Anatomy

1. Briefly describe the genitourinary tract

● Kidney
- produces urine, has endocrine function
● Ureter
- About 30 cm long, varies depending on height
- carry urine from kidneys to bladder
- peristaltic movement allows movement of urine downward and away from the kidneys
- Has sites of normal functional/ anatomic narrowing at UPJ, pelvic brim and UVJ
● Urinary bladder
- hollow organ located in lower abdomen,
- held in place by ligaments that are attached to other organs and pelvic bones
- Detrusor muscle relaxes and expands to store urine, contracts and flatten to empty urine
through the urethra
- Can store up to 400-500 mL of urine
● Urethra
- Maintain continence during storage via internal and external sphincters
- Internal sphincter​- smooth muscle, involuntary control (ANS), sympathetic control contracts
it, parasympathetic relaxes during micturition
- External sphincter​- skeletal, voluntary control
- approx. 20-25 cm In males, has segments: bladder neck, prostatic urethra,membranous
urethra, bulbous urethra, pendulous urethra and urethral meatus
- In females, approx 1-5 inches in length, below the clitoris, anterior to the vagina
- Females are prone to UTI because of its short length

2. Describe the gross anatomy of the kidney;

a. ​External structures​, location (including anatomic landmarks) and its position relative to other visceral organs.
● Retroperitoneal organ underneath the diaphragm
● Lie at borders of psoas muscle, obliquely placed
● R kidney related to liver, hepatic flexure and descending part of duodenum
● L kidney related to spleen, splenic flexure, stomach, pancreas and jejunum
● Superomedial: adrenal gland
● Anterior: peritoneum and abdominal organs
● Posterior: layers of lumbodorsal fascia, transversus abdominis and diaphragm
● Supported by perirenal fat, enclosed by renal fascia
● kidney- renal capsule- perirenal fat - renal fascia- pararenal fat
Internal structures​ of the kidney.
● Hilum- vertical slit, where branches of renal artery enter, veins and ureter leave, leads to sinus
● Renal sinus- wide space inside kidney containing:
- Branches of the renal artery
- Tributaries of the renal veins
- Renal calyces
- Renal pelvis
- Lymph vessel nerves and fat
● Outer cortex - contains the glomeruli
● Inner medulla
- renal pyramids converging renal tubules drains into minor calices at tip of renal papillae
- Contains the collecting ducts and columns of Bertin
● Minor calyx (fornix) — major calyx (infundibula)— Renal pelvis

b.Discuss briefly the ​gross anatomy of the adrenal glands​; compare and contrast both.
● Retroperitoneal organ, lies on upper pole of kidney
 ● Surrounded by Gerota’s Fascia but separated from kidney by perirenal fat
● Has cortex and medulla
● Right Suprarenal gland
- Pyramidal in shape
- Behind the right lobe of liver and Inferior vena cava
- Rest posteriorly in the diaphragm
● Left Suprarenal gland
- crescentic in shape
- Rest posteriorly in the diaphragm
- Behind the pancreas, lesser sac and stomach

3. Identify the major blood vessels, lymphatics, and innervation of the kidney​.
● Major Blood Vessel of the kidney
○ Renal arteries​ arise from the abdominal aorta at the level of IV disc between L1 and L2
■ Right Renal Artery - longer, passes posterior to IVC
■ Left Renal Artery
○ Each artery divide upon entering the hilum into ​segmental arteries​ which are end arteries
■ Corresponding area supplied by each segmental artery is an independent, sble unit
- ​renal segment
○ Segmental arteries
○ From Anterior Branch of Renal Artery
■ Superior (Apical) Segment - ​superior (apical) segmental artery
■ Anterior superior and anterior inferior segments - ​anterosuperior and
anteroinferior segmental arteries
■ Inferior segments - ​inferior segmental artery
○ Posterior branch of the renal artery
■ Posterior segmental artery ​ - posterior segment of the kidney
○ Renal Veins - anterior to the renal arteries. ​Left renal vein is longer and receives left
suprarenal vein, left gonadal vein and a communication with ascending lumbar vein
○ Each renal vein drain into the IVC

● Lymphatics
○ Renal lymphatic vessels follow renal veins and drain into right and left lumbar (caval and
aortic) lymph nodes

● Innervation
○ Nerves to the kidneys arise from the renal nerve plexus and consist of sympathetic and
parasympathetic
○ Renal nerve plexus - ​supplied by fibers from the abdominopelvic (especially the least)
splanchnic nerves. Visceral afferent fibers conveying pain sensation (resulting from
obstruction and consequent distention) follow the sympathetic fibers retrograde to spinal
ganglia and cord segments T11–L2. Ureteric pain is usually referred to the ipsilateral lower
quadrant of the anterior abdominal wall and especially to the groin
○ rich nerve supply of the suprarenal glands is from the ​celiac plexus and abdominopelvic
(greater, lesser, and least) splanchnic nerves.
Histology
1. Describe the histology of the proximal convoluted tubule, loop of henle, distal convoluted tubule, and collecting
ducts
● PCT - long convoluted part, located entirely in the cortex, with a shorter straight part that enters the
medulla
○ LE: simple cuboidal epithelium
 ○ Difference with DCT: longer, w/ long microvilli, lesser nuclei seen, more acidophilic
cytoplasm and the lumen is often star shaped
● Loop of henle - (or nephron loop), in the medulla, with a thin descending and a thin ascending limb
○ Descending limb LE: simple squamous epithelium with spherical nuclei bulging the lumen
○ Ascending limb LE: simple cuboidal epithelium
● DCT - consist of a thick straight part ascending from the loop of Henle back into the cortex and a
convoluted part completely in the cortex
○ LE: simple cuboidal epithelium
○ Have clear distinct apical border, short microvilli, lumen and wider and empty
● Collecting ducts - a short minor part linking the nephron to collecting ducts
○ LE: simple columnar epithelium

