4. Kidney Flashcards
Describe kidney anatomy
Paired, retroperitoneal
Partially protected by 11th + 12th ribs
Right slightly lower - liver
1% body mass
25% cardiac output
List main kidney functions
3 main functions; (maintain whole body homeostasis)
- Excrete waste
- Maintain ECF volume + comp
- Endocrine function
What does kidney function regulate?
Blood volume + composition
Electrolytes
Blood PH + acid-base balance
BP
Describe the nephron + its overall function
Nephron = structural + functional unit of kidney
- each kidney = 1m nephrons
Consists of;
- glomerulus: forms a protein filtrate from blood
- tubule: processes filtrate to form urine
Processes blood supplied + forms urine by;
- filtration
- reabsorption
- secretion
- excretion
Describe urine formation
Blood from afferent arteriole (renal artery) filtered at glomerulus
- forms protein filtrate
Glomerular filtrate passes along tubule;
- reabsorption of glucose, water, salts into blood in nearby peritubular capillaries
- secretion of unwanted substances e.g. K+ from blood into tubule
Urea + other unwanted substances dissolved in filtrate pass down tubule>bladder>excreted as urine
How does reabsorption occur at the kidney tubule (into the blood)? Give an example of a disease linked to this.
Selective receptors on luminal cell membrane
E.g. amino acids reabsorbed by sodium dependent transporters in prox tubule;
- Hartnup disease = deficiency of tryptophan a acid transporter
- results in pellagra (niacin deficiency)
How much urine needs to be produced each day?
300-500mLs of urine is needed to excrete adequate amounts of solute each day
What causes filtration to happen at the glomerulus?
Hydrostatic filtration
Divergence of high pressure blood into small capillaries forces water, glucose, urea + salts through capillary wall + into tubule
What is not filtered at the glomerulus?
Protein + blood cells remain in blood as to big to pass through capillary wall
How much filtrate is generated at the glomerulus + how much urine does this generate?
180L/day + most is reabsorbed so 1mL/min urine in healthy person
Describe renal endocrine function
Kidney = important site for synthesis of several hormones
Renal associated hormones include;
RENIN; enzyme participating in RAAS
- regulates angiotensin + aldosterone levels
- essential for Na+ retention + H2O balance
- expands ECF compartment + increases BP
EPO; glycoprotein cytokine secreted by kidney in response to cellular hypoxia
- stimulates RBC production in BM
- low levels constantly secreted to compensate for RBC turnover
CALCITRIOL; hormonally active metabolite of vit D
- increases level of Ca2+ in blood by;
- increasing uptake from gut
- increasing reabsorption from kidneys + excreting inorganic phosphate (counter ion of Ca2+)
How is a patient with kidney disease assessed?
BP: high can lead to CKD
Fluid status;
- hypervolemia common in renal failure as inappropriate fluid retention
Presence of uremic symptoms;
- nausea/vomiting
- fatigue/anorexia/weight loss
- muscle cramps
- pruritis
- altered mental status
- visual disturbances
- increased thirst
- PE: uremic frost/oral lesions/scleral icterus/hypertension
Lab assessment;
- diagnosis
- monitoring
- guide treatment
What is uremia and how does it relate to kidney disease?
Uremia = high levels urea in blood (excess protein catabolism end products in blood, e.g. creatinine that are normally excreted in urine)
Can occur at creatinine clearance <10-20mL/min
Heralded by onset of specific S+S;
- nausea/vomiting
- fatigue/anorexia/weight loss
- muscle cramps
- pruritis
- altered mental status
- visual disturbances
- increased thirst
- PE: uremic frost/oral lesions/scleral icterus/hypertension
What are renal function tests used for?
Detect renal damage
Monitor damage
Help determine cause
What tests are performed in a lab assessment of patients with kidney disease?
Urinalysis Glomerular filtration rate Creatinine Urea + electrolytes Urine protein Hb Bone profile Iron profile Hormones
Describe the use of urinalysis in kidney disease assessment
Use a dipstick;
- noninvasive
- inexpensive
Strip impregnated with reagents for substances in question in a urine sample
- substance level can be altered in disease within urinary tract
Measures;
- protein
- Hb
- glucose
- ketones
- urobilinogen
- nitrite
- leukocytes
- specific gravity
- pH
What is the glomerular filtration rate + what does it say about kidney function?
Expression of the quantity of glomerular filtrate formed each minute in the nephrons of both kidneys
- is an index of the number of functioning glomeruli
Decreased GFR = development of clinically relevant signs + symptoms of CKD
What does measuring GFR require? What criteria needs to be met?
Requires measurement of a substance in plasma/serum + urine
Substance should meet criteria;
- readily filtered from plasma at glomerulus
- neither reabsorbed/secreted by tubules
- conc should remain constant throughout urine collection
- measurement of conc in plasma is convenient + reliable
What is the general equation for calculating GFR using a substance?
GFR (vol/time e.g. ml/min) = (urine conc x urine flow rate) / plasma concentration
What is the normal GFR in adults?
~110ml/min
List the methods for measuring GFR
Measurement;
- Inulin clearance
- EDTA clearance
- Creatinine clearance
Calculation/estimation;
- Cockcroft-Gault formula
- MDRD formula
Describe the use of inulin to measure GFR
Inulin;
- polysaccharide not produced by body
GFR determined by injecting into plasma;
- not absorbed/secreted by kidney
- volume of blood from which inulin cleared in one minute = inulin clearance
Gold std for GFR
Disadvantage: reqs infusion of inulin - not suitable for routine use
Describe use of EDTA to measure GFR
[51Cr]EDTA
Advantages;
- handled by kidney as per inulin
- accurate GFR
Disadvantages;
- req’s facilities for handling radioactive substances
- injected via IV + requires highly trained staff
- general safety issues
- requires taking blood at set times
What is creatinine and how does it relate to kidney function?
