RENAL MODULE

1st MBBS Repeat Campaign - 2019

26TH BATCH – 2015/2016

Faculty of Medical Sciences – University of Sri Jayewardenepura
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1st MBBS Repeat Campaign – 26th Batch

Renal blood flow • Efferent arteriole resistance

Peritubular capillaries = 8mmHg
SEQ – Outline the renal blood supply and explain how renal blood supply is Renal vein = 4mmHg
regulated.

Renal artery
Regional blood flow
interlobar a.
Blood flow Function Oxygen
arcuate a. ml/g of extraction
kidney/min
interlobular a. Renal cortex 5 Filtration of Less ( less
large volumes metabolic
afferent arteriole of blood action)
through the
Glomerular capillary plexus glomeruli
Renal 2.5(outer Maintenance of High ( more
efferent arteriole medulla medulla) osmotic metabolic
0.6(inner gradient in the function,
peritubular plexus of capillaries Vasa recta medulla) medulla vulnerable to
hypoxia)
interlobular v.

Renal v.

• Renal blood flow = 25% of CO

• Determined by using Fick principle
Blood flow = amount of substance taken up by an organ
Arterio-venous difference

Pressure in renal vessels, when mean systemic arterial pressure is

100mmHg

• Afferent arteriole resistance

Glomerular cap.pressure = 45mmHg(40% of systemic p)
Only 1-3mmHg pressure difference across glomerulus
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1st MBBS Repeat Campaign – 26th Batch

Renal nerves Increased Sympathetic stimulation ( norepinephrine )

• Sympathetic - postganglionic efferents

Preganglionic fibers from lower thoracic and upper lumbar
segments of spinal cord
at the highest
renal tubular cells
Cell bodies of post ganglionic fibers in – sympathetic ganglion Beta 1 adrenergic threshold
chain receptors on JG cells
- Superior mesenteric
ganglion
- Along renal artery

Sympathetic fibers to – afferent arteriole , efferent arteriole , PCT , DCT ,

Juxtaglomerular cells , thick ascending limb of loop of henle(noradrenergic) Renin secretion alpha increase Na+
1&2adrenergic reabsorption
Some tonic discharge is seen even at rest
receptors
Systemic sympathetic stimulation – ex. Exercise , rising from
supine position , reduces renal blood f.

renal
• Parasympathetic – very limited, via vagus, uncertain function vasoconstriction
• Nociceptive afferents – thoracic and upper lumbar dorsal roots of (efferent > afferent)
spinal cord

Other renal afferents – mediate a renorenal reflex

RBF
Increase in ureteral P in one kidney leads to
a decrease in efferent nerve activity of the contralateral kidney. This
reduction permits an increase in its excretion of Na+ and water.

GFR
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1st MBBS Repeat Campaign – 26th Batch

Autoregulation of renal blood flow Glomerular capillary membrane and GFR

RBF = 20-25% of CO Filtrate is free of proteins and blood cells, and isotonic to plasma

RBF- determines GFR , modifies solute and water reabsorption , delivers GFR the amount of plasma filtered by all the nephrons of both the kidneys
nutrients to nephron cells per unit time. (125ml/min or 180l/day , lower in women)

RBF is regulated/maintained relatively constant within varying systemic Glomerular capillary membrane 3 layers with negatively charged
blood pressure range (70 and 210mmHg) by varying renal vascular glycoproteins
resistance.
1. Endothelial cells lining the glomerular capillaries(fenestrated)
This ensures that fluid and solute filtration is constant 2. The basement membrane ( no gaps or pores)
3. Podocytes (epithelial cells) of bowman’s capsule
Mechanisms of autoregulation
Restricts filtration on basis of size, electrical charge(albumin negatively
• Myogenic theory – by a direct contractile response to stretch of charged not filtered)
the smooth muscle of the afferent arteriole
• Metabolic theory – NO may also be involved Factors determining GFR
• At low perfusion pressures – angiotensin 2 constrict the efferent
1. The starling forces – hydrostatic pressure difference
arterioles, maintaining the glomerular filtration rate
• Osmotic pressure difference
2. Surface area
3. Permeability
Factors regulating renal blood flow 4. Renal blood flow

1. Norepinephrine – vasoconstriction (interlobular a. and Mechanism of filtration

afferent arterioles most affected)
2. Dopamine(kidney) - renal vasodilation and natriuresis Starling forces
3. Angiotensin 2 – vasoconstriction (efferent arteriole >>
• Hydrostatic p. determined by renal arterial and venous pressures,
afferent arteriole)
and by vasomotor state of afferent and efferent arterioles
4. Prostaglandins – increase flow in renal cortex, reduce flow in
• Oncotic pressure determined by plasma protein concentration
medulla
5. Acetylcholine – vasodilation
1. Driving forces – hydrostatic pressure in glomerular capillary
6. High protein diet – increases RBF
(45mmHg at afferent arteriole, 44mmHg at efferent arteriole)
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1st MBBS Repeat Campaign – 26th Batch

• Oncotic p in bowmans space – 3. Hydrostatic pressure changes in bowman’s capsule – uretral

0mmHg obstruction, oedema of kidney in tight renal capsule
2. Opposing forces - oncotic pressure in glomerular capillary
(-25mmHg at afferent art. , -34 mmHg at efferent art.) Renal clearance is the volume of plasma completely cleared of a substance
by the kidneys per unit time.
• Hydrostatic pressure in bowman’s
capsule (-10mmHg) The rate at which a substance is excreted in the urine – is a measure of
renal function
Net ultrafiltrarion pressure
Renal clearance (C) = urinary excretion rate of substance
Afferent art end = 45+0+(-10)+(-25) = 10mmHg
plasma concentration of substance
Efferent art end = 44+0+(-10)+(-34) = 0 mmHg
CX = UX VCX – clearance of substance “X”
Size of capillary bed can be reduced by contraction of mesengial cells
PXUX – concentration of “X” in urine
Agents regulating mesengial cells
PX– plasma concentration of “X”
Contraction – endothelins, angiotensin 2, vasopressin, norepinephrine,
platelet activating factor, PGF 2, histamine, leukotrienes C and D V –rate of urine formation
Relaxation – ANP, dopamine, PGE2, cyclic AMP 1. Filtered only
C=GFR (inulin)
PHYSIOLOGICAL control of GFR
2. Filtered + reabsorbed
1. Hydrostatic pressure in glomesrularcapillary is higher than in C<GFR (glucose)
systemic capillaries ( due to high vascular resistance of efferent 3. Filtered + secreted
arterioles) C>GFR (PAH)
2. RBF is autoregulated- when BP drops below the range causes fall
Characteristics of a substance used to measure GFR-
in GFR
1. Must be freely filtered across the glomerular capillaries
PATHOLOGICAL conditions affecting GFR
2. Cannot be reabsorbed or secreted by renal tubule nor
1. Oncotic pressure in glomerular capillaries change with plasma metabolized by kidney
protein concentrations – dehydration , hypoproteinaemia 3. When infused cannot alter the GFR
2. Affecting permeability and filtration rate(glomerular ultrafiltration
Amount of inulin filtered by glomerulus = the amount excreted in the urine
coefficient – Kf) – kidney disease
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1st MBBS Repeat Campaign – 26th Batch

Inulin is an ideal glomerular marker Tubular functions

Inulin clearance is a direct measurement of GFR Proximal tubular fluid – isotonic

SUBSTANCES USED TO MEASURE GFR – BUN, serum creatinine and Urine – hypertonic
measurement of creatinine clearance of kidney
Na+ reabsorption
1. Blood urea nitrogen
Varies inversely with GFR (less useful marker)
Rate of urea production is not constant. Rate;
site amount Transporters from Transport
• Increase – high protein diet, tissue
tubular lumen to from tubular
breakdown due to hemorrhage,
tubular cell cell to
trauma, or glucocorticoids interstitiam
• Reduce – low protein diet, Proximal 60%of Co transport with Na+/K+
malnutrition. tubule filtered glucose and amino ATPase
Na+ acids pump
Once BUN is elevated serum creatinine is a better guide to GFR. Na+/H+ exchanger
Thick 30% of Na+/K+/2Cl
2. Serum creatinine – plasma creatinine concentration (PCr) ascending filtered cotransporter
End product of muscle metabolism, solely excreted by kidneys limb of LOH Na+
Production rate proportional to the patients muscle mass thus DCT 7% of Na+/Clcotransporter
relatively stable overtime filtered
Na+
PCr varies inversely with the GFR
Collecting 3% of ENaC channels
Significant renal function is lost before the PCr rises ducts filtered
Na+
3. Creatinine clearance
Is the volume of plasma that is cleared of creatinine by the kidney
per unit of time
CCr= UCrV
PCr
Creatiniteis also secreted by the proximal tubule thus creatinine
clearance overestimates GFR,
Laboratory serum creatinine measurements errors cancel the
overestimation to give values closer to inulin clearance.
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1st MBBS Repeat Campaign – 26th Batch

