Renal Plasma Clearance Flashcards
What is GFR?
→ How much filtrate is removed from the blood each minute
What is the first step in urine formation?
→ Begins with glomerular filtration
What is the composition of glomerular filtrate like?
→ same as plasma
→ no cells
→ protein-free
What is proteinuria a sign of?
→ renal/ urinary tract disease
What is the primary force favoring filtration?
→ Glomerular capillary pressure = 60mmHg
What is the force opposing filtration?
→ Hydrostatic pressure in Bowman’s space = 15mmHg
→ Osmotic force of plasma proteins = 29mmHg
What is the urinary excretion rate?
→ GFR - reabsorption rate + secretion rate
What does GFR contribute to?
→ rapid removal of waste product
How much is the GFR per day?
→ 180L per day
How much is the body plasma volume?
→ 3L
What 2 factors is GFR determined by?
→ hydrostatic and oncotic pressures across capillary membranes
→ permeability of capillary filtration barrier & surface area available
How is GFR measured?
→ not directly but by the measurement of the excretion of a marker
→ a substance that is freely filtered but neither reabsorbed or secreted e.g creatinine
What is inulin?
→ inert polysaccharide
→ filters freely through the glomerular membrane
When does plasma inulin concentration become stable?
→ When inulin fusion rate = inulin excretion rate
What is the GFR equation for the inulin method?
→ GFR = Uin x V / Pin
→ V = urine vol/collection time
→ Pin = plasma inulin concentration
→ Uin = urine inulin concentration
What is the definition of renal clearance?
→ The volume of plasma that is completely cleared of the substance by the kidney per unit time (excreted in urine each minute)
What is the clearance of inulin?
→ same as the GFR
What are the drawbacks of the inulin method?
→prolonged infusion
→ repeated plasma samples
→ difficult routine clinical use
What is used clinically to measure GFR?
→ creatinine
What are the advantages of using creatinine ?
→intrinsic inert substance → released at a steady level in plasma from skeletal muscle → no infusion needed → freely filtered → not reabsorbed
What are the disadvantages of creatinine?
→ some is secreted into the tubule
What is trimethoprim?
→ competitive inhibitor of creatinine
→ given during kidney infections etc
How is creatine made?
→ Taken in the diet
→ found in the liver
What is creatine metabolized by?
→ metabolized to phosphocreatine by the muscle
What can creatine and phosphocreatine be metabolized into?
→ creatinine
→ non enzymatic reaction
What does the transporter that transports creatinine also transport?
→trimethoprim
→ higher affinity for trimethoprim
If plasma creatinine goes up what happens to the GFR?
→ GFR decreases
Why are there differences in GFR?
→ age
→ gender
→ muscle mass
What is eGFR?
→ estimated GFR
What factors are taken into account in eGFR?
→ age
→ gender
→ ethnicity
Why is eGFR a better method?
→ much simpler
→ requires one blood test
What are the 2 equations used in eGFR?
→ MDRD
→ CDK - EPI
What are the disadvantages of GFR?
→ it is an estimate
→ Inaccurate for people of extremes of body type
→ not valid in pregnant women, over 70 or children
→ Racial groups might not fit the MDRD equation
What does it mean if a substance has the same clearance as inulin?
→ freely filtered
→ not reabsorbed or secreted
What does it mean if a substance has a clearance less than inulin?
→ not filtered at the top
→ or freely filtered but reabsorbed
What is an example of a substance that is not freely filtered?
→ albumin
What is an example of a substance that is reabsorbed completely?
→ glucose
How is glucose handling by the kidney investigated?
→ infuse glucose and inulin together
→ calculate GFR using inulin
→ calculate the glucose filtration rate (GFR x plasma glucose concentration)
What is the equation for calculating glucose filtration?
→ GFR x Plasma glucose
What is the equation for calculating glucose excretion?
→ Uglucose (urine glucose concentration) x V (urine flow rate)
What is the equation for calculating glucose reabsorption?
→ [(GFR x Pglucose) - ( U glucose x V)]
What is the renal threshold of glucose?
→ 15 mM
What happens after the plasma glucose level > renal threshold?
→ glucose appears in the urine
→ glucose is excreted
What happens to the glucose < 20mM?
→ All the glucose that filters through is reabsorbed by the Na+/glucose co-transporter
What happens to the glucose after > 20mM?
→ All the transporters are saturated
→ Glucose reabsorption plateaus
→ Glycosuria
Why does glucose start appearing in the urine before 20mM?
→ Humans have 2 million nephrons
→ Each nephron has a slightly different transport maximum
→ Some nephrons will start excreting glucose earlier than others
Why does the clearance rate of glucose never reach the rate of inulin?
→ the transporters are still working unless they are completely blocked
What is a substance that is actively reabsorbed?
→ Amino acids
→ Ca2+, Na+, PO4 2-, Mg 2+
→ Water soluble vitamins
What do actively reabsorbed substances all have?
→ a TM
What are passively reabsorbed substances?
→ Cl-
→urea
→important drugs
What are endogenous substances that are secreted?
→ Weak organic acids & bases
→ Adrenaline
→ Dopamine
→ Steroids
What are exogenous substances that are secreted?
→Penicillin
→Probenecid
→ PAH (para amino hippuric acid)
Why does the concentration of penicillin fall rapidly when injected and how is this counteracted?
→ Renal tubular cells actively secrete it into the urine
→ Given with probenecid which competes for the same transport mechanism
What is RPF?
→ Rate at which plasma flows through the kidney
What is the composition of the blood?
→ 55% plasma
→ 45 % cellular components
What is PAH?
→ Weak acid metabolite found in horse’s urine
What happens to PAH once it enters the glomerulus?
→ Filtered freely + enters the filtrate
→ Large amount is still in plasma
→majority is secreted back into PCT
→Excreted as urine
How is PAH secreted?
→ Active transport occurs in the basolateral membrane
→ Passive transport across the luminal membrane into the tubule
What happens if PAH is below the Tm?
→ It is cleared in a single pass
What is the equation for renal plasma flow?
→ (U PAH x V) / Plasma PAH