Creatinine = a acid derivative
Found almost exclusively in skeletal muscle (90%)
End product of muscle metabolism;
- derived from endogenous sources by tissue creatine breakdown
Plasma concentration in normal individuals related to muscle mass
- produced at constant rate
- rises with kidney disease
Easily measured by well established assays;
- alkaline picarate, enzymatic, HPLC
In clinical practice creatinine clearance or estimate of GFR based on creatinine leve are used to measure GFR
Describe creatinine clearance as a method of measuring GFR
Creatinine clearance = volume of blood plasma cleared of creatinine per unit of time
Useful to approx. GFR
Advantages;
- no infusion required
Disadvantages;
- not as precise as inulin/EDTA clearance
- creatinine freely filtered by glomeruli but also actively secreted by renal tubules = creatinine clearance higher than true GRF
- difficulties in acquiring accurate 24H urine collection
What is the equation for calculating creatinine clearance?
CrCl =
[24H urine creatinine (mmol/24H) x 1000 x 1000] / [plasma urine conc (umol/L) x 1440]
Describe the advantages + limitations of serum creatinine as a method of measuring GFR
Advantages;
- simplest test to assess glomerular function
- useful to monitor changes in chronic renal disease
Limitations;
- serum creatinine measurements alone = insufficiently sensitive to detect moderate CKD
- many pts with reduced GFR have serum creatinine concs that fall inside conventional lab normal range
Why are equations based on serum creatinine used to estimate GFR?
Limitations of serum creatinine + creatinine clearance in urine due to unaccounted for factors
Equations to estimate GFR based on serum creatinine account for these factors
Describe the Cockcroft-Gault formula for estimating GFR
Commonly used as surrogate marker for estimating CrCl and then estimate GFR
Named after scientists that 1st published the formula
Uses serum creatinine measurement + pt weight to estimate CrCl;
[(140-age) x weight x 1.23 x (0.85 if female)] / serum creatinine conc (umol/L)
Disadvantages;
- unreliable if pt has;
- unstable renal function
- is v obese
- is oedematous
Describe the MDRD formula for estimating GFR
Most recently advocated formula for estimating GFR
Developed by Modification of Diet in Renal Disease Study Group
Most commonly used formula = "4-variable MDRD" Estimates GFR using 4 variables; - serum creatinine - age - race - gender
Labs now calculate + report MDRD estimated GFR along with creatinine measurements
How does the MDRD formula categorise CKD?
5 stages;
- eGFR 90+ : normal function but urine/other abn points to disease
- eGFR 60-89: mildly decreased function, must also have urine/other abn to be classified as CKD
- eGFR 30-59: moderately decreased kidney function
- eGFR 15-29: severely decreased kidney function
- eGFR =<14: v severe/endstage kidney failure (ESRF/ESRD)
What are the advantages + disadvantages of eGFR?
Advantages;
- no urine collection req’d
- no infusion
- easy to measure
- can be calc by lab comp systems
- as effective as CrCl at detecting early RD + monitoring progress
Disadvantages;
- estimate NOT precise measure
- limited by extremes of body size (e.g. weight lifters, amputees, v low weight individuals)
- not validated for use in paed/pregnant pop or acute kidney failure
- accuracy in different races questioned
Discuss the use of urea to assess kidney function
Urea = product of protein catabolism
- Synthesised by liver
Advantages;
- majority excreted by kidneys
- easily measured (enzymatic assay)
Disadvantages;
- partially reabsorbed in tubules
- non-specific, causes of high urea = dehydration/renal failure/ GI bleeding (equivalent of large protein meal)
What electrolytes are used to assess kidney function?
Potassium Sodium Bicarbonate Chloride Calcium Phosphate
Describe the use of urinary protein in assessing kidney function
Normally only small plasma proteins filtered at glomerulus + reabsorbed by renal tubule
However, small amount of filtered plasma proteins + protein secreted by the nephron (Tamm-Horsfall protein) can be found in normal urine
Normal total protein excretion does not usually exceed 150mg/24H
Analysis;
- dipstick
- albumin:creatinine ratio
- 24H urine collection
What types of proteinuria can be detected when assessing kidney function and what do they indicate?
Glomerular proteinuria;
- increased filtration of macromolecules (esp albumin) across glomerular cap wall
- sensitive marker for presence of glomerular disease
Tubular proteinuria;
- interference with prox tubular reabsorption = increased excretion of smaller MW proteins
Overflow proteinuria;
- increased excretion of low MW proteins can occur with marked overproduction of a particular protein
- almost always Ig light chains in MM
Have any novel biomarkers for kidney disease assessment been discovered?
Chiral amino acids are being assessed as a potential biomarker for kidney disease (2016)
D-a acids (enantiomers of L-a acids) sporadically detected in blood from pts with kidney disease
- usually v trace
Examined if chiral amino acids associated with kidney functions/comorbidities/prognosis of CKD
- some strongly assoc with kidney function (eGFR)
- some assoc with age
- some assoc with diabetes M
D-Ser + D-Asn significantly assoc with progression of CKD