2. Compare and contrast the histological differences of the renal cortex and medulla

The cortex contains both distal and proximal convoluted tubules ,glomeruli, and medullary rays.
Present also in the cortex are the interlobular arteries and interlobular veins. The medullary rays are
formed by the straight portions of nephrons, blood vessels, and collecting tubules that join in the medulla
to form the larger collecting ducts. The medullary rays do not extend to the kidney capsule because of
the subcapsular convoluted tubules. The renal cortex is easily identified even at low magnification
by the presence of renal corpuscles, which are absent in the renal medulla. However, the bulk of
the cortex is occupied by the proximal and distal convoluted tubules. The arcuate arteries and
veins help to demarcate the cortex from the medulla.

The medulla comprises the renal pyramids. The base of each pyramid is adjacent to the cortex
and its apex forms the pointed renal papilla that projects into the surrounding, funnel-like structure,
the minor calyx, which represents the dilated portion of the ureter. The area cribrosa is pierced by small
 holes, which are the openings of the collecting ducts into the minor calyx. The renal medulla consists
of closely packed tubules of two types: the loop of Henle and the collecting tubules and ducts, as
well as the vasa recta. The loop of Henle is a continuation of the proximal convoluted tubule. It dips
down into the medulla, where it loops back on itself and returns to the cortex to its own renal corpuscle,
becoming the first part of the distal convoluted tubule.

3. Identify and describe some of the histologically specialized cell in the renal parenchyma

Macula densa​- part of the distal convoluted tubule that lies adjacent to the vascular pole. These are closely packed
columnar cells with large prominent nuclei
Juxtaglomerular cells​- modified smooth muscle cells of the afferent arteriole with more rounded nuclei
Intraglomerular mesangial​ cells surrounding the glomerulus
*Lacis cells- extraglomerular mesangial cells

Biochemistry
1. Briefly discuss synthesis of your diuretic/anti-diuretic & adrenal hormones with emphasis on the
mineralocorticoids.
*wala pa ko makita ng biosynthesis of diuretics, ito nalang muna bsahin niyo
Diuretics/anti-diuretics
● Osmotic diuretics decrease water reabsorption by increasing osmotic pressure of tubular
fluid
○ Injection Into the bloodstream of substances that are not easily reabsorbed by the renal
tubules such as urea, mannitol, and sucrose cases a marked increase in the
concentration of osmotically active molecules in the tubules
○ the osmotic pressure of these solutes then reduces water reabsorption, flushing large
amounts of tubular fluid into the urine
○ ex. when the load of increased filtered glucose in the tubules exceed their transport
maximum, only a little of the extra glucose is reabsorbed and the rest remains in the tubules
acting as an osmotic diuretic - causing rapid loss of fluid into the urine.
● Loop diuretics decrease active sodium-chloride-potassium reabsorption in the TAL of LH
○ Furosemide, ethacrynic acid, a ​ nd ​bumetanide are powerful diuretics that decrease
reabsorption in the TAL OF LH by ​blocking the Na-K-2Cl co transporter
○ This results in an increase in urine output of sodium, chloride, potassium, and other
electrolytes, as well as water because!!
■ they increase quantities of soutes delivered to the distal parts of the nephrons, and
these solutes act as osmotic agents
■ disrupt countercurrent multiplier system* by decreasing absorption of ions from the
LH into the medullary interstitium - decreasing the osmolarity of the medullary
interstitial fluid
○ this impairs the ability of the kidney to ​either concentrate or dilute the urine
■ urinary ​dilution is impaired because of the inhibition of sodium and chloride
reabsorption in the LH causing more if these ions to be excreted along with
increased water excretion
■ urinary ​concentration is impaired bc the renal medullary interstitial fluid
concentration of these ions ( medullary osmolarity) is reduced.
○ the reabsorption of fluid from the CD is decreased, so the maximal concentrating ability of
the kidneys is greatly reduced
● Thiazide diuretics inhibit sodium-chloride reabsorption
○ Act mainly on the ​early distal tubules​ to block sodium-chloride co transporter.
○ These agents may cause 5-10% of the glomerular filtrate to pass into the urine
● Carbonic anhydrase inhibitors block sodium bicarbonate reabsorption in the proximal
tubules
○ Acetazolamide i​ nhibits carbonic anhydrase which is critical for the reabsorption of
bicarbonate* in the PCT
○ Carbonic anhydrase is abundant in the PCT which is the primary site of action of the
inhibitors
○ since H secretion and HCO3 reabsorption is coupled to Na reabsorption through the Na-H
ion counter-transport, ​decreasing HCO3 reabsorption also reduces Na reabsorption
○ These will accumulate and act as osmotic diuretic in the tubules*
○ Side effect is they cause some degree of acidosis bc of loss of HCO3 in the urine
● Mineralocorticoid receptor antagonists decrease Na reabsorption from and K secretion into
the collecting tubules
○ Spironolactone a ​ nd ​eplerenone are the antagonists that compete with aldosterone for
receptor binding sites in the collecting tubules - decreases the reabsorption of sodium and
secretion of K
○ Na remains in the tubules and act as a osmotic diuretic (increased excretion of water and
sodium na rin)
○ Also decrease secretion of K - move to the ECF
● Na channel blockers decrease Na reabsorption in the collecting tubules
○ Amiloride​ and ​triamterene ​ also inhibit Na reabsorption and K secretion
○ these act directly to block the entry of Na into the sodium channels of the luminal
membranes of collecting tubules
Mineralocorticoids

2. Define osmolarity, osmolality and tonicity

Osmolarity
Osmolarity is the measure of solute concentration per unit VOLUME of solvent.

