PHYSL
Important notes , tutorial
1st 5 lecs
mid1
LEC 1
Function of kidney “ slide 4+5” :
• Excretion
• Homeostatic function
• Biosynthesis/Metabolism
Type of nephron :
THE FILTRATION MEMBRANE:
1. Capillary Endothelium: negative charges that
restrict the passage of plasma proteins
2. Basement Membrane: mesangial cells are located
between the basal lamina and the endothelium.
3. Podocytes (Epithelium) : foot-like processes
all layers of glomerular capillary membrane have negative
charge provide a barrier to the filtration of plasma
proteins.
Juxtaglomerular Apparatus: “ slide 23 “
• The Macula Densa: Detect & respond to changes in
the sodium chloride levels in the distal tubule of the
kidney.
• Juxtaglomerular Cells : secrete renin
LEC 2
Glomerular Filtration:
The first step in urine formation is the
Glomerular filtration during which, large
quantity of water and solutes pass through the
filtration membrane from the blood into the
Bowman’s Capsule due to pressure gradient.
Abnormal value :
Microalbuminuria is 30–300 mg/24 hours
Macroalbuminuria is 300mg/24 hours
Factors affecting GFR:
• Changes in renal blood flow
• Changes in glomerular capillary hydrostatic pressure
– Changes in systemic blood pressure
– Afferent or efferent arteriolar resistance
• Changes in hydrostatic pressure in Bowman’s capsule
– Ureteral obstruction
– Edema of kidney inside tight renal capsule
• Changes in concentration of plasma proteins:
– Dehydration
– Hypoproteinemia, etc.
• Changes in Kf
– Changes in glomerular capillary permeability
– Changes in effective filtration surface area
Glomerular Capillary Hydrostatic Pressure (PG): “slide 15”
It is the primary means for physiologic regulation of GFR.
Increase PG raises GFR, and vice versa.
It is determined by three variables:
Arterial Pressure
Afferent Arteriolar Resistance
Efferent Arteriolar Resistance.
LEC 3
Remember
• Loop of Henle ascending : electrolyte
• Loop of Henle descending : only water
• Proximal convoluted tubule PCT: glucose and
amino acid 100% reabsorped
LEC 4
Remember
• Level of glucose in blood will cause TM and
it’ll cause threshold
• Threshold = 180-200
• The main function of urea is controlling water
balance and concentration of urine
• Ca and phosphate influenced by PTH
Lec 5
Most important substances secreted by the tubules
Is H+and K+
• H+
•
•
Important in regulating acid-base balance
Secreted in proximal, distal, and collecting tubules
• K+
•
•
Keeps plasma K+ concentration at appropriate level to maintain
normal membrane excitability in muscles and nerves
Secreted only in the distal and collecting tubules under control
of aldosterone
During acidosis H+ secretion is increase lead to
retention of K+.
small increase in plasma potassium will cause cardiac
arrhythmias, and higher concentrations can lead to cardiac
arrest or fibrillation.
small loss of potassium from the extracellular fluid could cause
severe hypokalemia.
rapid and appropriate compensatory response mechanism is
vital to avoid dangerous
Hyperkalemia(with bradycardia)
or Hypokalemia (with tachycardia )
Factor effecting secretion : slide 13+14+17
• Diet
• Aldosterone
• Acid base balance
• RAAS will reabsorb Na+ and excrete K+
– Renin–Angiotensin–Aldosterone system (RAAS)
– Increase of RAAS cause hypertension.
– RAAS is also responsible for fluid retention and EDEMA occurring in
congestive heart failure.
– Angiotensin Converting Enzyme inhibitor – ACE inhibitor drugs are
used for hypertension and congestive heart failure
• diuretics will block the Na+\K+ pump
• PAH is used to diagnose renal blood flow , cus it’s not
reabsorbed
• NSAID + Aspirin cause tubular damage, will cause in large
dose acute renal failure
Tutorial
For all the 5 lecs
Lec1
1-Biosynthesis/Metabolism FUNCTIONS OF
KIDNEYS?
– Renin secretion
– Erythropoietin
– Activation of Vitamin D> Calcitriol (1,25 DHCC)
– Other substances:
• Prostaglandin,
• Adenosine… etc ..
But the 1st 3 are most important
2-Homeostatic function of kidney ?
– acid-base balance
– Osmolality and volume of ECF
– blood pressure.
– water and electrolyte balances.
– Plasma ions concentration.
3-Excretion function of kidney ?
– metabolic end product, e.g. urea
– foreign substances, e.g. drugs, toxins
Parts of Nephron?
4-What is peritubular capillaries?
Around the tubules and its function is to reabsorb
substances from tubules
5-What is vasa recta ?
straight capillaries in the medulla
6-Difference b\w cortical and juxta medullary nephrons ?
7-What are the layers of Glomerulus?
