STRUCTURE AND FUNCTIONS OF NEPHRON

STRUCTURE AND FUNCTIONS OF NEPHRON

Renal failure

Dr. WASIF ALI KHANMD-PATHOLOGY (UNIVERSITY OF BOMBAY)

Assistant Prof. in PathologyAl Maarefa College

Urinary System

• Consists of– Urine forming organs• kidneys

– Structures that carry urine from the kidneys to the outside for elimination from the body• Ureters• Urinary bladder• Urethra

Urinary System

Nephron • Functional unit of the kidney• Approximately 1 million nephrons/kidney• Each nephron has two components

• Vascular component• Tubular component

• Arrangement of nephrons within kidney gives rise to two distinct regions

• Outer cortex– Renal cortex (granular in appearance)

• Inner medulla– Renal medulla– Made up of striated triangles called renal pyramids

The Nephron

Nephron (Vascular component)– Dominant part is the glomerulus

• Glomerulus is a tuft of glomerular capillaries. • large amounts of fluid & solutesare filtered from the

blood.

Juxtaglomerular apparatus

Nephron (Tubular component)

– Hollow, fluid-filled tube • single layer of epithelial cells

– Components• Bowman’s capsule• Proximal convoluted tubule• Loop of Henle

– Descending limb– Ascending limb

• Juxtaglomerular apparatus• Distal convoluted tubule• Collecting duct or tubule

Overview of kidney functions– Maintain H2O balance in the body.– Regulate the quantity and concentration of most

ECF ions—Na, K, cl, Ca, Mg, ph.– Acid-base balance in the body– Excreting (eliminating) the end products (wastes)

of bodily metabolism– Excreting many foreign compounds– Producing erythropoietin– Producing renin– Converting vitamin D into its active form

Excretion of Metabolic Waste Products

• Urea (from protein metabolism)• Uric acid (from nucleic acid metabolism)• Creatinine (from muscle metabolism)• Bilirubin (from hemoglobin metabolism)• Metabolites of various hormones

Excretion of Foreign Chemicals

• Pesticides• Food additives• Toxins• Drugs

Regulation of Water and Electrolyte Balances

• Water • Sodium • Potassium• Hydrogen Ions• Calcium, Phosphate, Magnesium, etc..

Regulation of Acid-Base Balance

• Kidneys– Excrete acids (kidneys are the only means of

excreting non-volatile acids, such as sulfuric acid and phosphoric acid.

– Regulate body fluid buffers ( e.g. Bicarbonate)

Regulation and production of hormones and enzymes

• The kidney produces:• Erythropoietin• 1,25 dihydroxycholecalciferol (Vitamin D3,

calcitriol)• Renin• Vasoactive Agents

Regulation of Erythrocyte Production

O2 Delivery Kidney

Erythropoietin

Erythrocyte Production in Bone Marrow

Hypoxia

Kidneys produce Erythropoietin: a hormone that

stimulates bone marrow to produce red cells.

Regulation of Vitamin D Activity

• Kidney produces 1,25- dihydroxycholecalciferol– The active form of vitamin D that important in

calcium and phosphate metabolism.

Renin production

• It is an enzyme secreted by the kidneys from granular cells of the juxtaglomerular apparatus.

• It activates the renin-angiotensin system by converting angiotensinogen to angiotensin I.

Vasoactive Agents

• Regulate the capacity of the vasculature– Endothelin– Thromboxanes– Prostaglandins– Nitric oxide– Natriuretic peptides

Metabolism of Hormones

Most peptide hormones are metabolized and excreted by the kidney (e.g., insulin, angiotensin II, etc.)

Regulation of Arterial Pressure

• Control of Extracellular Fluid Volume by excreting variable amounts of sodium and water.

• Endocrine Organ secreting vasoactive factors or substances– Angiotensin II– Prostaglandins

GLOMERULAR FILTERATION

Basic Renal Processes

• Glomerular filtration• Tubular reabsorption• Tubular secretion

Urine results from these three processes.

