex down to
the medulla
• Renal pyramids – between renal columns; already part
of the medulla
• Renal papillae – pointed ends (apex) of the renal
pyramid
o Projects or protrudes toward minor calyx
▪ Minor calices form or fuse together forming
major calyx
▪ Major calices join together forming renal pelvis
• Renal pelvis extends toward the ureter → urinary
bladder → urethra

Nephrons

• Nephrons are functional unit of the kidneys


o 1-1.5 Million per kidney
o Not capable of regeneration after damage
o Has two types:
Parts of a Nephron
▪ Cortical – 85-90%
▪ Juxtamedullary – 10-15% • (1) Renal Corpuscle: Bowman’s Capsule and
Glomerulus

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 2
LECTURE UNIT I: RENAL FUNCTIONS

o Bowman’s capsule: Encloses Bowman’s space Renal Functions

• The ability of the kidney to selectively clear waste


products from the blood and simultaneously maintain
body’s essential water and electrolytes is controlled by
nephron by the following functions:
o Renal Blood Flow
▪ How the blood enters the glomerulus and/or
kidney and how it exits it
o Glomerular Filtration
▪ How the glomerulus filter blood
o Tubular Reabsorption
▪ Has 2 layers: Parietal and Visceral o Tubular Secretion
 Parietal – Epithelial cells Renal Blood Flow
 Visceral – Podocytes (“Pod” = Feet/Foot-like
cells); attached to the capillary wall in the
glomerulus
o Glomerulus: has specialized capillaries that filters
blood.
▪ Exact structure that filters blood
▪ remove waste products so that the filtered blood
will be back to the circulation, while the waste
product will be eliminated through urine.
o Bowman’s space: in-between Bowman’s capsule
and glomerulus that marks the start of the urinary
space; adjacent to the proximal convoluted tubule.
• (2) Proximal Convoluted tubule (Wavy)
• (3) Loop of Henle
o Has 2 types: Ascending and Descending
• (4) Distal Convoluted tubule
• PCT + Loop of Henle + DCT = Renal Tubules
(Collective term)
• (5) Collecting Ducts
o Collecting ducts are not considered part of a
nephron
Figure 5. Parts of a Nephron • Kidney is supplied by blood by the renal artery, and it
should reach the glomerulus
• Blood enters the capillaries of the nephron through the
afferent arterioles → glomerulus → efferent arterioles
o Blood enters the glomerulus through the afferent
arteriole (A-Adto)
o Blood exits the glomerulus through the efferent
arteriole (E-Exit)
o There is already blood in the glomerulus to be
filtered out
• Products of Glomerular filtration:
o (1) Filtered Blood
▪ Blood cleaned of impurities
▪ After glomerulus, it won’t proceed to the PCT, as
it needs to go back to the circulation. Hence, it
exits through the efferent arteriole
o (2) Ultrafiltrate (urine) – composed of consolidated
impurities filtered out from the blood

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 3
LECTURE UNIT I: RENAL FUNCTIONS

▪ From the glomerulus, it will enter the PCT → ▪ Enough hydrostatic pressure is needed for the
descending loop → ascending loop → DCT → glomerulus to do its function
collecting duct → papillary duct → minor calyx →
• In a 70kg (1.73m2 body surface), the total renal blood
major calyx → renal pelvis → ureter → urinary
flow is 1200 ml/min (average body weight)
bladder → urethra
• Total renal plasma flow is 600-700 mL/min
• Blood from the efferent arterioles enter the peritubular
capillaries and vasa recta and flows slowly through the NOTE: The reference range of total renal blood/plasma flow
cortex and medulla close to the tubules. It will exit the vary depends on the weight of the person.
kidney via the renal vein, back to the circulation to be
reoxygenated
Glomerular Filtration

• Function: allows metabolic waste products to be


excreted from the body
• Glomerulus
o Specific structure of the kidney that allows the body
to filter the blood
o composed of coil of approximately 8 capillary lobes
referred to as capillary tufts enclosed within the
Bowman’s capsule
o Consolidation of 8 capillary lobes
• Glomerulus – Nonselective filter of plasma substances
with MW of less than 70,000 da
o Sieve = “salaan”
• Peritubular capillaries surround the PCT and DCT ▪ It can filter substances present in the plasma
o This is for immediate reabsorption of essential and blood provided that the molecular weight of
substances in the PCT and final adjustment of urine the substances is less than 70,000, which would
concentration in DCT end up in the urine.
o Larger substances (>70,000) (E.g. larger proteins)
• Vasa Recta surrounds the loop of Henle
▪ cannot be filtered by the glomerulus
o For major exchanges of salt and water
o Cortical nephrons do not have vasa recta due to ▪ they do not become part of the filtrate that leaves
their short loop of Henle the glomerulus, but it can still be excreted out of
the body via different mechanism.
Afferent vs Efferent Arteriole
Several Factors that Affect the Filtration Processes
Figure 4. Afferent and Efferent Arterioles
• (1) Structure of the capillary wall
• (2) Hydrostatic and Oncotic Pressure
• (3) Renin-Angiotensin-Aldosterone System

Capillary Wall Structure

• Structure of the Capillary Wall - walls of the capillary


that makes up the glomerulus
• Glomerular Filtration Barrier:
o Membrane of the fenestrated capillaries
▪ Does not allow passage of cells and large
molecules
▪ Fenestrated - there are pores present
• The afferent arteriole has a larger lumen than the ▪ Only small substances can enter the pores
efferent arteriole.
▪ Larger substances cannot squeeze through the
o (1) There will be more blood entering the glomerulus fenestra or pores of the capillaries. Thus, larger
compared to the blood that exits substances are not filtered.
▪ This ensures consistent and sufficient blood o Basement Membrane
supply in the glomerulus
▪ Above the lining of the capillaries
o (2) It produces hydrostatic pressure
▪ Repels some substances present in the blood
▪ Hydrostatic pressure is the pressure created by
o Podocytes of the Visceral epithelium of the
the entering blood in the afferent arteriole
Bowman's Capsule

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 4
LECTURE UNIT I: RENAL FUNCTIONS

REMEMBER: Renal corpuscle has two layers: parietal ▪ Larger substances are retained inside the
and visceral layer capillaries of the glomerulus and become part of
• Pedicels - foot processes that are attached to the the blood that will exit to the efferent arteriole.
capillary wall and are intertwined.
• Filtration Slit - formation of intertwining podocytes
which will not allow passage of cells and large Figure 6. Glomerular Filtration – Shield of Negativity
molecules

• Shield of Negativity
o Normal histologic structure of glomerulus
▪ Negatively-charged - cells and tissues making
up the glomerulus
o Rule of thumb: “If they are of the same charge,
they repel each other”
▪ If the substance to be filtered is the same as the
glomerulus, which is negatively charged (shield
of negativity), it cannot be filtered since it cannot
be squeezed out.
o E.g. Albumin
• Glomerular Filtration Barrier - act as a barrier that ▪ a negatively-charged and ionic protein that is
allow only smaller substances (E.g. water molecules, abundant in the blood
small proteins, and ions) and will restrict the passage of
large molecules that do not become part of the urine. ▪ Usually, there is little to no albumin in the urine
because the glomerulus does not filter it
o (1) Blood will flow into the glomerulus, where it will
be filtered.  They repel each other because they are both
negatively charged.
▪ As it circulates at the glomerulus, the large
substances present in the blood cannot pass 3 Pressure that Affects Glomerular Filtration
through the pores
 Smaller substances are filtered because they
can pass through the pores
▪ Basement Membrane - Outside the capillary
wall, which may help further repel the
substances passing through it
▪ Foot Processes of Podocyte – last structure
comprising the mechanism that contributes to
glomerular filtration
 Attached near the capillary walls
▪ Filtration Slit – spaces in between foot
processes
o (2) Hydrostatic Pressure
▪ Plasma will be pushed against the glomerulus • (1) Glomerular (Blood) Hydrostatic Pressure
and will exit via the glomerulus.
o Usually at 55 mm Hg
▪ Water molecules and other smaller substances o Pressure with the greatest impact to glomerular
in the blood can pass through pores and filtration
squeeze through filtration slits. If they are
o Pressure exerted by the blood that enters the
already out, they become part of the urine.
glomerulus via the afferent arterioles and fill up the
glomerulus.

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 5
LECTURE UNIT I: RENAL FUNCTIONS

