1. Anatomy and Physiology of the Kidney
Ali Abdi

3. Objectives Brief review of renal anatomy
Explanation of kidney function
The 3 basic renal processes
Understand and explain renal physiology
Glomerular filtration
Tubular reabsorption
Tubular secretion

4. آناتومی کلیه (Kidney Anatomy)
Is about 10 cm long, 5.5 cm wide, and 3 cm thick & weighs about 150 g

5. Internal Anatomy

6. Juxtaglomerular apparatus
At initial point of distal convoluted tubule
JG cells are present in the arteriole walls & act as mechanoreceptors to sense BP in the afferent arteriole
JG cells are enlarged, smooth mm cells filled w/secretory granules filled w/renin
Macula densa is a group of tall, packed cells in the distal tubule & lies adjacent to the JG cells
These are chemo/osmoreceptors that respond to changes in solute content of the filtrate in the lumen of the tubule

7. Structure of the Bowman’s (Glomerular) Capsule

9. Kidney physiology
Account for ~0.5% of total body weight yet consume 20-25% of all O2 used by the body at rest
Process ~188 L (47 gallons) of blood derived fluid/day
Only ~1% of this (1.5 L) actually leaves the body as urine
ml of blood/min pass through glomeruli (650 ml of which is plasma)
Equivalent to filtering your entire plasma volume >60x/day
Usually produce concentrated urine:
1200–1400 mOsm/L (4 times plasma concentration)

10. Functions of the kidneys
Regulation of H2O and inorganic ion balance – most important function!
Removal of metabolic waste products from blood and excretion in urine.
Acid-base balance
Removal of foreign chemicals in the blood (e.g. drugs) and excretion in urine.
Gluconeogenesis
Endocrine functions (e.g. renin, erythropoetin, 1,25-dihydroxyvitamin D)
Renal Gluconeogenesis
Glucose, after moving into cells, is phosphorylated into glucose-6-phosphate by enzymes like glucokinase or hexokinase. In this form, cells can trap glucose because cell membranes are impermeable to glucose-6-phosphate.[2] Only cells containing the enzyme glucose-6-phosphatase, which hydrolyzes glucose-6-phosphate to glucose, are able to release glucose into the circulation. Glucose-6-phosphatase is present in the liver, the renal cortex and the intestinal epithelium giving the above tissues the ability to release glucose.[2]
The view that gluconeogenic capacity of the kidney may be restrained by conditions, like starvation or acidosis supported by net organ balance studies, is no longer existing.[3] In glucose homeostasis, the kidney may be considered as two different organs: the renal medulla and the renal cortex. This differentiation refers to the distribution of various enzymes in these parts of the kidney. Medulla holds enzymes for glucose phosphorylation, glycolysis and glycogen synthesis, but lacks glucose-6-phosphatase and gluconeogenic enzymes. Consequently, renal medulla satisfy its energy needs through glycolytic division of glucose, which produce lactate and synthesizesa small amount of glycogen for intracellular consumption. Given the lack of glucose-6-phosphatase, the renal medulla has not the capacity to release glucose into the circulation. On the other hand, the renal cortex holds gluconeogenic enzymes, synthesize glucose-6-phosphate from precursors; for instance, lactate, glutamine, glycerol, alanine and is able to release glucose into the blood stream via glucose-6-phosphatase.[4–6]
Renal glucose release in the postabsorptive (12-h fasting) state is calculated by the net glucose balance and deuterated glucose dilution methods. The renal gluconeogenesis contribution to the total glucose release is ~20%, whereas liver glucogenolysis is ~50% and liver gluconeogenesis 30%.[7]Furthermore, the renal gluconeogenesis progresses as the glycogen stores are depleting during a prolonged fasting. According to the studies by Ekberg et al., 60 h of fasting may increase the renal glucose release by 2.5-times compared to the 12-h fasting state, whereas hepatic glucose release is decreasing by 25%.[8]
At the postprandial state, the renal glucose release increases by over 50% of the total endogenous glucose release. This unexpected phenomenon in combination with suppression of the hepatic glucose release facilitates the liver glycogen stores repletion.[9] This process seems to be regulated by the sympathetic nervous system activity.[10]

11. The three basic renal processes
Glomerular filtration
Tubular reabsorption
Tubular secretion

12. Nephron(واحد عملکردی کلیه)
The functional unit of kiney
Kidneys contain 2.5 million Nephron
Nephrons have two functional component one capillary system and other tubular system

13. THE NEPHRON STRUCTURES OF THE NEPHRON 1. BOWMAN’S CAPSULE
2. PROXIMAL CONVOLUTED TUBULE
3. LOOP OF HENLE
A. DESCENDING LIMB
B. ASCENDING LIMB
4. DISTAL CONVOLUTED TUBULE
THESE EMPTY INTO THE COLLECTING
DUCT OR TUBULES.

