Renal Blood Flow and Glomerular Filtration Flashcards
Why is there such a huge filtration rate (namely 180 litres a day)?
High rate of formation of glomerular fluid is needed to wash out the waste products fast enough to keep their blood level low
Generally, how is glomerular fluid formed?
Passive ultrafiltration of plasma across the glomerular membrane
What is the glomerular rate (GFR) set by?
- autoregulation
- renal sympathetic vasomotor nerve activity.
What does the glomerulus consist of?
Capillaries and the Bowman’s capsule.
What are the key features of glomerular filtration for small solutes?
Concentration in the glomerular fluid is equal to the concentration in the plasma
What are the key features of glomerular filtration for plasma proteins?
Concentration in the glomerular fluid should be almost zero
What is proteinuria?
Presence of proteins within the urine
What is proteinuria a sign of?
Renal/ urinary tract disease
What drives ultrafiltration?
Net pressure drop across the glomerular membrane
On what basis does the glomerular membrane sieve out solutes?
Molecular size
What drives glomerular fluid formation?
Imbalance of Starling’s forces
What are the three forces that contribute to glomerular fluid formation?
Pc - capillary blood pressure - around 50 mmHg.
πp - plasma colloid osmotic pressure - around 25 mmHg.
Pu - pressure in the Bowman’s space - 10 mmHg.
What are podocytes?
Cells in the Bowman’s capsule that wrap around the capillaries of the glomerulus.
Describe the filtration slits in between the podocytes.
- Glomerular fluid emerges through slit.
- Slit is about 30 nm wide.
- Central spine with lateral rungs
- Subdivides the filtration slit into pores that are 4 nm wide.
- Made of the proteins nephrin and podocin.
What do nephrin and podocin deficiency cause?
Nephrotic syndrome.
The glomerular membrane is 3 sieves in series of increasing fineness.
What are they?
- Fenestrated capillary
- Basement membrane
- Filtration sites of podocytes
Describe the fenestrated capillaries.
- Blocks big structures like RBCs
- Allow smaller molecules through, such as albumin, fibrinogen, and water.
Describe the basement membrane.
- Allow albumin and water through
- Block molecules like fibrinogen
Describe the filtration sites of podocytes.
- Allow small molecules through, such as water, glucose, NaCl, urea, creatinine
Why is GFR usually held constant? Why doesn’t it fluctuate?
- Usually held constant at 120 ml/min.
- Allows tubules to reabsorb filtrate and not be overwhelmed by excessive GFR.
What internal mechanism determines GFR?
Autoregulation
What are changes in urine production caused by?
- Changes in tubular reabsorption
- NOT by changes in GFR
What happens to renal plasma flow and GFR when blood pressure rises?
They stay relatively constant due to autoregulation.
What 2 mechanisms are responsible for the intrinsic control of GFR?
BAYLISS MYOGENIC RESPONSE
TUBULOGLOMERULAR FEEDBACK (TGF)
Describe the Bayliss Myogenic response.
- Increase in the perfusion pressure leads to an immediate increase in vessel radius
- Blood flow rises briefly
How does the myogenic response affect autoregulation?
Changes in diameter of the afferent arteriole alters the resistance, maintaining autoregulation.
Describe tubulo-glomerular feedback.
- Increased distal tubular sodium chloride concentration
- Causes basolateral release of adenosine from the macula densa cells.
- ATP signal leads to a contraction of afferent arterioles.
Describe how TGF controls the GFR and renal blood flow (RBF). PART 1
- Change in the RBF/ GFR
- Change in the NaCl delivery to the DCT
- Macula densa sense the change
Describe how TGF controls the GFR and renal blood flow (RBF). PART 2
- Affect afferent arterioles via paracrine/vasoactive agents
- Arterioles change diameter and resistance
- Restores RBF/ GFR
Describe the extrinsic control of GFR.
- Extrinsic control of neurohormonal.
- Renal sympathetic nerves (vasoconstrictor, noradrenergic) can reduce the GFR by resetting the autoregulation to a lower level.