▪ The influx of the entering blood exerts its own  10 mm Hg is the pressure that allows fluid to
pressure which is called hydrostatic pressure. leak out on the glomerulus to be filtered.
▪ Hydrostatic pressure allows the blood to press • Pressure affects the filtration
against the capillaries to be filtered.
• (2) Blood Colloid Osmotic Pressure Renin-Angiotensin-Aldosterone System
o Other term: Oncotic Pressure
o Has a lesser impact compared to hydrostatic
pressure
o 30 mm Hg
o Pressure exerted by proteins towards water.
▪ Proteins especially albumin have a natural pull
towards water molecules.
o Counteract the push provided by the hydrostatic
pressure.
• (3) Capsular Hydrostatic Pressure
o Pressure exerted by the renal capsule (Bowman’s
capsule)
o 15 mm Hg • Juxtaglomerular apparatus (JGA)
o Exhibits a push demonstrator of the fluids going o Composed of juxtaglomerular cells from the
back to the glomerulus. afferent arteriole and macula densa from the distal
• Oncotic and Capsular Hydrostatic Pressure go against convoluted tubules.
the direction exerted by the Hydrostatic Pressure. o Juxtaglomerular cells (afferent) and macula densa
(DCT) meet at the Juxtaglomerular apparatus
o Hydrostatic pressure “pushes” towards the o JGA is responsible for the activation of RAAS
capillaries; Oncotic and Capsular “pulls back” to the
glomerulus Blood Pressure
o Too much hydrostatic pressure will hasten the rate
of filtration. • The blood circulating the body exerts pressure against
o Hydrostatic will always be greater than the sum of the arteries in which it is flowing
the two.
o BP allows the blood to circulate.
NOTE: Observe which direction that the pressures direct the ▪ Hypertension – high blood pressure
fluids inside the glomerulus.
▪ Hypotension – low blood pressure
• Hydrostatic pressure, Oncotic pressure, and ▪ Both cases are problematic/deadly and must
Capsular pressure be corrected.
▪ RAAS is activated when the body experiences
hypotension or low blood pressure.
o Blood pressure is greatly affected by water volume
▪ High water volume → High blood pressure
(Hypertension)
▪ Low water volume → Low blood pressure
(Hypotension)
NOTE: Water volume in blood vessels is affected by salt
volume (sodium).
• Rule of thumb: Wherever salt goes, Water follows.
• NFP (Net Filtration Pressure) • If there is high volume of salt in the blood vessel, then
water will go to the blood vessel.
o NFP is the remaining pressure that facilitates
glomerular filtration. REMEMBER:
o NFP can be computed by:
• HYPERTENSIVE individuals follow a low salt diet to
• Formula prevent the increase of water volume in blood
o NFP = Glomerular Hydrostatic Pressure – Capsular circulation, hence preventing and increase in blood
Pressure – Oncotic Pressure pressure.
• Low plasma sodium and low water retention will result
• Or Hydrostatic Pressure – (Capsular + Oncotic) = NFP in a low overall blood volume, which will now lead to low
▪ E.g. 60 mm Hg – 18 mm Hg – 32 mm Hg = 10 blood pressure or HYPOTENSION.
mm Hg

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 6
LECTURE UNIT I: RENAL FUNCTIONS

CASE AT HAND: In times of Hypotension (Low BP), RAAS will pressure by triggering the sympathetic system to
be activated initiate sympathetic activity.

• Low Blood Pressure = Low water Volume = Low salt


volume in the blood ▪ Actions of RAAS (Effects of Angiotensin II):
• Q: How does the body correct low blood pressure? 1. Dilates the afferent arteriole and constricts the
o The body corrects it by activating the Renin- efferent arteriole
Angiotensin-Aldosterone System (RAAS) o It will make the afferent arteriole bigger so that
o If the body is able to detect that it is experiencing more blood will enter the glomerulus.
hypotension, it will trigger the juxtaglomerular o REMINDER: The kidneys should have a stable
apparatus to release renin. supply of blood which becomes difficult during
hypotension where there’s low blood delivery.
▪ To address this problem, the Angiotensin II
will dilate the afferent arteriole and narrows
down the efferent arteriole, leading to the
increase of blood flow going to the kidney to
ensure the sufficient blood flow in the kidney.
▪ It will also inhibit the exit of blood from the
glomerulus due to the constriction of the
efferent arteriole.
2. Stimulates sodium reabsorption in the proximal
convoluted tubule
o Angiotensin II will tell PCT to reabsorb sodium
(salt)
o If the salt is reabsorbed (transferred back to the
blood), then the water will follow which will now
lead to the correction of hypotension by restoring
the salt volume.
3. Triggers the adrenal cortex to release the sodium-
retaining hormone aldosterone to cause sodium
reabsorption and potassium excretion in the
collecting duct
o Aldosterone will allow the body to reabsorb
sodium (salts). By reabsorbing sodium, we are
also retaining water.
o Through this, we are correcting low blood
pressure by restoring water volume.
o Potassium must be excreted because it has an
adverse relationship with sodium.

4. Triggers antidiuretic hormone (ADH) release by


the hypothalamus to stimulate water reabsorption
• If there is HYPOTENSION:
in the collecting duct.
o (1) The juxtaglomerular apparatus will release o Antidiuretic hormone (ADH)/vasopressin/Arginine
RENIN vasopressin (AVP) is a hormone released by the
hypothalamus and is temporarily stored by the
▪ Renin is an enzyme which acts on
posterior pituitary gland.
ANGIOTENSINOGEN, a blood-borne substrate
o Once ADH is released by the hypothalamus, it
produced by the liver to produce ANGIOTENSIN
will tell the collecting duct to reabsorb more
I.
water.
 Angiotensin I, same with Angiotensinogen is o The reabsorbed water will then go to the blood. If
inactive and does not yet trigger biologic it is returned to the blood, we are restoring the
activities. blood volume by restoring water.
o (2) Angiotensin I is acted upon by Angiotensin-
converting enzyme (ACE) to convert to • Q: Are we correcting low blood volume? Are we
ANGIOTENSIN II (active form) correcting low blood pressure?

▪ Angiotensin II is active and can already trigger o Yes, by retaining sodium and water because blood
biologic activities. volume is greatly affected by water and salt.
▪ Angiotensin-converting enzyme (ACE) is an
enzyme present in the lungs
▪ Angiotensin II is the substance that will correct
low blood pressure. It will address low blood

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 7
LECTURE UNIT I: RENAL FUNCTIONS

CONCLUSION The pressures that drive glomerular filtration

• As a result of the glomerular mechanisms:


o Approximately 120 mL of water-containing low
molecular weight substances are filtered every
minute
o The only difference between the urine filtrate and
plasma is the presence of proteins
▪ Remember: proteins are most of the time not
filtered by the glomerulus, they are being
retained in the plasma.
o Analysis of the fluids as it leaves the glomerulus
shows to have specific gravity of 1.010
▪ Specific gravity will be adjusted when the tubular
reabsorption and tubular secretion will take
place.

Review (Source: Tortora) Regulation of the aldosterone secretion by the renin


angiotensin-aldosterone (RAA) pathway.
Relationship of a nephron’s structure to its three basic
functions: glomerular filtration, tubular reabsorption, and
tubular secretion

The filtration membrane

RAMOS, MATABALAO, BAUZON, NUEVO, CRUDA, BOYOSE, VILLANUEVA, EVANGELISTA, TEVES, MARASIGAN. PACANA BSMLS 3 8
[TRANS] LECTURE UNIT 02: RENAL FUNCTIONS PART 2

TUBULAR REABSORPTION
• RECALL: As a result of glomerular filtration, water
molecules are filtered out from the blood due to the
action of glomerulus. Hence, there is water loss.
• But the body cannot lose 120 mL of water every minute
• Therefore, some substances (water and other solutes)
in the urine need to be reabsorbed.
• Tubular Reabsorption – return of most of the filtered
water and many solutes to the bloodstream
o Transport of substances from the filtrate running
inside the renal tubule back to the blood circulating
in peritubular capillaries.
• Q: Why is there a need to return some substances? • Filtrate from glomerular filtration contains substances
that flows through the lumen of proximal convoluted
o Those substances have to be reabsorbed because
tubule (PCT) will be transported back to the blood
they are needed or can still be used by the body
through:
o Conservation of substances
o Active transport using ATP
• About 99% of filtered water are reabsorbed o Passive transport
• Proximal convoluted tubule cells make the largest
contribution in the reabsorptive process • Most of the time, a substance that is not reabsorbed
• 65% of filtrate is reabsorbed into body back to the blood are excreted in the urine

Cellular Mechanisms Involved in Reabsorption


Table 1. Summary of Tubular Reabsorption
Active Transport

• Movement of a substance across a cell membrane and MECHANISM SUBSTANCE LOCATION


against an osmotic gradient Glucose, amino
• Needs a carrier protein to transport substance acids, and salts
PCT

o Needs assistance/ pump Active transport Ascending loop of


Chloride
Henle
• Requires energy
Sodium PCT and DCT
Passive Transport PCT, Descending
Water loop of Henle,
• Movement is due to differences in the concentration Collecting ducts
or electrical potentials
Passive transport PCT and Ascending
Urea
o Movement of substances: loop of Henle

▪ From an area of higher concentration to area of Sodium


Ascending loop of
lower concentration Henle

▪ Due to the differences in electrical charges


between two compartments of the cell, where RECALL: Most substances (65%) are reabsorbed in the
one side has a positive charge and the other has proximal convoluted tubule (PCT)
negative charge
• MNEMONICS: USWAG –
• Does not need carrier protein molecules that can be
• Does not require energy reabsorbed in the PCT
o Urea
Process of Tubular Reabsorption o Salt (sodium)
o Water
Active and Passive Diffusion Processes o Amino acids
o Glucose
• Tubular cells – cells that make up the renal tubules

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 1
PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

Active Transport Loops of Henle

Maximal Reabsorptive Capacity (Tm – Tubular maximum) • Permeable to salt


• ALoH (Ascending Loops of Henle): Impermeable to
• Highest level a substance is reabsorbed before water
appearance of substance in the urine
o ALoH does not allow reabsorption of water
• Highest level of a substance that the renal tubule can o The walls/lining of ALoH is very thick: water cannot
reabsorb at a given time go out
• Usually expressed at mg/min. o The only thing that can be reabsorbed are just salts
• Ex: Glucose is at 350 mg/min.
• As filtrate moves thru the ascending limb, NaCl moves
o The renal tubules can only reabsorb a maximum of
out making the filtrate more and more dilute
350 mg of glucose per minute.
• Significance: Keep the renal medulla region of the
o When there is excess (e.g., 400 mg/min), the
kidney at high osmolarity so water can move passively
remaining 50 mg is not reabsorbed. Hence, they are
out of the filtrate in the CT
excreted and becomes part of the urine
o The renal medulla of the kidney has its own
Renal Threshold osmolarity – naturally salty
o It must maintain a certain osmotic gradient due to
• The plasma concentration of the substances at which the presence of salt
active transport of reabsorption stops o It should be salty to help facilitate water reabsorption
o Concentration of a substance in the blood affects from the filtrate
the ability of the tubule to reabsorb that substance o Rule of Thumb: Water follows salts