1. Capillary Endothelium
2. Basement Membrane
3. Podocytes (Epithelium)
8-What are the layers of Bowmans Capsule?
– Visceral > Podocytes ( which is the last layer of Glomerulus)
– Parietal
9-What is the specialty\feature of Capillary Endothelium?
Fenestrations =pores
10-What is the specialty\feature of Basement Membrane?
negatively charged
11-What is the specialty\feature of Podocytes ?
foot-like processes which helps in interlocking with other cells (gaps) to have
a better surface area
12-What are the layers of Filtration Membrane?
1. Endothelium
2. Basement Membrane
3. Podocytes
13-What is Juxtaglomerular Apparatus\ or what is the purpose
of them?
Regulatory center for nephron
14-What are the Cells in JG Apparatus?
The Macula Densa
Where located? DCT
What are they ? modified cells of DCT
What is the function? Detect & respond to changes in the sodium chloride
levels in the distal tubule of the kidney.
Juxtaglomerular Cells: also called granular cells
Where present? wall of afferent arteriole endothelium
What are they ? Modified cells of endothelium
What is the function? secrete renin
Which cells have granules? Juxtaglomerular cells
Extra Glomerular Mesangial Cells
B\W arteries and tubules
15 –Where’s the JG Apparatus Cells present?
Wall of efferent artery
16-What is the 1st step in urine formation ?
1.Glomerular filtration – GF
Then the 2nd and 3rd steps ..
2. Tubular reabsorption - TR
3. Tubular secretion - TS
Lec 2
17-What are the substances that are not filtered ?
– Blood cells
– Protein
– Protein-bound molecules (calcium, fatty aids, amino acids)
18-What is the Definition Glomerular Filtration Rate (GFR)?
– It is the Volume of plasma filtered by all nephrons of both
kidneys per unit time.
19-What is Normal GFR value?
125ml/min or 180L/day.
20-What are the factors Determine the GFR?
– NET FILTRATION PRESSURE which is : Sum of the hydrostatic
and colloid osmotic pressures across the glomerular
membrane
– Capillary Filtration Coefficient (Kf): Surface Area “Membrane
Permeability”= thickness
21-what is Net filtration Pressure value ?:
10mmHg
And it’s consisting of 4 pressures
Glomerular hydrostatic pressure
Glomerular colloid osmotic pressure
Bowman’s capsular hydrostatic pressure
Bowman’s capsular colloid osmotic pressure
22- 2 pressures helps in filtration ?
–
–
Glomerular hydrostatic pressure
Bowman’s capsular colloid osmotic pressure
23-Which pressure is used by body primarily for physiological
regulation of GFR? | What’s primary mean of physiological GFR?
Glomerular hydrostatic pressure
-Hydrostatic pressure could affected by ? Renal blood flow
24- 2 pressures Opposing filtration?
– Glomerular colloid osmotic pressure
– Bowman’s capsular hydrostatic pressure
• So all 7 factors affecting the GFR?
1.
2.
3.
4.
5.
6.
7.
Glomerular hydrostatic pressure
Glomerular colloid osmotic pressure
Bowman’s capsular hydrostatic pressure
Bowman’s capsular colloid osmotic pressure
Surface Area
“Membrane Permeability”= thickness
Renal blood flow
25-How the regulation of GFR is done?| the
methods of regulation in GFR?
1. Extrinsic mechanisms
2. Intrinsic mechanisms by Autoregulation
26-What are the Extrinsic mechanisms?
• sympathetic nervous system(autonomic)
• Baroreceptor reflex (mainly autonomic also)
27-What is the Intrinsic mechanisms ?
• Myogenic mechanism
• Tubuloglomerular feedback (TGF)
28-What is Myogenic mechanism?
increase ↑ pressure in capillary, the capp will be stretched , the
stretching will cause entry of ca into smooth muscle =
constriction of capillary
So ↑stretch = ↓ 𝐺𝐹𝑅
29-What is Tubuloglomerular feedback (TGF)?
It’s the func of Juxtaglomerular Apparatus
Detects how much Na+ loss or reabsorbed in blood ..will make it
balanced
30- what is Effect of Afferent Arteriolar Constriction of
FGR?
↓GFR, ↓Renal Blood Flow
31-What is the Effect of Efferent Arteriolar Constriction
of FGR?
↑ GFR, ↓ Renal Blood Flow
32-What is the Filtration Fraction (FF) and how much is it ?
ratio of the GFR to the renal plasma flow
(GFR/TRPF).
33-How much of blood flow goes to kidney= renal blood flow ?
– 20-25% of total cardiac output. = 1 L/min
34-Out of that how much plasma supply to kidney ?
• 625 ml
• Out of that 125 ml is filtered
35-So Filtration fraction normal value ?