Excretion = Filtration – Reabsorption + Secretion

Composition of the Glomerular Filtrate

• It is the fluid within the Bowman’s capsule that is essentially cell-free and protein-free and contains crystalloids in virtually the same concentrations as in the plasma.

• It is free from:– Blood cells– Protein– Protein-bound molecules(calcium, fatty aids, amino acids)

Glomerular Capillary Filtration Barrier Endothelium (fenestrated) Basement Membrane negatively

charged, restriction site for proteins Epithelial Cells, restriction site for

proteins. Characterized by foot-like processes (podocytes).

Glomerular Filtration Rate (GFR)

GFR: The volume of plasma filtered from both kidneys per minute.

GFR = 125 ml/min = 180 liters/dayPlasma volume is filtered 60 times per day

GFR= Filtration Coefficient (Kf) x Net Filtration Pressure(NFP)

Factors Affecting GFR

Filtration Coefficient (Kf)

Net Filtration Pressure(NFP)

Filtration coefficient

• Filtration coefficient (Kf): A measure of the

product of the hydraulic conductivity (water

permeability) and filtering surface area of the capillaries.

• glomerular capillary filtration coefficient = 12.5 ml/min per mmHg, or 4.2 ml/min per mmHg/ 100gm• (400 x greater than in tissues such a muscle)

Increased Glomerular Capillary Filtration Coefficient (Kf) Increases GFR• Normally not highly variable• Kf reduces by reducing the number of functional

glomerulus (decrease surface area) or by increasing the thickness BM (reducing its hydraulic conductivity).

• Diseases that can reduce Kf and eventually GFR- Chronic hypertension- Diabetes mellitus- Glomerulonephritis

Forces determining Net Filtration Pressure (NFP)

• Three physical forces involved– Glomerular capillary blood

hydrostatic pressure– Plasma-colloid osmotic

osmotic pressure– Bowman’s capsule hydrostatic

hydrostatic pressure

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1

Proximal convoluted tubule


CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg


Capsularspace


Efferent arteriole

Afferent arteriole

1 2



BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg



Capsularspace


Efferent arteriole

Afferent arteriole

1 2

3


•GFR = Filtration Coefficient (Kf ) x Net Filtration Pressure (NFP)

• GFR = 12.5 x 10 = 125 ml/min = 180 liters/day• GFR in females is less (110 ml/min)

Calculation of Glomerular Filtration Rate (GFR)

Tubular Reabsorption & Secretion

Urinary excretion =

Glomerular filtration - Tubular reabsorption + Tubular secretion

WHERE & HOW

Tubular reabsorption

• Reabsorption – return of most of the filtered water and many solutes to the bloodstream– About 99% of filtered water reabsorbed– PCT cells- largest contribution– Both active and passive processes– Reabsorbed substances carried by the peritubular

capillaries to the venous system.– Tubular reabsorption is highly selective (unlike

filtration).

Tubular Secretion

Tubular secretion is important for:

Eliminates urea and uric acid

Ridding the body of excess potassium ions

Controlling blood pH by secreting H+

Sodium Balance

• Na+ is major cation in ECF

Amount of sodium in ECF

Volume of ECF

Plasma volume

Blood volume

Blood pressure

OVERALL HANDLING OF NA+

Potassium handling by nephron

Potassium balance

Acid base abnormalities: ICF has considerable buffering capacity for H+ H+- K+ exchangeAlkalosis hypokalemia Acidosis hyperkalemia acid base disturbances often associated with K+

disturbances with the exception ofRespiratory acidosis & alkalosisAcidosis caused by organic acids (lactic acid,ketoacids)

Renal Failure

CLASSIFICATION• TWO TYPES• Acute and chronic

ACUTE RENAL FAILURE (ARF)1) onset—1-2 days2) Rapid decline in renal functions3) Azotemia—increase in urea, nitrogen, uric acid and creatinine.

