Renal function Flashcards
9 Major Renal Functions
- Excretion of metabolic waste and foreign substances
- includes hormone metabolites, drugs, toxins - Regulation of water and electrolyte balance
- Regulation of extracellular fluid volume
- Regulation of plasma osmolality
- Regulation of RBC Production
- Regulation of Vascular Resistance
- Regulation of Acid-Base Balance
- Regulation of Vitamin D production and bone mineral balance
- Gluconeogenesis
what are the waste products of proteins, nucleic acids, creatine, and hemoglobin
- protein = urea
- nucleic acid = uric acid
- creatine = creatinine
- hemoglobin = urobilin
Regulation of RBC Production is managed by what hormone
erythropoietin
↓ renal BP affects the juxtaglomerular cells how?
juxtaglomerular cells in afferent arteriole to release renin
Renin → peripheral vasoconstriction → ↑ BP
describe the characteristics of a healthy vs diseased kidney
- healthy
- Renal metabolism is equivalent to general BMR
- Lower oxygen in the body as a whole correlates with lower oxygen levels in the renal tissues
- Low oxygen levels trigger erythropoietin production by interstitial cells, leading to increased RBC production - diseased
- Renal metabolism is lower than the general BMR
- Hypoxia in the body as a whole does not necessarily equate to renal hypoxia
- Slower local oxygen consumption of diseased renal tissue means oxygen levels do not drop at the same rate as the rest of the body and erythropoietin production is blunted
what hormone made in the kidneys is a part of the regulation of Vitamin D production and bone mineral balance
Active vitamin D (calcitriol)
what process mostly occurs in the liver, but kidneys also contribute, especially in a prolonged fast
Gluconeogenesis
where are the kidneys located
Just below rib cage, retroperitoneal, near posterior abdominal wall
Curved side of kidney is ?
hilum
the kidneys are organized in pyramid-like structures collectively known as
renal medulla
kidney pyramids end in ___ that are serviced by ___
papillae
minor calyces
Medulla is surrounded by the ____, which itself is covered by a thin fibrous connective tissue capsule
renal cortex
fluid and cells that secrete ECM
Some cells secrete EPO
< 10% of renal volume
Interstitium
what is the working tissue mass
tubules (nephrons and collecting tubules) and blood vessels
what part of the renal system has tubules and blood vessels that are intertwined randomly
Cortex
Cortex also contains scattered spherical renal corpuscles
which part of the renal system has tubules and blood vessels that are arranged parallel
Medulla
___ and ____ nephrons have differing tubules
Cortical
juxtamedullary
beginning of nephron
Glomerulus + glomerular capsule
what part of the renal system is this
Renal corpuscle
multiple segments, each with their own functions
Eventually merge with tubules from other nephrons
what part of the renal system is this
Tubule
made from merged tubules
merges and terminates in the renal papilla
what part of the renal system is this
Collecting duct
Hollow sphere (Bowman’s capsule) made of epithelial cells, surrounding glomerulus
what part of the renal system is this
Renal corpuscle
carries blood into the corpuscle
what part of the renal system is this
Afferent arteriole
interconnected capillary loops
Plasma is filtered through this
Podocytes surround capillary loops of this structure
what is this?
Glomerulus
Podocytes surround capillary loops of the glomerulus to:
- Remove material trapped in the wall of the capillaries
- Contract capillaries if needed
carries the blood out of the corpuscle
what part of the renal system is this
Efferent arteriole
single epithelial cell layer on a basement membrane
what part of the renal system is this
Tubule
what is the first segment of the renal system
Proximal Tubule
which Proximal Tubule is in the cortex
Proximal convoluted tubule
which proximal tubule descends into medulla
Proximal straight tubule
what is the second segment of the renal system
Loop of Henle
what are the parts of the Loop of Henle
describe the system
- Descending limb - all begin at the same level, penetrate to different depths
- Thin ascending limb - absent in “shallow” nephron loops
- Thick ascending limb - distal portion - all begin at same level
- All loops return to the same capsule they started from - cells in thick ascending limb closest to the capsule are specialized cells known as the macula densa
what is the third segment
Distal Tubule
what is the last segment
Collecting Duct
joins tubules from nephrons
Collecting ducts merge to form successively larger ducts that eventually empty into a minor calyx
cause of renal fusion
thought to occur during fetal organogenesis
Pathophysiology of renal fusion
- Abnormal blood supply is common
- Abnormal course of ureters
- Often located lower than normal kidneys in the abdomen, due to the IMA
- Not protected by the ribcage
renal fusion is MC in who?
