Last Minute!

REVISION
RENAL PHYSIOLOGY

DONE BY:
Hadeel Alsulami
Moath Aleisa
Moneerah Aldraihem
Nouf Alharbi
Nouf Almasoud
Reem Labani
Sarah Aljasser
 Lecture 1: Renal Functions and Glomerular Filtration
What are the functions of the kidney?
● Regulation: Water, electrolytes, body fluid osmolarity, ABP and acid-base.
● Excretion : Waste products (urea & Creatinine) and drugs.
● Synthetic : Activation of vit.D, Ertheryopoietin and Renin.
Primary function of the kidney is to CLEAR unneeded substances from blood to be excreted in urine
What is the functional and structural unit of the kidney? THE NEPHRON.
Types of a nephrons:
Cortical (85%) Jusxtramedullary (15%)

Glomeruli in outer cortex Extend to medulla

Short loop of Henle Long loop of Henle

Renal blood vessels: Afferent > Glomeruli (capillaries) > Efferent > Peritubular
(capillaries)
How much from cardiac output goes to the kidneys? 20% (1200 ml/min)
Features of renal circulation: 1) High blood flow 2) Two capillary beds
What are the steps of urine formation?
● Glomerular Filtration
● Tubular Reabsorption
● Tubular Secretion
● Excretion
● Step 1: Glomerular Filtration: Filtration of fluid from glomerular capillaries into renal tubules.
Which need to go through a barrier: Glomerular Membrane, consists of three layers:
● Capillary Endothelium.
● Basement Membrane (-ve charge).
● Bowman’s Epithelium (podocytes).
Glomerular Filtration Rate (GFR): The rate of production of filtrate at the glomeruli from
plasma per minute.
What are the factors determining GFR?
● Net Filtration Pressure (NFP)
● Filtration coefficient (Kf)
Thus GFR can be measured as : GFR = NFP x Kf
Factors Affecting GFR:
↑Increase GFR ↓Decrease GFR

Afferent dilation, Efferent constriction, Afferent constriction, Efferent dilation,

Angiotensin II, fever, hyperglycemia and sympathetic stimulation
High protein diet, (norepinephrine) and aging.
 Lecture 2: Regulation of Glomerular Filtration

Definition of GFR The volume of filtrate produced by both kidneys per min (125 ml/min)

Changes according to According to the ABP -NFP (net force pressure)

Importance of ● To prevent loss of substances if it is high

regulation ● To prevent accumlation of substances (Azotemia develops )

● Autoregulation (within systolic pressure of 75-160 mmHg)

How it is regulated? ● Hormonal regulation
● Sympathetic

! Autoregulation

! Sympathetic Regulation:
When it is stimulated epinephrine cause vasoconstriction of the afferent arteriole
sympathetic also stimulates Angiotensin which acuse vasoconstriction of the efferent
 Lecture 3: Renal Clearance
Clearance is the volume of plasma that is completely
Renal Clearance cleared of a substance each minute
Cx = (Ux X V)/ Px
Cx = renal clearance of a substance
Clearance Equation (Ux X V) = Excretion rate
Ux = urinary concentration of a substance
V = urine volume

1-Measure GFR 2-Measure RPF

•Paraminohippuric acid
•Creatinine (endogenous)
(PAH)
•Inulin (exogenous)
Is rapidly and completely
These substances are freely
secreted by the renal
filtered and NOT reabsorbed
tubular cells.
neither secreted.

3-Determine renal handling

Notes:
of a substance
Importance
•Filtration fraction : It is the
• = inulin clearance; ratio of GFR to renal plasma
Only filtered not reabsorbed flow
or secreted •If excretion rate of a
• < inulin clearance; substance is greater than
Reabsorbed by nephron the filtered load, then the
tubules rate at which it appears in
• > inulin clearance; the urine represents the
Secreted by nephron tubules sum of the rate of
glomerular filtration +
tubular secretion