● It's not the same as tonicity. Osmolarity takes into account ALL of the solute concentrations, not just
the ones that can't cross the semipermeable membrane.

Osmolality
Osmolality is the measure of solute concentration per unit MASS of solvent​.
 ● You never measure osmolarity in practice, because water changes its volume according to
temperature (but mass remains the same, and so it is more convenient and consistent)
● Osmolality is the same in the ICF and the ECF.
● Both inside and outside, the osmolality is 285-290 mOsm/Kg

Tonicity
Tonicity is the measure of the osmotic pressure gradient between two solutions.
● Unlike osmolarity, tonicity is only influenced by solutes that ​cannot cross this semipermeable
membrane, because these are the only solutes influencing the osmotic pressure gradient.
● Thus, you can have iso-osmolar solutions which are not isotonic.

NTK
Dextrose and urea are the main ineffective osmoles.
In a diabetic patient, dextrose can still be an effective osmole.
The major "effective" osmole is SODIUM.
Sodium and its anion harem contribute to 86% of the osmolality and 92% of the tonicity.

3. Discuss the​ Osmoreceptor-ADH feedback system

- Antidiuretic hormone (ADH), also known as vasopressin, is a small peptide hormone which regulates
retention of water in the human body. ADH binds to receptors on cells in collecting ducts of kidney
and promotes reabsorption of water back into circulation. In absence of antidiuretic hormone
collecting ducts are virtually impermeable to water, and it flows out as urine.
- When plasma osmolarity is below a certain threshold,​ osmoreceptors are not activated and
secretion of antidiuretic hormone is suppressed.
- When osmolarity increases above threshold, osmoreceptors recognize it as a signal to
stimulate neurons that secrete antidiuretic hormone. When osmolarity (plasma sodium
concentration) increases above normal because of water decit, this feedback system
operates as follows:
1. An increase in extracellular uid osmolarity (which means an increase in plasma
sodium concentration) causes special nerve cells called osmoreceptor cells, located
in anterior hypothalamus near supraoptic nuclei, to shrink.
2. Shrinkage of osmoreceptor cells causes them to activate, sending nerve signals to
additional nerve cells in supraoptic nuclei, which then relay these signals down stalk
of pituitary gland to posterior pituitary.
3. These action potentials conducted to posterior pituitary stimulate release of ADH,
which is stored in secretory granules (or vesicles) in nerve endings.
4. ADH enter the bloodstream and is transported to kidneys, where it increases water
permeability of late distal tubules, cortical collecting tubules, and medullary
collecting ducts.
5. The increased water permeability in distal nephron segments causes increased
water reabsorption and excretion of a small volume of concentrated urine.
 - MOA of ADH​: ADH binds to V2 receptors in the LDT, CT and DT, increasing formation of cAMP and
activating protein kinases, stimulating the movement of intracellular protein aquaporin-2 (AQP-2) to
the luminal side of the cell membranes. AQP-2 molecules fuse with the cell membrane by exocytosis
to form water channels that permit rapid diffusion of water through cells.

Physiology
1.Discuss the fundamental processes involved in urine formation
● Basic Movements Involved in Urine Formation
○ Step 1: Filtration - (Glomerular) Filtration
▪ Movement from Glomerular Capillaries to Bowman’s Space
- From the glomerular capillaries into the Bowman’s capsule
- Most substances in the plasma, except for proteins, are freely filtered, such that
concentration in glomerular filtrate is almost the same as that in the Bowman’s
capsule.
- Urine is just a filtrate coming from the plasma of blood. Blood that has passed
through the glomerulus will be filtered out through the Bowman’s capsule. From
there, the glomerular filtrate has to undergo several modifications before it can be
excreted as urine.

○ Step 2: Reabsorption - (Tubular) Reabsorption

▪ Movement from Tubules to Interstitium to Peritubular Capillaries
- Electrolytes are highly reabsorbed, so that only small amounts appear in the urine.
- Certain nutritional substances, such as amino acids and glucose, are completely
reabsorbed from the tubules and do not appear in the urine even though large
amounts are filtered by the glomerular capillaries.
 ○ ​Step 3: Secretion - (Tubular) Secretion
▪ Movement from Peritubular Capillaries to Interstitium to Tubules
- End products of metabolism, such as urea, creatinine, uric acid, and urates, are
poorly reabsorbed and are therefore excreted in large amounts in the urine.
- Certain foreign substances and drugs are also poorly reabsorbed.
- Secretion is “adding up” to whatever was already filtered by the Bowman’s capsule,
and wastes, excess electrolytes or water, or toxic stuff are the ones usually secreted
- Decrease filtration fraction = Decrease in Absorption
- Afferent arteriole constriction​ is caused by:
■ Sympathetic nervous system
■ High levels of angiotensin II
- Efferent arteriole constriction​ is caused by:
■ Low levels of angiotensin II

● Excretion = (Amount Filtered) - (Amount Reabsorbed) + (Amount Secreted)

2.Discuss the processing of the glomerular filtrate at the different parts of the tubular system