Glucose reabsorption limb of LOH filtered

water
Usually 100% of filtered glucose is reabsorbed in thePCT by secondary Ascending Impermeabl Top of
active transport (Na+/glucose cotransporter) limb of LOH e to water ascending
limb –
Amount reabsorbed α plasma glucose concentration × GFR hypertonic
DCT hypotonic
This is true only up to the transport maximum for glucose( the maximum Collecting 10% of Acquaporin 2 hypertonic
rate for transport of glucose via Na+/glucose CT) ducts filtered channels (ADH)
water(uppe
When Tm is exceeded glucose will appear in urine r CD)

Renal threshold for glucose is the plasma level at which glucose first
appears in urine in more than normal minute amounts

Endocrine functions of the

Calculated renal threshold – 300mg/dl

Actual renal threshold–180mg/dl of venous blood, corresponds to arterial

level of 200mg/dl
kidney
Water reabsorption

180 l/day of fluid is filtered through the glomeruli

Hormones produced by the kidney
Average daily urine volume 1 l.
1) Erythropoietin
At least 87% of filtered water is reabsorbed 2) 1.25 Dihydroxycholecalciferol
3) Renin
site amount Transporters Basolateral Tonicity of
from tubular membrane tubular
lumen to lumen Erythropoietin
tubular cell ❖ A glycoprotein with a half- life of 5 hrs
(apical) ❖ Produced by –
Proximal 60-70% of Acquaporin-1 Acquaporin- isotonic 1. neonates & adults – Liver
tubule filtered 1
2. adults –
water
Descending 15% of Acquaporin-1 hypertonic 85%- kidney (interstitial cells of peritubularcapillaries )
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1st MBBS Repeat Campaign – 26th Batch

15%- liver ( perivenous hepatocytes –Kupffer cells ) ❖ Excess A11 – up regulates receptors in blood vessels
❖ Actions- Down regulates receptors in adrenal cortex
1. Increase the number of EP sensitive committed stem cells in ❖ Clinical significance of RAS
the bone marrow • Indomethacin – Inhibit PG synthesis , reduce renin
2. Inhibit the apoptosis of RBC • Propranolol – beta adrenergic blocker , reduce renin
3. Increase the development of RBC • Pepstatin – prevent formation of Angiotensin 1 by direct
4. Increase the growth & development of RBC action
Mature RBC appear in 2-3 days • Captopril, enalapril – ACE inhibitors
❖ EP receptor has tyrosine kinase activity • Losartan – selectively block AT1 receptors
• Saralasin – analogue of A11

❖ DeoxyHb stimulates transcription of EP gene

❖ Secretion –
▪ Stimulated by –
▪ Hypoxia
▪ Androgen
▪ Alkalosis
▪ Catecholamines
▪ Adenosine
▪ Cobalt salts
Inhibited by- adenosine antagonist – Theophylline
❖ Inappropriate secretion – polycythaemia rubravera
❖ Decreased secretion - cause anaemia
❖ Treatment – recombinant erythropoietin

Renin
❖ Angiotensin 11 receptors – 2 main types (AT 1 & AT2 )
• AT1A – blood vessels & brain
• AT1B – anterior pituitary
Adrenal cortex
AT2 – more in fetal& neonatal life
 Stimulation of renal
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1st MBBS Repeat Campaign – 26th Batch nerves

Norepinephrine
Preprorenin

ANP
prorenin
B adregenic
receptors on
Angiotensin II
Renin juxtraglomerular
cells
ADH Secretion is inhibited Secretion is
stimulated by

Low plasma K+ level

Prostaglandins

Increase Low Na+ and Cl-

catecholamines entering MD cells of
JGA
Glucocorticoids Increase circulating
levels Baroreceptors of AA
Thyroid hormone
stimulated
Oestrogens
Low arteriole
Cytokines pressure

Hypovoloemia and
hypotension

Angiotensinogen
Angiotensin I

ACE in endothelial cells of lungs

Angiotensin II
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1st MBBS Repeat Campaign – 26 th
Angiotensin
Batch II effects Post
ganglionic
sympatheti
Thirst
c neurons
center
Decrease sensitivity Anterior pituitary Post Pituitary Increase
of baroreceptor Increase
release of
reflex Release ACTH Increase ADH H2O
norepineph
Act on V2 rine
Contraction of receptors
Vasoconstri
mesengial cells
ction Solute free H2O
Decrease surface area absorption
Increase PR
Decrease GFR

Direct effect increase Na+

Adrenal cortex
reabsorption from renal
tubule Aldosterone
Increase ECF Act on P cells of CD
Increase BP Rapid action Slow action

Increase Na+ reabsorption

Increase water reabsorption

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1st MBBS Repeat Campaign – 26th Batch

Role of kidney in ion Na+/cl- enter

macula densa
increased Na+
in the cell
increased
Na+/K+/ ATPase

balance
via Na+/K+/2cl- activity

relaese of ca+
vasoconstiction more
Na + balance of afferent
into vascular
smooth
adenosine
❖ Depends on Na+ intake & excretion arteriole formed
muscles
❖ Excretion mainly regulated by kidneys
❖ Normally 96 – 99% of filtered Na+ is reabsorbed
❖ Urinary Na+ can vary from 1 mEq/d to 400 mEq/d
+
Na excretion is important, decreased GFR
As it is the most abandon cation in ECF & accounts for more than
90% of osmotically active particles in ECF . Thus it is the prime
determinant of ECF volume .
Na+ excretion depends on , Glomerular tubular balance
1. Amount filtered – depends on o The % of solutes reabsorbed is constant when GFR increases
• GFR & factors affecting GFR .solute reabsorption increases along with water .particularly
• Plasma concentration of Na+ prominent with Na+.
2. Amount reabsorbed – depends on o Factors involved are uncertain ,one factor may be :
• Tubular glomerular feedback Oncotic pressure in peritubular capillaries
• Glomerular tubular balance • When the GFR is high, there is a relative increase in
• Adrenocortical hormones oncotic pressure in efferent arteriole.
• ANP • Increase the oncotic pressure in peritubular capillaries –
• Angiotensin , PGE2 increase the reabsorption of Na+ / water from proximal
• Rate of tubular secretion of H+& K+ tubule .
Tubular glomerular feedback
o Maintain the consistency of the load to distal tubule Adrenocortical hormones ,ANP
o When the flow rate in the ascending LOH & distal tubule increases o Increase Na+ reabsorption in the CD in association with
the GFR of same nephron decreases . secretion of H+ or K+
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1st MBBS Repeat Campaign – 26th Batch
aldesterone

acts on P cell
inhibt renin
secretion
reduce
binds to nuclear receptor responsiveness
inhibit ADH
of zona
secretion
glomerulosa to
angiotensin II
alters the transcription of
mRNA

increse the production of direct effect on

ANP increase
proteins that alters the renal tubules to
capillary
cell function increase Na+
permeability
excretion

counteract the
pressor effects
increase GFR of angiotensin
II and
catecholamines
Rapid effects –

• Increase the activity of ENaC by

inserting them to the luminal
The rate of H+ / K+ secretion
surface
• Increase the synthesis of ENaC o When the rate increases ,the rate of Na+ excretion reduces (
• Increase the mRNA that make the 3 by the action of aldosterone )
subunits of ENac o H+ or K+ excretion depends on plasma concentration .
Non genomic actions Other humoral effects
• Increase the activity of Na/K 1) Reduction of dietary intake of Na+ - aldosterone
ATPase 2) PGE2 – cause natriuresis by increasing intracellular ca+&
inhibiting Na+/K+ ATPase thus inhibit Na transport via ENaC
• Increase H+
3) Endothelin& IL-1 – natriuresis by producing PGE2 .
4) ANP & related molecules- increase intracellular cGMP –
inhibit ENaC .
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1st MBBS Repeat Campaign – 26th Batch

5) Endogenously produced ouabain – inhibit Na+/K+ ATPase • Rate of flow in DCT- when flow rate
6) Amiloride – inhibit ENac increases , K+ secretion increases
❖ Prolong exposure to high levels of circulating mineralocorticoids does • K+ intake/ plasma K+- high plasma K+
not cause oedema in healthy people due to escape increase secretion by,
phenomenon. *increasing activity of basolateral Na+/K+
Escape phenomenon ATPase activity
*creates a gradient from interstitium to
o Increase in mineralocorticoids increase ECF volume. When
tubular cells
this pass a certain point there is an increase in Na+ excretion
* by stimulation of aldosterone Na+/K+
in spite the high levels of mineralocorticoids. This is due to
ATPase activity
Atrial Natriuretic peptide (ANP)