• TUBULAR TRANSPORT MAXIMUM : molecules such as glucose

and amino acids are reabsorbed via transporters which makes
them susceptible to saturation (TM)
• Exceeding the threshold means some of the nephrons do not
completely reasoned (little glucose in the urine )
• Exceeding the tubular transport maximum means All the
nephrons do not complete glucose abortion (glucose urea )
 Lecture 4: Physiology of Micturation
! Definition:
A complete autonomic spinal reflex to get urine out side the body, that is facilitated or
inhibited by higher brain centers
URINE NEEDS TO GO THROUGH:
o Pelvis: Collect urine from collecting ducts.
o Ureter: Peristaltic contraction.*
o Bladder: Holds urine.
o Urethra: Get urine to the outside.
*Peristaltic waves: are initiated by pacemakers in renal pelvis.
! Interruption of the flow of urine by obstruction (eg: stones) > ↑Pressure (Back up) > to
Pelvis >↑Hydrostatatic pressure of Bowmans’ > Hydronephrosis
! The autonomic pain fibers in ureter accounts for pain in kidney stones.
! How micturation take place?
o ↑ intravesical pressure up to 300 ml > ↑ Bladder tone (stretch receptors in trigone very
sensitive) > Signals get to pelvis nerves > Central S2, S3 & S4 > Parasympathetic:
" Relax the sphincters
" Contract the bladder
o Higher Control:
• Facilitatory area: Pontine.
• Inhibitory area: Midbrain

! Abnormality of micturition:
o Effect of spinal cord transection:
" 1st Stage: Spinal shock:
Unresponsive bladder.
" 2nd Stage:
No voluntary control.
 Lecture 5&6: Tubular Reabsorption & Secretion
! Introduction:
Excreted urine =GF1-TR2+TS3-Water conservation
Transport within tubules occur through:
o Active transport: Movement of substances against gradient.
• 1ary active transport: need ATP e.g Na2+-K+ ATPase &H-K+ ATPase
• 2ary active
● Co-transpor: uses the ATP of 1ary active transport. down gradient of one substance mostly
Na2+ both substances on same direction into the cell> ‫ ﻋﺸﺎ* )ﺪﺧﻞ ﻟﻠﺨﻠ"ﺔ‬.‫)ﻮ‬0‫ﻟﺼﻮ‬2 ‫)ﻌﻨﻲ )ﺘﻤﺼﻠﺢ ﻣﻊ‬
E.g SGLT1/2 & Na2-K+-2Cl.
● Counter-transport: same as co-transport but both substances on different direction
E.g Na2 - H+.
o Passive transport: Novement of substances with gradient.
• Simple diffusion : Cl- & HCO3, urea simple diffusion
• Facilitated diffusion: glucose at basal border by GLUTs
o Osmosis: either through ion channels or pinocytosis/exocytosis water mostly coupled
with Na2+. or paracellular
! Transport through tubules:
o PCT4: “coarse adjustment”
*Reabsorption:
● 65-70% of water and Na2+
● 90% of HCO3 ,Ca2+ ,K+ through passive diffusion
● 100% of glucose and amino acids through Na2+-glucose co-transport /Na2+-amino
acids co-transport.
*Secretion: Organic acids & bases (bile salts,oxalate,urate,catecholamines,some drugs)
• Why most of transport is in PCT?
" Many proteins = transport channels
" Rich in mitochondria→ more receptors /ATP
" Brush border → wider surface area
o Loop of Henle:
• Descending limb: water permeable Na-Cl impermeable 25% of water reabsorbed
• Ascending limb: water impermeable Na-Cl permeable(passive absorption)
• Thick ascending limb: impermeable to water Na2+-K+-2Cl- cotransport
Results in hypo-osmolar filtrates

1
Glomerular filtration
2
Tubular reabsorption
3
Tubular secretion
4
Proximal convoluted tubules
 o Distal convoluted tubules: “fine adjustment” It has 2 portions:
• Early: same as thick ascending but have macula densa cells→ sense change in NaCl.
• Late: here fine adjustment depending on what body needs “ hormonal control”:
" Aldosterone: control reabsorption of NaCl and secret K (in late portion of DCT5 by )
" ADH(vasopressin ):: absorb H2O (in the late portion).
" Parathyroid hormone: absorb Ca2+
Note: impermeable to urea
o Medullary collecting ducts: same as the late DCT but highly permeable to urea.

