Renal Physiology Lecture 6.pdf Pharm D 2

Pharm D

1. Renal Physiology
Dr. Najam-us-Sahar
Senior Lecturer

2. Structures involved
Following structures are involved:
 Kidneys
 Ureters
 Bladder
 Urethra

3. Location:
• The two kidneys lie on the
posterior wall of the abdomen,
outside the peritoneal cavity.
Weight and size:
• Each kidney of the adult
human weights about 150
grams and is about the size of a
clenched fist and bean shaped.
Physiologic Anatomy of the Kidneys

4. Physiologic Anatomy of Ureters
Location:
• The upper half of the ureter is
located in the abdomen and the
lower half is located in the pelvic
area.
Size:
• The ureter is about 10 to 12
inches long in the average adult.

5. Physiologic Anatomy of the Bladder
Location:
• The urinary bladder is a
muscular sac in the pelvis, just
above and behind the pubic bone.
Size and shape:
• When empty, the bladder is
about the size and shape of a pear.

6. Structure of kidney
•The kidney is surrounded
by a tough, fibrous
capsule.
•The medial side of each kidney
contains an indented region called
the hilumthrough which pass the
renal artery and vein, lymphatics,
nerve supply, and ureter.
Following are the parts:
•Renal pyramids
•Papilla
•Minor calyxes
•Major calyxes
•pelvis

8. Structure of Functional unit
The Nephron Is the Functional Unit of the Kidney.
Two types of Nephron
Cortical ( 70-80 %)
Juxtamedullary( 20-30 %)
Each kidney in the human contains about 1 million
nephrons, each capable of forming urine.
The kidney cannot regenerate new
nephrons.Therefore,with renal injury, disease, or normal
aging, there is a gradual decrease in nephron number.
After age 40,the number of functioning nephrons usually
decreases about 10 per cent every 10 years.

9. Each nephron contains:
A tuft of glomerular capillaries
called the glomerulus.
proximal tubule
Loop of Henle
Distal tubule
Collecting duct

11. Structure of bladder
•The Bladder is a balloon like
chamber with walls of smooth
muscles collectively termed as
Detrusormuscles
•Composed of two parts
i.Body
ii.Neck

12. Blood supply:
Renal artery
Renal segmental artery
Interlobular arteries
Arcuate arteries
Cortical radiate artery
Afferent arterioles
Glomerular capillaries
Blood flow to the two kidneys is normally about 22 per
cent of the cardiac output, or 1100 ml/min.
The renal artery enters the kidney through the hilum and
then branches progressively to form:
The renal circulation is unique in that it has two capillary
beds, the glomerular and peritubular capillaries.
High hydrostatic pressure in the glomerular capillaries
(about 60 mm Hg) causes rapid fluid filtration, whereas a
much lower hydrostatic pressure in the peritubular
capillaries (about 13 mm Hg)permits rapid fluid
reabsorption.

13. Regulation:
Renal functions are controlled by
Neural and hormonal
Regulations.
Neural Regulation:
•Mainly the regulation is of Urinary
bladder.
•Sympathetic, Parasympathetic and
somatic N.S controlled the
functioning.
•Cerebral cortex and Brain stem is
involved.

14. Hormonal Regulation:
ADH(hormone):
From the posterior pituitary acts on the Kidneys to promote
water reabsorption, thus preventing its loss in Urine.
Aldosterone:
From the adrenal glands act on the Kidneys to promote Na+
reabsorption; thus preventing its loss in urine.
ANH (atrial Natriuretic hormone:
From atrium of heart acts on Kidney to promote Na+
excretion.

16. General Functions
•Produce & expel urine
•Regulate the volume and composition of the extracellular fluid
•Control pH
•Control blood volume & blood pressure
•Controls osmolarity
•Controls ion balance
•Production of hormones
•Renin
•Erythropoitin
•Prostaglandins

17. Filtration of Blood:
Major function of the kidneys is to filter the Blood and produce Urine.

18. Basic Renal
Process
The basic renal process is the filtraton of
blood(Urine) by THREE processes:
1: Glomerular Filtration
2: Tubular Reabsorption
3: Tubular Secretion

19. Basic Renal Process
A(e)=A(f)+A(s) -A(ra)
A(e)= Amount excreted
A(f)= Amount filtered
A(s)= Amount secreted
A(ra)= Amount reabsorbed

20. The Nephron
•Simplified view of its functions
•Glomerular
Filtration
•Tubular
Reabsorption
•Tubular
Secretion
•Excretion

