Renal Function Flashcards
What are the major functions of the renal system?
Glomerular function
Tubular function
Endocrine function
Gluconeogenesis
What is the purpose of glomerular function?
Excretion of toxic end-products of metabolism
What is the purpose of tubular function?
Reabsorption of water, Acid-base and electrolyte balance
What is the purpose of endocrine function of the kidney?
1 Alpha Hydroxylase: Vitamin D metabolism
Erythropoetin: Haemoglobin synthesis
Renin: Renin-Angiotensin-Aldosterone Axis
Prostaglandins and endothelins
What is gluconeogenesis?
A metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids.
What are the physical features of the kidney?
Afferent arteriole Efferent arteriole Glomerulus Bowman's Capsule Distal tubule Proximal tubule Capillary network Loop of Henle Collecting duct Pelvis
What factors affect glomerular filtration?
Effective filtration pressure: -
- Increase resistance in efferent increases pressure in afferent vessels - counter pressure = oncotic pressure - passage of blood through glomeruli increase oncotic pressure so reduces filtration pressure
Molecular size and shape ( 70KD unlikely)
-ve charge. Basement membrane has a net -ve charge
What is glomerular filtrate?
Glomerular filtrate is an ultrafiltrate of plasma i.e plasma without most of the large proteins
What does glomerular function depend on?
Adequate renal blood flow and pressure
Number of functioning nephrons
What is the average glomerular filtration rate (GFR)?
120ml/min
170L/day
What is GFR related to?
Body surface area: higher in men
Age: decreasing in the elderly
What are the different structures in the tubule system of the kidney?
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting duct
What is the function of the Proximal convoluted tubule?
Reabsorption of water, glucose, amino acids, K, HCO3 Na+
What is the function of the Loop of Henle?
Concentration of ultrafiltrate
What is the function of the Distal convoluted tubule?
Secretion of urate
Na+-K+ via aldosterone;
Na+-K+/H+ exchange
What is the function of the Collecting duct?
Water reabsorption under ADH control
What are the features of proximal renal tubular function?
Reabsorption of: Water Bicarbonate Aminoacids Phosphate Glucose Electrolytes Proteins
Secretion of: Drugs Small amounts of Creatinine Urea
What is the function of the distal convoluted distal tubule?
Sodium reabsorption (Due to Aldosterone)
H+ excretion:
Water reabsorption (due to ADH)
How is the acid/base balance regulated?
Reabsorption of bicarbonate
Active secretion of hydrogen ions
Generation of bicarbonate.
Generation of ammonia.
What is clearance?
Clearance is the virtual volume of plasma completely cleared of a given substance per unit of time
What is the equation for calculating clearance?
Cs = (Us x V) / (Ps x T) ml/min
Where: Us is the urine concentration of substance, s Ps is the plasma concentration of s V is the urine flow rate in mL T is the time in mins
How is clearance measured?
Renal clearance can be measured with a timed collection of urine and an analysis of its composition with the aid of the clearance equation.
When the substance is creatinine, an endogenous chemical that is excreted only by filtration, the calculated clearance is equivalent to the glomerular filtration rate.
Inulin clearance is also used to estimate glomerular filtration rate. However, it must be given intravenously and therefore impractical
What are the advantages of using creatinine clearance to measure kidney function?
Steady state endogenous creatinine production and its release into body fluids is at a constant rate
Robust plasma and urine assays
What are the disadvantages of using creatinine clearance to measure kidney function?
Small quantities of creatinine are reabsorbed and secreted by the tubules.
Fluctuation of plasma levels – e.g protein meals, stenuous exercise
Creatinine clearance is ~7% greater than that of inulin
What causes variation in creatinine clearance?
Greatest error in creatinine clearance is collection of timed urine samples.
Analytical and Biological variation is 8 - 20%
What is the formula used to predict creatinine clearance from plasma creatinine?
CC = (Uc x V) / Pc
What are the symptoms of Proximal Renal Tubular Dysunction?
Polyuria Metabolic acidosis Aminoaciduria Phosphaturia Glycosuria Hypokalaemia Tubular proteinuria
What are the symptoms of Distal Renal Tubular Dysunction?
Urine salt loss -> hyponatraemia
Alkaline urine -> Metabolic acidosis
Polyuria
What are the 4 main mechanisms by which proteinuria occurs
Overflow: Excessive production & excretion of protein as in Bence-Jones protein, marked catabolism
Glomerular: Glomerular damage - albuminuria
Tubular: Tubular damage - α1 β2 microglobulinuria
Secretory: Tubular protein secretion – Tamm-Horsfall
What do urine dipsticks test for?
Protein Glucose Blood pH Nitrite Bile pigments Ketones
What is microalbuminuria?