Increase permeability of luminal membrane

for K+
K+ balance
3) Amount of Na+ reaching the DCT – with low Na+ ,K+
❖ An increase may cause cardiac arrhythmias & arrest
secretion decrease
❖ About 95% of total body K+ is intracellular
4) H+ secretion – with low H+ secretion , K+ secretion is
❖ Amount taken daily through diet should be excreted in order to
more (H+& K+ compete to be transported with Na+)
maintain balance & to prevent hyperkalaemia
❖ Depends primarily on excretion by kidney since amount excreted via
faeces is only 5-10 %
Renal K+ excretion depends on
Role of kidney in H+
• Filtration
• Reabsorption
balance
• Secretion
➢ Rate of K+ filtration is relatively constant because of auto ❖ Plasma pH = 7.35 – 7.45
regulation mechanism for GFR ❖ Plasma [H+] = 0.00004 meq/L
➢ Reabsorption- 65% in- PCT ❖ Addition of H+ into the body –ingestion of food / drink
20-30% in TAL of LOH – Na+/K+/2cl- Metabolic processes – exercise - lactic acid
Variations to maintain balance in –DCT & cortical part of CD ❖ During metabolism acidic waste products
* Fraction reabsorbed is relativelyconstant
➢ Secretion- by P cells
Volatile non volatile
1) Uptake of K+ by Na+/K+ ATPase from intestitium
2) Passive diffusion into tubules –depends on ( excreted via lungs ) ( mainly excreted via kidney )
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1st MBBS Repeat Campaign – 26th Batch

❖ Factors affecting acid secretion – Fate of H+ ions

• Intra cellular pCO2 • Limiting pH ( maximal H+ gradient ) – 4.5
• K+ ion concentration • Normally reached in collecting ducts
• Carbonic anhydrase level & activity • It is reached rapidly without urinary buffers
• Aldosterone & other adrenocortical hormones • 3 important buffers

1. HCO3-
Acidification of urine ( H+) secretion 2. HPO32-
H ions secreted in the – 3. NH3
➢ PCT
➢ DCT
➢ CD

HCO3-
PCT • Mostly important in the PCT where concentration is greatest ,
• + +
Na / H exchanger (secondary active transport ) carbonic anhydrase on the brush border catalyses formation
• For each H+ secreted , one Na ion & one HCO3- ion enters the of H2CO3
interstitial fluid • H+ + HCO3- H2CO3 CO2 + H2O
2-
HPO4
• Transport of HCO3 across the basolateral membrane is facilitated • This is not a important buffer in ECF , but in tubular fluid
o Na+/ K+ ATPase ,because of high concentration in the DCT & CD brought by
o Cl- / HCO3- exchanger less absorption & high absorption of H2O .
• Most H+ bind with HCO3- as long as they are present
• Hardly any change in pH due to presence of large number of • When HCO3- are not available H+ combines with HPO42-
buffers • HPO42- + H+ H2PO4

DCT/ CD NH3
• Occur in intercalated ‘I’ cells • In renal tubular cells
• Primary active transport – ATP driven proton pump (H+ ATPase ) • Glutamine glutaminase glutamate + NH4+
• Pumps are aldosterone mediated • Glutamate glutamate dehydrogenase
• For each H+ ion secreted one HCO3- reabsorbed alpha – ketoglutarate + NH4+
• Also by K+/ H+ ATPase in ‘p’ cells • NH4+ NH3 + H+
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1st MBBS Repeat Campaign – 26th Batch

• NH3 been lipid soluble diffuse into the tubular urine & react
with H+
Respiratory acidosis ( high Pco2 )
• In chronic acidosis the rate of NH3 production by the kidney
Decreased rate of pulmonary ventilation ( type 2 respiratory failure)
can increase .Therefore in chronic acidosis the dominant
mechanism by which acid is eliminated is excretion of NH3. ➢ Damage to the respiratory centres
• This also provides the most important mechanism of ➢ Decreased ability of lungs to eliminate CO2
generating new HCO3– during chronic acidosis . ➢ Obstruction of the respiratory tract ( defective gas exchange )
➢ The increase in H+ is mainly due to increased Pco2

Regulation of renal tubular

H+ ion secretion
Increase H+ ion secretion & HCO3- reabsorption
• High Pco2
• High H+ , low HCO3-
• Low ECF volume (increase Na+ reabsorption increase H+ sec )
• High angiotensin 11
• High aldosterone (conn’ s syndrome )
• Hypokalaemia

Decreased H+ secretion & HCO3- reabsorption

• Low Pco2
• Low H+ ,high HCO3-
• High ECF volume
• Low angiotensin 11
• Low aldosterone
• Hyperkalaemia
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1st MBBS Repeat Campaign – 26th Batch

➢ The compensatory response is increase in plasma HCO3- by Not enough H+ to react with all HCO3- that is filtered
kidneys . there is also increase in Cl– excretion to maintain electric
neutrality HCO3- excreted in urine

Metabolic acidosis ( Decreased HCO3- ) Metabolic alkalosis (increased HCO3-)

General causes Caused by increased HCO3- or loss of H+

➢ Failure of the kidneys to excrete metabolic acids normally • Vomiting gastric content
formed. • Excess aldosterone
➢ Formation of excess amounts of acids • Ingestion of alkaline drugs
➢ Addition of acids by ingestion or infusion ➢ The primary compensations are decreased ventilation & increased
➢ Loss of bases (HCO3- ) from body renal HCO3-excretion .
Specific causes
➢ Renal tubular acidosis pH [H+] Pco2 [HCO3-]
• Defect in renal secretion of H+ /reabsorption of HCO3- Normal 7.4 40meq/l 40 mm Hg 24 meq/l
• Inadequate amount of titratable acid & NH4+ Respiratory
• H+ retention acidosis
• Causes -chronic renal failure , insufficient aldosterone Respiratory
secretion (Addison ‘s disease ) alkalosis
➢ Diarrhoea Metabolic
➢ Diabetes mellitus ( ketoacidosis ) acidosis
➢ The primary compensation include increases ventilation rates Metabolic
which reduces Pco2& renal compensation by adding new HCO3- to alkalosis
ECF

Respiratory alkalosis ( Decreased Pco2)

➢ Caused by hyperventilation ( high altitude )
➢ The primary compensation is reduced plasma HCO3- by increased
renal excretion
Decreased Pco2

Decreased H+ secretion
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1st MBBS Repeat Campaign – 26th Batch

Concentration and Dilution of Urine • High permeability of thin descending limb to water ( aq-1)
• Active transport of Na+ and Cl- out of thick ascending limb
The ability of the kidney to modify volume and the osmolality of urine • Inflow of tubular fluid from the PCT and outflow into DT
helps to maintain the constancy of volume and the osmolality of ECF. • Impermeability of ascending limb to water

ADH/ Vasopressin LOH-Counter current In juxtamedullary nephrons with longer loops and thin ascending limbs,
multiplier -osmotic gradient is spread over a great distance and the osmolality at the
tip of the loop is greater. (greater the length of LOH greater the osmolality
that ca be reached at the tip of the medulla)
Concentration
and dilution of -thin ascending limb is relatively impermeable to water but permeable to
urine Na+ and Cl- .

Vasarecta – Counter Others – urea, 2.Countercurrent exchanger- passive process

current exchanger osmotic and water
diuresis
Counter current system H2O

Counter current system is a system in which the inflow runs parallel, NaCl,urea
counter, and in close proximity to the outflow for some distance.

Urine concentrating mechanism of LOH and CD depends upon the

maintenance of a gradient of increasing osmolality along the medullary
pyramids.

This gradient is produced by LOH as countercurrent multiplier and

maintained by vasa recta as countercurrent exchanger.

1.Counter current multiplier - active process

-solutes diffuse out of the ascending vessels and into the vessels
Depends on descending into the pyramid
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1st MBBS Repeat Campaign – 26th Batch

-water diffuses out of the descending vessels and into the ascending
vessels.
• Vasopressin has a vasoconstrictor action. It acts via V1A receptors
Solutes tend to recirculate in the medulla and water tends to bypass it on vascular smooth muscle. It helps to maintain BP in
and medullary hypertonicity is maintained. haemorrhage.

As the flow rate reduces, osmotic gradient increases. ADH secretion is stimulated by,

Therefore it is more efficient at lower rates of flow. • Increased plasma tonicity – detected by osmoreceptors in
hypothalamus
3.Role of Urea
• Decreased ECF volume – detected by low pressure receptors (
Urea contributes to renal medullary interstitium when the kidney is great veins , right and left atria , pulmonary vessels )
forming concentrated urine. • Decreased arterial pressure detected by baroreceptors.

• Urea transporters ( UT ) in the CD are regulated by ADH. ADH increased ADH Decreased
Increased plasma osmotic pressure Decreased plasma osmotic pressure
When ADH is high the amount of urea deposited in medullary interstitum Decreased ECF volume Increased ECF Volume
increases, increasing the concentrating capacity of kidney. Pain, emotion, stress, exercise Alcohol
Nausea and vomiting
Amount of urea filtered varies with the dietary intake of protein. Standing
Therefore, a high protein diet increases the ability of kidneys to Clofibrate , carbamazepine
Angiotensin II
concentrate urine.

4.ADH

Is a peptide hormone synthesized in the hypothalamus and is secreted by

posterior pituitary.

It acts on the V2 receptors of CD and increases the permeability to water.

Increases the number of aquaporin – 2 channels on the apical membrane

of principal cells.

Retention of water in excess of solutes.

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1st MBBS Repeat Campaign – 26th Batch

2. Diabetes insipidus

Defense of ECF Tonicity -syndrome due to vasopressin deficiency (central diabetes insipidus eg:
hypothalamus, posterior pituitary disorder ) or
Increased osmolality of ECF
- when kidneys fail to respond to the hormone ( nephrogenic diabetes
insipidus eg : mutations in V2 receptor or aq- 2 channels )
Thirst increased ADH secretion - results in polyuria ( passage of large amounts of dilute urine ) and
polydipsia ( drinking large amounts of fluid)

Increased water intake water retention Mechanisms of Diuresis

Diuresis is an increase in the production of urine by the kidneys.

Dilution of ECF 2 types.

1. Water dieresis
2. Osmotic dieresis
Abnormalities in ADH secretion
1. Water Diuresis
1. Syndrome of inappropriate ADH secretion
Produced by drinking large amounts of hypotonic fluid begins about 15 min
When ADH is inappropriately high relative to serum osmolality after ingestion of a water load and reaches its maximum in about 40 min.

Causes water retention in excess of solutes resulting in increased ECF The act of drinking produces a small decrease in ADH secretion before
Volume and dilutional hyponatremia. water is absorbed but most of the inhibition is produced by the decrease in
plasma osmolality after water is absorbed.
Causes salt loss in urine due to inhibition of RAA mechanism ( renin
secretion is inhibited by ADH ) Absorption of water by GIT

-Seen in cerebral causes ( tumors) and pulmonary ( lung cancers ) Hypervoleamia and drop in osmolality

Sensed by osmoreceptors in hypothalamus

Inhibition of ADH secretion

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1st MBBS Repeat Campaign – 26th Batch

Reduced water reabsorption via aquaporin – II channels in the CD Diuretic – is a substance that increases the rate of urine volume output.

2.Osmotic dieresis Agent Mechanism of action

Water Inhibits ADH secretion
Results from non reabsorbable osmotically active substance in the lumen Ethanol Inhibits ADH secretion
of renal tubules. Large amounts of osmotically active Osmotic diuresis
substances eg : Glucose , Mannitol
Eg : Mannitol , Glucose ( when renal threshold is exceeded ) Loop diuretics eg : Furosemide , Inhibit the Na+/ K+ / 2Cl- pump in the
Ethcarynic acid thick ascending limb of loop of
The osmotic pressure of these solutes greatly reduces water reabsorption henle.
and hold water in tubules Thiazide diuretics eg : Inhibits Na+ / Cl- co transporter in
chlorothiazide early distal tubule.
[Na+] in tubules is lowered K+ retaining diuretics Inhibits Na+ K+ exchange in CD.
eg : spironolactone Inhibits action of aldosterone
amiloride Inhibits action of ENaC

Limiting concentration gradient for Na+ is reached

Carbonic anhydrase inhibitors eg : Reduce H+ secretion therefore
Further proximal tubular Na+ reabsorption is prevented Acetazolamide increase Na+ and K+ excretion
Xanthenes eg : caffeine , Decrease tubular reabsorption of
More Na+ remains in the tubule with water theophylline Na+
Antagonists of V2 receptor eg : Inhibits the action of ADH on CD
In the loop of Henle, astolvaptan
Reabsorption of Na+ and water is decreased because medullary
hypertonicity is decreased secondary to decreased reabsorption of Na+ , K+
, and Cl- in the ascending loop.

More fluid passes through the distal tubule.

Decreased osmotic gradient along medullary pyramids therefore less water

is reabsorbed in collecting ducts.

• In water diuresis , amount of water reabsorbed in PT of nephron

is normal.
• In osmotic diuresis , amount of water reabsorbed mainly in PCT
and LOH is decreased so very large urine flow can be produced.
 20
1st MBBS Repeat Campaign – 26th Batch

Excretion of protein in urine because of increased glomerular permeability.

Any condition that increases increased permeability will lead to nephrotic
syndrome.

Abnormal Kidney Functions Characterized by,

Functions of the kidney : • Edema

• Heavy proteinuria
• Waste removal ( urea , creatinine )
• Hypoalbuminemia
• Fluid balance
• Hyperlipidemia
• Electrolyte balance
• Acid base balance Pathophysiology
• Hormone production ( erythropoietin , calcitriol)
Structural damage to glomerular basement membrane ( effacement of
Loss of structure / function of the nephron podocyte foot processes , slit diaphragm disruption , relative or absolute
depletion of podocytes )

Increase number and size of pores

Disordered renal function
Loss of negative charge on glomerular capillary membrane
Pathological classification
Filtration of protein molecules

Proteinuria

Edema
Vessels – renal Glomerular - Tubular – Interstitial –
glomerulonep acute pyelonephritis 2 theories :
artery stenosis ,
hritis tubular
venous
1. Overfill theory : primary tubular defect causing sodium retention
thrombosis necrosis
2. Underfill theory : proteinuria causing Hypoalbuminemia

Mainly in the face due to the laxity of subcutaneous tissue.

Clinical Syndromes : Complications :
1. Nephrotic syndrome
• Negative nitrogen balance
 21
1st MBBS Repeat Campaign – 26th Batch

• Thrombosis
• Dyslipidemia
Principles of treatment :
• Infections
• High cardiovascular risk ✓ Management of edema – diuretics , proteinuria reduction ,
• Acute kidney injury ( pre renal AKI) albumin
1. Negative nitrogen balance ✓ Treatment of complications – statins for Hyperlipidemia ,
• Tubular catabolism of filtered proteins and increased anticoagulators for hypercoagulation , vaccinations for infection
urinary protein loss. ✓ Disease specific therapy
2. Coagulation abnormalities
• Increased hepatic synthesis of coagulation proteins due
to increased loss
• Increased loss via urine
2.Acute kidney injury
• Volume contraction / hemoconcentration A clinical syndrome characterized by sudden impairment of kidney
• Increased platelet aggregability function over hours to days resulting in ,
• Immobility
• Hyperlipidemia causing atherogenesis • Failure of kidney to excrete nitrogenous waste products
3. Hyperlipidemia • Disturbance in fluid and electrolyte imbalance
• Increased hepatic synthesis of albumin due to • Disturbance in acid base homeostasis
Hypoalbuminemia accompanied with increased synthesis
of LDL , VLDL. Acute renal failure
• Defective peripheral lipoprotein lipase activity –
increased VLDL
• Urinary loss of HDL – excess cholesterol cannot be Pre renal Renal Post renal
removed.
4. Infections • Left • Vascular • Ureteric
• Large fluid collections – bacteria can grow easily ventricular disorder calculi /
• Nephrotic skin is fragile – creating sites of entry failure • Glomerulo strictures
• Oedema – dilute local humoral immune factors • Blood loss nephritis • Bladder
• Loss of IgG anf complement factors in urine – impairs • Renal • Interstitial neck
host’s ability to eliminate organisms artery nephritis obstructio
• Loss of Zinc and Transferrin in urine – required for stenosis • Tubular n
normal lymphocyte function necrosis • Enlarged
prostate
• Urethral
strictures
 22
1st MBBS Repeat Campaign – 26th Batch

Indices Pre renal Renal GFR < 60 ml/ min / 1.73 m2 for more than 3 months.
Specific gravity High ( > 1.020 ) Normal ( 1.010 )
Urine osmolality High Low 50% of the nephrons can be lost without much biochemical
UNa+ Low High derangement due to high functional reserve.
Fractional excretion of Low High
sodium Symptoms appear when > 75% nephrons are damaged.

Staging of CKD
Features :
Stage Description GFR
• Oliguria / anuria 1 Kidney damage with normal or >= 90
increased GFR
• Reduced urine flow rate
2 Kidney damage with mildly 60-89
• Uremia decreased GFR
3 Moderately decreased GFR 30-59
Complications :
4 severely decreased GFR 15-29
5 kidney failure Less than 15
• Sodium retention – oedema , pulmonary oedema , hypertension
• Hyperkalemia
• Metabolic acidosis Pathophysiology :

1. Initial damage to kidney

2. Maladaptation of kidney to initial damage
Principles of treatment :

✓ Treat the cause – pre renal , renal , post renal Damage to kidney
✓ Manage complications – hyperkalemia ( increase potassium
uptake by cells and facilitate its removal from body ) , acidosis
✓ Renal replacement therapy
✓ Stabilization of myocardium Vascular : Glomerular Tubules : Interstitium
: : toxins ,
Diabetes, Autoimmun Toxins, drugs
3. Chronic kidney disease
hypertensio e ,diabetes drugs, cysts
Progressive loss of functioning nephrons with evidence of kidney n
damage or
Features :
 23
1st MBBS Repeat Campaign – 26th Batch

• Oedema
• Hypertension 2) Anemia
• Elevated JVP 1. Reduced production
• Pulmonary oedema ✓ Malnutrition ( Fe, B12, folate )
• Normochromic normocytic anemia ✓ Inflammation – increased hepcidin ( reduced iron
• Low calcium , elevated phosphorous , and PTH absorption , trap iron within macrophages )
✓ Reduced erythropoietin production
Complications : ✓ Bone marrow suppression
2. Increased destruction
• Hematological anemia , thrombasthenia , thrombocytopaenia , ✓ Reduced red cell survival
bleeding 3. Increased loss
• Mineral bone disease ✓ Blood loss – thrombasthenia / thrombocytopenia , GI
• Cardiovascular – hypertension , heart failure bleeding , hematuria
• Neurological 3) Mineral bone disease ( renal osteodystrophy )
• Metabolic : acidosis , hyperkalemia , hyponatremia • Osteomalacia - softening of bones due to deficiency of protein
• Reproductive : hypogonadism , subfertility matrix
• Osteoporosis – total reduction of bone mass due to both mineral
and protein reduction
Physiological basis for complications : • Osteosclerosis – abnormal thickening of bone
• Ostetitis fibrosa cystica – increased osteoclastic activity , cyst
1) Polyuria and nocturia formation , bone marrow fibrosis
• Adynamic bone disease – both bone formation and resorption are
depressed
Loss of urine concentrating and diluting ability (concentrating mechanism
affected more than diluting mechanism )
Chronic kidney disease
Increase in urine volume and osmolality reduces
Reduce 1alpha hydroxylase activity
• Isosthenuria – urine specific gravity fixed at that of glomerular
filtrate ( 1.010) Reduced production and activity of calcitriol ( 1,25
Increased blood flow through functioning nephrons dihydroxycholecalciferol )

GFR of functioning nephrons increase by 50 - 100%

 24
1st MBBS Repeat Campaign – 26th Batch

Reduced plasma calcium ✓

ANS – impaired baroreceptor sensitivity ,
increased circulating catecholamines
Increased secretion of PTH 6) Reproductive system
✓ Males – impotence , infertility , loss of libido ,
Increased levels of PTH in blood ( secondary hyperparathyroidism) galactorrhea
✓ Females – oligomenorrhea . amenorrhea (
Increased osteoclastic activity absence of cyclical secretion of LH and FSH )

Reduction in bone mass Renal replacement therapy

1. Dialysis
Osteoporosis
Hemodialysis
Long standing secondary hyperparathyroidism
Peritoneal dialysis
2. Renal transplantation
Hyperplasia of parathyroid glands

IIIry hyperparathyroidism Micturition

Increased calcium levels in blood It is a spinal reflex facilitated and inhibited by higher centres in brain like
defecation . It is a two part cycle.
Increased bone density
1. Storage / filling phase
Osteosclerosis 2. Emptying phase
Alternative bands of porotic and sclerotic areas in bones – rugger
Reflex is uninhibited at birth , control is learnt as we mature.
jersey appearance
4) Cardiovascular –
✓ Hypertension – due to fluid and sodium overload Pelvic nerves Sympathetic –
✓ Arrhythmia \ S2,3,4 L1,2,3 inferior
hypogastric
✓ Left ventricular failure – hypertension , fluid parasympath
etic nerves
overload
✓ Pericardial effusion
5) Nervous system
✓ CNS – uremic encephalopathy , depression Bladder
Pudendal
✓ PNS – peripheral neuropathy
nerves S2,3,4
 25
1st MBBS Repeat Campaign – 26th Batch

Sympathetic nerves to bladder play no part in micturition but in males

they mediate the contraction of bladder muscle preventing the entry of
External sphincter semen into bladder during ejaculation.

Filling phase

Regular peristaltic contractions occurring one to five times per minute Stimulus – stretch in Afferents – Parasympathetic
move urine from renal pelvis to bladder. bladder fibers of pelvic nerves

Bladder has plasticity ; when it is stretched the tension initially produced is

not maintained .
Integration centre – sacral
pressure segments S2 3 4 of spinal cord

Efferents – To the higher centers

volume
parasympathetic fibers of
150 400 pelvic nerves facilitation inhibition

First urge to void is felt at 150 ml.

Effector – contraction of Facilitatory Inhibitory
A marked sense of fullness is felt at 400 ml. The flatness is due to law of detrusor muscle area – pons , area –
laplace. posterior midbrain
hypothalamus
P = 2T /R
External
- +
sphincter
The tension increases as organ fills but so does radius. Therefore the
relaxation
pressure increase is slight until the bladder is relatively full. Pudendal Nerve

Emptying phase

Contraction of the detrusor muscle is mainly responsible for emptying of +

bladder during micturition.
External sphincter
contraction

MICTURITION
 26
1st MBBS Repeat Campaign – 26th Batch

Effects of spinal cord transection further subdivides until 12 or more generations of tubules are
formed.
• Spinal shock – bladder is flaccid and unresponsive. It becomes ⬧ Tubules of 2nd order enlarge & absorb those of 3rd&4th orders
overfilled and urine dribbles through sphincter. (overflow forming minor calyces.
incontinence ) ⬧ Collecting tubules of 5th& successive generations elongate &
converge on the minor calyx forming renal pyramids,
• After spinal shock – voiding reflex returns. No voluntary control ,
⬧ Excretory system is formed from the metanephric tissue cap
no inhibition or facilitation from higher centers. Paraplegic which covers each of the newly formed collecting tubules.
patients train themselves to initiate voiding by pinching or ⬧ Under the inductive influence of the tubule, cells of the tissue cap
stroking the thigh, provoking a mass reflex. Bladder capacity is form small vesicles, which in turn give rise to small s- shaped
reduced as it becomes hypertrophied and is called a spastic tubules.
neurogenic bladder. ⬧ One end is deeply indented by a glomerulus & the proximal end of
the nephron forms the Bowman’s capsule, while the distal end
Renal Embryology forms an open connection with one of the collecting tubules.
⬧ Continuous lengthening of excretory tubule results in the
01. Briefly describe the development of kidneys.
formation of PCT, LOH & DCT.
⬧ At birth the kidneys have a lobulated appearance, but lobulations
⬧ Urinary system develops from the intermediate mesoderm and
disappear during infancy, with further growth of nephrons,
forms a series of overlapping urinary systems, 1. Pronephros
although there is no increase in no. after birth.
2. Mesonephros
⬧ Kidneys initially lie in the pelvic region, later shifts to a more
3. Metanephros
cranial position in the abdomen due to 1. diminution of body
Pronephros
curvature
⬧ Non- functional and rudimentary formed and disappear
2. Growth in lumbo-sacral region
completely within the 4th week
⬧ In the pelvis, metanephros receive its arterial supply from a pelvic
branch of aorta. During its ascent, it’s vascularized by branches
Mesonepros
originating at higher levels.
⬧ Formed in the 4th week
⬧ Finally when the true renal artery originates at L2 level, others
⬧ Disappear completely in females but caudal excretory tubules &
degenerate.
mesonephric duct persists in males forming the genital system.
⬧ Hilum of the kidney at first faces anteriorly, then gradually rotates
to face medially.
Metanephros
⬧ Definitive kidneys become functional near the 12th week, but are
⬧ Appear in the 5th week and form the permanent kidneys.
not responsible for excretion during fetal life.
⬧ Collecting ducts from ureteric buds, an outgrowth from
⬧ ANOMALIES
mesonephric duct close to its entrance to the cloaca.
1. Agenesis, hypoplasia, hyperplasia
⬧ Bud penetrates the metanephric tissues,which is molded over its
distal end as a cap. 2. Duplication of kidneys
⬧ Subsequently, the bud dilates, forming the primitive renal pelvis & 3. Anomalies of shape – horse shoe kidney, lobulated kidney,
splits into 2 or 3 portions representing major calyces,which pancake kidney
 27
1st MBBS Repeat Campaign – 26th Batch

4. Anomalies in position-pelvis kidneys ⬧ Initially, the mucosa of trigone of the bladder (formed by
5. Abnormal rotation incorporation of mesonephric ducts) is mesodermal in origin. It’s
6. Congenital polycystic kidney later replaced by endodermal epithelium and bladder is
completely lined by endodermal epithelium.
7. Aberrant renal arteries
⬧ Epithelium of urethra is endodermal while surrounding
connective and smooth muscle tissue is derived from visceral
Kidneys develop from 2 sources mesoderm.
1. Excretory units from metanephric mesoderm
2. Collecting system from ureteric bud

02. Write a short note on the embryological basis of horse-shoe kidney

(Refer madam’s book page)
⬧ ANOMALIES
1. Urachal fistula – due to persistence of the lumen of intra-
03. Describe the embryological development of bladder and urethra. embryonic part of allantois, urine drains from the umbilicus
⬧ Urinary bladder develops from 3 sources, 2. Urachal cyst – cystic dialationdue to persistence of local area of
1. Endoderm of vesico-urethral part of urogenital sinus- bladder allantois
epithelium 3. Urachal sinus – persistence of lumen of upper part of the allantois
2. Surrounding mesenchyme – muscles and connective tissue that is continuous with urinary bladder.
3. Mesonephric duct – trigone of bladder 4. Exstrophy of the bladder – Exposure of bladder mucosa due to a
⬧ During the 4th to 7th week of development cloaca divides into ventral body wall defect (failure of lateral body wall folds to close
anterior urogenital sinus and posterior anal canal with urorectal in the midline in the pelvic region)
septum in-between.
⬧ Urogenital sinus comprises of 3 parts, 1. Upper part - forms the
bladder
2. Pelvic part - forms prostatic &
membranous parts of urethra.
3. Phallic part
⬧ Initially the bladder is continuous with allantois, which then
obliterates forming the urachus.
⬧ Caudal portion of mesonephric ducts are absorbed into the wall of
urinary bladder, therefore ureters , which were outgrowths of the 04. Describe the embryological development of the ureter.
mesonephric ducts, now enter the bladder separately ⬧ Ureters develop from the ureteric bud, which is an outgrowth
⬧ As a result of the ascent of the kidneys, ureteric orifices move from the mesonephric duct, close to its entrance to the cloaca
further cranially and those of mesonephric ducts move close ⬧ Caudal portion of mesonephric ducts are absorbed into the wall of
together to enter the prostatic urethra, forming ejaculatory ducts urinary bladder, and ureter now enters the bladder separately
in males.
 28
1st MBBS Repeat Campaign – 26th Batch

⬧ As a result of the ascent of the kidneys, ureteric orifices move Polycystic kidney diseaseis a genetic disorder in which the renal tubules
further cranially and those of mesonephric ducts move close become structurally abnormal, resulting in the development and growth of
together to enter the prostatic urethra, forming ejaculatory ducts multiple cysts within the kidney.
in males. There are two types of PKD: autosomal dominant PKD and autosomal
recessive PKD.
Ureteric bud gives rise to This occur due to failure of collecting tubules and duct system during the
1. Ureter development
2. Renal pelvis
3. Major&minor calyces
4. Collecting tubules
RENAL ANATOMY
01. Describe the position of kidneys.
⬧ ANOMALIES ⬧ Kidneys are located in the posterior abdominal wall, behind the
1. Duplication of the ureter – partial complete splitting of peritoneum, largely under cover of the costal margin.
ureteric bud ⬧ Kidneys are in the upper part of the paravertebral gutters, tilted
2. Ectopic ureter- due to the development of 2 ureteric buds on against the structures at vertebral levels T11- L3 with its long axis
each side, while one ureter opens to the bladder, other opens parallel to the lateral border of psoas major muscle.
to vagina, urethra or vestibule ⬧ Therefore the anterior surface facesanterolateral and posterior
surface posteromedial and its superior extremity is medial to the
inferior extremity.
⬧ Due to the right lobe of the liver, right kidney lies at a lower
position than the left kidney. Superior extremity of the right
kidney overlies the 11th intercostal space & 12th rib while in the
left, it overlies 11th rib.
⬧ Hila of the kidneys lie at the trans pyloric plane, at the level ofL1
vertebrae, 5cm from the midline facing forwards and medially,
with the right just below the plane and left just above it.

02. Describe the arrangement of the coverings of the kidneys.

⬧ Kidney is covered by several tissue layers for protection.
1. Dense fibrous capsule
2. Perinephric fat
3. Renal fascia
4. Para renal fat
Capsule
⬧ Dense fibrous capsule closely invests the kidneys.
05. Describe the embryological basis of polycystic kidney. ⬧ Passes through the hilum and lines the renal sinus, becoming
continuous with the pelvi-calyceal system
 29
1st MBBS Repeat Campaign – 26th Batch

⬧ Normally this can be readily stripped, but when inflamed it gets ⬧ Bladder is relatively free in the surrounding loose extra-peritoneal
adhered to the kidneys firmly tissue except at its neck, which is held by pubo-prostatic or
Perinephric fat pubovesical ligaments, free to expand superiorly in the extra-
⬧ Consist of adipose tissue that fills the space between the capsule peritoneal tissue.
and renal fascia ⬧ Muscularis propria consist of thick smooth muscle bundle
⬧ Its thickest at the borders of the kidney and fills up the extra ⬧ Mucosa and submucosa are loosely adhered to underlying muscle
space in the renal fascia layer and are thrown into folds when the bladder is empty. It
⬧ This plays a role in retaining the kidney in position. Therefore stretches to expand when urine fills.
following severe weight loss, nephroptosis (floating kidney) may ⬧ Bladder is lined with transitional epithelium (urothelium). So the
develop, causing descent of kidneys to a lower level resulting in bladder capable of stretching and resists the acidity of urine. Tight
kinking of ureters obstructing urine flow. junctions between the adjacent cells prevent urine passing in to
Renal fascia the underlying tissues.
⬧ Fibro-areolar sheath surrounding the perirenal fat ⬧ Plasticity of smooth muscles of the bladder enables it to expand
⬧ It has an anterior and a posterior layer with numerous trabeculae without increasing the pressure inside the bladder. Therefore, the
connecting the renal fascia and fibrous capsule across the desire to empty the bladder occurs only when the bladder is filled
perirenal fat to an appreciable amount.
⬧ This is continuous laterally with the transversalis fascia and Emptying
medially at the hilum, fascia is attached to the renal vessels and ⬧ Bladder has 3 muscle layers which contract maximally to empty
ureter. urine.
⬧ Superiorly two layers enclose the supra-renal glands in a ⬧ The muscles of the bladder run radially in the region in which it
compartment separated by a fascial septum and then fuse with opens to the urethra, this act as an involuntary sphincter.
each other. ⬧ Stretch receptors have a good innervation giving the desire to
⬧ Inferiorly, the 2 layers may remain separated or loosely united urinate when the bladder is adequately full
enclosing the ureter. Anterior layer merges with extra-peritoneal ⬧ Intra-vesical part of ureter runs obliquely in the posterolateral
connective tissue of the iliac fossa and posterior layer blends with wall of the bladder. During contraction of the bladder, this
iliac fascia. prevents reflux of urine in to the ureter.
Para renal fat
⬧ Accumulation of extra-peritoneal fat between the peritoneum 04. Discuss the normal blood supply and lymph drainage of urinary
and the renal fascia forms a cushion for the kidney. bladder
⬧ Bladder is a hollow muscular organ that functions to store and
03. Describe the structural and functional adaptations of the bladder for empty urine.
storage and emptying of urine. ⬧ Blood supply and lymphatic drainage of bladder is of utmost
Bladder has microscopic and macroscopic features which enabling its clinical importance due to its involvement in spread of carcinoma.
maximum functioning, ⬧ Bladder receives it arterial supply mostly from superior and
Storage inferior vesical arteries of internal iliac artery. It also receives
⬧ Bladder has a storage capacity up to 400ml. small contributions from obturator, inferior gluteal, uterine and
vaginal arteries.
 30
1st MBBS Repeat Campaign – 26th Batch