21. 1:Glomerular Filtration:
It is the first step in Urine formation.It is a bulk flow process.
The contents filtered include small solutes, water, nitrogenous waste etc..
Unfiltered contents(proteins) leave through Efferent arterioles.
The Driving Force is the Hydrostatic & Osmotic pressure.
•180 liters/day filtered
•Entire plasma volume filtered 65 times/day
GFR:
25% of cardiac output,1.2 liter/min passes through kidney out of which only 10%
(120-130-ml/min) passes through the glomerulus . This is called GFR.
Normal Value is 120-130 ml/min

22. 2:Tubular Reabsorption:
It is a finely tuned process that is altered to maintain homeostasis of
blood volume,blood pressure,osmolarity & blood pH.
Rebsorption of any drug/agent detected if its excretion rate is less than GFR.
Contents reabsorbed are:
Water 99%
Na+ 99.5%
Urea 50%
It occurs through:
•Passive Diffusion
•Active Diffusion

23. Site of Reabsorption
Reabsorption of the substances occurs in almost all the segments of
tubular portion of the nephron
Substances reabsorbed from Proximal convoluted Tubule:
About 7/8 of the filtrate (88%) is reabsorbed in the proximal
convoluted tubule
The brush border of the epithelial cells in the proximal tubules
increase the surface area and thus increase reabsorption

24. Substances absorbed from proximal
tubules are;
i.Glucose
ii.Amino acids
iii.Sodium
iv.Potassium
v.Calcium
vi.Bicarbonates
vii.Chlorides
viii.Phosphates
ix.Urea
x.Uric acid
xi.water
2.Substances reabsorbed from Loop of Henle:
i.Sodium
ii.Chloride
3.Substances reabsorbed from Distal convoluted
Tubule
i.Sodium
ii.Calcium
iii.Bicarbonates
iv.water

25. 3: Tubular Secretions:
It is the transfer of materials from peritubular capillaries to the Renal tubular
lumen; opposite of Reabsorption. This secretion is caused by;
Active Transport & Passive diffusion
The contents that are secreted include;
Potassium
Hydrogen
Ammonium(IONS)
Creatinine
Urea
Drugs(Penicillin) etc…

27. The Nephron
Locations for filtration, reabsorption, secretion & excretion

28. EXCRETION
“The process of expelling Filtrate(Urine) into the collecting
duct & ultimately out of body is called excretion”
Done by process called “Micturition”

29. Micturition:
It is the storage,ejection of urine from the urinary bladder through
urethra to the outside of body. Its also called Urination.
OR
The urge to urinate can also be called as Micturition.
It has two phases:
1-The Storage phase:
A relaxed bladder in which urine slowly fills the Bladder.
2-The Voiding phase:
A contracted phase that forces the external sphincter to open for
urination.It is initiated by Nervous Reflex called Micturition reflex(autonomic
spinal cord reflex that can be inhibited or facilitated by centre in the cerebral
cortex or brain stem)

30. 1:As the bladder fills,stretch receptors are stimulated.The afferent fibres from these
receptors enter the spinal chord & stimulate the parasympathetic neurons which leads to
the contraction of detrusor muscles.
2:Inputs from stretch receptors also inhibits the sympathetic neurons to the internal
urethral sphincter muscle
Mechanism of Micturition:
3: Descending pathways from the Brain can influence this reflex.
4:These pathways stimulate both Sympathetic & Somatic motor nerves therefore
preventing Urination i.e., Voluntary control of external sphincter.

31. Renal Clearance:
“Renal clearance of a substance is the volume of the plasma cleaned
of that substance per unit time”
Clearance of substance S= mass of S excreted/unit time
Plasma conc of S

33. The kidneyscontrol acid base balance by excreting either
acidic or basic urine.
Excreting acidic urine reduces the amount of acid in extracellular fluid.
Whereas excreting basic urine removes base from the extracellular fluid.
Each day our body produces about 80mEq of nonvolatile acids, mainly
from the breakdown of proteins.
Each day our body produces 4320mEq of bicarbonate ions under normal
conditions.

