AUBF: Renal Function

Functions of the Kidney

Excrete waste products of metabolism.

Regulate acid-base balance

Regulate electrolyte balance

Regulate Blood pressure

Regulate red cell production (Erythropoiesis)

Waste product of muscle metabolism

Creatinine

Waste product of protein metabolism

Urea

Ideal pH of the blood

7.35 to 7.45

Two organs that help regulate pH level

lungs and kidneys

What regulates RBC production

EPO

Blood flow to the kidneys

Aorta -> Renal Artery -> Segmental Artery → Lobar artery → Interlobar artery → Arcuate artery → Interlobular artery → Afferent arteriole → Glomerulus → Efferent arteriole → Peritubular capillaries and vasa recta → Interlobular vein → Arcuate vein → Interlobar vein → Renal vein → Inferior Vena Cava

Nephron

Basic functional unit of the kidneys

1200ml/min

Total renal BLOOD flow

600 to 700 ml/min

Total renal PLASMA flow

Urine formation process

Filtration (at the glomerulus)

Reabsorption (in the renal tubules)

Secretion (in the renal tubules)

Urine formation pathway

PCT, Descending LH, Ascending LH, DCT, CD, Renal pelvis, Ureter, Urinary bladder, Urethra

Filtrate vs Urine

Filtrate undergoes different processes first before becoming urine

Cortical Nephron

• 85% of nephrons

• Removal of waste products

• Reabsorption of nutrients

• Does not extend the LH to the medulla

Juxtamedullary Nephron

• Concentration of urine

• Extends to the medulla

Glomerulus

The part of the nephron that acts as a sieve

Factors that influence the filtration process

• Cellular structure of the glomerulus

• Hydrostatic pressure

• Oncotic pressure

• Renin-angiotensin-aldosterone system (RAAS)

Glomerular Basement Membrane (Basal Lamina)

• < 70,000 MW

• Negatively charged (repels proteins)

Visceral epithelium (podocytes)

• Foot processes

• Slit membranes prevent the filtration of proteins

Hydrostatic pressure

The pressure that forces the fluid OUTSIDE the vessel.

Oncotic pressure

Maintains the fluid INSIDE the vessel

Constriction of EFFERENT arteriole

• Increased hydrostatic pressure

• Increased GFR

Constriction of the AFFERENT arteriole

• Decreased hydrostatic pressure

• Decreased GFR

Renin-angiotensin-aldosterone system (RAAS)

• Controls the regulation of blood to and within the kidneys

• LOW plasma pressure and LOW plasma sodium = RENIN PRODUCTION

Actions of the Angiotensin II

• Dilates the AFFERENT arteriole

• Constricts the EFFERENT arteriole

• Stimulates PCT reabsorption of Na

• Triggers release of aldosterone & ADH

Glomerular filtrate

• SG = 1.008 - 1.010

• pH = 7.4

• GFR = 120 ml/min

Glucose renal threshold

160 to 180 mg/dl

PCT reabsorbs

Water

Na+ 65%

K+

Glucose

Amino Acid 100%

Vitamins

Chloride

Urea 50%

HCO3 80 - 90%

Active Transport Reabsorption

Glucose - PCT

Amino acid - PCT

Chloride - Ascending LH

Sodium - PCT,

and DCT.

Passive Transport Reabsorption

Water, Urea: PCT and Ascending LH

Sodium: Ascending LH

Loop of Henle

• Hairpin-like loop

• Important in regulating the osmolarity of the medullary interstitial fluid

Countercurrent Multiplier System (Loop of Henle)

• Descending LH - Water is passively reabsorbed, permeable

• Ascending LH - Na & Cl are actively and passively reabsorbed; impermeable to H2O

Final concentration of the filtrate

• In the late DCT & Collecting Duct

High ADH

• increases permeabilty, reabsorption of water

• Low-volume urine or concentrated urine

Absence of ADH

• walls are IMPERMEABLE to water

• Large volume = dilute urine

Functions of Tubular Secretion

1. Elimination of waste products not filtered by the

glomerulus.