⬧ Veins of the bladder do not follow arteries. They form a plexus 06. Discuss the normal neural innervation of the urinary bladder
that converges on the vesicoprostatic plexus in the groove ⬧ Normal filling and emptying of the bladder are probably
between bladder and prostate gland. It drains back across the controlled exclusively by its parasympathetic innervation.
pelvic floor to the internal iliac veins. There is a similar plexus in ⬧ Efferent parasympathetic fibers from S2 to S4 via pelvic
females. splanchnic nerves accompany the vesical arteries to the bladder.
⬧ Lymphatics of the bladder drain alongside the vesical blood They convey motor fibers to the muscles of the bladder wall and
vessels mainly to the external iliac nodes. Some drain to internal inhibitory fibers to its internal sphincter.
iliac nodes including nodes in the obturator fossa. ⬧ Sympathetic efferents from L1 to L2 via the superior and inferior
hypogastric plexus are inhibitory to the bladder detrusor muscles
05. Describe the surrounding anatomical structures that are related to and motor to its sphincters & trigonal muscles although they may
the bladder which can be affected by spread of bladder carcinoma be mainly vasomotor in function.
There are 3 major methods for the metastatic spread of bladder carcinoma ⬧ External sphincter is made of striated muscles and supplied by the
1. Direct spread pudendal nerve. (S2, 3, 4)
2. Lymphatic spread ⬧ Sensory fibers from the bladder are conveyed in both sympathetic
3. Blood spread and parasympathetic nerves, but the parasympathetic pathway is
Direct spread the most important.
⬧ This may metastasize to surrounding structures of the 08. What are the extensions of the extravasated spread of urine
bladder, following the
▪ Anteriorly- pubic symphysis and retro pubic fat A) Rupture of urethra above the inferior fascia of the external urethral
▪ Posteriorly – rectum, termination of vas sphincter
deferens and seminal vesicles in males B) Rupture of the urethra below the inferior fascia of the external
-vagina and supravaginal part of urethral sphincter
cervix in (Refer madam‘s book)
females.
▪ Superiorly- Coils of small intestine and sigmoid
colon.
-Body of uterus in female
▪ Laterally – levator ani and obturator internus
▪ In males, neck of bladder fuses with prostate
gland.
Lymphatic spread
⬧ This metastasizes to structures draining in to internal and external
iliac nodes

Blood spread
⬧ This metastasizes to structures supplied by internal iliac arteries.
 31
1st MBBS Repeat Campaign – 26th Batch

Tissue layers through which the suprapubic catheter is inserted in the Importance of knowing the drainage area of particular group of lymph
order of penetration. nodes,

Suprapubic catheter (SPC) is a device inserted into the bladder if you can’t Spread of infections
urinate on your own.
Spread, Staging and prognosis of malignant tumors
Normally a catheter is inserted into the bladder via the urethra but SPC is
used when urethra or genitals aredamaged and can’t hold a catheter and Could be determined.
SPC has a low risk of getting infected.
Main lymph drainage of the bladder is to the External Iliac lymph node.
SPC is inserted 2 finger breaths above the pubic symphysis at midline.
Some parts drain to the Internal iliac lymph nodes and nodes of obturator
As the bladder gets filled, bladder goes in between peritoneum and fossa.
anterior abdominal wall therefore the tissue layers through which catheter
is inserted in order from superficial to deep are,
Anatomy of male urethra and anatomical significances which should be
Skin
taken into consideration when performing urethral catheterization.
Camper’s fascia (Superficial fascia)
3 parts- Prostatic , Membranous, Spongy (Penile)
Scarpa’s fascia (Membranous fascia)
Total length= 20cm
Linea alba
Prostatic (3-4cm)
Transversalis fascia
Widest and most Dilatable
This procedure will never pierce the peritoneum as the filled bladder
Runs downwards and backwards from internal meatus
comes up superficial to the peritoneum.
Passes through the substance of prostate
Rectus abdominis and pyramidalis muscles are retracted apart in order to
avoid piercing. Then bends at the middle of its length and continues downwards and
forwards.

Therefore the urethra lies closer to the anterior surface of the prostate
Lymph drainage of the bladder
gland.
 32
1st MBBS Repeat Campaign – 26th Batch

Emerge from the anterior aspect of the apex of prostatic gland. Shortest and least dilatable

Urethral crest Lies within urogenital diaphragm surrounded by sphincter urethrae.

Throughout the whole length of prostatic urethra is a midline ridge known Occurs 2.5cm behind pubic symphysis
as urethral crest projecting into lumen from the posterior wall.
Spongy or Penile Urethra (15cm)
Prostatic sinus
Occurs within the corpus Spongiosum
Shallow depression on either sides of crest.
Divided into 2 as
Seminal Colliculus or Verumontanum
Bulbous- Part within the posterior part of corpus spongiosum’s bulb whch
Midline rounded eminence at the midlength of the crest is attached to undersurface of perineal membrane

Prostatic utricle In the bulb urethra takes a right angled direction

Small recess representing fused ends of paramesonephric (mullerian) ducts Pendulous part-Continues in the Corpus Spongiosum within the body of
which opens to middle of the verumontanum. the penis.

Ejaculatory ducts opens on either sides of utricle opening. Navicular fossa

Preprostatic part of prostatic urethra A short dilated region just proximal to external urethral meatus at the tip
of glans.
Proximal part of prostatic urethra
Epithelium= Stratified Squamous epithelium
Surrounded by cylinder of smooth muscles which is an extension of the
circular muscle at bladder neck (Rest of the epithelium of urethra is Transitional epithelium)

Function=When this muscle contract it prevents seminal regurgitation into Lacunae

the bladder during ejaculation.
Small blind ending pockets in urethral mucosa.
Membranous Urethra(1.5cm)
Glands of littre =Urethral glands
After leaving prostate the prostatic urethra becomes the membranous
urethra and pierce the perineal membrane. Cause of spiral stream of urine

Urethra is horizontal in cross section but the meatus is a vertical slit.

 33
1st MBBS Repeat Campaign – 26th Batch

Anatomy that should be considered during catheterization Posterior relations of the ureter

Urethra narrowest at external meatus Passes down on Psoas Major

Most dilated and widest at prostatic part Crosses infront of genitofemoral nerve

Navicular fossa Leaves Psoas major muscle at the bifurcation of the common iliac artery
over sacroiliac joint and passes into the pelvis.
Right angled change of direction in bulbar part of spongy urethra before
entering to membranous urethra. Anterior relations of ureter

Membranous urethra is the narrowest and least fixed. Right Ureter anterior relations

Presence of Large lacunae on the roof of navicular fossa therefore Upper part of right ureter is behind 3rd part of duodenum
catheter passing via the external meatus should initially point towards
the floor of fossa. Lower down it is crossed by right colic artery

By holding the penis upwards S-shaped curve of the urethra is converted to Iliocolic vessals
J shaped curve.
Root of mesentry
Catheter should pass easily along in a normal urethra into the bladder, a
Left ureter anterior relations
slight resistance is felt in the membranous part as its not dilatable and no
resistance back again in prostatic part. Crossed anteriorly by left coliccolic vessels At pelvic brim crossed by apex
of sigmoid meso colon

Lies lateral to inferior mesenteric vessals.

Ureter – 25cm
Ureters can be distinguished from vessals ina aliving body, In that it’s
2 parts- abdominal part
whitish colour,non pulsatile cord with peristaltic activity when piched
Pelvic part with forceps.

Both parts are equal in length Surface marking-Tip of the 9th coastal cartilage to common iliac artery
bifurcation
Narrowest caliber are at pelvi-uteric junction (where it crosses the pelvic
brim) In Radiographs-
 34
1st MBBS Repeat Campaign – 26th Batch

Medial to tips of the transverse processes of lumbar vertebrae. Turns forward and medially above the pelvic floor to enter the base of the
bladder.
Cross pelvic brim at sacroiliac joint.
Here in males vas deferens crosses above the ureter.
Passes towards ischial spine and from there to pubic turbecle.
In females ureter lies in the base of broad ligament and it is crossed above
Pelvic part of ureter by uterine artery.
Cross pelvic brim in the region of the bifurcation of common iliac artery.

On the left it underlies the apex of sigmoid mesocolon. In both sexes the ureter runs obliquely through the bladder wall for 1-2cm
before reaching their orifices at the upper lateral angle of trigone.

Runs over External iliac artery and vein.

Nerve supply of the kidney and ureter and anatomical basis of renal colic
Then descend along side wall of pelvis infront of Internal iliac artery
pain and Renal pain.
(behind the ovary and crosses obturator nerve
Kidney
Obliterated umbilical Artery
Sympathetic supply
Obturator Artery
Sympathetic preganglionic cells lies in the T12-L1 segment of spinal cord
Obturator Vein
Preganglionic fibers goes via thoracic and lumbar splanchnic nerves

synapses with ganglions of coeliac plexus and some synapse with

On the right side appendix in pelvic position also crosses it.
renalganglions

function of sympathetic supply-vasomotor function

Reach ischial spine
Afferent Supply

Afferent fibers or pain fibers accompany sympathetic nerve fibers.

