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UG Biochemistry > 4. Kidney > Flashcards

4. Kidney Flashcards

1
Q

Describe kidney anatomy

A

Paired, retroperitoneal

Partially protected by 11th + 12th ribs

Right slightly lower - liver

1% body mass

25% cardiac output

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2
Q

List main kidney functions

A

3 main functions; (maintain whole body homeostasis)

  1. Excrete waste
  2. Maintain ECF volume + comp
  3. Endocrine function
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3
Q

What does kidney function regulate?

A

Blood volume + composition
Electrolytes
Blood PH + acid-base balance
BP

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4
Q

Describe the nephron + its overall function

A

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
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5
Q

Describe urine formation

A

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

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6
Q

How does reabsorption occur at the kidney tubule (into the blood)? Give an example of a disease linked to this.

A

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)
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7
Q

How much urine needs to be produced each day?

A

300-500mLs of urine is needed to excrete adequate amounts of solute each day

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8
Q

What causes filtration to happen at the glomerulus?

A

Hydrostatic filtration

Divergence of high pressure blood into small capillaries forces water, glucose, urea + salts through capillary wall + into tubule

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9
Q

What is not filtered at the glomerulus?

A

Protein + blood cells remain in blood as to big to pass through capillary wall

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10
Q

How much filtrate is generated at the glomerulus + how much urine does this generate?

A

180L/day + most is reabsorbed so 1mL/min urine in healthy person

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11
Q

Describe renal endocrine function

A

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+)
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12
Q

How is a patient with kidney disease assessed?

A

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
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13
Q

What is uremia and how does it relate to kidney disease?

A

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
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14
Q

What are renal function tests used for?

A

Detect renal damage

Monitor damage

Help determine cause

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15
Q

What tests are performed in a lab assessment of patients with kidney disease?

A 
Urinalysis
Glomerular filtration rate
Creatinine
Urea + electrolytes
Urine protein
Hb
Bone profile
Iron profile
Hormones
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16
Q

Describe the use of urinalysis in kidney disease assessment

A

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
17
Q

What is the glomerular filtration rate + what does it say about kidney function?

A

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

18
Q

What does measuring GFR require? What criteria needs to be met?

A

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
19
Q

What is the general equation for calculating GFR using a substance?

A

GFR (vol/time e.g. ml/min) = (urine conc x urine flow rate) / plasma concentration

20
Q

What is the normal GFR in adults?

A

~110ml/min

21
Q

List the methods for measuring GFR

A

Measurement;

  • Inulin clearance
  • EDTA clearance
  • Creatinine clearance

Calculation/estimation;

  • Cockcroft-Gault formula
  • MDRD formula
22
Q

Describe the use of inulin to measure GFR

A

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

23
Q

Describe use of EDTA to measure GFR

A

[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
24
Q

What is creatinine and how does it relate to kidney function?

A

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

25
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
26
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]
27
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
28
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
29
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
30
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
31
How does the MDRD formula categorise CKD?
5 stages; 1. eGFR 90+ : normal function but urine/other abn points to disease 2. eGFR 60-89: mildly decreased function, must also have urine/other abn to be classified as CKD 3. eGFR 30-59: moderately decreased kidney function 4. eGFR 15-29: severely decreased kidney function 5. eGFR =<14: v severe/endstage kidney failure (ESRF/ESRD)
32
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
33
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)
34
What electrolytes are used to assess kidney function?
``` Potassium Sodium Bicarbonate Chloride Calcium Phosphate ```
35
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
36
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
37
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

UG Biochemistry (14 decks)

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