Prof.Dr.P.Vijayaraghavan’s unit

Dr.B.Elavazhagan

THE KIDNEYANATOMY AND PHYSIOLOGY

EMBRYOLOGY

Development starts at 4th week intermediate mesoderm primordial components ----

pronephros ,mesonephros,metanephros pronephros :appear as solid cell groups in cervical

region ,which then regresses mesonephros : forms glomerulus bowman’s capsule, which

opens into mesonephric duct except mesonephric duct rest of these structures regresses mesonephric duct forms internal genitalia in males , an out

growth from it forms ureteric bud

metanephros forms excretory part of definitive kidney upto

DCT ureteric bud forms the rest, from collecting

tubules upto trigone of the bladder interaction between metanephros and ureteric

bud initiates development of kidney growth factors :metanephros ----WT1,GDNF,HGF ureteric bud-----FGF2,BMP7

CLINICAL CORRELATES

persistant fetal lobulations [DROMEDARY HUMP] -----a normal variantUreteric bud branches normally and metanephric

differentiation faulty -----multicystic dysplastic kidneyFailure of ureteric bud branching (GDNF)-----renal

agenesis B/L renal agenesis ----POTTER’S SEQUENCE

(anuria ,oligohydramnios,hypoplastic lung) POTTER’S FACIES ----(flattened facies,beak nose,club

foot)

ARPKD ----cyst arises from collecting duct only ADPKD-----cyst arises from all segments of

nephrons WILM’S TUMOUR ---- due toWT1 mutation premature termination of ureteric bud branching

causes low nephron mass ----preterm babies Normal –1 million nephrons at birth Pre term babies –2.25 lakh nephrons

at bith , hence prone for CKD

GROSS ANATOMY position : T12 - L3. Rt kidney -lower ,Lt kidney- medial size: 11×6×3 consists of 1) cortex (renal arches ,renal columns ) 2) medulla (pyramids,papillae,major

calyx,minor calyx) 3) renal sinus (pelvis,renal vessels and

lymphatics ) Blood supply : abdominal aorta at the level of L2 renal veins drains into IVC

Vascular anatomyAorta renal artery segmental artery inter lobar artery arcuate artery inter lobular artery afferent arteriole glomerular capillary efferent arteriole peritubular capillary

Inter lobular vein arcuate vein inter lobar vein segmental vein renal vein ivc

Glomerulus 1) Vasculature : afferent arteriole , glomerular capillary,efferent arteriole 2) Bowman’s capsule : visceral epithelium , parietal epithelium 3) Filtration barrier : formed by podocytes of

visceral epithelium ,basement membrane , capillary endothelium

4) Mesangial cells : between capillary endothelium

and basal lamina, contractile in nature

Diagram illustrating hypothetical assembly of nephrin forming the filter of the podocyte slit diaphragm. Nephrin molecules from adjacent interdigitating foot processes are shown in different shades of purple. X indicates proteins interacting with nephrin and connecting with the plasma membrane

Tubules : 1) PCT---Brush border cells,tight epithelial

junctions ,lateral inter cellular spaces

2) LOOP OF HENLE ---descending

ascending (thin,thick) 3) DCT 4) COLLECTING DUCT --- P-cells I-

cells

RENAL PHYSIOLOGY Excretory function : 1)glomerular filtration 2)tubular reabsorption 3)tubular secretion Endocrine function :1) erythropoitein 2) ca2+ & po4

metabolism 3) RAAS 4) Kinins

GLOMERULAR FILTRATION Normal GFR: 125ml/min Factors : A) Favouring :1)capillary hydrostatic

pressure 2)tubular oncotic

pressure B) Opposing :1) capillary oncotic

pressure 2) tubular hydrostatic

pressure Permeability : Neutral substances < 4nm 4-8nm >8nm Anionic & cationic substances

What is GFR?What is CLEARANCE?What is EXTRACTION RATIO?What is FILTRATION FRACTION?

Clearance of a substance=U x.V\P x =GFR + tubular

secretion – tubular

absorption Extraction ratio depends on tubular absorption

and secretion

Filtration fraction =GFR RPF

MEASUREMENT OF GFR Methods used :1) inulin clearance (gold

standard) 2) creatinine clearance

(clinically used) 3) cr51 ,EDTA ( most sensitive ) 4) cystatin C ( endogenous ,not

affected by age ,muscle

mass,sex)

AUTOREGULATION systemic arterial pressure

increases

afferent arteriole constricts

systemic arterial pressure drops

efferent arteriole constricts

GLOMERULO TUBULAR BALANCE When GFR increases ---more solutes and

water reabsorbed from tubules

% of solute reabsorption is constant

Mech : Increase in oncotic pressure in peritubular capillaries

TUBULO GLOMERULAR FEEDBACK Increased solute delivery to the distal

tubule

sensed by macula densa

increased ATPase & formation of adenosine

Constriction of afferent arteriole

TRANSPORTERS OF RENAL TUBULE PCT : co-transporters

----Na/glucose,Na/po4,Na/A Na/lactate

exchangers ----Na/H+,Cl/base

Thick ascending limb :Na +K+2CL- Na+H+ exchanger

DCT : Na- cl co transporter

COLLECTING DUCT :ENaC

Na-Cl reabsorption Except thin portions of loop of Henle ,Na is

actively transported out of all parts PCT -60% TALH-30% DCT -7% CD-3% Glucose ,amino acids ,bicarbonate ---

reabsorb along with Na in

early PCT Chloride reabsorbed along with Na in distal

PCT ,TALH,DCT

Water reabsorption60 – 70 % in PCT;15% in descending loop of henle ;5

% in DCT 15 % in collecting duct;

Absorption in collecting duct is solely dependent on ‘vasopressin ‘;

Plasma osmolality vasopressin release

V 2 receptor– aquaporin 2

water absorption Water diuresis / osmotic diuresis

Vaptans- V 2 receptor antagonist;

H + /HCO3–SECRETION / ABSORPTIONPCT-- Na + /H +

transporter--Na dependent;

DCT & collecting duct –H+/ATPase –Na independent ;

Buffers :- 1.HCO3¯ –in PCT 2.HPO4 ²¯-in DCT &

collecting duct 3.NH3 – in PCT &

DCT ,non ionic diffusion H + secretion depends

on pCO2 ,K,CA, & aldosterone ;

CKD & RTA – defective H + secretion

COUNTER CURRENT MECHANISM

CC mutiplier: loop of henle makes the medullary interstium more hypertonic more towards tip of pyramid.

CC exchanger: vasarecta keeps hypertonic interstium stable. it is a passive process.

JUXTA GLOMERULAR APPARATUSMacula densa in

distal tubule.Juxta glomerular

cells in AA (renin secreting)Lacis cells.

RENIN ANGIOTENSIN SYSTEM

RENIN by sympathetic

activity prostaglandins hypotension cirrhosis cardiac failure Angiotensin 2 – vasoconstriction aldosterone

secretion Na reabsorption

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