• Different substances have different renal threshold ▪ Wherever salt is, water follows = if the medulla is
salty, water from the filtrate can go out bound to
Table 2. Renal Threshold the medulla
Countercurrent Mechanism
SUBSTANCE RENAL THRESHOLD
Glucose 160-180 mg/dL
Ketone bodies 3 mg/dL
Calcium 10 mg/dL
Bicarbonate 30 mEq/L
• Ex: Glucose is at 160-180 mg/dL
o Concentration of glucose in the blood/plasma that
the tubules can reabsorb
o If it exceeds the renal threshold, the excess is not
reabsorbed, becomes part of the urine/ filtrate.
o Application: patients with Diabetes Mellitus
(hyperglycemia) – high blood sugar
▪ There is a possibility that their blood glucose can
reach as high as 300 mg/dL
▪ Blood containing 300 mg/dL of glucose is filtered
out by the glomerulus and reach the renal
tubule.
▪ Once in the renal tubule, out of 300 mg/dL, only • Reabsorption already happened in the PCT
180 mg/dL is reabsorbed back to the blood • The filtrate will continue to go down to the (1)
descending loop to (2) ascending loop to the (3)
▪ The remaining 120 mg/dL becomes part of the
distal convoluted tubule, (4) collecting
filtrate.
duct and to the (5) urinated duct
▪ Glucose appears in the urine. Patients will • (1) The medulla should be salty to
exhibit glucosuria maintain the osmotic gradient
▪ Glucosuria - presence of glucose in the urine; o Why: As the filtrate continues to go
common for people with high blood sugar down the descending loop of Henle,
▪ Urinalysis: positive for glucose because it water will be reabsorbed
exceeded the renal threshold
▪ The water will come out to the
filtrate that’s flowing in the
descending loop

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 2
PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

▪ Why is water able to move out? • Renal concentration begins in the loop of Henle where
 The arrow (pointing the H20) means it is being filtrate is exposed to a high gradient of the renal medulla
reabsorbed. The water goes out to be part of o The salinity of the medulla helps in pulling out the
the medulla (peritubular capillaries are water from the filtrate that is running inside
present but not visible in the picture) o The water will leak out to be reabsorbed from the
 Water is being pulled out by the salinity of the medulla to the vasculature, to the capillaries
medulla • Water is reabsorbed through osmosis in the descending
o Water reabsorption is possible in the descending loop of Henle
loop because of the osmotic gradient of the medulla. o The principle of water movement is osmosis
• (2) The filtrate will go up to the • Na and Cl are reabsorbed in the ascending loop of
ascending loop of Henle Henle
o The ascending loop of Henle o Water is not included since it cannot exit the thick
has thick walls and will not walls of the ALoH
allow the water to go out o It is very important to avoid dilution of the medulla
▪ Salts can only go out
because of active transport QUESTION: Which of the following descriptions would
▪ Water molecules are just best characterize the urine as it leaves the ascending loop
being retained inside the of Henle?
filtrate
o The filtrate in ascending loop is losing salt but not • Hypotonic or Hypertonic? Hypotonic
water
o COUNTERCURRENT MECHANISM: the thickness • What is the concentration of the filtrate that leaves the
of ascending loop not allowing the water to go out • ALoH and enters the DCT?
o Hypotonic – more water, less salt - diluted
QUESTIONS: Why is Countercurrent Mechanism o Hypertonic – more salt, less water - concentrated
Important? Why is not allowing water to exit the ALoH
▪ Hypotonic because water is retained
important? Why is it a necessary process?
▪ Eventually, the salt concentration will be
• Water must not continually lose in the ALoH adjusted as the filtrate continues to the DCT and
into the medulla in the collecting ducts.
Tubular Reabsorption Cont.

NOTE:
• If more water molecules enter the medulla, the
salt/salinity of the medulla will be diluted
• The medulla will lose its osmotic gradient, then it can’t
help reabsorbing water in the descending loop anymore
• Water reabsorption in the collecting duct will also be
affected
• Do not allow excessive water to go through ALoH to
maintain the normal gradient/salinity of the medulla

• Reabsorption of sodium continues in the collecting


ducts but is now under the control of the hormone
aldosterone.
o Aldosterone exerts its function in the DCT, but
recent molecular evidence suggests that it exerts
function in the collecting ducts.
o Sodium reabsorption in the collecting ducts is not
anymore influenced by the osmotic gradient of the
medulla for any matter but it’s influenced by the
hormone aldosterone

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LECTURE UNIT 02: RENAL FUNCTIONS PART 2

• The final concentration of the urine takes place in the • Low blood osmolality in a well-hydrated person (blood is
late distal convoluted tubule and continues in the not viscous) → No stimulation of Pituitary gland
collecting duct. (posterior) → No release ADH → No increase
expression of aquaporin channels in the collecting duct
o Necessary adjustments in the filtrate concentration
= NO REABSORPTION OF WATER = HYPOTONIC
can be made in the distal convoluted tubules (DCT)
URINE
and continue to reabsorb water
o Water adjustments can also take place in the o No reabsorption = water can be freely urinated out
collecting duct.
• CD reabsorb NaCl
• Reabsorption is now dependent on the osmotic gradient • Water remains in urine
of the medulla and the hormone Antidiuretic hormone
(Vasopressin). Summary

o ADH will allow for water reabsorption in the


collecting duct IF REQUIRED.
Influence of ADH (Antidiuretic Hormone)

• Important in CONTROL OF WATER LOSS in our body


o How concentrated or diluted your urine is
depends upon the body’s state of hydration
▪ E.g., When drinking water
 The more water we drink = the more we
urinate and vice versa
o Urination is a form of water loss because majority
of the components of the urine is water

Dehydration

• Inadequate amount of water in the body= hypertonic


urine (more concentrated urine) TUBULAR SECRETION
• High blood osmolality in a dehydrated person →
stimulates Pituitary gland (posterior) → release ADH →
act on collecting duct→ ↑ aquaporin channels, ↑ CD’s
water permeability= REABSORPTION OF WATER=
HYPERTONIC URINE = Not much water loss
o High blood osmolality = blood becomes viscous
▪ It should be lessened (osmolality) as it is deadly.
o High blood osmolality will trigger the hypothalamus
to produce ADH, which is temporarily stored in the
posterior pituitary gland
o Once needed, the posterior pituitary gland will
release ADH, and the ADH will act on the collecting • Passage of substances from the blood in the peritubular
duct (CD) capillaries into the tubules
• Opposite of tubular reabsorption
▪ What is the action of ADH in collecting duct?
• Transport of substances from the blood flowing in the
 ADH increases the expression of aquaporin peritubular capillaries to the filtrate flowing in the renal
channels in the collecting duct, allowing for tubules
the reabsorption of water.
o Peritubular capillaries are adjacent or positioned
o Water must go back to the blood to reduce the near the tubules to facilitate easy reabsorption and
osmolality/viscosity. secretion
o Reabsorption of water to the blood = lose less water o Peri = near; -tubular = renal tubule
in the urine = urine is HYPERTONIC (concentrated)
▪ More concentrated urine = did not loose that • Renal tubes =
much water and the color is very yellow where the filtrate is
moving
Drink a Large Amount of H2O

• Hypotonic urine (called water diuresis) • Peritubular


capillary = where
o Hypotonic = more water, less salt the filtered blood is
o Diuresis (urination) = urinating because of drinking flowing
too much water

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PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

Functions • Three Regions:


o Proximal
(1) Elimination of waste products not filtered by the
convoluted
glomerulus
tubule cell =
cell lining the
• Even if glomerular filtration is a nonselective process, it
renal tubule;
cannot filter everything. Substances that are essentially
a cell
small, smaller than 70,000 Daltons in size, can only be
comprising
filtered.
the PCT
• For whatever the glomerular filtration cannot remove,
o Lumen of
tubular secretion can
PCT – where
o Urea, uric acid, bile acids, ammonia, the filtrate
catecholamines, prostaglandins, and little creatine and potential urine is passing through
are substances the glomerulus cannot filter but o Bloodstream – blood flowing in the peritubular
can be eliminated by tubular secretion (TS) capillaries adjacent to the PCT.
o TS also clears the blood of pollutants, morphine,
penicillin, aspirin, and other drugs • Trace the Secretion of Hydrogen to Regulate Acid-Base
Balance
▪ Many drugs are large. When broken down into
(1) Conserving Bicarbonate
simpler components, it is still large that the
glomerulus cannot filter them.
• Bicarbonate - Naturally present in the blood and
▪ These drugs should not stay in the blood as they naturally filtered by the glomerulus
are poisonous and are eliminated through
tubular secretion. o Bicarbonate must not be lost that much. It has to be
retained in the body
• Many foreign substances such as medications (e.g., o It is an alkalinizing substance, thus too much
penicillin) are not filtered by the glomerulus because bicarbonate = alkaline environment
they are bound to proteins, but they develop an affinity
to the tubular, which causes them to dissociate from • Body is naturally acidic due to many metabolic
their protein carriers = SECRETED processes inside the body.
o (1) Penicillin takes effect on the body o Blood has the highest tendency to be acidic. But the
o (2) The body will break down the penicillin into body has buffer systems that can neutralize its own
smaller component acidity.
o (3) Penicillin metabolites will be bound to proteins
especially albumin • GOAL: Reabsorb bicarbonate back to the blood by
secreting hydrogen
▪ In the body, penicillin is attached to the protein.
o Renal tubular cells secrete hydrogen  lumen of
Since they are compound, it becomes large
proximal tubule  hydrogen + bicarbonate =
o (4) Since it is large, the glomerulus cannot filter it 𝑐𝑎𝑟𝑏𝑜𝑛𝑖𝑐 𝑎𝑛ℎ𝑦𝑑𝑟𝑎𝑠𝑒 𝑒𝑛𝑧𝑦𝑚𝑒
carbonic acid (H2CO3) →
and will be part of the filtered blood and will exit by
water and CO2
the efferent arteriole then→ peritubular capillaries
o (5) Penicillin will be more attracted to the squamous ▪ Carbonic acid will be acted upon by the enzyme
endothelial cells in the peritubular capillaries than carbonic anhydrase to break down into water
the carrier albumin that it will detach from albumin and CO2
and becomes smaller → the peritubular capillaries
 Water – can become part of the filtrate or
will secrete the penicillin to the filtrate → becomes
diffuse into the cell
part of the urine = TUBULAR SECRETION
 Carbon dioxide - will certainly diffuse back to
the cell
𝑐𝑎𝑟𝑏𝑜𝑛𝑖𝑐 𝑎𝑛ℎ𝑦𝑑𝑟𝑎𝑠𝑒 𝑒𝑛𝑧𝑦𝑚𝑒
o CO2 + water → carbonic acid
 spontaneously dissociate into hydrogen and
bicarbonate
▪ Carbonic anhydrase enzyme – can facilitate a
reversible reaction
(2) Regulation of acid base balance in the body through  Can break down or make carbonic acid
the secretion of hydrogen
▪ Bicarbonate will be reabsorbed back to the
• Renal tubular cells can secrete hydrogen blood to neutralize the acidity of the blood
 Neutral pH – 7.3 to 7.45
o A lot of hydrogen ions can make a certain
fluid/environment acidic ▪ Hydrogen ion – can be used again to repeat the
cycle