! RECAP!! Solutes handling:

Solute PCT Loop of Henle DCT Collecting ducts

Thin descending: non Aldosterone present

K+ Passive absorption Thin ascending: passive secretion by principal Same as DCT
Thick ascending :Na-K-2Cl cells

Only absorbed in PCT: HCO3+H+= H2CO3+CA6 =H2O+ {CO2}→Into the cell CO2+H2O +CA=H2CO3→
HCO3
HCO3+H+ into interstitium → vasa recta

Coupled with other Thin descending: non

Aldosterone present
Na+ solutes co-transport Thin ascending: passive Same as DCT
active transport
Thick ascending :Na2-K+-2Cl

Only absorbed in PCT : from tubular lumen to cell through Na-Glucose co-transport. from cell to
Glucose
interstitium GLUTs. 100% if not >375 mg/min

25% thin descending: passive

65% reabsorption Reabsorption
H 2O thin ascending: non Same as DCT
passive with Na Under ADH7 control
thick ascending : non

! Rgulation of tubular reabsorption and secretion :

o Hormonal:
" Aldosterone: Na+ reabsorption and K+ , H+ excretion
" PTH8: ↑ Ca2+ reabsorption and ↓PO4 reabsorption
" ADH: ↑water reabsorption in DCT and collecting tubules
" ANP9: ↑ Na+ secretion and ↑ diuresis
o Nervous:
" Sympathetic: ↑Na+ reabsorption
o Other:
" Atrial pressure (hyprostatic): ↑ in it ↓reabsorption
" Atrial oncotic pressure: ↑ in it ↑ reabsorption.

5
Distal convoluted tubules
6
Carbonic anhydrase
7
Antidiuretic hormone
8
Parathyroid hormone
9
Atrial natriuretic peptide
 Lecture 7: Renal Regulation of Body Fluids
! Fluid Compartment:
● Fluid compartment is approximately 60% of the body weight.
● ICF = ⅔ of TBW
● ECF = ⅓ of TBW
● Plasma = ¼ of ECF
● Interstitial fluid = ¾ of ECF
! ECF :
● Osmolality of ECF is determined by the amount of extracellular NaCl and
water, which depends upon balance between intake and excretion of
these substances.
● Normal plasma Na+ = 140-145 mEq/L
● Osmolarity = 300 mOsm/L
● To stay in a state of fluid balance: Fluid intake = Fluid output
! Control of ECF osmolarity and sodium concentration :
● Is controlled by:
○ osmoreceptor-ADH feedback system
○ Thirst center
● Factors increase the thirst:
○ High osmolarity
○ Low ECF volume
○ Low blood pressure
○ Angiotensin ||
● Gastric distention decrease the sensation of thirst
! Osmoreceptor mechanism:
High ECF osmolarity → Shrinkage of osmoreceptors ( in anterior hypothalamus) → firing and
send signal through supraoptic nuclei to posterior pituitary gland → release of ADH →
enters the bloodstream → increase water reabsorption

● ADH synthesis is happening in supraoptic and paraventricular nuclei of the hypothalamus.

● ADH is released from posterior pituitary gland.

● Non-osmotic stimuli; effect on ADH :

" Low arterial blood volume → increase ADH
" Drinking cooler fluid → decrease ADH
" Hypoxia and hypercapnia → increase ADH

• Ang II & aldosterone don’t have a major role in controlling the osmolarity of ECF.
 Lecture 8: Urine Concentration & Dilution
● Diluting and concentrating mechanisms of the kidney
○ Urine osmolality varies widely in response to changes in water intake.
○ Human urine osmolarity may reach up to 1200 mOsm/L as concentrated
urine and may decrease to 50 mOsm/L as a diluted urine.

● Production of dilute urine:

○ Produced when circulating ADH is low { e.g: water intake, central diabetes
insipidus) or when ADH is ineffective {nephrogenic diabetes insipidus}
○ Mechanism (NO ADH):
■ PCT → Solutes & H2O absorbed in equal proportion (isosmotic with the
plasma)
■ Thick ascending loop of henle and early distal tubule → tubular fluid
diluted due to 1Na-1K-2Cl and impermeable to water even in the
presence of ADH, tubular fluid osmolarity = 100 mOsm/L .
■ Late Distal tubule & collecting tubule → tubular fluid becomes further
diluted due to absence of ADH, tubular fluid osmolarity = 50 mOsm/ L.