- Glomerular filtrate is the filtrate that accumulates after filtering the blood. It passes through the Tubular System.
Tubular System consist of the following:
1. Proximal Convoluted Tubule​ (​PCT​)
- Reabsorb:
- 66% of filtered Na​+​, K​+​, H​2​O (34% will be filtered by Loop of Henle)
- 100% of filtered Glucose and Amino acid
- Secretes:
- Most acids
- It has the greatest number of Carrier-mediated transport
- Convolutions = greater surface area
- Presence of Microvilli
2. Loop of Henle
 a. Descending Limb
- Permeable to ​Water ONLY
b. Ascending Limb
- Permeable to ​Solutes ONLY
i. Thin Ascending Limb
ii. Thick Ascending Limb​ (​TAL of LH​)
- Also called Diluting Segment
- Have Na-K-2Cl symport/co-transport
- Reabsorb:
- Na​+​, K​+​, 2 units of Cl​-
- Negates the principle of where Na​+ goes, water
follow bec TAL of LH is ​ONLY PERMEABLE TO
SOLUTES
3. Distal Tubule​ (​DT​)
a. Early DT
- Also called Cortical Diluting Segment
- Similar to TAL of LH because it is also PERMEABLE TO​ SOLUTES ONLY
- Macula densa, a Na+ sensor, found b/n the boundary of TAL of LH and
early DT. It stimulates JG cells when it detects low Na+ conc.
- So kapag nadetect niyang malabnaw si Glomerular filtrate mo it will
cascade to the activation of RAAS
b. Late DT
● Contains 2 Cells
○ Principal cells​ - Reabsorb: Na​+​ and H​2​O
■ Secretes: K​+
○ Intercalated cells ​- Reabsorb: K​+
■ Secretes: H​+
● Aldosterone ​- ​stimulates both ​Principal and Intercalated cells
○ Greater K​+​ secretion than reabsorption
○ NET EFFECT: INC. VR, Intravascular Volume, Cardiac Output, and BP
○ Reabsorbs: Na​+​ and H​2​O
○ Secretes: K​+​ and H​+

4. Collecting Duct​ (​CD​)

- Where ​ADH​ a ​ ct to exert its effects
- ADH
- Insert ​Aquaporin Type 2 → Reabsorb​ ​H2O ​back into the blood
- INC Aquaporin Type 2
- Urine: INC Urine Concentration, DEC Urine Vol (because
REABSORB nga si H​2​O)
- Blood: ​INC Intravascular Vol ( Eto yung INC. VR, Cardiac Output,
and BP in the Late DT na inactivate ni ​Aldosterone mo sila Principal
and Intercalated cells)
- INC Urea Transporter Type 1
- INC. Urea Reabsorption → INC Urine Conc. = DEC Urine Vol
- MAGNIFY the effects of ​Aquaporin Type 2

3.Explain renal handling of the different solutes e.g. sodium, potassium, calcium, phosphate, magnesium, glucose,
amino acid, urea, and creatinine
Sodium

Early PCT

•​ Na and water​ reabsorbed using ​co-transport with HCO3-, glucose, aa, phosphates, lactate

• ​Na reabsorbed using ​countertransport with H (Na-H exchange) which is linked directly to reabsorption of
filtered HCO3-

Late PCT

• Na is reabsorbed with Cl

TAL of LH

- Inhibited by ​furosemide (loop diuretic)

- Aka diluting segment of the nephron
- • Impermeable to water
- • TF/PNa and TF/Posm<1.0
- contains Na-K-2Cl symport
- absorption of Na, K (2) Cl but no reabsorption of water

Has lumen-positive potential difference • Some K diffuses back into the lumen, making the lumen
electrically positive

DT AND CD
o ​EDT

Aka cortical diluting segment

• Relatively Impermeable to water

Contains Na-Cl Symport, Macula Densa

LDT

Aldosterone stimulates both principal and intercalated cells

→ ​Principal Cells

• R: Na (using ​ENaC Channels ​– synthesis of which takes several hours causing delay in RAAS effects)
and H2O

• S: K

→​ 𝝰 -Intercalated Cells

• R: K via H-K-ATPase pump

• S: H via H-ATPase pump and Na-H antiport

● Angiotensin II
- ↑ Na-H exchange in the PCT
● Aldosterone Effects​ on the KIDNEYS: →
- Na+ reabsorption - will inc salt also result to intravascular volume which will inc Venous Return >
inc CO > inc BP
- K+ secretion
- H+ secretion
- Aldosterone exerts its greatest effect on the LDT which includes the CORTICAL COLLECTING
DUCT

Potassium

● Normal plasma K+ =​ 4.2 mEq/L

● 1st line of defense -​ ​ Movement of ECF and ICF
- HYPERkalemia = ECF to ICF

- HYPOkalemia = ICF to ECF

● K-balance​ – urinary excretion = dietary intake

● Normal K+ filtration = ​756 mEq/L
● 25% - 30% a​re regulated and secreted at ​distal tubule while approximately ​65% is reabsorbed
in the thick ascending loop of Henle​.
● Principal Cells: secrete K
● Intercalated Cells: reabsorbed K (active in low K diet)
- Both cells are found in the​ late distal tubule.

● K SECRETION ​IN THE​ DT​ USING ​PRINCIPAL CELLS

INCREASE in plasma secretion​ to the urine will make you prone to ​hypokalemia​.

DECREASE in plasma secretion ​to the urine will make you prone to ​hyperkalemia​.