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PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

(2) Excretion of Secreted Hydrogen Ions combined with • Direct release of hydrogen to the tubular lumen to meet
Phosphate to Reduce Acidity with ammonia
o Regulate acid base balance by the direct excretion
• Hydrogen ions can contribute to the acidity. Thus, to of hydrogen ions
regulate acid-base balance, some hydrogen ions must
be removed. • Ammonia
• If hydrogen does not pair with bicarbonate, some o Produced by the renal tubular cell
hydrogen can actually be still secreted to the renal o By-product of breakdown of amino acid glutamine.
tubule o Can be secreted to the lumen and fused with
o In the renal tubule, they don’t pair with bicarbonate hydrogen to form ammonium ion, that is directly
but instead with phosphate / hydrogen phosphate excreted.
molecules
• Urine contains ammonium, and has ammoniacal
o When hydrogen attach to phosphate, it becomes
scent.
dihydrogen phosphate which can just be excreted
in the urine
RENAL FUNCTION TESTS
• Even if another round of bicarbonate is not absorbed,
acid-base balance is still regulated by releasing • Q: Why test for Renal function?
hydrogen in its self. o (1) To assess the functional capacity of kidney
o (2) Early detection of possible renal impairment
o (3) Monitor severity and progression of the
TUBULAR SECRETION
impairment
o (4) Monitor response to treatment
o (5) Monitor the safe and effective use of drugs which
Renal Peritubular are excreted in the urine
Tubular
Tubular Cell
Lumen Plasma
PROCEDURES AND METHODS TO ASSESS FOR
HPO4- H++ HCO-3 THE RENAL FUNCTION
HCO-3
H 2CO3
Glomerular All
HPO4- + H+
Filtration clearance
Carbonic Tests (GFT) tests
anhydrase

H2PO4
H 2O + CO2 CO2
RFT Tubular Urine
Reabsorption concen
Tests tration
tests

(3) Excretion of Secreted Hydrogen Ions combined with


Ammonia produced by the Tubules
Tubular
Secretion PAH,
TUBULAR SECRETION and Renal Titratable
Blood Flow acidity,
Tests Urinary
Ammonia
Tubular Renal Peritubular
Lumen Tubular Cell Plasma

NH3 • 4 renal functions:

NH3 + H+ o (1) Glomerular filtration tests


H++ HCO-3 HCO-3 o (2) Tubular reabsorption tests
o (3) Tubular secretion tests and (4) Renal blood flow
H 2CO3 tests
▪ Same principle and methods
Carbonic ▪ PAH = Para Amino Hippuric acid
anhydrase
NH4+ CO2 RENAL FUNCTION TESTS - GFR
H 2O + CO2
• About 1200 ml of blood (650 ml plasma) passes through
the kidneys, every minute.
• About 120-125 ml is filtered per minute by the kidneys &
this is referred to as glomerular filtration rate (GFR).

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PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

(1) Glomerular Filtration Tests • Disadvantage:

• To asses for GFT, perform clearance tests – gold o (1) 40% of the filtered urea is reabsorbed by the
standard tubules = hydration needs to be done

o Measures the rate by which the kidneys are able to ▪ The actual amount that is filtered would be
remove a filterable substance from the blood. reduced due to the reabsorption. Thus, the
actual value cannot be measured
• Sample used is a 24-hour urine
▪ Hydration of patient = extra procedure
o In a 24-hour (1 day) period, all urine outputs of the
Inulin
patients must be collected in one container then
submit to the laboratory for measurement
• Polymer of fructose
• Criteria for the clearance test • Advantages:
o The substance must be neither reabsorbed nor o (1) Highly stable in a 24-hour collected
secreted by the tubules. o (2) Neither reabsorbed nor secreted
▪ The substance should only be filterable. • Disadvantage:
▪ The substance should not be reabsorbed o (1) Exogenous – requires infusion at a constant
because it would reduce its actual value thus, rate because it is not a normal body constituent.
may cause a false decrease.
Radionucleotides/ Radioisotopes
▪ If the substance was secreted, it may cause a
false increase in its value.
• Tested by its disappearance from the plasma, thereby
 Secretion is one way of elimination. It will eliminating the need for urine collection.
contribute to the increment of the volume or
amount of the substance. o If the radionucleotides cannot be monitored from the
plasma, then that means it has already been filtered
o The substance must be stable during the 24-hour out by the kidney.
collection
▪ E.g., 125 I-iothalamate
▪ Stable = not degraded, should remain intact
• Advantage:
o Substance’s availability in the body
o Enables visualization of the filtration in the kidneys
▪ Endogenous substance is preferred
 Endogenous = present inside the body • Disadvantage:

▪ Exogenous substance is not preferred o Exogenous – not a normal constituent of the body;
needed to be infused in the patient’s body in order
 Exogenous = not a normal constituent of the for it to be detected.
body; artificially infused; foreign substance) o Since it is foreign, it is never without risks.
o Consistency of plasma level Cystatin C
o Availability of the test in the lab

Clearance test • Low molecular weight


• Potential marker for long-term monitoring of renal
• Urea function
• Inulin • Constant in serum levels
• Radionucleotides • Not secreted by the tubules
• Cystatin C • Independent of age, gender, and muscle mass
• Beta-2-microglobulin • Ideal clearance test substance
• Creatinine • Higher analysis cost
Urea o There are no laboratory methods in the lab that is
readily available to detect for it
• Earliest glomerular filtration tests Beta-2-microglobulin
o Considered as a conventional substance used in
clearance testing in the past • Forms part of the class I MHC present in leukocytes
o Currently, urea is no longer used (11,800 da)
• Dissociates at a constant rate from WBCs and is rapidly
• Advantages:
removed from the plasma by the kidneys (through
o (1) Present in all urine specimens filtration)
o (2) Available lab methods
o (3) Endogenous

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 7
PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

• However, test is not reliable in patients with Compute for Glomerular Filtration Rate (GFR)
immunologic diseases, viral infections, and malignancy
• Reported in mL/min
o There can be fluctuations in its level which makes it
• Normal is 120mL/min
hard to standardize results
o Males: 107-139 mL/min
o Females: 87-107 mL/min
• In computing GFR, one must first know the following:
o (1) Urine concentration of substance (creatinine) in
mg/dL
▪ Get the concentration in a 24-hour urine
Creatinine
o (2) Plasma concentration of substance (creatinine)
in mg/dL
• Most widely used endogenous procedure o (3) Urine volume or urine flow in mL/min
o Waste product of muscle metabolism and found at a ▪ Calculated as the number of mL of urine divided
constant rate in the blood. by the minutes used to collect the specimen
• Formula
𝑼𝒙𝑽
𝑪=
𝑷
𝑈𝑟𝑖𝑛𝑒 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑥 𝑈𝑟𝑖𝑛𝑒 𝐹𝑙𝑜𝑤
𝑮𝑭𝑹 =
𝑃𝑙𝑎𝑠𝑚𝑎 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛

Sample Problem

• Calculate the GFR for a 24-hour specimen measuring


1440ml. Urine creatinine is 120mg/ dL while plasma
• Disadvantages: creatinine is 1.0mg/ dL
o (1) Secreted by tubules and secretion increases as (1) Compute first for urine volume or urine flow
blood level increases
o (2) Chromogens in the plasma can react in the
chemical analysis for creatinine • Convert 24-hrs into minutes
o (3) Bacteria will break down urinary creatinine if • Urine volume = volume of urine in mL/minutes of
specimen is kept at room temperature for extended collection
period of time. o Urine volume = 1440mL/ (24 hours x 60 minutes/hr)
o (4) Chromogens in the plasma can react in the o Urine volume = 1440mL/1440 minutes
chemical analysis for creatinine o Urine volume = 1mL/minute
o (5) Bacteria will break down urinary creatinine if the
specimen is kept at room temperature for an (2) Compute for the GFR
extended period of time
Urine Concentration x Urine Flow
▪ This is a potential risk because 24-hr urine 𝐆𝐅𝐑 =
sample is used which contains bacteria. The Plasma Concentration
bacteria can consume or breakdown the 120mg/dL x 1mL/min
𝐆𝐅𝐑 =
creatinine thereby decreasing its level in the 1.0mg/dL
urine, resulting in a false decrease result. 𝐆𝐅𝐑 = 𝟏𝟐𝟎𝐦𝐋/𝐦𝐢𝐧
o (6) A diet heavy in meat consumed during the
collection of a 24-hr urine will influence the What if the surface body area is not equal to 1.73 m2?
creatinine level
• Assumption: 1.73 m2 is the standardized human body
▪ Meat intake can contribute to the creatinine level surface
present in the body, which may not be an actual • Make adjustments by multiplying GFR by 1.73/A
representation of GFR because of increased
consumption o “A” stands for the body surface of the patient
o Compute the surface body of the patient then divide
o (7) Not reliable in patients with muscle-wasting it in 1.73
diseases o Then multiply the answer with the computed GFR
▪ Muscle-wasting disease: A disease in which
your own body is digesting your own muscles
abnormally thereby producing more creatinine
• Despite its disadvantages, creatinine is still use as
clearance test substance because it is endogenous and
readily available in the body