(GFR/TRPF) = 0.2( 20%)
Measurement of GFR:
•
Characteristic of substance used for measurement:
– 1- Freely filtered (not reabsorbed not secreted)
– 2- Not metabolized by the kidney
– 3- Not toxic and stable
– 4- Not bound to plasma protein
– 5- Does not change renal plasma flow
36-Substance used to Measurement of GFR?
– Inulin
lec3
37-Transport mechanism used
in reabsorption ?
active
Primary active
Sodium-potassium
pumps in
basolateral
membrane.
passive
Secondary
active
co-transport
(glucose, amino
acids, fatty acid)
counter-transport
(K+, H+)
38-What are the Substance utilize for co-transport for
many substances in renal tubule ?
Na+ (sodium )
-GLUT depends on ? Facilitated diffusion
39-Glucouse utilizes which type of transport?
co-transport or 2ry active transport
40- H+ ion utilizes which type of transport ?
mostly counter-transport
41-Common Substances Reabsorbed in PCT:
–
–
–
–
–
–
–
–
Sodium
Chloride
Glucose
Water
Amino acid
Bicarbonate
Phosphate
Urea
65%
50%
100%
65%
100%
90%
42-What is the specialty of Loop of Henle?
descending limb: highly permeable to water
Ascending limb: only permeable to electrolyte and
impermeable to water.
43-What is the specialty Late DCT and Cortical Collecting Tubule?
Hormone regulation
- Which Hormone can control the Permeability of substances
in Water?
Anti diuretic Hormone (ADH) or Vasopressin
44-What are the type of cells present in the segment ?
Principal cells +Intercalated cells
45-What is the function of Principal cells ?
Have receptors for hormones like aldosterone , help in
reabsorption of electrolytes
46-What is the function of Intercalated cells?
Acid base balance , control reabsorb and excretion of H+ ions
and Bicarb
47-Medullary Collecting Duct importance?
– Last step where any change can occur into the tubular
fluid , after that the tubular fluid is passed on as urine
48-What are the factors or mech that help in reabsorption?
– Mostly hormones (aldosterone, angiotensin II,(ADH)…
etc.)
– Then same forces, pressures in GFR
49- What is pressure natriuresis ?
↑ blood pressure, ↑ loss of NA+
50- What is Pressure diuresis ?
↑ blood pressure , ↑ loss of H2O
Na+ sodium
51-Where’s reabsorbed?
in the tubule (including aescending limb of Loop of
Henle) except descending limb of Loop of Henle
52-What’s the effect of aldosterone on Na+?
↑ NA reabsorption
53-What’s the effect of aldosterone on K+?
↑ K+ excretion
Aldosterone : ‫صائد الصوديوم طارد البوتاسيوم‬
54-What’s the effect of Na on urea and chloride ?
↑ their reabsorption by passive transport
Just remember that
Tubular Reabsorption – Sodium:
• Proximal convoluted tubule
65 - 67%
• Loop of Henle (thick ascending limb)
25 %
• Distal and Collecting Tubule
8%
Tubular Reabsorption – Water:
• Proximal convoluted tubule (PCT) – 60-70%. It is
passive.
• Loop of Henle(Descending Limb) – 15%.
• DCT and CT – 20%. DCT – 5%. CT – 15%.
• In DCT and CT, water is reabsorbed under the action of
ADH (Anti-Diuretic Hormone) or Vasopressin.
Lec 4
55-How’s glucose reabsorbed?
Co-transportation or 2ry active transport
56-Whare glucose is reabsorbed?
PCT
57-How much of glucose is reabsorbed by PCT?
100%
58-What is Tubular Maximum (Tm) of glucose ?
the maximum amount of glucose which can be
reabsorbed after that point glucose appears in urine
59-Normal value of Tm?
375 mg/minute.
60-What is the renal threshold
concentration of glucose at which glucose will
appear in the urine
61-Normal value or the renal threshold ?
180mg % - 200mg %.
62-Urea reabsorbed?
proximal tubule
63-Urea secreted ?
loop of Henle.
64-reabsorbed again in?
the medullary collecting duct
65-Under the influence of?
Hormones
66-What is Obligatory Urine Volume?
minimum amount of urine which has to be
formed in excretion of harmful substance each
day
67-Normal value of Obligatory Urine Volume?
0.5 L/day
Lec 5
68-What are the substance important for
secretion:
H+ and K+
69-Factors affect secretion?
1. Diet
2. Aldosterone
3. Acid base balance
70-What is the affect of H+ ion on K+ secretion ?
– Whenever Acidosis (↑H+) , K+ retention occurs , so
hyperkalemia will occur
Normal values
GFR value: 125ml/min or 180L/day
Net filtration Pressure value: 10mmHg
Renal blood flow : 20-25% of total cardiac output. = 1 L/mi
Plasma supply to kidney: 625 ml
Filtration fraction normal value: 0.2( 20%)
Tm: 375 mg/minute.
Renal threshold: 180mg % - 200mg %.
Obligatory Urine Volume: 0.5 L/day