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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
Q

Describe creatinine clearance as a method of measuring GFR

A

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
Q

What is the equation for calculating creatinine clearance?

A

CrCl =

[24H urine creatinine (mmol/24H) x 1000 x 1000] / [plasma urine conc (umol/L) x 1440]

27
Q

Describe the advantages + limitations of serum creatinine as a method of measuring GFR

A

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
Q

Why are equations based on serum creatinine used to estimate GFR?

A

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
Q

Describe the Cockcroft-Gault formula for estimating GFR

A

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
Q

Describe the MDRD formula for estimating GFR

A

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
Q

How does the MDRD formula categorise CKD?

A

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
Q

What are the advantages + disadvantages of eGFR?

A

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
Q

Discuss the use of urea to assess kidney function

A

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
Q

What electrolytes are used to assess kidney function?

A 
Potassium
Sodium
Bicarbonate
Chloride
Calcium
Phosphate
35
Q

Describe the use of urinary protein in assessing kidney function

A

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
Q

What types of proteinuria can be detected when assessing kidney function and what do they indicate?

A

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
Q

Have any novel biomarkers for kidney disease assessment been discovered?

A

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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