24 h urine albumin 30mg - 300mg.
Therefore, increased urine albumin excretion but urine Dipstick –ve
What new marker can be used to test for clearance?
Cystatin C
- Small protein produced by all nucleated cells
- Not affected by muscle mass, age, gender or race
NGAL- Neutrophil Gelatinase Associated Lipocalin
- Marker of acute kidney injury (urine & serum)
- Early detection of AKI
What are the problems with urine dipstick tests?
Detect ~ 300mg/L albumin
Protein error of indicators
- don’t detect Bence Jones protein
- False positives (alkaline urine, various contaminants)
What is the criteria for stage 1 AKI?
Creatinine increase ≥ 26μmol/L within 48hrs or increase ≥1.5 to 1.9 X reference Serum Creatinine
Urine output 6 consecutive hrs
What is the criteria for stage 2 AKI?
Creatinine increase ≥ 2 to 2.9 X reference SCr
Urine output 12hrs
What is the criteria for stage 3 AKI?
Creatinine increase ≥3 X reference SCr or increase ≥354μmol/L or commenced on renal replacement therapy (RRT) irrespective of stage
Urine output 24hrs or anuria for 12hrs
What is reference serum creatinine?
The reference serum creatinine should be the lowest creatinine value recorded within 3 months of the event
If a reference serum creatinine value is not available within 3 months and AKI is suspected repeat serum creatinine within 24 hours
What are the stages of CKD
1 2 3A 3B 4 5
Describe stage 1 CKD
Normal kidney function, but urine findings or structural abnormalities or genetic trait point to kidney disease
Describe stage 2 CKD
Mildly reduced kidney function and other finding (as for stage 1)
Describe stages 3A and 3B CKD
Moderately reduced kidney function
What is the difference between stages 3A and 3B?
Stage 3A - GFR=45 - 59
Stage 3B - GFR=30 - 44
Describe stage 4 CKD
Severely reduced kidney function
Describe stage 5 CKD
Very severe, or endstage kidney failure (sometimes called established renal failure)
What is the GFR for the different stages of CKD?
Stage 1 - 90+ Stage 2 - 60-89 Stage 3A - 45-59 Stage 3B - 30-44 Stage 4 - 15-29 Stage 5 -
What are the metabolic effects of AKI?
Retention of:
Urea & creatinine
Water: Oliguria/Anuria
Pulmonary oedema
H+: Metabolic Acidosis
Electrolytes: K+ - hyperkalaemia
Na+
What tests can be done to differentially diagnose the causes of acute renal failure?
Ultrasound:
To exclude obstruction
May show intrinsic renal disease
Renal Biopsy:
Identify cause of renal disease
Describe the features of AKI
Characterised by oliguria (
What happens after AKI?
May proceed to Chronic Renal Failure
What are the clinical features of Chronic Renal Failure?
Skin: - Pruritis - Purpura CNS and PNS: - Lethargy - Peripheral Neuropathy CVS: - Hypertension - Pericarditis - Anaemia GIT: - Nausea and vomiting - Anorexia GUS: - Impotence - Nocturia Musculoskeletal: - Myopathy - Stunted growth - Bone pain
Describe the features of CRF
Similar to ARF
- Increased serum urea /creatinine
- Increased serum K+
- Metabolic acidosis
- Hyperphosphataemia
But also loss of endocrine function
- Hypocalcaemia & Osteodystrophy (secondary or tertiary hyperparathyroidism)
- Normochromic normocytic anaemia
Why do patients develop anaemia with CRF?
In chronic renal failure lack of erythropoetin (stimulates haemogloblin synthesis) causes anaemia.
Why do patients develop hypocalcaemia with CRF?
Loss of 1 alpha hydroxylase leads to Decreased 1,25 (OH)2 Vitamin D leads to Hypocalcaemia: due to decreased gut Ca2+ absorption leads to Increased parathyroid hormone (PTH) leads to Bone disease (renal osteodystrophy)
What are the different phases of AKI?
Oliguric Phase: Predominantly impaired glomerular function
Diuretic phase: Improved glomerular function but impaired tubular function
Recovery phase
How is CRF managed?
Water and salt: Low salt diet avoid dehydrate or volume overload Dietary protein restriction Hyperphosphataemia: Oral phosphate binders Hypocalcaemia: 1 (OH) Vitamin D Treat hypertension vigorously Anaemia: Erythropoetin Dialysis - Haemodialysis - Peritoneal dialysis Renal transplantation
What is acute on chronic renal failure?
Patients with chronic renal failure may develop acute renal failure
Anaemia and hypocalcaemia in subjects with acute renal failure is indicative of underlying Chronic Renal failure i.e Acute on chronic renal failure
