Renal Anatomy %26 Physiology MIU BCPS 2015

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Taher Hegab, PharmD, PhD, BCPS


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The basic anatomy of the kidneysThe basic functions of the kidneys

The basic physiologic processes occurring in

the nephronRenal clearance and its calculations

Taher Hegab, Kidney Introduction2015


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The basic histological and functional unit ofthe kidney is the:1. Bowman capsule.

2. Podocyte.

3. Nephron.

4. Filtration membrane.

5. Glomerulus.



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The basic histological and functional unit ofthe kidney is the:1. Bowman capsule.

2. Podocyte.

3 Nephron

4. Filtration membrane.

5. Glomerulus.



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How does kidney work? What are theprocesses that occur inside the kidney?



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Kidney work to adjust and regulateA. Urine composition

B. Blood composition



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1

Regulation of water and electrolytes

(Na, K, Ca, Mg, P, H+etc) to maintain totalbody homeostasis or balance (intake =output)

2

Excretion of metabolic waste

(urea, uric acid, creatinine, acid, etc)

2

Excretion of bioactive substances

(hormones, foreign substances, e.g. drugs)



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4

Regulation of arterial blood pressure

Through renin-angiotensin-aldosterone system(RAAS) and via sodium and water balancemaintenance.

5

Regulation of red blood cell production:

Production of erythropoietin by interstitial cellsin response to low O2pressure, anemia,hypoxia, low renal blood flow.

6 Activation of vitamin D:

Hydroxylation of 25 OH vitamin D to form 1,25dihydroxyvitamin D3.



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1. Filtration:water and solutes in blood pass thru thefiltration barrier into Bowmans space. 125ml/min = 180 L/day.

2

Secretion:

Solutes move from tubular epithelial cells intotubular lumen

3

Reabsorption:Substances move from tubular lumen thrutubular epithelial cells and then eventually intothe blood



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Cortex:Outer layer of the kidneyContains: The glomeruli

Proximal tubules

Distal tubules

MedullaInner part of the kidneyArranged into 7-9 pyramids (cone shaped regions)Contains Loops of Henle

Collecting ducts



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Nephron is composed of:Glomerulus

Tubules:

Proximal tubule

Loop of Henle Distal tubule

Collecting duct



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Glomerulus is a ball consisting of capillaries,lined by endothelial cells

Bowmans capsule is a pouch that surrounds theglomerulus. It collect the filtrate and direct it to

the proximal tubule Mesangium is a collection of cells that hold the

capillaries of the glomerulus together, Mesangialcells can contract to influence filtration

Podocytes are a specialized epithelial cells that

cover the outer surface of the capillaries. It havea foot like processes that connect to form the slitdiaphragm



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Urine formation startwith a filtration processthat occur in theglomeruli

The filtering barrier(the filter) consists of: Fenestrated capillary

endothelium

Glomerular basementmembrane

Podocyte slit diaphragm



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Filtration barrier allowthe passage of water andsmall dissolved soluteswhile retaining proteinsand cells.

Molecular weight is themain determinant ofpassage.

Inulin 5KDa pass freely Proteins greater than 60-70

KDa are retained (albumin67KDa is retained)



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20% of the cardiac output enters the kidneythrough renal artery

Renal artery bifurcate several time as inter thekidney

Arcuate arteries are arch like arteries whichrun through the boarder of the cortex andouter medulla



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Kidney have 2 capillary beds1. Glomerular bed:

From: Afferent arterioles

To: Efferent arterioles

Pressure gradient: 40-50 mmHg

2. Peritubular bed:

From: Efferent arterioles

To: Venules

Pressure gradient: 5-10 mmHg



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between the afferent and efferent arteriolesJGA contains 3 cell types

1) Granular juxtaglomerular cells in the walls of the afferent

arterioles- secrete renin activating RAAS system

2) extraglomerular mesangial cells

3) macula densa cells (specialized TAL cells)- detect luminalsalt content at the end of the TAL and contribute to control of

GFR and renin secretion. High salt concentration will lead to adecrease in GFR



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Proximal tubulesLoop of Henle

Distal nephron



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Proximal convoluted tubule andproximal straight tubules

Reabsorb 60% of filtered Na+, K+, Ca2+, and water 90% of filtered HCO3

-

All glucose All amino-acids Phosphate (as regulated by parathyroid

hormone)

Secrete

Organic anions and cations (important indrugs and toxins elimination)

Rich in Na K ATPase



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Loop of Henle is 3 parts Descending thin limb Ascending thin limb Thick ascending limb

Reabsorbs 10% of filtered water 20% of filtered Na and Cl Most Mg reabsorption (TAL)

The site of Na+K

+2Cl

-co-transporter

The site of action of loop diuretics



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Distal nephron involves: Distal convoluted tubules