● HYPERALDOSTERONISM: could affect K secretion; for example, increased K secretion could be

secondary to an aldosterone-producing tumor (a.k.a. Conn’s Syndrome).
● REGULATION
Inc. ECF K+ → Inc. Na-K-ATPase pump action → Inc. intracellular K+ → inc. K+ diffusion to the lumen

Inc. ECF K+ → prevents backleak of K+ from the inside of the cells to the basolateral membrane

Inc. ECF K+ → stimulates Aldosterone → inc. secretion of K+

● INCREASED ALDOSTERONE​ STIMULATES ​PRINCIPAL CELLS

– Increases ​Na-K pump​ (​NOT​ the Na-K-ATPase pump)

– Increases permeability of the luminal membrane to potassium

-When K intake is now EQUAL to K output, there will be a decrease in aldosterone

● INCREASED TUBULAR FLOW RATE​ ​STIMULATES PRINCIPAL CELLS

– Prevents K+ from accumulating in the lumen → increases driving force for diffusion of K+ from the cells
to the lumen

– Increased tubular flow rate occurs in: (1) Volume Expansion, (2) High Sodium Intake, (3) Use of
diuretics

– Helps preserve normal K+ excretion during high sodium intake

 ● EFFECT OF ​HIGH SODIUM INTAKE​ ON R
​ ENAL EXCRETION OF POTASSIUM​:

• A high-sodium diet decreases plasma aldosterone, which tends to decrease potassium

secretion by cortical collecting tubules.

• High-sodium diet simultaneously increases fluid delivery to cortical collecting duct, which tends
to INCREASE potassium secretion.

• The opposing effects of high-sodium diet counterbalance each other, so there is little change in
potassium excretion.

● ACIDOSIS

– ​ACUTE ACIDOSIS ​= ​ INHIBITS K+ secretion

• MOA: Inhibition of Na-K-ATPase Pump → dec intracellular K+ → dec diffusion of K+ into the lumen –

--​CHRONIC ACIDOSIS​ = ​STIMULATES K+ secretion

• MOA: Dec H2O and Na reabsorption in the PCT → inc tubular flow rate → inc K+ secretion

Calcium

● important for MUSCLES, whether skeletal, smooth, or cardiac type.

● Provides power
● very little free-ionized calcium in the plasma.
● free-ionized calcium = biologically active; involved in muscle contraction.
● Plasma Ca2+ = 2.4mEq/L
● Hypercalcemia = Can cause arrhythmias
● Hypocalcemia = Can cause tetany
● ​Calbindin ​- Stimulated by​ vit D​; binds with calcium in the ​intestines
● 60% of plasma Ca2+ is filtered
● PCT and LH - reabsorbs 90% of filtered Calcium
● DT and CD reabsorbs 8% of filtered Calcium
● PTH, THIAZIDES increases Ca Reabsorption
 ● LOOP DIURETICS decreases Ca Reabsorption

Phosphate

● involved in the maintenance of bone and teeth as well as synthesis of nucleic acids. •
● Transport Maximum = 0.1mM/min
● PCT: reabsorbs 85% of filtered Phosphate via Na-PO4 cotransport;
● Remaining 15% is excreted in the urine
● - This 15% of unreabsorbed PO4 serve as urinary buffer for H+ •
● Phosphate has a NEGATIVE CHARGE.
● Reabsorption inhibited by PTH (adenylate cyclase and cAMP inhibition of the Na-PO4
cotransport) •
● Causes Phosphaturia (increased urinary PO4) and increased urinary cAMP

Magnesium

● Plasma Mg2+ = 1.8mEq/L

● 50% stored in the bones
● Only 10% of plasma Mg excreted daily
● PCT -25% reabsorption
● TAL of LH – 65% reabsorption
● In the TAL of LH, Ca2+ and Mg2+ compete for reabsorption
● Hypercalcemia causes hypomagnesemia
● Hypocalcemia causes hypermagnesemia
● magnesium is unique in a sense that MOST of it is absorbed in the THICK ASCENDING LIMB of
the Loop of Henle.

Glucose

● MOST Solutes (glucose or para-aminohippuric acid) are actively reabsorbed or secreted exhibit:
- Glucose is filtered and 100 % reabsorbed by the PCT utilizing SGLT-2 (secondary active
transport
 - Para-aminohippuric acid (PHA) is filtered, secreted and never reabsorbed (mainly secreted in the
PCT)

● RENAL THRESHOLD

200 mg/dl – Glucose Threshold – where you will start to excrete glucose (green line) and is unable to
reabsorb the glucose that you wanted.

SOME nephrons affected → Substance start appearing in the urine → Plasma concentration by which
one nephron will already be saturated → Some nephron is already saturated

● RENAL TRANSPORT MAXIMUM

Transport Maximum: ~375 mg/dl

All nephrons are saturated (all 1 million nephron’s SGLT has been used)

Rate of reabsorption will be a constant value = PLATEAU

● SPECIAL NOTE ON TM CURVE Tm Curve of Glucose

Normal: Filtered, 100% reabsorbed

Filtration: proportional to plasma glucose concentration

Reabsorption: occurs using SGLT-2 in PCT

Renal Threshold: plasma glucose 200mg/dL (some nephrons saturated)

Renal Transport Maximum: plasma glucose > 375mg/dL (all nephrons saturated)

Splay: between 200mg/dL – 375mg/dL (glucose excretion before complete saturation of all nephrons)

● filtered, 100% reabsorbed, never secreted, find only in the blood

Amino acid

● 100% filtered AA reasorbed in PCT

● Never secreted
● Found only in blood

Urea

REGULATION

● PCT: reabsorbs 50% of filtered Urea via simple diffusion

● Thin Descending Limb of LH: secretes urea via simple diffusion
● DT, Cortical Collecting Ducts and Outer Medullary Collecting Ducts: Impermeable to Urea