2. Regulation of the acid-base balance

Renal tubular acidosis

• alkaline urine

• Renal tubules cannot release hydrogen ions

Urine pH

Reflects the ability of the kidney to maintain normal hydrogen ion concentration

Nephron: PCT secretes

• creatine (minute)

• Urea

• H+

• NH4

Glomerular Filtration Rate

• Clearance Test

• Measure the rate at which the kidneys can remove or clear a filterable substance from the blood

• Removal of a substance from plasma into urine over a fixed period

Clearance markers should be:

• Not bound to proteins

• Filtered

• Neither reabsorbed nor secreted

Exogenous substance

administered or

introduced into the body

Endogenous substance

Already present in the body; naturally occuring

↑ efficient excretion

• increase GFR

• Increase in efficient excretion of marker

↓ inefficient excretion

• Low GFR

• Kidneys are less efficient in filtering

Exogenous markers

• inulin (reference method)

• Radioactive markers (125I-ioithalamate, 99m Tc-DTPA, Iohexol, 51Cr-EDTA)

Inulin

• Soluble, freely filtered, neither secreted nor reabsorbed

• Normal values:

  • Male: 127 ml/min/1.73m2

  • Female: 118 ml/min/1.73m2

Creatinine Clearance

• endogenous

• 113 Da

• Most widely used marker for GFR

• Produced constantly, not bound to proteins, not reabsorbed, minimally secreted (PCT)

• NV

  • Male: 85-125 ml/min

  • Female: 75-112 ml/min

Improperly timed urine specimen

Greatest source of error in a clearance procedure

Methods that DO NOT require 24-hour urine

• rate eGFR using serum creatinine

• Cystatin C

• Beta 2 - microglobulin

Cockcroft & Gault

• Variables: age, sex, weight in kg

• Female - multiply by 0.85

Modified of Diet in Renal Disease (MDRD)

• Six variables: age, sex, serum urea nitrogen, serum creatinine, race, and serum albumin.

Simplified MDRD

4 variables:

• serum creatinine

• Age

• Race

• Sex

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 92021)

• Variables: Serum creatinine, age, sex

Improving Global Outcomes (KDIGO)

• Stage 1: > 90 mL

• Stage 2: 60-89 mL

• Stage 3: 45-59 mL

• Stage 4: 15-29 mL

• Stage 5: <15 mL

Urea Clearance: Endogenous

• major end product of protein and amino acid metabolism

• Freely filtered by the glomeruli

• variably reabsorbed by the tubules

Cystatin C

• screening and monitoring GFR

• Small protein

• Readily filtered by the glomerulus

• Reabsorbed and broken down by the RTEs

• Not secreted by the tubules

Beta 2 - Microglobulin

• MW 11,800

• Uses enzyme immunoassay for quantification

• Increase beta 2 - microglobulin: decreased GFR

Fishberg Test

• patients are deprived of fluids for 24 hours

Mosenthal Test

• compares the volume and specific gravity of day and night samples

Specific gravity

Screening test for tubular reabsorption

Osmolality

• Serum: 275 to 300 mOsm

Specific Gravity vs Osmolality

• Specific gravity: number and density

• Osmolality: no. Of particles in a solution

Instrument Measurement of Osmolality

• Freezing-point osmometers

• Vapor pressure depression

Freezing point osmometers

• measures the freezing point depression

• Directly proportional to the amt of solute present

Vapor pressure osmometers

• magnitude of the vapor pressure decrease is directly proportional to the molar concentration of solute

Function of Antidiuretic Hormone (ADH)

Its function is to conserve water. If you have enough ADH and you conserve water, the urine output will be low and will be concentrated.

Water Deprivation Test (Normal Result)

After depriving a patient of water for 12 hours, a normal result is a urine osmolality of 800 mOsm or higher.

Water Deprivation Test (Abnormal Result)

If the urine osmolality is < 800 mOsm, it means your tubules do not have the concentrating ability to produce concentrated urine.

ADH Challenge Test

A test where the patient is injected with ADH, and serum and urine are collected after 2 and 4 hours.

Neurogenic Diabetes Insipidus

• Problem: The body doesn't produce enough ADH.

• ADH Test Result: After injecting ADH, the urine osmolality is corrected/normalized. This means the kidney responds to ADH, and the problem is only the absence or lacking of ADH.

Nephrogenic Diabetes Insipidus

• Problem: The kidney is unable to respond to ADH. This suggests a problem with the kidneys' ADH receptors.

• ADH Test Result: Even if you administer ADH, the urine osmolality is still low. This means that even if you have enough ADH, you still cannot produce concentrated urine.

Free water clearance

• amount of solute-free water excreted per day

Free water clearance Results

• Negative: Less than the necessary amount of urine is excreted (concentrated)

• Positive: Excess water is excreted

• Zero: Kidney is producing urine with respect to the plasma

P-aminohippuric clearance test (PAH Te)

A test using a nontoxic substance that is loosely bound to plasma proteins, which permits its complete removal as the blood passes through the peritubular capillaries.

Titratable Acidity and Urinary Ammonia

A test to measure urinary ammonia. A person excretes approximately 70mEq/day of acid in the form of titratable acid (H+), hydrogen phosphate ions (H2PO4–), or ammonium ions (NH4+). Since urine is naturally acidic, we can perform titration.