RED Kidney 2 Learning objectives PDF

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1. Describe the physical forces involved in glomerularfiltrationNet filtration pressure is determined by physical forces (4 Starling forces) whichdrive the movement of fluid between plasma and tubule1. Glomerular capillary hydrostatic pressure (PG) This is pressure exerted by blood within the glome...

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1. Describe the physical forces involved in glomerular filtration Net filtration pressure is determined by physical forces (4 Starling forces) which drive the movement of fluid between plasma and tubule 1. Glomerular capillary hydrostatic pressure (PG)  This is pressure exerted by blood within the glomerular capillaries. The afferent arteriole is predominantly wider than the efferent this means that any fluid moving from the afferent arteriole causes pressure to build up in the glomerulus as the fluid leaves through a smaller diameter arteriole. The narrow exit creates pressure within the glomerulus and this creates the hydrostatic pressure. This high pressure pushes fluid out of the glomerulus and into the Bowman’s space  Dependent on contraction of the heart and blood flow resistance of afferent and efferent arterioles  Arterial BP affects PG as it is the force that drives blood into the glomerulus  High BP= High PG= High GFR  Low BP= Low PG= Low GFR  Favours filtration  But in reality the kidneys regulate blood pressure to maintain a constant flow 2. Plasma-colloid osmotic pressure (∏G)  The osmotic pressure is exerted due to the unequal distribution of plasma proteins across the glomerular membrane. Plasma proteins are not filtered therefore present in glomerular capillaries and absent in the bowmans capsule. Then osmosis occurs as H20 moves down its concentration gradient from the bowman’s capsule to the glomerular capillaries  Opposes filtration  High ∏G= Low GFR and this occurs if there is an increase in plasma protein which is seen in dehydrating diarrohea  Low ∏G=High GFR occurs with severe burns as there is loss of protein rich plasma 3. Bowman’s capsule hydrostatic pressure (PB)

 This pressure pushes fluid out of the bowman’s capsule into the glomerulus  Opposes filtration  Low PB= High GFR  High PB= Low GFR seen in urinary tract obstruction- kidney stone, enlarged prostate 4. Bowman’s capsule colloid osmotic pressure (∏B)  Under normal conditions, PIEB is practically zero, ultrafiltrate is nearly protein-free therefore osmosis into the bowmans capsule will not occur  SB has negligible influence on filtration Net filtration: Difference between forces favouring pressure filtration and forces opposing filtration. Then multiple with kf to get GFR

forces favouring ( PG +

∏B )

minus -

forces opposing (

PB + ∏G )

2. Define glomerular filtration rate (GFR) and explain the factors influencing GFR Definition: the amount of filtrate produce from blood flowing through the glomerulus per unit time ( mL/min) GFR is influenced by two factors:  Filtration coefficient, K f  Net filtration pressure

GFR = K × net filtration pressure f Under normal physiological conditions, Kf is relatively constant and so does not play a role in daily regulation of GFR (i) Filtration coefficient, Kf

Kf = glomerular surface area

X

glomerular capillary permeability

Under normal physiological conditions, Kf is relatively constant and so does not play a role in daily regulation of GFR Increased Kf raises GFR and decreased Kf decreases GFR There is a decreased Kf in kidney disease due to a reduced no. of glomeruli ( reduced SA) and with increase thickness of capillary membrane (e.g. hypertension, diabetes) as this causes decreased permeability

