what is the function of kidneys
what part constitute nephrons
cortical and juxtamedullary
renal blood supply
― 20% of the cardiac output
― Blood flow to the medullary region is poor at the best of time; risk of hypoxia significant
vascular supply to kidney
blood coming in from afferent arterioles, into glomerular capillaries, exit into efferent arterioles and enter peritubular capillaries
what r the steps in urine formation
filtration (glomerular function), how does it work?
1. glomerulus - high pressure filtration system, composed of a specialized capillary network.
2. Blood supplied to the glomerulus through the Afferent Arterioles (AA) and removed by the Efferent Arterioles (EA)
― Large molecules are generally unable to pass through the glomerular membranes
3. It generates an ultra filtrate that is free of blood and significant amounts of blood proteins.
4. Ultra filtrate passed into the tubular system for processing eg reabsorption of water & electrolytes, regulation of concentration, etc
what id GRF
― Glomerular filtration rate (GFR) is a key marker of renal function
― Index of renal function would thus ideally measure GFR
how is GFR maintained? what happen when there is reduction in any of these drivers
GFR usually maintained by factors such as cardiac output, SNS tone, blood pressure, vascular volume, etc.
- Reduction in any of these drivers will lead to reduced GFR and hence urine production
describe the physiological defense mechnism that kidneys have to maintain GFR
The kidneys have inbuilt physiological defense measures to counteract reduced inflow using Prostaglandins and Angiotensin II In conditions of stress to the kidneys (eg CKD, DM, HTN, CCF)
- these mechanisms become increasingly important to maintain GFR.
what is urine =
Urine = GF -TR +TS
what is the function of proximal tubule
― 70% of Na is reabsorbed in the PCT
what is the function of loop of henle
― 20 % of Na, Cl and K reabsorbed
― urine concentration and dilution occurs in the LOH through an osmotic gradient provided by the countercurrent mechanism
― urine flow rate is regulated by NaCl, prostaglandins, adenosine
and urine volume presented to the macula densa
what is the function of distal tubule
― secretes K and bicarbonate
― proximal segment of distal tubule is impermeable to water (urine dilution)
― distal segment (cortical collecting tubule): K and bicarbonate secretion
what is the function of collecting duct
― regulates final urine concentration
― aldosterone receptors regulate Na uptake and K excretion
― ADH increases water reabsorption. In the absence of ADH, the collecting duct is impermeable to water (Predominant)
describe the autoregulation of GFR
― A feedback mechanism that keeps renal blood flow (RBF) and GFR constant despite changes in arterial blood pressure.
1. As RBF increases, GFR increases, leading to an increase in NaCl delivery to the macula densa.
2. a feedback loop through the macula densa to the juxtaglomerular cells of the afferent arteriole results in increased vascular tone, decreased renal blood flow and a decrease in GFR.
3. NaCl to the macula densa then decreases leading to relaxation of the afferent arteriole (increasing glomerular hydrostatic pressure) and increases renin release from juxtaglomerular cells of afferent and efferent arterioles
4. renin increases angiotensin I, then converted to angiotensin II which constrict efferent arteriole increasing hydrostatic pressure returning GFR to normal
physiology of renal blood flow
The kidneys have inbuilt physiological defense measures to counteract reduced inflow using Prostaglandins and Angiotensin II In conditions of stress to the kidneys (eg CKD, DM, HTN, CCF) these mechanisms become increasingly important to maintain GFR.
draw the macula densa feedback mechanism for autoregulation
why do we assessment renal function
Evaluate organ function
Determine extent of kidney disease (stage)
Determine appropriate management (action plan) if kidney disease is an issue
Determine appropriate dose for drugs excreted through the kidney
Prevent further damage by using nephrotoxic agents
what is GFR? what does it measure? what is normal GFR?
• Glomerular filtration rate (GFR): is the rate (volume per unit of time) at which ultra filtrate is formed at the glomerulus.
GFR primary measure of renal function & hence critical knowledge to evaluate drug dosage
Normal is 100 to 120 ml/min
• Cannot be measured directly
what constitute an ideal indicator for testing renal function
1. produced at a constant rate. present in circulation
2. freely filtered and totally cleared.
3. no reabsorption or secretion.
Inulin-exogenous filtration markers
– Inulin was the first substance used and remains gold standard against which other markers are evaluated.
– Requires continuous IV infusion to achieve steady state and bladder catheterization with multiple timed urine collections.
– Cumbersome technique, difficult chemical assay-hence has not been used widely in clinical practice
what is urea? where does it filtered and reabsorbed? give reference level
End product of protein and amino acid catabolism– serum urea concentrations are influenced by both rate of
protein breakdown and renal urea excretion
Filtered at glomerulus & reabsorbed in tubules (40-60%)
A relatively insensitive marker of renal function— serum levels rise only when the CrCl below 50 mL/min
Usually measured along with serum creatinine
what is creatinine? what is it metabolised? normal range?
• Waste product of muscle metabolism
— formed by the liver via breakdown of creatine (from muscle)
— usually produced at a constant rate dependent on muscle mass
Excreted by kidney - glomerular filtration (10% via secretion)
— SCr is both a reflection of both muscle mass and kidney function
— SCr is inversely proportional to glomerular filtration rate
— doubling of SCr (even within the reference range) represents a 50% reduction in renal function
Good indicator of renal function (better than urea) becuase of no reabsorption
- high serum creatinine level= less GFR = more kidney damage
what is the relationship between SCr and CrCl?
how to assess CrCl
― Creatinine clearance (Cr Cl) is considered the best overall index of renal function in health and disease.
what is Cockcroft & Gault equation
― Cockcroft & Gault (1976) – estimate of Cr Cl from subject age, weight, gender and serum creatinine.
― This is considered the most useful nomogram for estimation of CrCl from serum creatinine
what r the assumption behind CG equation
Assumptions: relatively stable renal function; normal muscle mass for age, sex, weight;
Recommended for renal dosing of medications
Not corrected for BSA
what weight is used in CG equation
ideal body weight, can be calculated using ideal weight equation
- IBW needed for Cockcroft & Gault calculation as creatinine produced by muscles, and hence relies on muscle mass only
Note: if individual is under IBW, use actual body weight in calculation (not IBW)
grade of renal impairment using CrCl
— Various guidelines for the staging of kidney disease have been developed
— Staging based on eGFR now the accepted standard
– Does Creatinine Clearance (Cr.Cl) = GFR?
– Cr.Cl overestimates GFR due to tubular secretion of creatinine
– Relative contribution of tubular secretion to total creatinine clearance increases with decreasing GFR
– C-G evaluation becomes increasingly inaccurate at the extremes of weight and serum creatinine and in the setting of an unstable creatinine
– Protein and albumin in urine mean?
– Evaluation of urinary protein or albumin is now a standard tool to characterize the severity of CKD and to monitor the rate of disease progression
– Excessive amounts of proteins in the urine also indicates increased cardiovascular risk
– Persistent proteinuria or albuminuria that is present on at least 3 occasions over a period of 3 to 6 months is now considered a principal marker of kidney damage
– Urine ACR (albumin: creatinine ratio) predicts renal and CVD risk
– Urine ACR is more sensitive than Protein: Creatinine Ratio (PCR)
– Albuminuria is present if two out of three ACR tests are positive
– CKD is present if albuminuria is persistent at least for 3 months
– Factors other than CKD known to increase albuminuria
– Urinary tract infection (UTI)
– High protein intake
– Heavy exercise (within 24 hours) – Drugs (NSAIDs)
– In many people, haematuria is related to menstruation or UTI
– Persistent haematuria, or haematuria in conjunction with other indicators of kidney damage needs further investigation
– Dipsticks may be used as a screening
future marker for kidney testing
Future Markers: Cystatin C shows promise-used in other countries