2x in males
sx of renal fusion
- ⅓ - asx; found incidentally
- UTI - most common presenting complaint in children
- May have atypical s/s (abdominal pain and bloating) - Abdominal pain and nausea
- Increased incidence of complications
- other genitourinary malformations/abnormalities
complications with renal fusion
- Ureteropelvic junction obstruction (MC)
- Renal lithiasis
- UTI - severe/upper
- Vesicoureteral reflux
- Increased incidence of renal tumors/cancer
Diagnostic Studies for renal fusion
- CT with Intravenous Pyelogram
- May also do abdominal/pelvic CT or US - Urinalysis/Urine Culture often performed
- Renal function labs
tx for renal fusion
- Medical - to manage disorders that
could predispose to complications - Surgical - to manage complications
as they arise
describe the bowmans capsule
- Glomerular filtrate - like plasma, but minus large plasma proteins (albumin, globulins, etc.)
- Substances present in filtrate at the same concentration as plasma = “freely filtered”
- Na, K, Cl, HCO3
- glucose, urea, amino acids
- insulin, ADH - Glomerular Filtration Rate (GFR) - volume of filtrate formed per unit of time (usually mL/min)
- Healthy young adult male - 180 L/d (125 mL/min)
- Entire plasma volume is filtered by the kidneys approx. 60 times/day
describe the proximal tubule
- Reabsorbs…
- ~60% of NaCl and H2O
- ~90% of filtered HCO3-
- Almost all glucose, amino acids
- Most K, PO4, Ca, Mg, urea, uric acid - Produces ammonia
- Secretes…
- organic anions (e.g., urate)
- organic cations (e.g., creatinine, dopamine, Ach, epinephrine, histamine)
- Urea
- Ammonia
- Protein-bound drugs, chemo rx, toxins
describe the loope of henle as a whole
- concentration of urine = countercurrent mechanism
- Site of action for most potent class of diuretics (loop diuretics) → thick ascending limb of the loop of Henle
- Reabsorbs…
- H2O → descending
- ~25% NaCl → ascending
- Some calcium and most magnesium
describe the Descending Loop of Henle
Highly water-permeable
Reabsorbs ~15% H2O
describe the Thin Ascending Loop of Henle
Impermeable to water and ions except Na+ and Cl-, which are reabsorbed by diffusion
describe the Thick Ascending Loop of Henle
- Very low water permeability
- Reabsorbs…
- NaCl via Na+/K+/2 Cl- pump - loop diuretics
- Some Calcium and Magnesium
- May HCO3- reabsorption - May see secretion of urea
describe the distal tubule
- Reabsorbs…
- ~5% of NaCl
- little H2O (low permeability)
- May reabsorb urea - Major site of active regulation of calcium
- Site of action for thiazide diuretic
- Secretes K+
- Regulates pH by either of the following:
- reabsorbing HCO3- and secreting H+
- reabsorbing H+ and secreting HCO3-
describe the collecting duct
- Cortical Collecting Duct
- Principal cells
— reabsorb NaCl and H2O
— secrete K+
— Site of action for aldosterone, eplerenone, and other K+-sparing diuretics
- Intercalated cells - mediate HCO3- and H+ secretion and reabsorption - Medullary Collecting Duct
- Final modification of urine
- Reabsorb NaCl, water and urea
- Secretes ammonia and H+
- Secretes or reabsorbs K+
sudden loss of renal function?