3. Describe the processes involved in autoregulation of renal blood flow and GFR. Autoregulation of renal blood flow & GFR occurs to maintain a constant renal blood flow and glomerular filtration rate over the physiological range of mean arterial pressure . protective” against - hypertensive irreversible renal damage - hypotensive ischaemia Kidney can “autoregulate” quite rapidly to changes in blood pressure by adjustment of diameter of the afferent arteriole : 1. myogenic – intrinsic property of vascular smooth muscle When there is an increase in blood pressure the blood vessels constrict to minimise distention and the diameter. When blood pressure decreases we have less blood flow leading to vasodilation to maintain the blood flow to organs 2. tubuloglomerular feedback The juxtaglomerular cells screte renin and are located in the wall of the affertent arteriole. There are also macular densa cells which are tubular cells and they detect changes in fluid flowing through the tubules such as the concentration of NaCl, in response to such changes they secrete vasoactive chemicals which constrict/ dilate blood vessels. When there is high arterial pressure there is a high GFR due to high net filtration pressure. This increases the flow rate in the loop of Henle therefore there is less time for sodium and chloride reabsorption. Consequently, the macula densa cells detect a rise in NaCl concentration in the filtrate and release vasoactive agents such as endothelin, adenosine, and ATP. These agents increase resistance to blood flow in the afferent arterioles via

vasoconstriction and this therefore returns GFR as the hydrostatic pressure decreases towards normal as this decreases blood flow to the glomerulus. When there is low arterial pressure there is a low GFR and therefore a decreased flow rate in the loop of Henle. This gives more time for sodium and chloride absorption in the loop of Henle and the macula densa cells recognise this as there is a decreased concentration of NaCl in the filtrate. This results in increased renin release from the granular juxtaglomerular cells of the afferent and efferent arterioles. Renin stimulates angiotensin 2 production and therefore promotes vasoconstriction of the efferent arterioles to return the GFR back to normal by increasing hydrostatic pressure. The macula densa cells could also release vasoactive agents such as NO which decrease the resistance to blood flow in the afferent arterioles as they are vasodilators returing GFR back to normal.

4. List the three main equations used to estimate GFR, and indicate their appropriate use in defining renal function Why estimate GFR? • GFR can provide an estimate of how efficiently the kidney filters wastes from blood • Essential part of assessing patients with kidney disease by providing information on - severity and course of the kidney disease - approximate percentage of kidney function e.g. fall in GFR means disease is progressing and rise in GFR indicates partial recovery - influences how much of a drug you can prescribe

 Creatinine clearance Clearance – defined as volume of plasma that is completely cleared of a substance by the kidneys per unit time Creatinine is used to estimate GFR as it is almost completely cleared from the body by glomerular filtration - Creatinine is derived from breakdown of creatine phosphate (muscle)

• Need to consider: Skeletal muscle, mass and age • Measure: o o o o

Plasma creatinine level [P]CR (mmol/mL) Urine output collection (24h) urine flow rate, V (mL/min) urine creatinine concentration, [U]CR (mmol/mL)

CCr Creatinine clearance = [U]CR x V mL/min __________________________ [P]CR

 Doesn’t take into account gender or age. At ages above 40, every 10 years you get 10%loss in nephrons  In impaired kidney function the body doesn’t get rid of creatinine as well therefore get more in plasma and less in urine  Need 24 hour urine collection

 Cockcroft & Gault formula  Takes into account the gender, age and weight of the patient  Doesn’t take into account ethnic origin of the patient  Far easier to measure, just need blood sample and do not need to collect urine for 24 hours

Estimated creatinine clearance, mL/ min =

(140 – age [yrs]) x weight [kg] x constant

_________________________________________ Serum creatinine ( micromol/L) Constant 1.23 in males

1.04 in females

 Modification of diet in renal disease (MDRD) formula  

The most reliable measure of renal function Accounts for serum creatinine levels, gender, age, ethnic origin, serum nitrogen urea and albumin

eGFR = 170 x [serum creatinine] - 0.999 x (Age)- 0.176 x (0.762 if female) x (1.180 if the patient is black) x [serum urea nitrogen] -0.170 x [Albumin]0.318 Units are in mL/min/1.73m2 (m2 refers to body surface area) 

Should NOT be used for children, malnourished patients, in pregnancy, in acute renal failure or oedema & extremes of muscle mass (e.g. amputee, body builder, muscle-wasting disease) as the equation assumes the body surface area of the patient is 1.73m^2...