RENAL PHYSIOLOGY DR SYED SHAHID HABIB MBBS DSDM FCPS Associate Professor Dept. of Physiology College...

RENAL PHYSIOLOGY

DR SYED SHAHID HABIBMBBS DSDM FCPSAssociate ProfessorDept. of Physiology

College of Medicine & KKUH

DR SYED SHAHID HABIBMBBS DSDM FCPSAssociate ProfessorDept. of Physiology

College of Medicine & KKUH

1) Introduction2) Glomerular Filtration3) Tubular Processing4) Urine Concentrating

Mechanism5) Micturition

Renal Physiology

RENAL PHYSIOLOGY

TUBULAR PROCESSINGTUBULAR

REABSORPTION & SECRETION

URINE COMPOSITIONURINE COMPOSITION

pHpH usually acidic (pH 6) usually acidic (pH 6) range= 4.8 - 7.5range= 4.8 - 7.5

ColourColour Bright Yellow & Bright Yellow & transparenttransparent

VolumeVolume 1 - 2 L per day1 - 2 L per day

GlucoseGlucose NoneNone

REABSORTION PATHWAYS

Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion RateUrinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate

inulininulin ureaurea

glucgluc CreatCreat

GlucoseUrea

% of Filtered Load Reabsorbed

Glucose (g/day) 100Bicarbonate (mEq/day) >99.9Sodium (mEq/day) 99.4Chloride (mEq/day) 99.1Potassium (mEq/day) 87.8Urea (g/day) 50Creatinine (g/day) 0

PROXIMAL CONVOLUTED TUBULE•many mitochondria •brush border•tight junctions•lateral intercellular spaces.

GLUCOSE AND AMINO ACID REABSORPTION IN NEPHRON

TUBULAR TRANSPORT MAXIMUM

• The Maximum limit/rate at which a solute can be transported across the tubular cells of kidneys is called TUBULAR TRANSPORT MAXIMUM

Tm for Glucose is 375 mg/min

GLUCOSE REABSORPTION

•FBG=60-110 mg/dlFBG=60-110 mg/dl•RBG=110-200 RBG=110-200 mg/dlmg/dl

Transport maxTransport max375 mg/min375 mg/min

Renal ThresholdRenal Threshold 200mg/dl200mg/dl

HYDROGEN

•Secreted in Proximal Tubule and LOH by Counter Transport with Na

Na-H COUNTER Na-H COUNTER TRANSPORTTRANSPORT

Luminal MembraneLuminal Membrane

PCT & LOHPCT & LOH

CotransportNa

G

CotransportNa

AA

CountertransportNa

H+

Cl-

water water Reabsoprtion Reabsoprtion

65%65%

PCTPCT

ATP

Na

K

SODIUM HANDLING

Na+ moves by co transport or exchange from the tubular lumen into tubular epithelial cells

From cells into interstitium it moves by primary active transport

In DCT and CT it is under hormonal control

SODIUM HANDLING

Renal tubular reabsorption Solute reaborption in the proximal tubule

is isosmotic (water follows solute osmotically and tubular fluid osmolality remains similar to that of plasma).

65% of water and sodium reabsorption occurs in the proximal tubule100% of glucose & amino acids

Proximal tubules: coarse adjustment Distal tubules: fine adjustment

(hormonal control).

THIN LOOP OF HENLE•few mitochondria•flattened with few microvilli

THIN DESCENDING LOOP OF HENLE•few mitochondria•flattened with few microvilli

SolutesSolutes

HH22OO

THICK ASCENDING LOOP OF HANLE AND EARLY DCT

Many mitochondria and microvilli, but fewer than in the proximal tubule

ASCENDING LOOP OF HENLEMany mitochondria and microvilli, but fewer than in the proximal tubule

SolutesSolutes

HH22OO

ECF LumenEpithelial Cells

Events inEvents inThickThickALOHALOH

Sodium potassium 2 chloride co transport

Absorption through loop of Henle:Descending limb: is water permeable and allow absorption of 15% of filtered H2O. It is impermeable to Na-CL.

Thin ascending limb: is impermeable to H2O, but permeable to Na-Cl, where they are absorbed passively in this part .

Thick ascending limb: is impermeable to H2O. Na-K-2Cl co-transport occur in this part (25% of Na).

HYDROGEN•Secreted in Proximal Tubule and LOH by Counter Transport with Na

Na-H COUNTER Na-H COUNTER TRANSPORTTRANSPORT

Luminal MembraneLuminal Membrane

PCT & LOHPCT & LOH

ASCENDING LOOP OF HENLE

LATE DCT AND CORTICAL COLLECTING DUCT

• Mitochondria and microvilli decrease. • Principal Cells (Na Abs and ADH related Water abs)• Intercalated Cells (Acid Sec and HCO3 Transport)

DCT AND COLLECTING DUCT

•Principal Cells (Water reabsortion)•Intercalated Cells (Acid Secretion)

I CellI Cell

P CellP Cell

Events Events inin

DCTDCT

Intercalated cell

Events inEvents inDCT & CTDCT & CT

Principal Cell

Events inEvents inDCT & CTDCT & CT

AldosteroneAldosterone

Distal convoluted tubule and collecting ducts

• What happens here depends on hormonal control:

• Aldosterone affects Na+ and K+

• ADH – facultative water reabsorption

FACTORS AFFECTING ADH

Increase ADH Decrease ADH↑Osmolarity ↓Osmolarity

↓ Blood volume ↑ Blood volume↓ Blood

pressure ↑ Blood pressure

Clinical applications

• Thiazide diuretics

• Loop diuretics:

• K+ sparring diuretics:

MEDULLARY COLLECTING DUCT

REABSORPTION OF WATER IN DIFFERENT SEGMENTS OF TUBULES

PART OF NEPHRON PERCENTAGE

REABSORBEDProximal tubules 65

Loop of Henle 15

Distal tubules 10

Collecting ducts 9.2

Passing into urine 0.8

RENAL PHYSIOLOGY

TUBULAR SECRETION

DR SYED SHAHID HABIB

MBBS, FCPS

TUBULAR SECRETION

• Tubular Secretion may be by Passive or Active Mechanisms

• The most important secretory processes are for H, K and Organic Ions

HYDROGEN

• Secreted in Proximal Tubule by Counter Transport with Na

• In DCT and CT it is secreted by Hydrogen ATP ase

• When body fluids are more acidic H secretory process is accelerated and Vice Versa

HYDROGEN

•Secreted in Proximal Tubule and LOH by Counter Transport with Na

•Secreted in DCT by H ATP ase Primary Active Transport

Na-H COUNTER Na-H COUNTER TRANSPORTTRANSPORT

Luminal MembraneLuminal Membrane

PCT & LOHPCT & LOH

I Cell in DCT

RENAL PHYSIOLOGY COUNTER CURRENT

MECHANISM

COUNTER CURRENT MECHANISM

• KIDNEYS HAVE – MECHANISMS FOR

EXCRETING EXCESS WATER– MECHANISMS FOR

EXCRETING EXCESS SOLUTES

NEPHRON TYPES

Superficial (cortical) [85 %]o Capable of forming dilute urine

Juxtamedullary [15 %]o Capable of forming

concentrated (> 300 mOsm/kg) urine

EXCRETION LIMITS

• At least 600 mmol of solutes must be excreted each day – minimum volume = 600/1200 = 0.5L

– maximum volume = 20 Liters

EXCRETION LIMITS

COUNTER CURRENT MECHANISM

• LOOPS OF HENLE OF JUXTA MEDULLARY NEPHRONS establish hyperosmolality of interstitium of medulla. They are called COUNTER CURRENT MULTIPLIERS

• VASA RECTA maintain hyperosmolality established by counter current multipliers. They are called COUNTER CURRENT EXCHANGERS

400

300 300

300

300 200300

300 250300

400 300400

500 400500

700 600700

600 500600

800 800800

1200 12001200

1000 10001000

Cortex

Medulla

OsmolalityOsmolality

DISORDERS OF URINARY CONCENTRATING ABILITY

• Failure to Produce ADH: "Central" Diabetes Insipidus.

• Inability of the Kidneys to Respond to ADH: "Nephrogenic"

Diabetes Insipidus.

RENAL PHYSIOLOGY

MICTURITION

DR SYED SHAHID HABIBMBBS DSDM FCPSAssistant ProfessorDept. of Physiology

College of Medicine & KKUH

DR SYED SHAHID HABIBMBBS DSDM FCPSAssistant ProfessorDept. of Physiology

College of Medicine & KKUH

MICTURITION

It is the process by which the urinary bladder empties when it

becomes filled

Filling of bladder.Micturition reflex.Voluntary control.

Nervous Connections of the Bladder

Urogenital diaphragm

Micturition Reflex

• Actions of the internal urethral sphincter and the external urethral sphincter are regulated by reflex control center located in the spinal cord.– Filling of the urinary bladder activates the stretch receptors,

that send impulses to the micturition center.• Activates parasympathetic neurons, causing rhythmic

contraction of the detrusor muscle and relaxation of the internal urethral sphincter.

– Voluntary control over the external urethral sphincter.

• When urination occurs, descending motor tracts to the micturition center inhibit somatic motor fibers of the external urethral sphincter.

AUTONOMIC SPINAL REFLEX

Nerves Characteristic Function

1 Pelvic nerves (parasympathetic fibers)S-2 and S-3

Both sensory and motor nerve fibers

Contraction of bladder The sensory fibers detect the degree of stretch in the bladder wall

2 Pudendal Nerve somatic nerve Fibers that innervate and control the voluntary skeletal muscle of the sphincter

3 Hypogastric Nerves

sympathetic innervation (L2)

Stimulate mainly the blood vessels and have little to do with bladder contraction. Sensory nerve fibers of the sympathetic nerves also mediate the sensation of fullness and pain.

INNERVATION OF THE BLADDER

CYSTOMETROGRAM