causes?
acute nephron injury/loss
Hypotension (blood loss, septic shock, dehydration, heart failure)
Obstruction of urine flow (BPH, renal stone, tumor)
Substances (medications, toxins, myoglobin)
slow, gradual loss of renal function?
causes?
chronic nephron injury/loss
DM
HTN
Autoimmune diseases
Infection/Inflammation
Polycystic disease
Nephrotoxic Substances
increased size of each cell in nephron
- Compensatory renal hypertrophy
- Generally produces no major ill consequences
- If previously healthy → achieve ~80% function
Compensatory renal hypertrophy is seen in situations of ongoing ?
- hyperfiltration
- Pts born with one kidney
- Loss or donation of a kidney
- Pregnancy
End Stage Renal Disease (ESRD) results from…
- Resection of significant amount of renal mass (~80%)
- Destruction of a significant amount of nephrons
if nephrons cannot compensate with injury/loss what is the result?
maladaptive deterioration
progressive nephron loss after severe or persistent disease
Renal Progression
Rate of glomerular filtrate formation = ?
sum of filtration rates in all functioning nephrons
Gives rough estimate of the # of functioning nephrons? what is a normal value?
Glomerular Filtration Rate (GFR)
Normal - 125 mL/min/1.73 m2 (180 L/d)
GFR of 60-99 mL/min/1.73 m2 for 3+ mo with kidney damage markers is indicative of?
early CKD
GFR < 60 mL/min/1.73 m2 for 3+ mo is indicative of ?
chronic CKD
GFR seen with Pts with kidney disease
- may have decreased GFR, or normal or increased GFR
- Hyperfiltration at the glomerulus
- Disease affects a different area of kidney
what can be more helpful than an isolated GFR
- following GFR measurements
- Assess if GFR is stable, improving, or deteriorating
- Assess changes in GFR following interventions
Stable GFR ≠ stable disease
Improved GFR ≠ improved disease
Normal GFR ≠ no kidney disease
GFR is difficult to measure directly, what freely filtered substances are observed to help determine kidney function
- Blood Urea Nitrogen (BUN)
- Serum Creatinine (sCr)
- Cystatin C
Other methods for determining renal function
- 24 hr Creatinine Clearance (CrCl)
- Estimation equations
- Cockroft-Gault, MDRD, CKD-EPI, Lund-Malmo, EKFC
Factors Affecting GFR Estimation
- Body Surface Area (BSA)
- Kidney function is proportional to kidney size, which is proportional to BSA
- Smaller body size → lower metabolic demands, less muscle mass - Age
- GFR typically declines gradually with age, even in pts with no dx of CKD
- Declining GFR is an independent risk factor for adverse health outcomes - Gender
- Males tend to have higher avg muscle mass and creatinine generation
- GFR calculations take this into account! - Race
- African Americans tend to have higher average muscle mass and creatinine generation
- Newer recommendations (2021) suggest not using race
- No globally used modifications for other ethnic groups
describe Creatinine Metabolism
- Creatine is…
- 50% made by the liver
- 50% absorbed from food (meat) - Taken up by high-metabolism tissues (skeletal muscle, brain)
- Metabolized by creatine kinase into creatine phosphate, which can be used to fuel production of ATP - Creatinine is a waste by-product and is produced at a fairly steady rate
Estimates renal function at a higher level than GFR
“The upper limit of what the true GFR may be”
Requires 24-hr urine measurement
Creatinine Clearance (CrCl)
at higher level bc creatinine is secreted by proximal tubule as well as filtered by the glomerulus
Obtaining a Urine Sample for 24-hr CrCl
- Begin in the AM after waking up and emptying bladder for the first time that day
- Note time at initial urine voiding and collect all urine for the next 24 hrs
- Collect urine at both day and night, including urination with defecation
- Do not collect feces - Finish with collecting the first urine