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 8
PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

Problem: Cockcroft-Gault Formula • REMEMBER: Concept of Hydration


o Hydrated – not much need to reabsorb to conserve
• What if medications for renal failure need to be started water so it is okay to lose water in the form of urine
prior to waiting for 24-hour urine collection?
▪ Urine will have more water, thus diluted and low
o Compute Estimated GFR (EGFR) if 24-hr urine
specific gravity
collection is not possible
o Estimated GFR is presented by the Cockcroft- o Dehydrated – body will try to conserve water by
Gault Formula allowing water to be reabsorbed, since the body is
o Factors in computing EGFR: age, bodyweight & absorbing water
sex
o For men: ▪ Urine output will have less water and be more
concentrated
(140 − 𝑎𝑔𝑒) 𝑋 𝑏𝑜𝑑𝑦𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
𝑪𝒄𝒓 = ▪ Less water more solute, high specific gravity
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 (𝑚𝑔/𝑑𝐿) 𝑋 72
Concentration Test
o For women: • The ability of kidneys/tubules to form a concentrated
(140 − 𝑎𝑔𝑒) 𝑋 𝑏𝑜𝑑𝑦𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔) urine after states of dehydration
𝑪𝒄𝒓 = 𝑋 0.85 • Reflective of tubular reabsorption process
𝑠𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 (𝑚𝑔/𝑑𝐿)𝑋 72

For GFR interpretation, consider the following: Water Deprivation test

• It is determined not only by the number of nephrons • Fishberg Test - patients deprived of fluid for 24 hours
but also by their functional capacity prior to measuring the specific gravity

o GFR is a reflection of the functions of your nephron, o Expected result:


not necessarily the number of the nephrons but also ▪ Specific gravity must be higher, hence urine
by their functional capacity must be concentrated
▪ Kidneys can compensate for each other • Mosenthal Test – compared the volume of day and
o Example: night urine samples to evaluate concentrating ability

▪ One half of the nephrons are nonfunctional, GFR • Both tests make use of specific gravity to measure the
still remains normal if the remaining nephrons concentration of urine sample
double their capacity • Both are obsolete
▪ When nephrons are damaged because of kidney o Specific gravity (as a means to measure the
disease, remaining nephrons can compensate concentrating ability of nephron, as a means to
for the damaged nephrons measure the final urine output) is not much valuable
• Conclusion: to asses for tubular reabsorption.

o It cannot detect early renal disease Specific Gravity vs. Osmolality


▪ It is more on monitoring of the progress of the • Osmolality – measures the number of dissolved
disease particles in a solution
o It can only evaluate the extent of nephron damage o Better measurement of urine concentration of the
▪ GFR is impaired – if nephron damage is too tubular reabsorptive capacity of kidney than specific
severe that remaining nephron cannot gravity
compensate o E.g., Scenario: A beaker contains a solution and has
3 molecules of glucose.
o It can also be used to determine if a person can be
started on a medication ▪ Osmolality will just simply count the glucose
molecules in the solution. Therefore, osmolality
(2) Tubular Reabsorption Test (Concentration test) result is 3 and is low.

• Loss of tubular reabsorption capacity is the first sign of • Specific gravity – measures the number and density of
renal disease the particles in the solution
o Tubular reabsorption is a more complicated process o Count the number of dissolved particles in the
solution and the weigh each particle as to its density
• As previously mentioned, ultrafiltrate that enters the and molecular weight.
tubules have specific gravity of 1.010 and it is expected o Using the same scenario above:
that the final urine can be more concentrated or diluted
depending on hydration. ▪ Specific gravity will count how many glucose in
the solution which is 3 and then, will weigh each
o Diluted sample if <1.010 specific gravity glucose molecule #1, #2, and #3.
o Concentrated sample if > 1.010 specific gravity
▪ Specific gravity can be high since it took
consideration its density

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 9
PACANA
LECTURE UNIT 02: RENAL FUNCTIONS PART 2

Fluid Deprivation Test o Nephrogenic Diabetes Insipidus – kidneys cannot


respond to the stimulation of ADH
• Makes use of osmolality than specific gravity
▪ Collecting ducts are ignoring the ADH →
• (1) Overnight water/fluid deprivation test for 12 hours collecting ducts are not stimulated to reabsorb
(8pm to 8am) water → no reabsorption of water → excessive
o No fluid intake for 12 hours urination
• (2) Urine is collected after 12 hours (8am), and measure ▪ Production of ADH is enough and is not the
urine osmolality problem

o Expected result: Tubular Secretion and Renal Blood Flow Test


▪ Urine must be concentrated – more salt, less • Test to measure tubular secretion of nonfiltered
water substances and renal blood flow
o If the urine osmolality is above 800moSm or higher o Substance used: secreted not filtered
– NORMAL
o IF the urine osmolality is below 800moSm, fluid • (1) Phenolsulfonphthalein Test
restriction is continued for two more hours o Obsolete test
• (3) After two hours, urine and plasma are collected. o A dye that is not filtered but secreted
Osmolality is tested. ▪ Injected to the patient
o Normal- urine osmolality of or above 800moSm or if o If seen in the urine = tubular secretion is present
the urine to serum osmolality ratio of or greater
than 3:1 • (2) ρ-amino hippuric acid test (PAH)
o Expected result:
o Injected to the patient
▪ Osmolality of urine must be higher since the o Eliminates out of the body via tubular secretion
water content is less because the patient is o After injecting of PAH to the body, renal Blood Flow
deprived of water than in plasma which has a delivers PAH to the kidneys → PAH cannot be
higher water content. filtered in the blood → goes to the peritubular
• (4) If the test continues to be abnormal, additional capillaries → secreted to the tubules
testing should be done to diagnose diabetes insipidus o If PAH is seen in the urine = tubular secretion is
present
o Abnormal – urine output is very dilute, the patient is
not reabsorbing water ▪ Renal Blood Flow is enough
• (5) Patient is injected with ADH • (3) Titrate Acidity & Urinary Ammonia
• (6) Serum and urine are collected after 2 and 4 hours o Ability of kidney to produce acid urine depends on
o If test becomes normal = Neurogenic Diabetes tubular secretion of hydrogen and production of
insipidus ammonia by the cells of the PCT, DCT, and CD
o If test result is below 400moSm or ratio is 1:1 = o Inability to produce acid urine = Renal Tubular
Nephrogenic Diabetes Insipidus Acidosis

Diabetes Insipidus ▪ Failure of tubular secretion of hydrogen


▪ RTA happens if the renal tubular cells cannot
• Diabetes mellitus – glucose is the problem secrete hydrogen to the lumen, the hydrogen
• The problem of DI is Antidiuretic hormone (ADH) ions remain inside the cells and cells of renal
tubules acidifies the urine instead of the
• Signs and Symptoms: hydrogen ions.
o Polyuria – excessive urination o Measurement of total hydrogen ion excretion in
o Urine – too watery, high-water content urine
o Hardly form a urine that is concentrated
▪ Check urine pH
• 2 types of DI
▪ Perform Titratable Acidity
o Neurogenic Diabetes Insipidus – problem is in the
 Measures free hydrogen ions by performing
production in the nervous system specifically
titration
hypothalamus
 Titration can also check the total acidity of the
▪ ADH is produced abnormally less urine sample
▪ ADH is low → lesser ADH that will stimulate ▪ Measurement of ammonia = check the
nephrons to reabsorb water → less water ammonium
reabsorption → excessive urine output
 Get the difference between the titratable acid
(acid from free hydrogen) and total acid →
urinary ammonium

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 10
PACANA
[TRANS] LECTURE UNIT III: INTRODUCTION TO URINALYSIS

THE BEGINNING OF LABORATORY MEDICINE o In cases of kidney damage or


kidney diseases, albumin can
• The study of urine can be found in the drawings of be found in the patient’s urine
cavemen
• By means of boiling, white
Edwin Smith (1862) precipitates were formed
o Signifies the presence of
• Edwin Smith Surgical
protein in the patient’s urine
Papyrus
(albuminuria)
o Egyptian hieroglyphics
o Ancient Egyptian Microscope invention (17th century)
medical text named
after the one who • The invention of the microscope in the 17th century
bought it, Edwin Smith, introduced the microscopic examination of urine
in 1862. sediments.
o Oldest known surgical o They were looking or examining the presence of
treatise on trauma urine sediments found in the patient’s urine.
• Pictures of early physicians commonly examining urine Richard Bright (1827)
in bladder-shaped flask
• By examining or looking at urine, they were able to • Richard Bright (1827) –
obtain diagnostic information British physician who
o Color introduced the concept of
o Turbidity/Clarity urinalysis as part of
o Odor doctor’s routine patient
o Volume examination.
o Viscosity o Urinalysis as part of the
o Sweetness routine laboratory test is
▪ Before, physicians used to taste the patient’s still applicable today
urine to identify the underlying condition. • In 1836, he was the first to describe the clinical
manifestation of the kidney disorder known as Bright’s
Hippocrates (5th century BCE) disease, or nephritis
• In 5th century BCE, Hippocrates wrote a book on urine o Bright’s disease = old name
examination entitled “UROSCOPY”. o Acute glomerular nephritis = new name
o Uroscopy is the historical medical practice of ▪ Inflammatory disease of the kidneys
visually examining a patient’s urine
Thomas Addis (1911)
▪ Observing (using the naked eye) for the
presence of pus (WBCs), blood, and other • Thomas Addis (1911) – a Scottish
symptoms of disease that can manifest in the physician scientist and a pioneer in
patient’s urine. the field of nephrology introduced the
• During the Middle Ages, physicians concentrated their method for quantifying urine
efforts intensively on urine exam as part of their sediments (Addis count)
training o Addis count - Technique for the
o Urinalysis should be part of the routine test quantitative determination of
performed in terms of diagnosing the underlying cells (rbc/wbc) as well as proteins
condition of the patient. by means of utilizing 12-hour
urine sample
Frederik Dekkers (1694)
19th century – Up’s and Down’s
• In 1694, Frederik Dekkers discovered albumin
(albuminuria) in urine by boiling it. • Early 19th century led to the near dissolution of
urinalysis in routine medicine due to complexities of the
o Albumin – protein normally found in the blood and various test.
being filtered by the kidneys
o There was a difficulty in performing urinalysis tests
and methods due to unadvanced technology

