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Review of Normal Renal

Physiology

Syed I. A. Zaidi, Ph.D.


Assistant Professor
Department of Physiology & Biophysics
Phone (202) 806-9867
sizaidi@howard.edu

Review of Normal Renal


Physiology
Anatomy of the excretory system
How the kidney is organized
How the nephron works to filter blood, recycle,
secrete, and excrete
How filtration is regulated
Urination reflex

Kidney Functions: Overview

Homeostatic regulation: ECF volume,


osmolarity, ion & pH balance
Excretion: Metabolic wastes & foreign
molecules
Regulating hormones & enzymes
Blood pressure regulation
Gluconeogenisis
Erythropoises (erythropoitin)
Vitamin D activation (Calcitriol ---- reabsorption
of Ca++)

1.

Regulation of body fluid


osmolarity and volmue

2.

Regulation of electrolyte
balance

3.

Regulation of acid-base
balance

4.

Excretion of metabolic
products

5.

Excretion of foreign
substances (pesticides,
chemicals etc.)

6.

Gluconeogenisis

7.

Blood pressure regulation

8.

Erythropoises
(erythropoitin)

9.

Vitamin D activation
(Calcitriol
reabsorption of Ca++)

Cortical

Juxtaglomerular

Regulation of GFR

Figure 19-9: The juxtaglomerular apparatus

Vesa recta (1%)

Blood flow in kidneys and other organs


Organ

Approx. blood flow


(mg/min/g of tissue)

Kidney

4.00

A-V O2 difference
(ml/L)
12-15
(depends on reabsorption of Na+ )

Heart

0.80

96

Brain

0.50

48

Skeletal muscle (rest)

0.05

Skeletal muscle (max. exercise)

1.00

Filterablility of plasma constituents vs. water


Constituent

Mol. Wt.

Filteration ratio

Urea

60

1.00

Glucose

180

1.00

Inulin

5,500

1.00

Myoglobin

17,000

0.75

Hemoglobin

64,000

0.03

Serum albumin

69,000

0.01

Nephron Functions: Filtration, secretion and excretion

Filtration pressure in the renal corpuscle

GFR 125 ml/min (180L/day)


(about 1% is excreted)

Regulation of GFR
Autoregulation
Myogenic stretch
Tubuloglomerular
feedback
Macula densa
J G cells
ANS-Sympathetic
Arteriole vasoconstriction
Hormones/paracrines
Angiotensin II
Prostaglandins
Catecholamine
Serotonin
Vasopressin

Extrinsic factors
influencing renal flow
Stress
(exercise, cold, heat)
Vasomotor activity
Pyrogens
General anesthesia

Autoregulation of GFR

Myogenic mechanism
eg. Local infusion of cyanide

Urine
(6 ml/min)

Tubuloglomeruar feedback
e.g. response to increased arterial pressure

Vasoconstrictors
Sympathetic nerves
Angiotensin II
Endothelin

Vasodilators
Prostaglandings
(PG1, PG2)
Nitric oxide
Bradykinin

Qualities of agents to measure GFR


Inulin: (Polysaccharide from Dahalia plant)

Freely filterable at glomerulus


Does not bind to plasma proteins
Biologically inert
Non-toxic, neither synthesized nor metabolized in kidney
Neither absorbed nor secreted
Does not alter renal function
Can be accurately quantified

Low concentrations are enough (10-20 mg/100 ml plasma)

Creatinine:
End product of muscle creatine metabolism
Used in clinical setting to measure GFR but less accurate than inulin
method
Small amount secrete from the tubule
High readings because of non-specific chromagens in plasma

Para-aminohippurate (PAH):

An organic anion not present in body


Freely filtered, secreted but not reabsorbed by nephron
Non-toxic, neither synthesized nor metabolized in kidney

Low concentrations are enough (10 mg/100 ml plasma)

Solute Clearance:
Rate of removal from the Blood

Figure 19-16: Inulin clearance

/PAH

Concept of clearance
Qx extracted = Qx excreted
Px . Cx = Ux . V

GFR = Cx =

Where,
Cx = Clearance of substance X (mg/min)
Ux = Urine concentration of X (mg/ml)
Px = Plasma concentration of X (mg/ml)
V = Urine flow rate of X (ml/min)

Ux . V
Px

Effective renal plasma flow =GFR


Effective renal blood flow =

Renal blood flow =

Extraction ratio (0.9) =

ERBF = Cx =

RBF =

ERPF
1 - Hct

Hct=hematocrit

ERBF
Extraction ratio

APAH - VPAH
APAH

APAH = arterial plasma PAH


VPAH = vein plasma PAH

Clearance Ratio of X =

Cx
Cin

Cx < 1 means reabsorption


Cx > 1 means secretion

Net reabsorption rate:


Tx = (GFR . Px) (Ux . V)
Filtration - Excretion

Net secretion rate rate:


Tx = (Ux . V) (GFR . Px)
Excretion - Filtration

GFR = Cx = Clearance of inuline (mg/min)


Ux = Urine concentration of X (mg/ml)
Px = Plasma concentration of X (mg/ml)
V = Urine flow rate of X (ml/min)

Reabsorption:
Passive
Transport &
Trancytosis

Passive reabsorption of urea


in the proximal tubule

Reabsorption: 1 Active
Transport
0

(Passive diffusion in)


Active Transport
Na+ to ECF
K+ into cell
ATP-ase
Uses energy

Na+ ECF peritubular capillaries


Reabsorption blood

Reabsorption: Secondary
Active Transport
Na+ linked 20 transport
Symport
Glucose
Ions
Amino acids

Proximal tubule, key site

Figure 19-12: Sodium-linked glucose reabsorption in the


proximal tubule

Reabsorption: Passive
Transport & Trancytosis
Passive Transport of urea
Na+ pumped out
H2O follows
Passive
[urea]

[urea] higher than ECF


passive diffusion to ECF

Trancytosis of proteins

Reabsorption: Receptors can


Limit
Transport maximum
Saturation (# of receptors)
Competition
Specificity

Renal Threshold
Example: glucosuria

Reabsorption: Receptors can Limit

Figure 19-15: Glucose handling by the nephron

Secretion: From Peritubular


Blood vessels & ECF

Active Transport into nephron tubules


Example: K+ & H+ (more on this next unit)

Secretion: From Peritubular


Blood vessels & ECF

Figure 19-2 : Filtration, reabsorption, secretion, and excretion

Excretion:
All Filtration Products that are not
reabsorbed

Figure 19-5: The filtration fraction

Urination: Micturation reflex


Rugae folds

Detrusor
-Adrenergic
receptors

Hypogastic nerves (L1, L2, L3)


Sympathetic
Pelvic nerve
Visceral afferent pathway

Fundus
Sacral
Parasympatheti
c
(S1, S2, S3)

Skeletal muscle

Sacral
Pudential
nerves
Figure 19-18: The micturition reflex

Formation of Water Pores:


Mechanism of Vasopressin Action

Kidney Hydrogen Ion Balancing: Proximal Tubule

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