Lecture 4: Introduction to the glomerulus Flashcards
What is the role of the kidney?
- maintain a steady internal environment
- controls concentrations of key substances
- excretes waste products
- endocrine role: synthesis of renin, EPO, prostaglandins
- metabolism: activeform of vit D, catabolism of insulin
What products are recovered in the kidney?
> 99% of filtered water
99% of filtered sodium and chloride ions recovered
100% of bicarbonate, glucose, AA’s removed
Just a few waste products not recovered
What is the role of the kidney in fluid balance?
Filters very large amount of ECF
- forming ultrafiltrate: water, ions, all small molecules
- 180L/day, recovering almost everything, leaving about 1.5L per day of urine
What does the kidney directly regulate?
All of the extracellular fluid (not intracellular)
What are the electrolyte compositions of intra/extra-cellular fluids?
Intra: high K+, low Na+, large organic anions
Extra: low K+, high Na+, main anion is Cl- and HCO3-
Maintained by sodium pumps (mainly Na+/K+)
What is the difference b/w osmolality and osmolarity?
Osmolality: solute per kilogram of solvent
Osmolarity: number of osmoles (charged particles) of solute per litre
What is oncotic force?
Osmotic force due to charged proteins
Where do you find the glomerulus in the kidney?
Cortex
What is the GFR?
140-180L of glomerular filtrate produced per day
= 125ml/min
What is the filtration fraction?
The proportion of fluid reaching the kidneys that passes into the renal tubules (normally 20%)
GFR/RPF=FF
What is the rough renal plasma flow (RPF) and the renal blood flow (RBF)?
RPF: 800 mL/min
RBF: 1100 mL/min
How much blood is filtered at a time from the renal artery?
20% of blood is filtered at any one time
80% of blood exits via efferent arteriole (unfiltered)
What is the normal range for GFR?
90-120 mL/min
- contains now blood cells/platelets
- contains no proteins
- composed of mostly organic solutes with a low molecular weight and inorganic ions
What is the structure of the glomerular capillary membrane?
- endothelial cells line the capillaries an dthey have gaps called fenestrations b/w them allowing filtrate to pass through
- endothelial cells are attached to basement membrane
- podocytes and podocyte processes line the basement membrane forming filtration slits
- podocytes are also negatively charged to repel the negatively charged proteins in the blood
What is each foot of a podocyte called?
Pedicel (podocyte processes)
What is proteinuria?
The negative charge on the filtration barrier is lost, so therefore proteins are more readily filtered through. You end up with protein in the urine.
What is haematuria?
Blood cells get filtered and appear in the urine
What forces enable filtration?
PUSHING: mainly hydrostatic pressure in capillary (pushing plasma through the fenestrations)
PULLING: hydrostatic pressure in Bowman’s capsule, oncotic pressure difference (proteins in capillary draws water)
These all together give us the NET FILTRATION PRESSURE
What is Starlings forces?
- firstly at start of glomerulus is the hydrostatic pressure of the capillary pushing fluid out
- then further along is the hydrostatis pressure in Bowman’s capsule pushing back in
- lastly due to the loss of plasma to Bowman’s capsule, their is a higher concentration of charge proteins which then draws water back in
What is the average net filtration pressure?
13 mmHg
What factor can affect net filtration pressure?
-blood pressure
What are the mechanisms involved in autoregulation to keep RBF/RPF/GFR constant?
- myogenic mechanism
- tubuloglomerular feedback
What is the myogenic mechanism?
Arterial smooth muscle responds to increases and decreases in vascular wall tension
-increase in renal arteriole pressure: afferent artery constricts to decrease GFR
(property of preglomerular vessels: arcuate, interlobular, afferent arteriole)
How do you decrease the GFR?
Constrict the afferent arteriole, reducing the amount of blood reaching the glomerulus, reducing pressure
Dilating the efferent arteriole, easier for blood to leave glomerulus, reducing pressure
How do you increased the GFR?
Constrict efferent arteriole, causing backup of blood in glomerular capillary, increasing the pressure
Dilate the afferent arteriole, allowing more blood to flow into the glomerular capillary, increasing the pressure
How does tubuloglomerular feedback work?
Macula densa cells in DCT detect rate of movement of Na+/Cl- into the cells (higher flow of filtrate, higgher the Na+ conc)
- macula densa cells detect flow of solutes which send signals to the juxtaglomerular cells, and then this causes constriction/dilation of the efferent or afferent arterioles
- if BP increases, more signals of ATP are sent causing vasoconstriction
- if BP decreases, less signals of ATP, causing less vasoconstriction
Why is it not ideal if the flow in the tubules is faster than usual?
Won’t be able to reabsorb as much as normal
What is the signalling molecule from the macula densa cells?
ATP
Why is low blood pressure dangerous?
<60 mmHg
- causing activation of sympathetic nerves, causing systemic constriction
- lead to renal failure (as blood flow through glomarular apparatus is too slow)
What happens when there is very low blood pressure to prevent acute renal failure?
-prostaglandins sent from macula densa cells causing vasodilation of the afferent arteriole
(if patient is on NSAIDS they are unable to produce prostaglandins)
-juxtaglomerular cells release renin: angiotensinogen>angiotensin 1>angiotensin 2= causes constriction of efferent arteriole
(if patients are on ACE inhibitors they won’t be able to produce angiotensin 2)
What are the systemic effects when blood pressure is fatally low?
Constriction of the efferent arteriole means that the blood leaving the glomerular apparatus has a higher colloid osmotic pressure, so more water is reabsorbed back into blood= increasing blood pressure systemically
Angiotensin 2 causes an increase in aldosterone, which results in reabsorbing more NaCl, and therefore more water is reabsorbed= increase blood volume
What is renin release stimulated by?
- sympathetic nerve stimulation
- decreased stretch of afferent arteriole
- signals from macula densa