BAGAL. BAUZON. BOYOSE. CRUDA. EVANGELISTA. NUEVO. MANZANO. MATABALAO. MARASIGAN. TEVES. VILLANUEVA. BSMLS 3 1
RAMOS. PACANA
LECTURE UNIT III: INTRODUCTION TO URINALYSIS

• Middle 19th century up to the present became a ▪ pH, osmolality, protein, urea, creatinine, glucose
milestone due to the development of modern testing ▪ Uses reagent strips or pads which are
techniques, rescued routine urinalysis and remained supplemented with different reactions to pH,
integral part of patient examination. protein, blood, urobilinogen etc.
o Improved technology is helpful in the development o (3) Microscopic examination
of routine urinalysis
▪ To observe sediments in the patient’s sample.
▪ There are now advance machines that can yield These sediments can include RBCs, WBCs,
urinalysis result readily. urinary casts, crystals (normal or abnormal), and
Urine as a Specimen of Choice bacteria.
Urine Composition
• Two popular characteristics of urine as specimen of
choice: • Generally, urine contains urea, and other organic and
o (1) Readily available and easily collected inorganic chemicals dissolved in water
• Composition can vary depending on:
▪ Readily available as long as the patient stays
hydrated (drinking water) o dietary intake
▪ Easily collected using midstream clean catch, ▪ Including water intake
unlike in blood that requires venipuncture or
o physical activity
phlebotomy.
o body metabolism
o (2) Contain information which can be obtained by o endocrine functions
inexpensive lab test, about many of the body’s major o position
metabolic functions.
▪ Standing, sitting, etc.
▪ Urine is a waste product that can be tested to
• Urine is 95% water and 5% solutes
give information about the body’s metabolic
function. o 5% solutes including:
URINALYSIS ▪ urea, sodium, potassium, phosphate
and sulfate ions, creatinine, uric acid
• Provides information about the state of the kidney and
urinary tract  Urea (56%) – major organic
• Can reveal diseases that have gone unnoticed because composition of the urine
they do not produce signs and symptoms  Chloride (14%) - major inorganic
composition of the urine
o Abnormalities upon lab testing indicates a problem
in the kidneys
o Examples:
▪ Diabetes mellitus
▪ Various forms of kidney failure
▪ Chronic urinary infections

Organic Components of the Urine

• Urea – major dissolved solid


• Creatinine
• Uric acid
• Hormones
• Vitamins

• Three Integral Parts of Urinalysis Inorganic Components of the Urine


o (1) Physical examination • Chloride – major inorganic solid
▪ Gross appearance • Sodium
• Potassium
▪ Color, volume, clarity of urine
o (2) Chemical examination
▪ Comes first before microscopy

BAGAL. BAUZON. BOYOSE. CRUDA. EVANGELISTA. NUEVO. MANZANO. MATABALAO. MARASIGAN. TEVES. VILLANUEVA. BSMLS 3 2
RAMOS. PACANA
LECTURE UNIT III: INTRODUCTION TO URINALYSIS

Urine Volume Table 1. Diabetes mellitus vs. Diabetes insipidus

• Dependent on the amount of water that the kidney DIABETES DIABETES


excretes MELLITUS INSIPIDUS
• Affected by state of hydration
• Influenced by fluid intake, fluid loss from nonrenal Malfunctioned
Decrease in production
Definition of pancreas/
sources, secretion of ADH, and need to excrete or function of ADH
the Disease malfunctioned insulin
dissolved solids production (Antidiuretic Hormone)
• Urine Output References:
Urine
o Normal: 1200-1500 ml/day Specific Increased Decreased to normal
o Acceptable: 600-2000 ml/day Gravity

Conditions Associated with Urine Volume


• Urine Specific Gravity
• Oliguria
o To identify whether it is diabetes mellitus or diabetes
o Decrease in the daily urine volume; commonly seen insipidus
in states of dehydration o Normal Urine - 1.010 – 1.040
o Diabetes mellitus - 1.030 – 1.040
▪ Infants: Less than 1 ml/kg/hr
▪ Children: 0.5 ml/kg/hr ▪ Due to the presence of sugar (e.g. glucose)

▪ Adults: less than 400 ml/day o Renal threshold of glucose is 160-180 mg/dL. Once
the glucose level will go pass the renal threshold,
o Dehydration can be caused by: the tubules won’t be able to absorb the remaining
glucose and then it will be excreted in the urine.
▪ Diarrhea
o The glucose present in the urine will be dissolved
▪ Vomiting
causing the increased in urine specific gravity.
▪ Perspiration
o Diabetes insipidus
▪ Burns
▪ Patients will have diluted urine; hence their urine
• Anuria specific gravity may be decreased to normal.
o Cessation of urine flow
Specimen Collection
▪ Absence of urine
• Urine should be collected
▪ Can be caused by serious kidney damage or in a clean, dry, leak-proof
decreased blood flow to the kidney. containers (disposable)
 Kidney diseases that can affect the normal • Disposable containers
function of the kidney will lead to lesser or eliminate the chance of
cessation of urine production. contamination due to poor
washing.
▪ It may also occur because of some severe
obstruction like kidney stones or tumors. • Wide-mouth containers
recommended for females
• Nocturia • Should have wide flat bottom to avoid overturning
o An increased nocturnal secretion of urine • Containers should be clear to assess urine color and
clarity.
▪ Urine production is increased at night • Recommended capacity should be 50mL (12mL is the
▪ Normal is 2-3 times less than the day urination average volume required)
• Should be labelled with name, age, sex, identification
▪ Can be caused by global polyuria and bladder
number and date and time of collection
storage disease.
• Label should be on the container, not on the lid
• Polyuria • Improperly labelled specimens should be rejected
o Increase in daily urine volume
▪ Greater than 2.5 L/day in adults, and 3L /day in Specimen Integrity
children • Urine should be delivered to the lab within 2 hours
▪ Associated with diabetes mellitus and diabetes after collection. If cannot, urine should be refrigerated
insipidus or added with appropriate preservative.
▪ Can also be because of alcohol, caffeine and o There are some analytes that will be affected
diuretics (increased or decreased)
Types of Specimen

Random specimen

• Most common

BAGAL. BAUZON. BOYOSE. CRUDA. EVANGELISTA. NUEVO. MANZANO. MATABALAO. MARASIGAN. TEVES. VILLANUEVA. BSMLS 3 3
RAMOS. PACANA
LECTURE UNIT III: INTRODUCTION TO URINALYSIS

• Ease of collection; convenient for the patient o Less traumatic compared to the suprapubic and
• Affected by diet and physical activity catheterized urine specimen
• Routine screening o Just void the first portion of the urine and collect the
mid portion
First Morning Specimen
• Method for bacterial culture and routine urinalysis
• Ideal routine specimen • Specimen is less contaminated with epithelial cells and
• Concentrated specimen bacteria, since it is middle portion of the urine.
o Can detect chemicals and cells not detected in Clean catch procedure for females
diluted specimen
• Good for testing for pregnancy
• For evaluating orthostatic proteinuria

Second Morning/Fasting Specimen

• Second voided urine after a period of fasting


• Will not contain any metabolites from previously
ingested food
• Good for urine glucose determination

2-Hour Postprandial Specimen

• Patient is asked to void shortly after a meal and to


collect urine 2 hours after eating. The specimen is
tested for glucose.
• Monitoring of effectivity of insulin therapy • (1) Wash hands
o avoid contamination
Glucose Tolerance Specimens
• (2) Remove lid from the container without touching the
• Collected to correspond to blood samples drawn during inside of the container or lid
GTT
• Tested for glucose and ketones o Avoid any form of contamination

o Fasting • (3) Separate skin folds (labia)


o 1 Hour
o 2 Hour
o 3 Hour

24-Hour Specimen (Timed) Specimen

• Quantitative analysis of urine


• For substances greatly affected by exercise, meals and
metabolism
o Catecholamines
o 17-hydroxysteroids
o Electrolytes
• Patient must begin and end with an empty bladder
• (4) Cleanse from front to back on either side of the
Catheterized Specimen urinary opening with antiseptic towelette, using a clean
one for each side of labia
• Urine is collected under sterile conditions by passing
o Wiping will lessen the contamination that will affect
through a hollow tube through the urethra and through
the test result.
the bladder
• Bacterial culture • (5) Hold the skin folds apart and begin to void into the
toilet the first portion.
• (6) Bring the urine container into the stream of urine and
collect an adequate amount of urine. Do not touch the
inside container or allow the container to touch the
genital area
o Adequate amount of urine – almost 3/4 of the
container
o Collect the middle portion of the urine
Midstream Clean-Catch Specimen
• (7) Finish voiding into the toilet
• Safer, less traumatic method for bacterial culture and
urinalysis