● Production of concentrated urine:

○ Two requirements is needed to form a concentrated urine :
" High levels of ADH {water deprivation}
" High osmolarity of the renal medullary interstitial fluid
○ The High osmolarity of the renal medullary interstitial fluid:
" Is established by countercurrent multiplication and urea recycling.
" is maintained by countercurrent exchange in the vasa recta.
○ The major factors creating hyperosmolar medulla:
" Passive reabsorption of NaCl by the thin ascending limb of Henle.
" Reabsorption of Na+,2Cl-,K+ by the thick ascending loop of henle.
" Facilitated diffusion of large amounts of urea from the inner medullary
collecting ducts.
○ Maintenance of hyperosmolar medulla:
■ The medullary blood flow is very small {removal of solutes is minimized}
■ Countercurrent exchange (vasa recta mechanism)

● Any conditions increase medullary blood flow {osmotic diurisis} → decrease urine
concentrating ability.
● Any conditions decrease medullary blood flow {volume depletion} → increase urine
concentrating ability.
 Lecture 9&10: Basics of Acid Base & Buffer Systems
pH↑ = ↓H+ = Alkalosis pH↓ = H↑ = Acidosis
! pH=7.35 - 7.45
o 6.8 - 8 more or less death occurs
o Why important? 1- Enzymes function 2- Effect electrolytes
3- Effect hormones 4- Maintain normal synapse

! Sources of acids? Food, Metabolism of protein and lipid and cellular metabolism.
! Body defense:
o 1st line = Chemical buffer system
" Bicarbonate:
Components: Sodium bicarbonate (NaHco3) and weak acid (carbonic acid)
Acts: in both extracellular(most important) and intracellular.
Concentration in blood =22-27 mEq/L
" Phosphate: Major intracellular
o Why important in renal tubules?
1- Concentrated (low permibility cannot be reabsorbed easily)
2- Pka=6.8 (close to PH in tubular fluid)
" Protein: most abundant (Hb,plasma protein,intracellular protein)

o 2nd line = Physiological buffers

" Respiratory Mechanism
● Only volatile Gas ,not Fixed gases like Lactic acid
● Sense the changes by chemoreceptors
● Central chemoreceptor sense Co2 ,Prepheral sense H2,Co2
● Buffers by hyperventilation > wash Co2 (in acidosis)
● Hypoventilation > accumulates Co2 (in alkalosis)
" Renal mechanism *most effective buffer*
● Action by 3 main process:
1-Reabsorb HCO3
2-Generate new HCO3
3-Excrete H+
● To excrete H+ it has to be buffered:
o Ammonia forming ammonium NH3>NH4
o Phosphate forming di-hydrogen phosphate
● In PCT H+ secreted & New one molecule of HCO3 is formed (doesn’t affect PH)
● In DCT & Collecting tubules gets rid of 80 mEq of H+ per day ,most of H+ combine
with buffers but still it affect urine acidity (and also for each H+ there is New HCO3
formed).
 Lecture 9&10: Basics of Acid Base & Buffer Systems cont.

Reabsorption of HCO3 & secretion of H+ Generation of new HCO3 & secretion of H+

In PCT In DCT & Collecting tubules

Secretion of H+ & Ammonium formation

and Bufffer

Secretion of H+ & Phosphate Buffer

 Lecture 11: Disorders of Acid Base
! What is Respiratory Acidosis?
↑ in PCO2 (above 45 mmHg)
! What are the possible causes ?
- Depression of respiratory centres
- Paralysis of respiratory or chest muscles.
- Emphysema/COPD.
- Pulmonary edema.
! How will the body compensate?
1- Renal: reabsorption & forming new HCO3 (↑ plasma HCO3)
2-Buffers
! What is Respiratory Alkalosis?
An ↓ in PCO2 (below 45 mmHg)
! What are the possible causes?
- Oxygen deficiency at high altitudes.
- »timulate respiratory centres lead to decrease in plasma PCO2(caused by
hyperventilation)
! Compensation:
By renal increased renal excretion of HCO3
! What is Metabolic Acidosis?
↓ in HCO3 (below 22 mEq/L)
! Causes:
- Loss of bicarbonate e.g. severe diarrhea.
- Hypoaldosteronism.
- Accumulation of acids e.g. Diabetic ketosis
! Compensation:
1- Respiratory: By Increased ventilation rate
2-Renal : By adding new HCO3 to the ECF
! Metabolic Alkalosis
↑ in HCO3 (above 27 mEq/L)
! Causes:
- Excess vomiting = loss of stomach acid.
- Excessive use of alkaline drugs.
- Certain diuretics.
- Endocrine disorders: Hyperaldosteronism.
- Severe dehydration
! Compensation:
1- Respiratory: By Decreased ventilation rate, which raises PCO2.
2-Renal: By increasing HCO3 renal excretion
 Lecture 11: Disorders of Acid Base cont.

! Disorders of ADH secretion: