Renal Function Tests & Nitrogen Metabolism

Renal Function Tests & Nitrogen Metabolism

1. WHAT do we assess? WHY? HOW?

   • When you ask for a test, you should be ASKING A QUESTION!
     • INFECTION? kidney or UTI?
     • SATURATION OF FILTRATION SYSTEM - glucose in diabetes?
     • FAT METABOLISM - ketones?
     • RENAL FAILURE?
     • Remember 95% reference ranges normal
     • U&E MOST REQUESTED TEST ON WARDS

2. GFR / eGFR

   • Substance used to determine GFR...
     • GFR estimated CLINICALLY using CREATININE, rather than inulin clearance (must be given via IV - so ONLY in research setting)
   • To estimate GFR: CKD-EPI equation (2009) - Don't learn equation, but learn variables
     • Gender Ethnicity Creatinine Age
   • eGFR is a non-invasive method for testing kidneys

3. URINE

   • Volume charts
     • Especially important when pt on IV fluid
     • NB. also insensible H2O losses via: exhalation, sweating (with Na+), stool
   • Dipstick
     • Sterile container, Midstream, Visual analysis (colour, clarity), RECORD results of stick
     • Blood, ketones, nitrites, pH, glucose, proteins
     • FASTED patient = KETOGENESIS - fatty acid metabolism > ^ketones
       • (Acetoacetate detected by dipstick – not acetone or βOHB)
         • KETOACIDOSIS

4. DEHYDRATION

   • Dehydration = Loss of salt VS. Loss of H2O
   • Revisit signs of dehydration (first mind map)
   • Kidneys vital in THERMOREGULATION
     • Factors affecting Body Temp
   • Kidneys vital in BLOOD PRESSURE
     • Decrease in blood volume > Postural (orthostatic) hypotension - BP falls rather than rises when stand up *CVS lectures
       • Plasma Renin Activity (PRA) is higher when UPRIGHT than supine. Also higher in NORMOvolaemic people than HYPOvolaemic people (renin regulates BP)

5. ENDOCRINE FUNCTION of kidney

   • Activation of Vitamin D is occurs in kidney and is highly regulated
     • 25-hydroxycholecalciferol
       • 1,25-dihydroxycholecalciferol BIOLOGICALLY ACTIVE FORM
         • 1α-hydroxylase
     • Enhanced by vPhosphate, v1,25-OHD, ^PTH
     • HYPOCALCAEMIA
     • HYPERCALCAEMIA

6. SALTS HOMEOSTASIS Na+ & K+

   • Na+ and K+
     • NHS = <6g of NaCl/day. We need ~500mg.
       • [Chemistry! Mr[Na] = 23, Mr[Cl] = 35.5 (Mr is amount in 1g). Therefore Na+ per day = 6x (23/58.5) = 2.4g/day]
     • NICE = 1mmol/kg/day of Na+ & K+
       • If pt on IV fluids, need 25-30ml/kg/day
         • NB. 0.9% saline is 154mmol/L NaCl (but can also use 5% dextrose - stops pt becoming ketotic)
       • eg. 65kg pt = needs ~65mmol K+. Can use 2L fluid in one bag: 1x bag of 20mmol K+, 1x bag of 40mmol K+
         • How many g of K+ is this? Mr Mole lives under the Mass
           • Mr [K] = 40. Moles = 20+40mmol = 60mmol = 0.06moles
             • 40 x 0.06 = 2.4g of K+