BAGAL. BAUZON. BOYOSE. CRUDA. EVANGELISTA. NUEVO. MANZANO. MATABALAO. MARASIGAN. TEVES. VILLANUEVA. BSMLS 3 4
RAMOS. PACANA
LECTURE UNIT III: INTRODUCTION TO URINALYSIS

• (8) Cover the specimen with the lid. Touch only the side
of the lid and container
• (9) Label the container with name and time of collection
o After collecting, submit it to the laboratory for testing
Clean catch procedure for Males

• (1) Wash hands


• (2) Remove lid from the container without touching the
inside of the container or lid.
• (3) Cleanse the tip of the penis with antiseptic towelette
and let dry. Retract foreskin if uncircumcised.
• (4) Void into the toilet. Hold back foreskin if necessary.
• (5) Bring the urine container into the stream of urine and
collect an adequate amount of urine. Do not touch the
inside of the container or allow the container to touch
the genital area.
o Adequate amount of urine – 3/4 of the container
• (6) Finish void into the toilet
o After collecting the middle part of the urine, void the
rest part of it.
• (7) Cover the specimen with the lid. Touch only the side
of the lid and container
• (8) Label the container with name and time of collection
NOTE:
• Do not forget to label the container before submitting it
to the laboratory

BAGAL. BAUZON. BOYOSE. CRUDA. EVANGELISTA. NUEVO. MANZANO. MATABALAO. MARASIGAN. TEVES. VILLANUEVA. BSMLS 3 5
RAMOS. PACANA
[TRANS] LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

PHYSICAL EXAMINATION OF URINE o Not necessary to assume directly that a patient has
pathologic condition if he/she presents a urine
• First procedure performed after receiving and verifying sample that is uncommon.
urine specimen submitted in the laboratory
• Precedes chemical and microscopic examination ▪ A patient has just ingested a certain food or
drugs that tends to contribute to a different urine
• Includes the determination of urine color, clarity, and
color
specific gravity.
▪ The patient’s urine is dark yellow because of
o Odor – not part of routine urinalysis but is a dehydration due to strenuous physical activity or
noticeable property once the container is opened just through normal metabolism
▪ Most routine urine samples smell the same way • Target: Aid in the diagnosis of a patient based on
 They are aromatic or odorless at times pathologic conditions by reporting the urine color that
▪ If there is deviation on the normal smell of urine, can be seen physically so that the physician could
it should be verified further, before reported. correlate everything in the urinalysis report with the
However, cases like this are rare conditions seen on the patient.
• Early physicians used a ‘wheel of urine’
o Taste – not part of modern routine urinalysis and
should not be done because of safety reasons o Importance of the
performance of
• Already performed by early physicians urinalysis was
already known
o They were already aware that deviation on the
during early times
normal urine color, clarity, odor, and taste
→ especially the
corresponds to a disease state
differentiation of the
• Provides preliminary information on disorders different urine
• Can be used to confirm or to explain findings in the colors that may be
chemical and microscopic areas of urinalysis seen on the
patient’s urine
o Should not immediately conclude that a patient is o Used glass flasks
suffering from something based on physical called ‘matula’ to
examination alone. view urine samples
o To confirm the source of the abnormality in the
physical examination of urine, chemical and ▪ Clear container should be used when examining
microscopic examination are done. a urine color
• NOTE: A physician should not rely on laboratory results o Terms used before: ‘white as well water’, ‘ruddy
alone when diagnosing a patient because lab tests work as pure intense gold’, ‘black as dark horn’
in conjunction with other tests as well as the ▪ Different urine colors correspond to a certain
examination of patient’s history, vital signs, etc. description, and a certain disease correlation
▪ “To be as objective as they can” when examining
URINE COLOR
urine samples:
 Terms used in colors are compared to the
objects → to eliminate subjectivity in the
analysis of urine color
▪ White – does not really point to the white color;
colorless characteristic (comparing urine sample
that is so dilute → looks like water)
▪ As the urine color changes, it could point to a
• There is a spectrum of different urine colors that may be disease state.
exhibited by the patient’s urine
• Varies from almost colorless to black • Common descriptions: pale yellow, yellow, dark
yellow
o May be due to normal metabolic functions, physical
activity ingestion of food or drugs, or pathologic o Intensity has variation
conditions o Dark yellow – commonly observed in hydrated
patients

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 1
PACANA
LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

• Examine sample under a good light source → to o Common reason: If patient has to be
properly differentiate the color subjected to urinalysis, they have
the tendency to drink lots of water to
o Examine on a test tube/ transparent container
induce urination
• Urochrome: pigment responsible for the yellow color of ▪ Commonly received: random
urine specimens which are collected
o Product of endogenous metabolism; produced at a at any time of the day.
constant rate
• Polyuria in diabetes insipidus: increased 24-hour
▪ The variation on how yellow the sample is can volume and low SG, negative glucose test result
be correlated on the patient’s hydration state o Early physician taste test: “bland/tasteless”
o It does not vary → correlate different conditions
based on the intensity of the yellow color
• Polyuria in diabetes mellitus: increased 24-hour
▪ Example: If the urine sample of the patient is volume, high SG, and positive glucose test result
pale yellow → it is a dilute because the patient is o Higher SG than diabetes insipidus because of the
well hydrated presence of glucose
 Dark yellow – the sample is very o The early physicians do taste test.
concentrated; the patient is dehydrated
▪ If the urine tastes like honey or sweet, it is
o Dependent on body’s metabolic state diabetes mellitus
o Gives a rough estimate of urine concentration
o Mellitus – “honey-like”
• Additional pigments:
II. Dark Yellow to Amber
o May be present on urine sample but exists in
smaller concentrations compared to urochrome → • Concentrated specimen
they are overwhelmed by its presence; their colors • Commonly observed: first morning
do not manifest always urine
o Uroerythrin: pink color in refrigerated specimens
o No water consumption during sleep,
▪ This tend to be present in samples that have the color of urine upon waking up
been standing for quite some time, or in tends to be dark yellow or amber
specimens that are not fresh, or specimens
which underwent preservation • Intake of B complex vitamins

o Urobilin: orange-brown color to urine that is not o (B2) Riboflavin imparts a dark yellow color to urine
fresh once it is metabolized

▪ Ex. Leaving urine sample to stand at room • Dehydration


temperature for quite some time, even if it is • Incorporation of acriflavine: urinary antiseptic
yellow from the start → orange-brown color o Commonly mistaken with positive bilirubin as they
• Urochrome and urobilin are the same (based from other have same color. If this is the case:
references) ▪ Perform bile test results
• Based on Strasinger: There is a stark difference
between the urochrome and urobilin  Bilirubin: yellow foam when shaken and
positive chemical test for bilirubin
 (+) = bilirubin; (-) = acriflavine
I. Colorless to Pale Yellow
▪ Can also perform fluorescence test
 Acriflavine = negative bile test results and
possible green fluorescence
• Nitrofurantoin: prescribed in UTI
o Patient who has taken nitrofurantoin or complex
vitamins cannot be distinguished in the laboratory.
o Further inquiry about patients' drug history, medical
history, etc. is needed. It is up to the physician to
correlate everything the lab reports.

III. Dark Yellow

• Bilirubin
• Dilute random specimen o One common way to detect if bilirubin is present is
o Because of recent fluid consumption by performing reagent strip.
▪ Patients is well-hydrated. ▪ Examination of urine will test positive on the
bilirubin strip.

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 2
PACANA
LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

o Old way – shake the sample for several minutes VII. Blue Green
o Yellow foam when shaken and positive chemical
test for bilirubin • Amitriptyline: antidepressant
• Methocarbamol (Robaxin): Muscle
▪ Yellow foam – positive relaxant which may be green to brown
indicator for bilirubin in
• Clorets
a dark yellow to amber
colored urine. o Similar to a candy which contains
▪ White foam – Presence chlorophyll.
of protein in urine with o Excessive ingestion can cause blue-green
color other than dark discoloration to urine
yellow • Methylene blue: used in fistulas
IV. Orange Yellow o Fistulas – abnormal connections or pathways
between blood vessels or organs.
• Phenazopyridine (Brand name: Pyridium) o Underwent in procedure to determine the presence
o Antibiotic responsible for discoloration of fistulas.
o Injection of methylene blue dye to color the areas
• Phenindione with fistulas, which is then eliminated through urine.
o Anticoagulant (rarely used), orange yellow in • Phenol: When oxidized (people exposed to benzene)
alkaline urine, colorless in acid urine. • Indican: the patient has bacterial infections and/or
▪ Rarely used in cases of hypersensitivity intestinal disorders (e.g., blue diaper syndrome)
reactions. • NOTE: Physicians should explain the side effects of
medications (change in urine color) thoroughly to the
▪ Warfarin – commonly used anticoagulant
patients so as to avoid unnecessary stress and shock.
▪ Apparent on alkaline or basic urine.
Blue Diaper Syndrome
V. Dark Yellow Green
• A rare, genetic metabolic disorder characterized by the
• Bilirubin oxidized to biliverdin incomplete intestinal breakdown of tryptophan
o Urine is no longer fresh o The amino acid tryptophan did not completely
o Oxidation upon prolonged standing and improper breakdown which caused it to accumulate. Thus, the
storage (e.g., exposed to light) accumulated tryptophan will be broken down by the
▪ Urine samples should be tested immediately to bacteria in the intestine which would result to
detect the presence of bilirubin during chemical indican.
examination. o By virtue of the excessive breakdown of tryptophan
which caused an accumulation of indican will then
o Formation of colored foam in acidic urine and false- result to a blue urine color.
negative chemical test for bilirubin
• Intestinal bacteria break down
▪ Bilirubin is positive in immediate testing. tryptophan resulting to increased
▪ False negative – bilirubin might have been amounts of indicant.
detected or tested positive on its fresh state.
o Commonly observed in infants
 If bilirubin is not anymore detected, it could wherein their diapers turn blue or
cause erroneous implication on the patient’s have blue stains when they urinate.
diagnosis.
VIII. Pink
VI. Green
• Due to the presence of few hemoglobin and few red
• Indicate the presence of active Pseudomonas infection blood cells
o Confirmation through positive urine culture o These could point to the presence of blood in urine
▪ Negative culture – do not have Pseudomonas from urinary tract or from menstrual contamination
infection. IX. Red
 Look for other conditions for the patient’s
urine turning green. • Most common abnormal urine color
• Red blood cells (intact)
o Cloudy urine, positive chemical test
for blood, seen under the microscope
• Hemoglobin
o Clear urine, positive chemical test for blood;
intravascular hemolysis
▪ You may not see intact RBCs under the
microscope