Connecting tubules

Cortical and medullary

collecting ductsFinal regulation of

Na+,K

+,Cl

-and acid

secretion

Site of action of aldosteroneand vasopressin



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About 180 liters isfiltered every day

Glomerular filtrationrate (GFR) is

dependent onDiameters of afferent

and efferent arterioles

Oncotic pressure in

glomerular capillariesand Bowmanscapsule



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Afferent arteriole Efferent arteriole

Glomerulus

Afferent arterioledilatation

Efferent arterioleconstriction

GFR

Prostaglandins,Kinins,

Dopamine (lowdose), ANP, NO

Angiotensin II(low dose)



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GFR is the rate of filtration at the glomerulusUsually expressed as ml/min

A measure of renal function and is used for: Dosage adjustment

To assess and stage chronic kidney disease



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To measure GFR a marker substance withfollowing characteristics is needed: The substance must be neither absorbed no

secreted by the renal tubules freely filterable across the glomerular membranes Not metabolized or produced by the kidney Stable in blood and urine and easily measured

Inulin (5 KDa sugar) is commonly usedAlternate substance include iothalamate,

iohexol



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Creatinine is produced endogenously at aconstant rate

It is not metabolized It is excreted by the kidneys by glomerular

filtration It is not reabsorbed by the renal tubules10-40% of total creatinine in urine is

actively secreted by renal tubulesCreatinine clearance can be used to

estimate GFR



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Should we use serum creatinine concentrationto evaluate kidney function?

A. Yes

B. No



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Creatinine level is affected by not onlyglomerular filtration but also by:

Age

Sex

Race Weight

Diet

Muscle mass and level of activity



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Creatinine clearance may not be very accuratein estimating kidney function in the followingpatientsA. El Shahat Mabrouk in his days

B. A malnourished Somali women during 1992famine

C. Hypotensive patient in ICU with no urine output

D. A quadriplegic elderly female that weighs 35 Kg

E. All of the above



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Almost all sodium filtered throughglomerulus is reabsorbed by renal tubules

Sodium is absorbed at:1. Early proximal tubule: Na+dependent co-

transporter and Na

+

/H

+

exchanger2. Late proximal tubule: Na+/H+ exchanger and Cl-

exchanger3. TAL: NKCC2 co-transporter (furosemide sensitive)4. Distal convoluted tubule: Na+/ Cl-co-transporter

(thiazide-sensitive carrier)5. Collecting duct: epithelial Na+ channel (amiloride

sensitive channel)



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Increased sodium reabsorption by: Sympathetic nervous system stimulation (e.g. in

response to decreased firing from volumereceptors)

Renin-angiotensin system Aldosterone

Antidiuretic hormone (ADH)

Sodium loss is caused by:

Atrial natriuretic factor



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Kidney respond to fluctuation in water intakeby changing the volume and concentration ofurine

Kidney can concentrate the urine to less than

1 liter per day in response to dehydrationOr increase the volume to as much as 14 liter

per day in response to excessive water intake

These changes can be accomplished withouteffecting solute excretion



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Nonapeptide secreted by neurons of supraopticand paraventricular nuclei of the hypothalamus

ADH is released in response to increase inplasma osmolarity above 285 mOsm/kg

ADH regulates water permeability in distalnephron especially collecting ducts

ADH open channels in the collecting duct leadingto water moving from the lumen of the tubules tothe interstitial space



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10% of filtered potassium is secreted in urinewhile 90% is reabsorbed

60-70% of filtered potassium is reabsorbed at

the proximal tubules

More K+absorption occur in TAL

In The collecting duct K+is both secreted and

reabsorbed



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K+

absorption at the proximal tubules andTAL is mostly unchanged with potassiumintake

Collecting duct K+secretion change inresponse to increase K intake from diet, andis the main regulator of potassiumhomeostasis



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Loop diuretics and thiazides inhibit NaClabsorption at loop of Henle and distal tubuleleading to increase the flow of fluid in thecollecting duct, which causes increase K

secretion.

Diuretics cause volume depletion, whichstimulate aldosterone secretion, which in turnincrease potassium secretion.



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ADH is sensitive to changes in:A. Blood volume

B. Osmolality

Aldosterone is sensitive to changes in:

A. Blood volume

B. Osmolality



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ADH is sensitive to changes in:A. Blood volume

B

Osmolality

Aldosterone is sensitive to changes in:

A Blood volume

B. Osmolality



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Bicarbonate reabsorption: Most filtered HCO3

-is reabsorbed

Excretion of H+:

Acid formed during metabolism consumes HCO3-and secrete H

+to regenerate HCO3

-to maintain

constant pH

H+ is excreted as phosphate or ammonium salt



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Renal Anatomy %26 Physiology MIU BCPS 2015

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