7. NITROGEN METABOLISM

   • N2 Balance
     • -ve N2 balance due to MALNUTRITION (lack of essential aa) or RECENT TRAUMA (surgery, burns, sepsis)
     • +ve N2 balance due to GROWTH, PREGNANCY, CONVALESCENCE
     • Healthy = net 0 N2 balance
       • N2 found in NUCLEIC ACIDS & PROTEINS (& COFACTORS eg. NAD+, HORMONES eg. adrenaline, NEUROTRANSMITTERS eg. serotonin)
         • Virtually all N2 originates from proteins in diet (nucleic acids have smaller mass).
           • Proteins constantly formed/degraded. Unlike carbohydrates, AA's CAN'T BE STORED As excess amino acids cannot be stored so their breakdown takes precedence over breakdown of carbohydrate and fat.
   • AA SYNTHESIS
     • So long as have the appropriate a-keto acids we can make AA’s. So long as glycolysis and citric acid cycle (CENTRE OF METABOLISM), PENTOSE PHOSPHATE PATHWAY are working, we can make all these:
       • Some AA are non-essential (green), conditionally essential (white), and essential (red)
         • We cannot synthesise ESSENTIAL (red), but plants and bacteria can > Dietary for us
           • We can synthesis CONDITIONALLY ESSENTIAL to some degree. Absolutely required in CHILDREN and/or during CATABOLIC STRESS
             • AAs essential to make...
             • PROTEIN: Men need 55g/day. Women need 45g/day. Shouldn't exceed 100g/day.
               • Countries which risk too high protein: UAE, Greece, Iceland. BUT averages!
                 • DISEASES
                   • Protein deficiency
                     • MARASMUS (starvation)
                     • KWASHIORKOR (protein)
                   • PHENYLKETONURIA (PKU) (inborn problem with AA metabolism)
                     • Phenylalanine (Phe) = essential AA. 75% is converted to Tyrosine (Tyr) AA.
                       • In PKU, a gene defect for Phe hydroxylase stops this conversion.
                         • Phe accumulates in blood
                           • elevated Phe in brain > GLYCOLYSIS & MYELINATION reduced
                             • Tyr and Trytophan can't cross BLOOD-BRAIN BARRIER as transporter is saturated with Phe
                               • Mental retardation. Affects ~1:10,000. Mild PKU treated with Phe-restricted diet.
                         • Tyr is reduced
                           • NEUROTRANSMITTERS from Tyr are reduced
   • AA BREAKDOWN
     • Proteins broken down to AA's inside cells
       • AA's in muscle transported to liver as GLUTAMINE or ALANINE
       • produces NH3/NH4+ = HIGHLY TOXIC > removed as urea (in urine)
         • fish > NH3 directly into water birds > uric acid (white bird poo)
         • UREA = highly soluble, uncharged, low toxicity but only formed in LIVER (not muscles)
       • Making alanine in MUSCLE:
         • 1) GLUTAMATE + PYRUVATE = ALANINE, and reforms α-KETOGLUTARATE
           • 2) ALANINE transported to LIVER ('carries' PYRUVATE to liver)
             • 3) Once in LIVER, ALANINE converted back to PYRUVATE + GLUTAMATE
               • 4) Glutamate into UREA CYCLE
                 • 5) GLUTAMATE is deaminated in LIVER MITOCHONDRIA > releases NH4+ Regenerates α-ketoglutarate (needed in mitochondria for citric acid cycle)
                   • CITRIC ACID CYCLE IN MITOCHONDRIA
                     • How are Urea cycle & CAC linked? Urea cycle consumes aspartate, produces fumarate...
                       • AA Breakdown Overview:
                         • (Some AAs can be both)
                         • "GLUCOGENIC" AAs donate their carbon skeletons > PYRUVATE for GLUCONEOGENESIS
                           • "KETOGENIC" AAs donate their carbon skeletons > ACETYLCoA and thus KETONE BODIES (as well as entering the citric acid cycle)
                   • NH4+ into UREA CYCLE IN LIVER
                     • We excrete ~25g urea/day
               • 4) Pyruvate for GLUCONEOGENESIS - back to glucose)
       • Making glutamine in MUSCLE:
         • 1) AA's + α-KETOGLUTARATE (intermediate of citric acid cycle) = GLUTAMATE + α-KETO ACIDS.
           • 2) Glutamine synthase then uses NH4+ (from nucleotide degradation) and ATP to make GLUTAMINE.
             • 3) GLUTAMINE is transported to LIVER ('carries' NH4+ to liver)
               • 4) Once in LIVER, GLUTAMINE converted back to GLUTAMATE, releasing NH4+
           • α-keto acids leftover in muscle used to make new molecules/as fuel *see citric acid cycle

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