15. Factors determining filtration combination
Molecular size Molecule charge Molecules<20 Ao and without charge filtrated easily Molecules>40 Ao was not filtrated 20 Ao <molecules<40 Ao filtation is dependent to their electrical charge Albumin= 35.5 Ao and it is anion (negative charge)
آلبومین یک پروتئین آنیونی با شعاع مولکولی 35/5 انگستروم است که 7 گرم در وز دفع می شود.
در حالیکه گرم در روز از گلومرول عبور میکند یعنی کمتر از 0.01 درصد از آن دفع می شود.

16. Glomerular filtration
Mostly a passive process driven by hydrostatic Presure
Glomerular filtration membrane is 1000s x more permeable than regular capillary membranes
Glomerular BP is higher than in other caps (55 mmHg versus <18 mmHg)
Kidneys produce ~ 180 L filtrate/day while other body caps produce ~3-4 L/day combined
Usually, molecules <3 nm (water, glucose, AAs, nitrogenous wastes) can pass…molecules >7-9 nm are usually completely barred from entering tubule
Plasma proteins in the caps help maintain osmotic P
proteins./RBCs in urine usually indicates a problem w/the filtration membrane

17. Forces Involved in Glomerular Filtration
فشار خالص اولترافیلتراسیون در انتهای آوران 17 و در انتهای وابران 8 میلی متر جیوه می باشد.
ضریب نفوذپذیری مویرگهای گلومرولی نسبت به سیستمیک 1000 برابر بیشتر است.
فشار هیدوراستاتیک مویرگهای گلومرولی تقریباً 2 برابر مویرگهای سیستمیک است.

18. Glomerular Hydrostatic Pressure (GHP)
Is blood pressure in glomerular capillaries
Tends to push water and solute molecules:
out of plasma & into the filtrate
Is significantly higher than capillary pressures in systemic circuit:
due to arrangement of vessels at glomerulus

19. Capsular Hydrostatic Pressure (CsHP)
Opposes glomerular hydrostatic pressure
Pushes water and solutes:
out of filtrate & into plasma
Results from resistance to flow along nephron and conducting system
Averages about 15 mm Hg

20. Blood Colloid Osmotic Pressure (BCOP)
Tends to draw water out of filtrate & into plasma
Opposes filtration
Averages 25 mm Hg

21. Forces Involved in Glomerular Filtration
فشار خالص اولترافیلتراسیون در انتهای آوران 17 و در انتهای وابران 8 میلی متر جیوه می باشد.
ضریب نفوذپذیری مویرگهای گلومرولی نسبت به سیستمیک 1000 برابر بیشتر است.
فشار هیدوراستاتیک مویرگهای گلومرولی تقریباً 2 برابر مویرگهای سیستمیک است.

22. Glomerular filtration rate (GFR)
The total amount of filtrate formed by the kidneys per minute (avg. 125 ml/min)
About 10% of fluid delivered to kidneys leaves bloodstream & enters capsular spaces
It is directly proportional to the net filtration pressure
Glomerular BP- (osmotic P of glomerular blood + capsular hydrostatic P of other fluids in glomerulus)
An increase in NFP (arterial BP) increases GFR & vice versa (dehydration will increase glomerular osmotic pressure & decrease GFR)

23. Glomerular Filtration Rate (GFR)

24. 3 factors governing GFR at cap beds
1. Total surface area available for filtration
2. Filtration membrane permeability
3. Net filtration pressure
The normal GFR in both kidneys in adults is ~125 ml/min (7.5 L/hour..180 L/day)

25. 3 controls of renal blood flow
These all function to keep GFR at a fairly constant level
1. Renal autoregulation (intrinsic)
2. Renin-angiotensin system (hormonal)
3. Neural controls (SNS)