Inner Medullary Collecting Ducts: ADH increases permeability of these ducts to via facilitated diffusion
transporter for urea (UT1) Urea Transporter Type I (Facilitated Diffusion type of carrier protein, (caused to
reabsorbed more Urea, in osmolarity in the renal medulla, further concentrate the urine, amplifies the
effects of ADH in urine formation

→ Contributes to urea recycling and development of corticopapillary osmotic gradient

→ Increased ADH secretion → Increased Water AND Urea reabsorption → Low Urine Flow Rate → Inc
BNP= gold standard in diagnosis of left sided heart failure → PTH- does not like phosphate, secreted in
hypocalcaemia
 ● Catecholamine derivative of tyrosine NT and hormones (Dopamine, NorEpi and Epi) →

Natriuretic = sodium loss

- ANP and BNP = decrease sodium reabsorption (naturally occurring diuretics

- → ANP: Cardiac atrium; BNP: Cardiac Ventricles (Elevation is a gold standard for Left sided heart
failure)
- PTH: Phosphate Trashing Hormone (Secretion: decrease of Calcium)

● UREA RECYCLING

Contributes to the hyperosmolarity of the renal medulla up to 50% of renal medullary interstitial osmolarity

ADH stimulates Urea Receptors (UT-1)

Determines osmolarity at tip of LH: from 600-1200mOsm

 Creatinine
● Filtered alone
● Not secreted
● Not reabsorbed
● Clearance equal to GFR: inulin, creatinine
● Reason: filtered but not secreted not reabsorbed
● More concentrated at the end of PCT that at the start of PCT: Creatinine
● Marker for Kidney function/GFR (glomerular marker) ( GFR = kidney failure)
● Crea Clearance = Crea excreted/plasma crea concentration

Relative clearances ​(di na to kasama sa question pero baka gawin side question)
● Relative Clearances:
● PAH (para-amino hippuric acid)> K > inulin > urea > Na > glucose, amino acids and HCO3- •
● Highest Clearance: PAH
- Reason: Filtered and Secreted, not reabsorbed (found in urine only) •
- Used to estimate for Renal Blood Flow (RBF) and Renal Plasma Flow (RPF)
- basically, it follows the blood supply
- Example: If PAH is injected in the renal artery, that all of the units PAH will be found in the
urine.

● Lowest Clearance: Protein, Na, Glucose, amino Acids, HCO3- and Cl (nutrients)
- Reason: Not filtered (protein), or filtered but mostly reabsorbed (everything else listed above)
- Normally not found or found in small amounts in the urine (found in blood)
- Never Secreted
- Example: If 100 units of glucose is injected in renal artery, all 100 units will be found in the blood. It
make sense because these (glucose and amino acids) are nutrients

4.Discuss the regulation of acid-base balance

Basic acid-base physiology
● Acids
○ ​Proton donors
 ○ Strong acids: Dissociate rapidly into ions (e.g. HCl)
○ Weak acids: do not dissociate easily (e.g. H​2​CO​3​)
● Bases
○ Proton acceptors
○ Strong bases: OH​-​​
○ Weak bases: HCO​3​-
● Buffer
○ Mixture of weak acid and its conjugate base or weak base and its conjugate acid
○ Resists a change in pH
Acid-Base Balance
● Plasma H+ concentration: 0.00004 mEq/L (40 nEq/L)
○ H​+​ concentration is expressed in logarithm scale:
pH = [H1+ ] = - log [ H + ]
○ Minus sign in the logarithm expression, reversal is necessary
○ H​+​ concentration increases, pH decreases, and vice versa
● Normal arterial blood pH = 7.35 – 7.45
○ pH 6.8 – 8.0 is compatible with life
● pH and H​+ ​concentration of bodily fluids

● < pH 7.35 → ACIDEMIA (↑H​+​ concentration in blood); ACIDOSIS (physiologic state)

● > pH 7. 45 → ALKALEMIA (↓H​+ ​concentration in blood); ALKALOSIS (physiologic state)
● pH and H​+​ concentration are inversely proportional
● pH and OH​-​ concentration are directly proportional
Systems that Regulate H​+​ Concentrations
● Body fluid buffer systems
○ CO​​2​ ​+ H​2​O = H​2​CO​
​ 3=
+​
​ H​ + HCO​3​
-

○ Bicarbonate buffer system is regulated by both the lungs and the kidneys
○ The first reaction (hydration/dehydration of CO​2​) is the rate-limiting step. Enzyme:
Carbonic anhydrase
○ Phosphate buffer system (H​2​PO​​4​-​ and HPO​4​-​)
○ Intracellular proteins
● Respiratory center
○ Controls PCO​2​​ (Respiratory acidosis/alkalosis)
○ Acidotic→ increase breathing→ ↓CO​2 and ​ H​2​CO​​3
○ Alkalotic → decrease breathing →↑ ​ CO​2 ​and H​2​CO​3​
● Kidneys
○ ​Control HCO​​3​-​ (Metabolic acidosis/alkalosis)
○ Acidotic → release excess acids → retain bases and create new bases
Henderson - Hasselbach Equation
 ● Used to calculate the pH of a buffered solution of a weak acid (HA) and its conjugate base (A-)
● Used in titration and charge of amino acids
● Predicting shifts in the bicarbonate buffer system
○ CO​2​​ ​+ H​2​O = H​2​​CO​3 ​= H​+ ​+ HCO​3​-
● Distribution and excretion of drugs

○ CHARGED acid/base is water soluble and can be excreted.

● pH can be determined if level of both HCO​3​- ​ and PCO​2 is

​ known
● ↑ bicarbonate = ↑pH
○ Regulated by the kidneys
● ↑ carbon dioxide = ↓pH
○ Regulated by the respiratory rate
Respiratory Control of Acid-Base Balance
● Responds to H​+ ​levels
○ Increased H​+​ → increase RR→ ↓PCO​2 ​and H​2​CO​3​
○ Decreased H​+​ → decrease RR →↑ ​PCO​2 and ​ H​2​CO​​3
● 50-75% pH returning to normal within 3-12 minutes
● Increase RR causes RESPIRATORY ALKALOSIS
● Decrease RR causes RESPIRATORY ACIDOSIS
● Respiratory compensation
○ Metabolic acidosis: hyperventilation → remove CO​2​ → ↑pH
○ Metabolic alkalosis: hypoventilation →retain CO​2 → ​ ↓pH
Renal Control of Acid-Base Balance
● Metabolic compensation
○ Respiratory acidosis: reabsorb HCO​3​-​ , excrete H​+​ , ↓H​+ ​→↑pH
○ Respiratory alkalosis: excrete HCO​3​-​ , retain H​+​ , ↑H​+​ →↓pH
● Secretion of H​+
○ Na​+​-H​+​ Countertransport in the PCT , LH, DT
○ H​+​ATPase pump in the Distal Tubules and CD
○ 80 – 90% at proximal tubule
○ 10% in the thick ascending limb
○ 5% in early distal tubules
● Reabsorption of HCO​3​-
○ Coupled to H​+​ Secretion
○ Excess HCO​3​- ​ will not be reabsorbed, instead excreted into the urine
○ Excess H​+​ will cause all filtered HCO​3​-​ to be reabsorbed and urinary buffers for H​+​ to be
activated → H​+​ excreted into the urine

● Production of new HCO​3​-

○ Use of ammonia (NH​3​) and phosphate(NaHPO​4​-​) buffers
Phosphate and Ammonia Buffer System of the Urine
● Phosphate Buffer System
○ Buffering of secreted H​+​ by filtered phosphate (NaHPO​4​). The new HCO​3​−​ is returned to
the blood for each NaHPO​4​ that reacts with a secreted H​+​.

○ Buffering of hydrogen ion secretion by ammonia (NH​3​) in the collecting tubules. Ammonia
diffuses into the tubular lumen, where it reacts with secreted H​+​ to form NH​4​ +​​ , which is
then excreted. For each NH​4​+​ excreted, a new HCO​3​-​ is formed in the tubular cells and
returned to the blood.
Acid-Base Disturbances

● Respiratory Acidosis
○ DECREASED VENTILATION (RR)
○ E.g. Opiates, Sedatives, Anesthetics, Guillan-Barre Sydrome, Polio, Amyotrophic Lateral
Sclerosis, Multiple Sclerosis, Airway Obstruction, ARDS, COPD
○ CO​2​ retained → increased carbonic acid → RESPIRATORY ACIDOSIS
● Respiratory Alkalosis
○ INCREASED VENTILATION (RR)
○ E.g. Pneumonia, Pulmonary embolus, High Altitude, Psychogenic, Salicylate Intoxication
○ Treatment: Breathe in paper bag → ↑CO​2
● Metabolic acidosis
○ EXCESS ACID OR LOSS OF BASE
○ E.g. Severe diarrhea, Renal Tubular Acidosis, Diabetic Ketoacidosis, Ingestion of acids
like ASA and methanol (forms formic acid), Vomiting of Intestinal Contents, Chronic
Renal Failure
○ Macroscopic electron neutrality: Number of cations = number of anions in the same
compartment
 ○ Serum anion gap = [Na​+​] – [Cl​-​] + [HCO​3​-​]
○ Two types of metabolic acidosis:

○ Treatment: Sodium Bicarbonate (oral)

■ Neutralize excess acids
■ Sodium lactate and sodium gluconate maybe given IV
● Metabolic alkalosis
○ LOSS OF ACID OR GAIN OF BASE
○ E.g. Administration of Loop Diuretics (Except Carbonic Anhydrase Inhibitors), Thiazide
drugs, Vomiting of Gastric Contents, Hyperaldosteronism, Ingestion of Alkaline Drugs
(Sodium Bicarbonate)
○ Treatment: Ammonium Chloride (oral)
5.Discuss the commonly used diuretics and their mechanism and sites of action in the nephron
● Loop Diuretics
○ In regulating K​+ ​- causes INC K​+ secretion leading to Hypokalemia. It acts on Late DT by
stimulating Principal cells
○ In regulating Ca​2+ ​- it INC Ca​2+ reabsorption. It acst on the PCT, LH, DT, and CD where
Ca​2+​ reabsorption happens
○ It causes ​Metabolic​ ​Alkalosis
● Thiazide Diuretic
○ In regulating K​+ Conc ​- causes INC K​+ secretion leading to Hypokalemia. It acts on Late
DT by stimulating Principal cells
○ In regulating Ca​2+ - it INC Ca​2+ secretion. It acts on the PCT, LH, DT, and CD where Ca2+
reabsorption happens
○ It causes ​Metabolic Alkalosis
● K-sparing Diuretics
○ In regulating K​+​ Conc ​- causes DEC K​+​ secretion leading to Hyperkalemia