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1st MBBS Repeat Campaign – 26th Batch

Ureter Convergence-Since 1st order neuron of both the sites synapses with the
same 2nd order neuron brain cannot identify the source of pain correctly
Sympathetic supply since somatic pain is common brain recognize it as a upper abdominal or
back pain.
T10-L1 segment send pre ganglionic nerve fiibers
Facilitation- sincevisceral pain is dull and diffused somatic pain fibers gets
Preganglionic nerve fibers form the splanchnic nerve
excited to enhance the pain.
Reach coeliac or hypogastric plexus and synapse with the ganglions
Renal Colic pain
Post ganglionic fibers reach the ureter
Occurs due to a urinary stone obstruction.
(Unlike in kidney there are no ganglions in contact with ureter)
Classical sites where urinary stones lodge.
Parasympathetic supply
Pelvi-ureteric junction (PUJ)
Reach the ureter via pelvic splanchnic nerve.
Mid ureter where it crosses the iliac vessels
Renal Pain
Vesico-Ureteric junction (VUJ)
Occurs due to a disease or injury to a kidney causing stretching of kidney
Features of the pain
capsule or spasm of the smooth muscles in renal pelvis.
Loin to groin pain
Pain is dull one sided ache in upper abdomen side or back.
Colicky pain (pain come and go)
Afferent pain fibers
Vomiting
Follow sympathetic nerves to the spinal cord segments corresponding
sympathetic nerve supply that is T12-L1 via dorsal root of spinal cord. Obstruction to flow
Since T12 –L1 spinal cord also receives pain fibers fromupper abdomen, Causes release of prostaglandins
side and back visceral renal pain is referred to these particular regions
Prostaglandins cause ureteric smooth muscles to go into spasms and
**Referred pain-irritation of visceral organs produce pain in somatic vasodilation of surrounding vessels.
structures
Spasms of smooth muscles cause the colicky pain
2 theories
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1st MBBS Repeat Campaign – 26th Batch

Loin to groin pain is because ureter’s pain fibers synapsing with spinal Podocytes -type of cells with long cytoplasmic projections to embrace
segments T10-L1 also synapses with somatic pain fibers coming from loin capillaries.
to groin.
Glomerular basement membrane seperates the podocytes and capillary
Vomiting is due to vagal afferents that gets excited. endothelium.

Afferent arteriole is larger than efferent arteriole (low diameter in efferent

arteriole helps to maintain pressure gradient to enhance filtrations at
efferent side)

Function Epithelium Features

Bowman’s Permeability Simple Flat cells form
Histological significances of different regions of renal tubules
Capsule barrier Squamous parietal layer pf
epithelium Bowman’s
Renal Corpuscle+Renal tubule=Nephron
capsule.
Podocytes form
Renal tubule
the visceral
layer of
Renal Corpuscle= Glomerulus+Bowman’s capsule
Bowman’s
capsule.
Glomerulus
Space between
Globula network of capillaries which is inside bowman’s 2 layers is the
bowman’s
Capsule. space.
Thick basement
Space between capillary loops in each glomerulus is membrane
Tight junctions
filled with mesengial cells.
Proximal Facilitated Simple cuboidal Micro villi
convoluted diffusion of epithelium (brush border)
Mesengial cells have long cytoplasmic processes.
tubule glucose and Increase
Capillary endothelium is fenestrated cell nuclei buldge into capillary amino acids surface area
65% glomerular Coiled tube
lumen.
filtrate (14mm)
reabsorbed. Occurs in Renal
Mesengeal cells are separated from capillary lumen by only the
cortex
endothelium. Small lumen
Large cells
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1st MBBS Repeat Campaign – 26th Batch

stains intensely Large clearly

(due to increase defined lumen
content of Small pale cells
organelles with less
mainly organelles.
mitochondria) Collecting Na+ Simple Cuboidal 2 cells
Loop of Henle tubules reabsorption epithelium Principal
4 parts (formed by ADH dep water cells=Scanty
1)Thick 1)Simple 1)Extend down convergence of absorption organelles
Descending Cuboidal to outter several renal K+ secretion Short micro villi
limb epithelium medulla tubules) Pale cytoplasm
2)Thin 2)No active Intercalated
descending transport 2)Simple cells=Dark
limb Low energy Squamous cytoplasm
3)Thin required (increase
Ascending 3)No active 3)Simple mitochondria
Limb transport Squamous polyribosomes
4)Active 4)Simple vesicles)
4)Thick transport of Cuboidal 4)Have
ascending Na+ basolateral
limb No facilitated processes that
diffusion interdigitate
with each
other.
Mitochondria
present in
processes
Tarum Horsfall
protein present
(protective
function)
Distal Na+ pump 1st part of DCT Anterior Relations of Kidney
Convoluted is Macula
tubules Densa
In the cortex
No brush
border
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1st MBBS Repeat Campaign – 26th Batch

Posterior Relations of Kidney

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1st MBBS Repeat Campaign – 26th Batch

BIOCHEMISTRY PRACTICAL • Add 3ml of urine to test tube

• Add (NH4)2SO4 crystals. Mix and add crystals until saturated(until
TIME-1hr and 10 minutes it no longer dissolves)
• Add 5% sodium nitroprusside 8 drops and mix well.
• You will be given one or more urine samples.
• Add Nh3 along the wall without shaking.
• Some samples maynot show positive results atall to
• Purple ring-positive result.(ketone bodies present)
anytests. So do not panic.
Confirmatory test.-gerhartdts test
• A normal urine sample will also be provided for
• Add 3ml of urine to the test tube.
comparison.
• Add 3% fecl3 drop by drop while mixing.
• Conduct tests to confirm the abnormal constituents. • Stop adding fecl3 when ppt is no longer generating.
• An answer sheetwill be provided. draw a table as given in • If negative acetoacetate absent , acetone present.
the instruction sheet you will be handed over there and • Filter and take the filterate.
fill it after each test conducted. • Continue toad fecl3 drop by drop until purple colour appear.
• Label the test tubes. • Heat it .ifcolour appears acetoacetate present.
• Leave them as it is with the tested samples without • If colour persist salicylate present.
spilling them out when you leave. 3.Test for reducing substances
Compare all the tests with a control. (normal urine)
Preliminary test-benedicts test(control)
1. Test for bile salts or pigments
• Add 2.5 ml of benedicts reagent to a boiling tube
Preliminary test- hays test (Do a control) • Add 4 drops of urine
• Take 5ml urine in test tube.sprinklesulphur carefully and • Mix and boil vigorously to 2 mins
slowly. • Ppt yellow to orange to brick red.
• If powder sink bile saltspresent. • Positive –reducing substances present
• If powder floats no bile salts.
Confirmatory tests

Confirmatory test- fouchets test 1. Clinsttix strip test-for glucose

• To 2ml of urine add 1ml of 10% Bacl2 mix and filter. 2. Seliwanoffs resorcinol test-for fructose
• Filter the ppt and dry the filter paper over the Bunsen Better do the clinistix strip test first (seliwanoffs answers for glucose
flame. when it heats extensively therefor
it is better to do the clinistix test first and confirm if there is glucose or
• Add 2 or 3 drops of fouchets reagent on the ppt and
not and then do seliwnoffs)
observe for colour change
• If green bile pigments present. clinistix (label)
2.test for ketone bodies (do a control)
• take 4 to 5 ml of urine to a test tube
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1st MBBS Repeat Campaign – 26th Batch

• dip the test strip in urine sample

• remove excess urine by touching the side of the container
• compare the colour developed with the given colour chart in the bottle.

Seliwanoffs (label)

• Take 5 ml of seliwanoffs reagent to a test tube.

• Add 10 drops of urine. And 5ml of seliwanoffs
• Heat notboil for 40 -30 secs
• If cherry red colour appears fructose present

4 Test fpr proteins

Preliminary test – heat precipitation test

• Take a boiling tube and fill ¾ th of it with the abnormal sample.

• Heat the top 1/4th of it slanting over the Bunsen burner.
• If turbidity in upper boiled area proteins and phosphates may present.
• Add 10% acetic acid drops if turbidity remains proteins present.
• If turbidity disappears phosphates present.

Confirmatory test- sulphosalicylic acid test

• Take 1ml of urine to a test tube

• Add 3% sulphosalicylic acids 2-3drops
• If ppt or turbidity appears proteins present.