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 3
PACANA
LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

• Myoglobin ▪ After 2 hours = urine is entirely black


o Clear urine, positive chemical test for blood; due to o Additional instructions can be given if the doctor
muscle damage suspects that the patient is suffering from
alkaptonuria
▪ It is up to the doctor to determine whether the
red blood color in due urine is due to hemoglobin • Malignant melanoma: Presence of
by virtue of any hemolytic conditions; melanin oxidized from melanogen
▪ Or due to the presence of myoglobin which could o Urine darkens on standing and
point to an existing muscle damage in the patient reacts with nitroprusside and
ferric chloride
• Beets: alkaline urine of genetically susceptible persons
o If malignant melanoma is
o A plant (product) suspected, additional instructions
o Selective, based on the individual that is consuming may be given to let the urine
the plant, it may cause their urine will change into stand for quite some time or
red. perform chemical examinations
o The pH of the urine must be basic (alkaline) on the urine sample using
nitroprusside and ferric chloride
• Rifampin: drug for Tuberculosis
o Some patients who are medicating for TB may • Medications
exhibit a red-colored urine o Phenol derivatives
o Argyrol (an antiseptic)
• Menstrual contamination o Methyldopa or levodopa
o Not advisable to submit sample when having a o Metronidazole (Flagyl)
menstruation because the presence of red blood
cells might mask an actual pathologic condition TO CONSIDER:

X. Port Wine Munchausen Syndrome

• Presence of porphyrins • A form of factitious disorder where a person fabricates


or induces an illness to assume the patient role
o Negative test for • One method: Tampering with laboratory specimens
blood, may require
• Variation: Munchausen syndrome by proxy
additional testing
o Cloudy dark red = o A person will induce or fabricate an illness to a
Port Wine person they are taking care of
▪ E.g., A mother will fabricate an illness to her
child
• Examples:
o Artifactual / Factitious hematuria
▪ Presence of RBCs on the patient’s urine sample,
making it red in color
XI. Red Brown ▪ Done by injuring themselves and adding drops of
blood into their urine sample
• RBCs oxidized to methemoglobin ▪ They do not have a renal disorder or any
o Seen in acidic urine after prolonged standing; abnormality in their urinary tract, but they present
positive chemical test for blood hematuria
• Prolonged standing of red-colored urine  During specimen collection, the patient added
drops of blood on their urine sample
o Red color will darken into red brown
▪ In routine urinalysis, witnessed collection is not
o Fresh urine: Red
allowed unlike in drug testing
• Myoglobin  Once submitted in the laboratory, the sample
• Rifampin is considered true
• Make sure to test the sample immediately and not allow
the sample to stand for so long o Factitious proteinuria

XII. Brown/Black Patients add egg white to their urine sample for
appearance of protein
• Homogentisic acid (alkaptonuria) • Be aware of highly variable results and/or incompatible
o Excessive accumulation biochemical profiles
o Alkaline urine turns black after standing o There are analytes which do not change drastically
▪ Stand for 15 minutes = shows in a short span of time
darkening at the surface ▪ E.g., serial monitoring

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 4
PACANA
LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

▪ On day one, the result is very high. On day two, o Cloudy or slightly cloudy sample is not always
results are very low. On day three it is very high abnormal
▪ Suspect that maybe something is not right, or • Clarity should correspond with the amount of material
the results are incompatible with the biochemical observed under the microscope
profiles
o If the sample is clear = may not see many materials
 If the urine sample is positive for glucose, under the microscope
expect that the blood sample will also test o If the sample is cloudy = many materials or
high for glucose because the renal threshold substances are observed under the microscope
has been crossed
▪ Materials, substances, cells, casts, or crystals
 If the urine sample is positive for glucose but
seen under the microscope explains the
the blood sample for glucose is normal,
changes in the clarity of the sample.
suspect that there is something wrong
▪ But consider first maybe the lab is the erroneous Non-pathologic Turbidity
one
• Normal causes of a cloudy urine
 Error in the preanalytical or analytical phase • Presence of squamous epithelial cells and mucus
o In the absence of lab workflow errors, consider o There is contamination if the sample is not collected
sample manipulation through clean-catch or midstream clean-catch
o It’s not just urine sample that is being compromised, method
it includes blood samples
• Specimens allowed to stand or that are refrigerated
▪ A person injected themself with insulin prior to
an FBS so that the glucose result will be low → o White precipitate in alkaline pH: amorphous
They will be diagnosed with hypoglycemia and phosphates and carbonates
will be admitted in the hospital o Pink precipitate in acidic pH: amorphous urates

• People with Munchausen syndrome love to be admitted, ▪ Due to uroerythrin, a minor pigment present in
to talk to doctors, to consider that they are urine sample
knowledgeable of their disorders • Semen, spermatozoa, prostatic fluid
o Most people with this case have moderate to o Reported in special cases only
advanced medical knowledge
o Many of them are health professionals because they ▪ Medicolegal cases (e.g., when trying to ascertain
know how to tamper with a laboratory result whether rape happened)
• Common way to detect a patient with Munchausen ▪ Assessment of vasectomy
syndrome or Munchausen syndrome by proxy is that • Fecal contamination (more common in infants)
many admissions or many check-ups in span of a year • Radiographic contrast media: contrast materials used in
o Some patients have 200 admissions in three years x-rays and CT scans; high SG (>1.040)
in different doctors/hospital (really high) o A radiographic contrast media was introduced to
o Actual incidence or prevalence of Munchausen color certain parts of the patient’s anatomy
syndrome in a given population here in the o The excretion of these contrast media causes
Philippines is underreported turbidity to a urine sample
▪ We do not share medical records with other ▪ High SG (>1.040) = presence of radiographic
hospitals, so we don’t know if patients have been contrast media should be suspected
treated just a week ago in another hospital
• Talcum powder
▪ Unlike in US, they have a medical record sharing
wherein a doctor can view the records of the o Especially in infants when applied on the genital
patient in another hospital just to check whether area
the patient has been admitted prior, in a similar
• Vaginal creams
condition in another hospital
URINE CLARITY Pathologic Turbidity

• Refers to the transparency or turbidity of a specimen • May be due to the following:


• May be reported as clear, hazy/slightly cloudy, cloudy, o Red blood cells
turbid, or milky o White blood cells
• Freshly voided urine is usually clear o Bacteria (in inflammation or urinary tract infection)
o Abnormal amounts of non-squamous epithelial cells
o Especially if it is a random specimen from a patient
who drank lots of water to induce urination ▪ Have to be reported
o Clear urine is not always normal
o Yeast (in diabetic patients)
• Precipitation of phosphates and carbonates may cause o Trichomonads (due to T. vaginalis)
white cloudiness o Abnormal crystals
o Lymph fluid: Chyluria in filariasis
o Which are normal

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 5
PACANA
LECTURE UNIT 04: PHYSICAL EXAMINATION OF URINE

▪ Chyluria – presence of lymph fluid in the urine o Patients who are vomiting
sample
• Maple Syrup Urine Disease (MSUD): maple syrup
▪ Patient has filariasis because the lymph fluid is • Phenylketonuria: mousy
leaking into the kidneys • Tyrosinemia: rancid butter
o Lipids • Isovaleric acidemia: sweaty feet
o Calculi (renal stones/kidney stones/renal calculi) • Methionine malabsorption: cabbage, hops
• Trimethylaminuria: rotting fish
• Bleach: contamination
SPECIFIC GRAVITY
• Measures the kidney’s ability to concentrate glomerular
filtrate by tubular reabsorption

• Methods:
o Urinometry: buoyancy
▪ Employs the principle of buoyancy
▪ Uses urinometer
▪ Not recommended by CLSI
 Very high or very large amounts of sample are
needed
 There are corrections that needs to be done
o Refractometry: refractive index
▪ Better than urinometry due to small volume
needed
 1-2 drops of urine
▪ Uses the principle of the change in refractive
index
▪ Not commonly used due to the corrections that
needed to be done
o Harmonic oscillation densitometry: sound waves
▪ Very accurate but tedious to perform
▪ Measures the change in the sound waves that
are allowed to pass through a sample depending
on its concentration
o Osmolality: colligative properties
▪ Good method
▪ If measuring one of the four colligative properties
that will indicate change in the urine
concentration, it is tedious
o Reagent strip: change in pH
▪ Most common and routinely performed in the
laboratory
▪ Included in chemical examination
▪ Measure the change in pH
ODOR
• Freshly voided urine: odorless to aromatic
• Not fresh urine: ammoniacal
o Due to the breakdown of ammonia by the presence
of bacteria
• Bacterial infections: strong, unpleasant
• Ketones: sweet or fruity
o Mostly in Diabetes Mellitus cases
o Patients who are starving

BALIZA. CARBAJOSA. CORPUZ. MANINGO. MALASAGA. MORENO. RATILLA. RAMOS. ROSALINDA. TAMBA. TABUDLONG. BSMLS 3 6
PACANA

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