Case Questions
1. At this point, what is your primary working impression?
Diabetic nephropathy secondary to uncontrolled diabetes Mellitus
a.As a follow up question, what are the salient features in the case that led you to your PWI?
- Foamy urine
- hyperpigmented/black patches which are pruritic (acanthosis nigricans)
- BP 170/90
- Diabetic nephropathy aw pogi ni paolo AW AW AW AW
2. What other laboratories would you request for this patient
For me wala na since emergency na. Pero pangdagdag lang is mga ito:
- eGFR (estimated Glomerular Filtration Rate)
- to measure your level of kidney ​function​ and determine your stage of kidney disease.
- A GFR test is used to help diagnose ​kidney disease at an early stage, when it is most
treatable. GFR may also be used to monitor people with ​chronic kidney disease (CKD) or
other conditions that cause kidney damage. These include ​diabetes and ​high blood
pressure​.
- Your doctor can calculate it from the results of your ​blood creatinine ​test​, your age, body
size and gender.
- UACR (Urine Albumin to Creatinine Ratio)
 - Albumin is a major ​protein normally present in blood, but virtually no albumin is present in
the urine when the kidneys are functioning properly. However, albumin may be detected in
the urine even in the early stages of ​kidney disease​. The urine albumin test (formerly called
microalbumin) detects and measures the amount of albumin in the urine to screen for kidney
disease.
- Most of the time, tests for albumin and ​creatinine are done on a urine sample collected
randomly (not timed) and an ​albumin-to-creatinine ratio (ACR) is calculated. This is done
to provide a more accurate indication of the how much albumin is being released into the
urine. Creatinine, a byproduct of muscle metabolism, is normally released into the urine at a
constant rate and its level in the urine is an indication of the urine concentration. This
property of creatinine allows its measurement to be used to correct for urine concentration
when measuring albumin in a random urine sample.
- The presence of a small amount of albumin in the urine may be an early indicator of kidney
disease. A small amount of albumin in the urine is sometimes referred to as urine
microalbumin or microalbuminuria. "Microalbuminuria" is slowly being replaced with the term
"albuminuria," which refers to any elevation of albumin in the urine.
- Renal Scintigraphy
- Renal scintigraphy uses small amounts of radioactive materials called radiopharmaceuticals,
a special camera and a computer to evaluate your kidneys' function and anatomy and
determine whether they are working properly
a.As a follow up question, what are the expected findings of the said diagnostics.

- eGFR test

- UACR
- Thirty mg albumin/day has been conventionally accepted as the upper limit of normal for
urine albumin excretion. The conventional urine dipsticks become 1+ positive at a
concentration of 30 mg/dL albumin, equivalent to 300 mg/L or—if assuming a daily urine
output of 1 L of urine—300 mg/day. The range of urine excretion above the normal of 30
mg/day and below the dipstick sensitivity of 300 mg/day has traditionally been called
microalbuminuria.​ Urine excretion >300 mg/day has been called ​macroalbuminuria or ​clinical
albuminuria​. However, albuminuria appears to be a continuous biomarker, and the
distinction between values higher or lower than 300 mg/day does not reflect a physiological
barrier, but merely the sensitivity of the clinical measuring tools that have been available.
With the wide use of techniques to measure low levels of albuminuria, the terms
microalbuminuria and macroalbuminuria will likely disappear.
- CBC
a. HGB – 9.0 g/dL LOW: 14-18
b. HCT – 38% LOW: 39-54
c. MCV – 88.8 fL NORMAL: 80-100
 d. MCH – 28 picograms NORMAL: 27-35
e. MCHC – 31.6 NORMAL: 31-37
f. WBC – 10 NORMAL: 3.8-11
g. Normal differential count
- Blood Chem
a. Na – 132mmol/L LOW: 135-145
b. K – 5.9 mmol/L HIGH: 3.5-5.1
c. Cl – 100mmol/L NORMAL: 96-109
d.Creatinine – 2.5mg/dL NORMAL: 0.6-1.2
- Urinalysis
a. Protein – 3+ HIGH (normal is trace)
b. Glucose – 3- HIGH (dapat wala)

b.Correlate your laboratory findings to the clinical picture of the patient.

DIFFERENTIAL DIAGNOSIS
- Normocytic normochromic anemia​ + yung symptom na fatigue
- Low sodium due to DM (3P’s)
- High K due to decreased kidney function
- U/A indicates that the maximum threshold for glucose is reached since glucose is present in the
urine as well as protein is also present due to damage to the kidney.
3. Given the case, what is your recommended treatment, and explain why is it important? From mayo clinic and
clinical key
● Treat and control diabetes and if needed, high blood pressure. Good management of blood sugar
and hypertension can prevent or delay kidney dysfunction and other complications
● ACE (angiotensin converting enzyme) inhibitors or Angiotensin II receptor blockers used to treat high
bp
● Additional components include lifestyle modifications, treatment of comorbidities and when needed
renal replacement therapy
● Tx: ACE inhibitor or Angiotensin Receptor Blocker; Sulfonylureas and Metformin are
contraindicated in advanced renal insufficiency
● ACE inhibitor - ​work by preventing a natural body substance called angiotensin I from
converting into angiotensin II, which causes blood vessels to narrow and constrict. By preventing
this change, the blood vessels remain relaxed and blood pressure decreases.
● ARB - also affect angiotensin, but they prevent angiotensin II from binding to an area on
blood vessels called receptors. They have the same result as ACE inhibitors in that blood vessels
remain relaxed and blood pressure decreases.
● Sulfonylureas - Mechanism of action - rises plasma insulin concentrations; consequently
they are effective only when residual pancreatic β-cells are present. The rise in plasma insulin
levels occurs for two reasons. Firstly, there is stimulation of insulin secretion by pancreatic
β-cells, and secondly, there is a decrease in hepatic clearance of insulin.
● Metformin - This medication is used to decrease hepatic (liver) glucose production, to
decrease ​GI​ glucose absorption and to increase target cell insulin​ sensitivity.

4. As a 5-star Bedan Physician, how are you going to manage this patient (Medical and non-medical)?