34. THE OVERALL MECHANISM FOR THE
EXCRETION OF ACIDIC OR BASIC URINE
Large numbers of HCO3-(metabolic alkalosis) are filtered continuouslyinto
tubules and if they are excrete into the urine this removes base from blood.
Large numbers of H+ ion(metabolic acidosis) are also secreted into tubular
lumen by the tubular epithelial cells, thus removing acid from blood.
“Large numbers of H+ ions is secreted than HCO3-is filtered, there will be a net loss of
acid from the extracellular fluid(Recovery of acidosis). Conversely, if more HCO3-is
filtered than H+ ions is secreted, there will be net loss of base(Recovery of alkalosis)”

35. SointhiswayKidneysMaintainthePhofbloodby
increasingordecreasingtheH+concentrationinthe
bloodbyReabsorptionorsecretionrespectively

37. Kidney maintains blood pressure through
RAAS(RENIN-ANGIOTENSIN ALDOSTERONE
SYSTEM) .
MAINTAINENCE OF BLOOD PRESSURE
RAAS is a hormone system that is involved in the regulation of blood pressure
and plasma sodium concentration.
WHAT IS RAAS?

38. PROCESS/PATHWAY
•When the blood pressure falls cause prorenin cells to split and
release renin.
•Mostrenin enters blood and passes out of the kidney to circulate
throughout of the body
•Reninacts on angiotensinogenand convert intoangiotensin-I has
vasoconstrictor properties but not enough to cause changes in
circulation
•Reninremains in blood for 30 mins

39. •ACE(angiotensin converting enzyme) is an enzyme that is present in the
endothelium walls of the capillaries of lungs.
•ACE converts the angiotensin 1 into angiotensin-II which is extremely
powerful vasoconstrictor
•It stimulates the sympathetic activity, aldosterone secretion and increase
blood volume.

41. RENIN AND ITS ROLE IN RAAS
Renin is protein released by kidneys when arterial pressure
falls low.
Renin is synthesized and stored in an inactive form called
prorenin in the juxtaglomerular cells of the kidneys.
When arterial pressure falls low kidney themselves cause
prorenin molecules to split and release renin.

42. ROLE OF ANGIOTENSIN:
•It is a plasma protein
•Renin acts on angiotensin to release angiotensin-I
•Angiotensin-I has vasoconstricting properties but not
enough to cause changes in circulatory function.
Role of ACE:
•Angiotensin converting enzyme(ACE) is produced by the endothelium walls
of capillaries of Lungs.
•It acts on Angiotensin-l and convert it into Angiotensin-ll,the potent form.

43. Role of Angiotensin-ll:
•It causes the release of Aldosterone from the adrenal glands
•It also stimulates the pituitary gland to release ADH.
ROLE OF ALDOSTERONE:
•Aldosterone function is to cause increase in sodium and water
reabsorption by the kidney tubules.
•To increase the volume of blood

44. So in this way the BP is controlled by the
reabsorption and secretion of water and ions like Na+.

46. ROLE OF KIDNEYS IN THE REGULATION OF WATER AND
ELECTROLYTE BALANCE:
•The kidneys have primary responsibility for regulating the body's water and solute
balance including electrolytes (of Na+, K+, HCO3–and H+) Of the 180 L per day
that are filtered at the glomerulus, about 98 to 99 per cent is reabsorbed throughout
the course of the renal tubule.
•The kidney can produce a concentrated urine or a dilute urine, depending on the
needs of the body.
•Several hormones, notably aldosterone, ADH, PTH, and calcitonin, as well as
vitamin D, are important in the regulation of water and solutes.

47. For the cells of the body to function properly, they must be bathed in extracellular
fluid with a relatively constant concentration of electrolytes and other solutes.
OSMOLARITY:
The total concentration of solutes in the extracellular fluid and therefore the
osmolarity is determined by the amount of solute divided by the volume of the
extracellular fluid.
Thus, to a large extent, extracellular fluid sodium concentration and osmolarity are
regulated by the amount of extracellular water. The body water in turn is controlled by
(1) Fluid intake, which is regulated by factors that determine thirst, and
(2) Renal excretion of water, which is controlled by multiple factors that influence
glomerular filtration and tubular reabsorption
Cont..

48. REGULATION OF WATER:
•For water balance to occur, water intake through ingested liquids and
foods and cellular metabolism must equal water output via sweating,
urine, feces, and breathing.
•Water balance is essential for the body to be properly hydrated, avoiding
both dehydration and over-hydration.
The Kidneys Excrete Excess Water by Forming a Dilute Urine:
•The normal kidney has tremendous capability to vary the relative proportions of
solutes and water in the urine in response to various challenges.
•When there is excess water in the body and body fluid osmolarity is reduced,the
kidney can excrete urine with an osmolarity as low as 50 mOsm/L, a concentration
that is only about one sixth the osmolarity of normal extracellular fluid.

