Clinical Microscopy – TSFT No. 1

Renal Anatomy, Renal Function Tests, Urinalysis, Renal Diseases

Nephron

The basic structural and functional unit of the kidney

1 to 1.5 million

There are approximately how many functional units in each kidney?

Cortical nephrons

Location: Cortex of the kidney
Function: Removal of waste products and reabsorption of nutrients

What type of nephron?

Juxtamedullary nephrons

Location: Longer loops of Henle that extend deep into the medulla
Function: Concentration of urine

What type of nephron?

1. Glomerulus

2. Proximal Convoluted Tubule (PCT)

3. Loop of Henle (LH)

4. Distal Convoluted Tubule (DCT)

5. Collecting Duct (CD)

6. Calyx

7. Renal Pelvis

Order of urine formation (first to last):

1. Renal Artery

2. Afferent Arteriole

3. Glomerulus

4. Efferent Arteriole

5. Peritubular Capillaries

6. Vasa Recta

7. Renal Vein

Order of renal blood flow (first to last):

Glomerulus

Blood is filtered in the?

Bowman’s capsule

Water and small solutes move from the blood and into the __________ to form the filtrate.

Proximal Convoluted Tubule (PCT)

Where useful substances (such as glucose, amino acids, ions) and most of the water are reabsorbed from the filtrate back into the blood.

Loop of Henle (LH)

Where further reabsorption of water and salts occurs, concentrating the filtrate.

Descending limb of the loop of Henle

Where further reabsorption of water occurs, concentrating the filtrate.

Ascending limb of the loop of Henle

Where further reabsorption of salts occurs, concentrating the filtrate.

Distal Convoluted Tubule (DCT)

Where additional reabsorption of ions and water as well as secretion of wastes and excess ions occur which help fine-tune the filtrate.

Collecting Duct (CD)

Where further reabsorption of water (influenced by ADH) and some ions occurs, finalizing urine concentration.

Calyx

Urine flows from the collecting ducts into the _______.

Renal Pelvis

Urine from the calyces drains into the ____________ and is passed to the ureter.

Renal Artery

The ____________ supplies blood to the kidney.

25%

Approximately, the kidney receives ___ of the blood pumped through the heart at all times.

hydrostatic pressure differential

The varying sizes of the arterioles help create a ___________________.

Peritubular Capillaries

• Surround the PCT and DCT

• Immediate reabsorption of essential substances from PCT and final adjustment in DCT

Vasa Recta

• Adjacent to the ascending and descending loop of Henle in juxtamedullary nephrons

• Major exchanges of water and salts take place between the blood and medullary interstitium

• Maintains osmotic gradient (salt concentration)

1.73 m²

Approximate total renal blood flow and renal plasma flow are based on an average body size of?

1200 mL/min

Approximate total renal blood flow:

600 to 700 mL/min

Approximate total renal plasma flow:

Glomerulus

• A coil of 8 capillary lobes within the Bowman’s capsule

• Resembles a sieve and filters 120 mL/min (1/5 of renal plasma)

• A non-selective filter of plasma substances <70,000 MW

8

The glomerulus is a coil composed of how many capillary lobes?

120 mL/min or 1/5 of the renal plasma

The glomerulus resembles a sieve that filters plasma at a rate of?

<70,000

The glomerulus is a non-selective filter of plasma substances that are _________ MW.

1. Capillary Wall Membrane

2. Basement Membrane (basal lamina)

3. Visceral epithelium of the Bowman’s capsule

The three glomerular filtration barrier cellular layers:

Shield of Negativity

Additional structure of glomerular filtration (aside from the three cellular layers):

1. Cellular structure of capillary walls and Bowman’s capsule

2. Hydrostatic pressure

3. Oncotic pressure

4. Feedback mechanism of the RAAS

Factors affecting the actual filtration process (4):

+55 mmHg

Forces involved in glomerular filtration: magnitude of hydrostatic (blood) pressure

-15 mmHg

Forces involved in glomerular filtration: magnitude of hydrostatic (ultrafiltrate in Bowman’s space) pressure

-30 mmHg

Forces involved in glomerular filtration: magnitude of oncotic (protein in the blood and not in ultrafiltrate) pressure

+10 mmHg

Forces involved in glomerular filtration: magnitude of net pressure

Tubular Reabsorption

The first function to be affected in cases of renal disorder

Tubular Reabsorption

The process wherein substances are removed from the glomerular filtrate and returned to the blood

160 to 180 mg/dL

Renal threshold for glucose:

Active Transport

Movement of a substance across cell membranes into the bloodstream by electrochemical energy

Passive Transport

Movement of molecules across a membrane by diffusion because of a physical gradient

PCT

Strasinger 7th ed.

Tubular Reabsorption

Membrane Transport: Active
Substance: Glucose, amino acids, salts
Location: ___________

Ascending LH

Strasinger 7th ed.

Tubular Reabsorption
Membrane Transport: Active
Substance: Chloride
Location: ___________

PCT, DCT

Strasinger 7th ed.

Tubular Reabsorption

Membrane Transport: Active
Substance: Sodium
Location: ___________

PCT, descending LH, CD

Strasinger 7th ed.

Tubular Reabsorption

Membrane Transport: Passive
Substance: Water
Location: ___________

PCT, ascending LH

Strasinger 7th ed.

Tubular Reabsorption

Membrane Transport: Passive
Substance: Urea
Location: ___________

ascending LH

Strasinger 7th ed.

Tubular Reabsorption

Membrane Transport: Passive
Substance: Sodium
Location: ___________

Glucose, amino acids (proteins), Na+, Mg2+, Ca2+, HCO3-, phosphate, sulfate, uric acid

Brunzel 4th ed.

Tubular Reabsorption

Location: PCT
Mode of Absorption: Active
Substance: ___________

H2O, Cl-, K+, urea

Brunzel 4th ed.

Tubular Reabsorption

Location: PCT
Mode of Absorption: Passive
Substance: ___________

H2O, urea

Brunzel 4th ed.

Tubular Reabsorption

Location: LH (thin descending, u-turn, thin ascending) and CT (medullary)
Mode of Absorption: Passive
Substance: ___________

Urea

Brunzel 4th ed.

Tubular Reabsorption

Location: LH (thick ascending)
Mode of Absorption: Passive
Substance: ___________

Na+, Cl-

Brunzel 4th ed.

Tubular Reabsorption

Location: LH (thick ascending)
Mode of Absorption: Active
Substance: ___________

Na+, Cl-, sulfate, uric acid

Brunzel 4th ed.

Tubular Reabsorption

Location: LH (DCT)
Mode of Absorption: Active
Substance: ___________

H2O

Brunzel 4th ed.

Tubular Reabsorption

Location: LH (DCT)
Mode of Absorption: Passive
Substance: ___________

H2O, Cl-

Brunzel 4th ed.

Tubular Reabsorption

Location: CT (cortical)
Mode of Absorption: Passive
Substance: ___________

Na+

Brunzel 4th ed.

Tubular Reabsorption

Location: CT (cortical)
Mode of Absorption: Active
Substance: ___________

RAAS

This regulates the flow of blood to and within the glomerulus.

vasodilation, vasoconstriction

Action of RAAS: Causes __________ of the afferent arterioles and __________ of the efferent arterioles.

aldosterone, antidiuretic hormone

Action of RAAS:

• PCT: sodium reabsorption

• DCT and CD: sodium reabsorption and potassium excretion triggered by the hormone _________.

• CD: water reabsorption triggered by the hypothalamic hormone _________.

enzymes

Renin and ACE are (enzymes / hormones / inactive precursors)?

hormones

Angiotensin II, aldosterone, and ADH are (enzymes / hormones / inactive precursors)?

inactive precursors

Angiotensinogen and Angiotensin I are (enzymes / hormones / inactive precursors)?

Tubular Secretion

The passage of substances from the blood in the peritubular capillaries to the tubular filtrate

PCT

The major site for removal of unfiltered substances

• Elimination of waste products

• Regulation of acid-base balance

Two major functions of tubular secretion:

Renal Tubular Acidosis

Inability to produce urine

Type 1 (Distal RTA)

Type of RTA: The far end of the tubules cannot properly secrete acid into the urine. It is often caused by autoimmune diseases (e.g., Sjögren's syndrome, lupus) or certain medications

Type 2 (Proximal RTA)

Type of RTA: The beginning of the tubules fails to reabsorb bicarbonate (a base that neutralizes acid). It is rarer, often occurs in infants, and can be part of a broader condition called Fanconi syndrome

Type 4 (Hyperkalemic RTA)

Type of RTA: The tubules cannot remove enough acid and potassium. It is the most common type and is frequently linked to diabetes, kidney damage, or specific medications (such as blood pressure drugs)

H+, NH3, weak acids and bases

Brunzel 4th ed.

Tubular Secretion

Location: Proximal tubule
Substance: ___________

Urea

Brunzel 4th ed.

Tubular Secretion

Location: Loop of Henle
Substance: ___________

H+, NH3, K+, uric acid (some drugs)

Brunzel 4th ed.

Tubular Secretion

Location: Distal tubule
Substance: ___________

H+, NH3, K+ (some drugs)

Brunzel 4th ed.

Tubular Secretion

Location: Collecting tubule
Substance: ___________

Clearance test

• These are standard tests used to measure the filtering capacity of the glomeruli.

• Measures the rate in mL/min at which the kidneys can remove (to clear) a filterable substance from the blood

Exogenous procedure

Clearance test that requires an infused substance as the point of reference in measuring clearance rate

Endogenous procedure

Clearance test wherein the substance measured for clearance rate is already present in the body

Urea clearance

• Earliest glomerular filtration test

• Measured because of its presence in all urine specimens

Inulin clearance

• Gold standard method

• An extremely stable substance that is neither reabsorbed nor secreted by the tubules

• Not a normal constituent of the body

Creatinine clearance

• The most used method

• Waste product of muscle metabolism

• Normally found at a relatively constant level in the blood

Improperly timed specimen

Greatest source of error in the creatinine clearance test:

1. Neither absorbed nor secreted by the tubules

2. Stability

3. Consistency of its levels in the plasma

4. Availability

Four factors to consider in selecting a clearance test substance:

BAGS:
Body weight, Age, Gender, Serum Creatinine

GFR: Cockgroft and Gault Formula variables (4)

C = (140 - age)(body weight in kg) / 72 x serum creatinine in mg/dL

GFR: Cockgroft and Gault Formula?

0.85

In the Cockgroft and Gault formula for GFR, the female patients’ results are multiplied by?

BRAGS:
BUN, Race, Age, Gender, Serum Albumin & Creatinine

GFR: Modification of Diet in Renal Disease (MDRD) System Formula variables (5)

GFR = 170 x serum creatinine^-0.999 x age^-0.176 x BUN^-0.170 x serum albumin^+0.318

x 0.822 (if female)

x 1.1880 (if black)

GFR: Modification of Diet in Renal Disease (MDRD) System Formula?

GFR = 175 x serum creatinine^-1.154 x age^-0.203

x 0.742 (if female)

x 1.212 (if black)

GFR: MDRD-IDMS Traceable Formula?

MDRD-IDMS Traceable Formula

GFR formula recommended by the National Kidney Disease Education Program (NKDEP)

Stage 1

Stage of Chronic Kidney Disease: GFR >90 mL/min/1.73m

Stage 2

Stage of Chronic Kidney Disease: GFR 60 – 89 mL/min/1.73m

Stage 3

Stage of Chronic Kidney Disease: GFR 45 – 59 mL/min/1.73m

Stage 4

Stage of Chronic Kidney Disease: GFR 15 – 29 mL/min/1.73m

Stage 5 (end-stage renal disease [ESRD])

Stage of Chronic Kidney Disease: GFR <15 mL/min/1.73m

Cystatin C

Another substance used for eGFR:

• A small protein produced at a constant rate by all nucleated cells

• Serum concentration can be related directly to the GFR

• Monitoring its levels is recommended for pediatric, diabetic, elderly, and critically ill patients

• Advantage: independent of muscle mass

Beta-2 Microglobulin

Another substance used for eGFR:

• Used to distinguish disorders of the kidney as either glomerular or tubular

  • Glomerular disorder

    • Increased B2M in blood

    • Decreased B2M in urine

• Used to identify ESRD and early rejection of a kidney transplant

• Not reliable in patients who have a history of immunologic disorders or malignancy

Radionucleotides

Another substance used for eGFR:

• Exogenous procedure; more labor-intensive and costly

• Exogenous markers:

  • Chromium-51 ethylenediaminetetraacetic acid (51 Cr-EDTA)

  • Technetium-99-labeled diethylenetriaminepentaacetate (99-Tc-DPTA)

• Iohexol – a nonradioactive contrast agent used for children

Concentration tests

Tubular reabsorption tests that determine the ability of the tubules to reabsorb the essential salts and water that have been filtered by the glomerulus

Osmolality, Specific Gravity

Commonly used concentration / tubular reabsorption tests:

• __________ – measures only the number of particles in a solution

• __________ – influenced by both the number and density of the particles

Fishberg test, Mosenthal test

Obsolete concentration / tubular reabsorption tests:

• __________ – patient is deprived of fluid for 24 hours, then urine specific gravity is measured (SG = ≥1.026)

• __________ – compare day and night urine in terms of volume and specific gravity

Titratable Acidity (TA) Test

A tubular secretion test that evaluates the ability of the tubules to secrete hydrogen ions (H+) leading to acidic urine

P-aminohippuric acid (PAH) test

A tubular secretion test that is more accurate than the TA test and uses infused exogenous PAH