26. Regulation of Filtration Pressure

27. Intrinsic controls (autoregulation)
Maintains GFR despite changes in local blood pressure and blood flow by changing diameters of afferent arterioles, efferent arterioles, and glomerular capillaries (Myogenic mechanism)
Reduced blood flow or glomerular blood pressure triggers:
dilation of afferent arteriole, dilation of glomerular capillaries, & constriction of efferent arterioles
Rise in renal blood pressure:
stretches walls of afferent arterioles, causes smooth muscle cells to contract, constricts afferent arterioles, & decreases glomerular blood flow
ماده موثر ماکولا دنسا احتمالاً آدنوزین است این ماده در اکثر بستر های عروقی متسع کننده بوده ولی در شریانجه آوران منقبض کنننده عروقی است.

28. Intrinsic controls (autoregulation), cont.
Tubuloglomerular feedback mechanism – directed by macula densa of JGA
Cells respond to high filtrate flow rate & increased osmotic signals that leads to a release of chemicals to cause severe vasoconstriction of the afferent arterioles
When macula densa cells are exposed to slowly flowing filtrate or filtrate w/low osmolarity they promote vasodilation of afferent arterioles
Macula densa cells also send signals to JG cells to set renin-angiotensin mechanism into motion

29. SNS control of GFR
SNS (+) causes vasoconstriction of afferent arterioles & slows filtrate production
W/extreme stress or an emergency, the autoregulatory mechanisms may be overcome in order to shunt blood to vital areas like the brain, skeletal mm, & heart at the expense of the kidneys
This also indirectly (+) the renin-angiotensin mechanism by (+) the macula densa cells
SNS can also directly (+) JG cells to release renin by the binding of norepinephrin

30. Renin-angiotensin mechanism

31. Triggers of renin release
1. Reduced stretch of JG cells (hemorrhage, salt depletion, deH2O)
2. JG cell (+) via macula densa cells
promotes vasodilation of afferent arterioles while simultaneously (+) JG cells to vasoconstrict efferent arterioles
3. Direct (+) of JG cells via SNS fibers due to decline in osmotic concentration of tubular fluid at macula densa

32. Tubular reabsorption
Our total blood volume is filtered every 45 minutes so the majority of filtrate must be reabsorbed & returned to the blood
Virtually all organic nutrients are reabsorbed (glucose, AAs, etc)…kidneys function to maintain or restore normal plasma levels
Reabsorption of H2O and many ions is continuously monitored & adjusted in response to hormonal signals
Reabsorption may be either active or passive

33. Potassium: 86.1% reabsorbed Calcium: 98.2% reabsorbed
Tubular Reabsorption
Water: 99% reabsorbed
Sodium: 99.5% reabsorbed
Potassium: 86.1% reabsorbed
Calcium: 98.2% reabsorbed
Urea: 50% reabsorbed
Bicarbonat:99.9% reabsorbed
Glucose: 100% reabsorbed

34. Proximal convoluted tubule
The most active section for reabsorption
All glucose, lactate, & AAs
65% of Na in filtrate/~65 % of H2O
90% bicarb, 50% Cl, 55% K
Of the 125 ml/min of filtered fluid into the renal tubules, ~40 ml remains to enter the loop of Henle

35. Loop of Henle Epithelium permeability changes dramatically from PCT
For the first time, H2O reabsorption is not coupled w/Na reabsorption
25%Na, 10%H2O, 35% Cl, 30% K

36. Distal convoluted tubule
Most reabsorption by this time is hormonally regulated as the body needs
If necessary, nearly all H2O & Na reaching this point can be reclaimed
Reabsorption of the remaining Na is largely dependent on aldosterone (causes collecting ducts to become more permeable to Na)
w/o hormones, the DCT & collecting duct are relatively impermeable to H2O
Reabsorption is now dependent on ADH, which makes the collecting ducts more permeable to H2O

37. Secretion and Reabsorption

38. Tubular secretion Essentially the reverse of tubular reabsorption
Blood entering peritubular capillaries:
contains undesirable substances that did not cross filtration membrane at glomerulus
More dominant in the PCT (& DCT/C.D.’s)
Important for:
1. Disposing of substances not already in the filtrate (i.e. certain drugs – penicillin)
2. Elimination of certain undesirable end-products reabsorbed by passive processes (urea/uric acid)
3. Ridding the body of excessive K ions
4. Controlling blood pH

39. Thank You!