49. •Conversely, when there is a deficit of water and extracellular fluid
osmolarity is high, the kidney can excrete urine with a concentration of
1200 to 1400 mOsm/L.
•Equally important, the kidney can excrete a large volume of dilute urine or
a small volume of concentrated urine without major changes in rates of
excretion of solutes such as sodium and potassium.
•This ability to regulate water excretion independently of solute excretion is
necessary for survival,especiallywhen fluidintake is limited.
Cont..

50. ELECTROLYTE BALANCE:
•The kidneys help regulate the concentrations of plasma electrolytes, sodium, potassium,
chloride, bicarbonate, and phosphate by matching the urinary excretion of these
compounds to the amounts ingested.
•The control of plasma Na+ is important in the regulation of blood volume and pressure;
the control of plasma K+ is required to maintain proper function of cardiac and skeletal
muscles.
ELECTROLYTES:
•Electrolytes are inorganic compounds that dissociate in water to form ions.
•They get their name because they can conduct an electrical current in solution.
•Sodium is the most abundant ion of the extracellular fluid and is the main contributor
to the osmolarity or solute concentration of blood.

52. Severe kidney diseases are divided into two categories:
1-Acute renal failure
2-Chronic renal failure

53. Acute Renal Failure:
•Sudden interruption of kidney function resulting from obstruction,
reduced circulation, or disease of the renal tissue
•Results in retention of toxins, fluids, and end products of metabolism
•Usually reversible decrease in GFR
•May progress to end stage renal disease, uremic syndrome, and death
without treatment
Persons at Risks
•Major surgery
•Major trauma
•Receiving nephrotoxic medications
•Elderly
Medical treatment
•Fluid and dietary restrictions
•Maintain Electrolytes
•May need dialysis to jump start
renal function
•May need to stimulate production
of urine with IV fluids, diuretics, etc.
•Dialysis

54. Causes
Prerenal:
•Hypovolemia, shock, blood loss, embolism, pooling of fluid d/t
ascites or burns, cardiovascular disorders, sepsis
Intrarenal:
•Nephrotoxic agents, infections, ischemia and blockages,
polycystic kidney disease
Postrenal:
•Stones, blood clots, urethral edema from invasive procedures

56. Chronic Renal Failure:
•Results form gradual, progressive loss of renal function
•Occasionally results from rapid progression of acute renal
failure
•Symptoms occur when 75% of function is lost but considered
chronic if 90-95% loss of function
•Dialysis is necessary because toxins produce changes in major
organs

57. Causes:
1-Acute Renal failure
•pre renal causes
•Intra renal causes
•Post renal causes
2-Chronic renal failure
•Hypertension
•Diabetes
•Acute renal failure

58. •Medical treatment
•IV glucose and insulin
•Na bicarbonate, Ca+2,Vit.D, phosphate
binders
•Fluid restriction, diuretics
•Iron supplements, blood, erythropoietin
•High carbs, low protein
•Dialysis -After all other methods have
failed
Chronic Renal Failure Treatment

59. Dialysis
•½ of patients with CRF eventually require dialysis
•Diffuse harmful waste out of body
•Control BP
•Keep safe level of chemicals in body
•2 types
•Hemodialysis
•Peritoneal dialysis

60. 1-Peritoneal dialysis
•Semipermeable membrane
•Catheter inserted through abdominal
wall into peritoneal cavity
•Cost less
•Fewer restrictions
•Can be done at home
•Risk of peritonitis

61. 2-Hemodialysis
Hemodialysis removes wastes and water by
circulating blood outside the body through an external
filter, called a dialyzer, that contains a semipermeable
membrane.
•3-4 times a week
•Takes 2-4 hours

62. Peritoneal DialysisHemodialysis

63. Kidney transplant
A kidney transplant is a surgical procedure to
place a healthy kidney from a live or deceased donor
into a person whose kidneys no longer function properly.
The indication for kidney transplantation
is end-stage renal disease (ESRD),
Indication:

65. A diuretic is any substance that increases the rate of
flow of urine.
Definition:
All diuretics increase the excretion of water from body.
Antidiuretic hormone is antagonist to Diuretics.
Classification:
1.High ceiling/loop diuretics
2.Thiazides diuretics
3.Carbonic anhydrase inhibitors
4.Potassium-sparing diuretics
5.Calcium-sparing diuretics
6.Osmotic diuretics
7.Aldosterone Antagonist
Diuretics are used to treat:
•Heart failure
•Hypertension
•Water poisoning
•Kidney diseases

66. Aldosterone
Antagonist
Osmotic
diuretics