When may renal sympathetic nerves alter GFR?
- standing upright (orthostasis)
- heavy exercise
- haemorrhage
What is the role of extrinsic GFR control?
Conserve body fluid during physical stress.
What aids the renal sympathetic nerves in extrinsic GFR control?
Circulating vasoconstrictor hormones such as adrenaline, angiotensin, and vasopressin.
Describe the two major clinical disorders of the GFR. PART 1
Nephrotic Syndrome
- Filtration slit disordered by nephrin deficiency
- Glomeruli too leaky to plasma protein:
- Cause proteinuria, hypoproteinaemia and oedema.
- Respond well to steroids.
Describe the two major clinical disorders of the GFR. PART 2
LOW GFR
Chronic glomerulonephritis - non-functioning glomeruli.
When the GFR gets to <30 ml/min, this is considered chronic renal failure.
The 2 kidneys, which make up about 0.5% of the body weight, receive nearly a quarter of the resting cardiac output.
Why?
- Large blood flow is not related to the metabolic needs of the kidney
- Function of the role that the kidneys play in the regulation of the ECF and blood volume regulation and rapid waste disposal.
What are the 4 main functions of the kidney?
→Control volume & composition of body fluids
→To get rid of waste material from the body
→Acid-Base balance
→As an endocrine organ – EPO, Renin
What can the kidney not regenerate?
→ new nephrons
What are the 2 sets of capillaries that a nephron has?
→ Glomerulus
→ Peritubular capillaries
What are the 2 stages of urine formation?
→Glomeruli produce the liquid
→The tubules modifies its volume and composition
What urine output equates to renal failure?
→ <5ml/day
What is the net effect on glomerular capillaries as a result of the forces acting on it?
→net effect is an outward force of approximately 15mmHg
→drives fluid out of the capillary into the BC
What happens as blood flows through the capillary with respect to pressure?
→As the blood flows through the capillary, there is a slight drop in pressure from the afferent end to the efferent end.
What happens to the plasma as the blood flows along?
→ plasma also gets more concentrated as the blood flows along due to fluid loss
What is the relationship between net filtration force and net absorptive force?
→net filtration force is always more than the net absorptive force
What is the blood pressure entering the glomerulus and what does this result in?
→The blood pressure in the afferent arteriole is higher than the colloid osmotic pressure (COP) entering the glomerulus
→ resulting in a net filtration pressure out of the capillaries into the tubule.
What is the blood pressure like as you exit the glomerulus and what does this result in?
→As we travel out of the glomerulus into the efferent arteriole, the pressure begins to drop.
→COP rises because fluid is lost from the capillaries
→ exerting a greater force driving fluid back from the tubule into the capillary
Why can blood not pass through the fenestrae?
Blood cells cannot fit and are trapped
What can travel through the fenestrae?
→ Anything that dissolves in water
→ Passes through the basal lamina (glycocalyx)
Why does albumin not appear in the urine even though it can fit through the fenestrae and podocytes?
Trapped in the 4nm pores
What is myeloperoxidase?
→ Albumin sized protein which is held up at the filtration slits
What does myeloperoxidase produce?
→black precipitate
What is myeloperoxidase used to prove?
→ Myeloperoxidase injected into plasma
→ Penetrates through basal lamina but piles up at filtration slits
→ Same size as albumin so albumin cannot pass into urine
What would happen to GFR if there were no autoregulation and an increase of BP occurred?
→Relatively small increase in BP would cause a similar 25% increase in GFR
What do TGF and the myogenic response do together?
→stabilise renal function by preventing pressure-induced fluctuations in RBF (Renal Blood Flow) and GFR
→delivery of filtrate to the distal tubule
What must autoregulation be mediated by?
→mediated by changes in afferent arteriolar resistance
What does an increase in osmolality and NaCl in the juxtaglomerular apparatus result in?
→results in a release of ATP
→ leads to a contraction of the afferent arteriole
→ contributes to the maintenance of pressure in the Bowman’s capsule