passed the next morning
- Within 10 min of 24 hour mark
Limitations of 24 hr Urine CrCl
- Incomplete urine collection
- <24 hrs = low measured excreted Cr - Cumbersome - Poor pt compliance
- Increased creatinine secretion as GFR falls
- Especially in early CKD! - Overestimation of GFR
describe Urea Metabolism
- made by liver as a waste by-product of the digestion of protein
- Freely filtered by the glomerulus
- Approx 30-70% reabsorbed in the renal tubules
- Reabsorption decreased in volume replete pts
- Reabsorption increased in volume deplete pts
normal BUN:Cr ratio
10:1 to 20:1
Volume depletion - ratio may increase (20:1 or higher)
Factors that increase BUN
- Dehydration
- Catabolic (cell breakdown) states
- GI bleed, cell lysis, corticosteroids - Increased dietary protein
- Decreased renal perfusion
- HF, RAS - Tetracycline
factors that decrease BUN
- Liver disease
- Malnutrition
- Sickle cell anemia
- SIADH
Notes about using BUN to obtain GFR
- BUN varies inversely with GFR
- BUN can change independently of GFR
- Rate of urea production is not constant
- 40-50% of filtered urea is passively reabsorbed
— increased in volume depletion
— BUN rises out of proportion to change in GFR and Cr -
LESS USEFUL < sCr for calculating GFR
- Greatest utility - severe CKD pts
describe Cystatin C Metabolism
- Cystatin C is a protein produced at a fairly steady rate by all nucleated cells in the body
- Freely filtered by the glomerulus
- Does not get reabsorbed in the tubules, but does get metabolized
-
Less directly affected by muscle mass and metabolism < creatinine
- Not as impacted by age, sex, gender, or race as creatinine but still varies
factors that increase cystatin C
- Male sex
- Greater body mass
- greater height and weight
- higher lean body mass
- higher fat mass - Chronic disease
- DM
- High inflammatory markers (CRP, WBC)
- Hyper- or hypothyroidism
- Malignancy - Glucocorticoid use
- Smoking or Alcohol
factors that decrease cystatin C
Female sex
Smaller body mass
Notes about Using Cystatin C to obtain GFR
- varies inversely with GFR
- Cystatin C production varies less than other markers
- However, many potential confounding factors - Expensive
- Mostly used when high risk for creatinine not being as accurate
- Elderly patients
- Body builders
- Acutely ill patients, especially those with acute changes in muscle mass
what is the Cockcrault-Gault Equation
- Estimates CrCl based on serum Cr in a pt with stable Cr
- Accounts for assumptions that Cr production:
- Decreases with advancing age
- Should be greater in individuals with higher weight - Overestimates CrCl - low accuracy
multiply result by 0.85 for female patients
limitations of Cockcrault-Gault Equation
Developed when obesity was far less common - does not account for BSA
Highly dependent on serum Cr
what is the MDRD Study Equation
- Estimates GFR adjusted for body surface area
- Based on data from adult patients
- More accurate than Cockroft-Gault formula
- Not studied in different populations (elderly, obese, diverse ethnic/racial backgrounds)
multiply result by 0.742 for female patients
multiply result by 1.21 for black patients
what is the CKD-EPI Study
- More accurate estimate of GFR
- Better for normal or mildly reduced GFR
- Equal to MDRD for pts with mod-severe reduction in GFR
- Better risk prediction
- More accurate CKD prevalence
- No longer adjusted for racial status in US
- Some east-Asian countries, such
as Japan, do adjust racial parameters
what are the other GFR equations
- Revised Lund-Malmo Equation
- European Kidney Function Consortium (EKFC)
- similar variables of sex, race, age, and renal markers (creatinine and/or cystatin C)
- suggest equal/greater accuracy for GFR, but CKD-EPI 2021 is preferred in the US bc no race variable