BUN - 10 to 20 mg/dl.UREA - 15 to 40 mg/dl.Creatinine - 0.5 to 1.5 mg/dl.

4) Decrease in GFR

TYPES OF ARF

• PRE-RENAL • INTRINSIC OR INTRA-RENAL• POST RENAL

PRE-RENAL ARF CAUSES1) HYPOVOLEMIA HemorrhageDehydrationLoss of GI fluidsBurns

2) Decreased vascular fillingAnaphylactic shockseptic shockVasoactive agentsDrugsRadiocontrast agents3) Heart failure

INTRINSIC OR INTRARENAL ARF• ACUTE TUBULAR NECROSIS-ATN CAUSES1) Renal ischemia2) Nephrotoxic agents—aminoglycosides,

gentamicin, chemo-cisplatin, ifosfamide.3) Heavy metals4) Intra-tubular obstruction—Hb, Mg, Myeloma,

light chains.ACUTE RENAL DISEASE—glomerulonephritis and

pyelonephritis.

POST-RENAL ARF• Bilateral ureteric obstructions• Bladder outlet obstructions• BPH• Urethtral malignancies, stone.


BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg



Capsularspace


Efferent arteriole

Afferent arteriole

1 2

3


Clinical Features

• Oliguric phase• Diuretic phase• Phase of recovery

• ATN is reversible ; Proper Mgt. means the difference between full recovery and death.

Symptoms of ARF• Decrease urine output (70%)• Edema, esp. lower extremity• Mental changes• Heart failure• Nausea, vomiting• Pruritus• Anemia• Tachypenic• Cool, pale, moist skin

CHRONIC RENAL FAILURE-CRFDefinition—kidney damage—abnormalities in pathological,

biochemical and imaging studies orGFR-<60 ml/min/1.73 m2 for > 3 months1) Months to years2) Progressive3) Not reversible4) Nephron loss5) End stage of all chronic renal conditions6) Azotemia + uremia

Chronic Renal Failure Causes

• Diabetic Nephropathy• Hypertension• Glomerulonephritis• HIV nephropathy• Reflux nephropathy in children• Polycystic kidney disease• Kidney infections & obstructions

NATIONAL KIDNEY FOUNDATION-STAGES OF CRF

STAGE DESCRIPTION GFR(ml/min/1.73m2)

1 Kidney damage with normal or increased GFR

≥ 90

2 Kid damage with mild decrease in GFR

60-89

3 Mod. Decrease in GFR 30-59

4 Severe decrease in GFR 15-29

5 Kidney failure <15 or dialysis

Chronic Renal Failure: ESKD

Clinical manifestations of CRF

• PRIMARY UREMIC MANIFESTATIONS1) Metabolic acidosis Increase H ion and decrease in HCO3 ion leads to increased respiratory rate.2) Hyperkalemia cardiac arrythmia, weakness, nausea, intestinal colic,

diarrhoea, muscular irritability and flaccid paralysis.3) Sodium and water imbalanceHypervolemia, circulatory overload and CCF.•

4) Hyperuricemia- uric acid deposits in joints and soft tissues-gout5) Azotemia SECONDARY UREMIC MANIFESTATIONS1) Anemia2) Integumentary system- deposist of urinary pigment-urochrome in the skin causes

yellow colorUrea content increases in sweat and plasma- on evaporation

of perspiration-urea remains on face as powdery ‘’uremic frost’’

6) Cardiovascular systemIncrease in workload—CCF7) Respiratory system-Pulmonary congestion and edema.Uremic pneumonitis8) Digestive systemMucosal ulcerations in GITGI irritation--Nausea, vomiting and diarrhoea.

9) Skeletal systemRenal osteodystrophyOsteomalacia—Decrease in vit D—decrease Ca absorption-def

leads to dec Ca in bones.Osteitis fibrosa

References• Essentials of Pathophysiology by carol Mattson

Porth-third edition—LWW.• Text book of physiology by Guyton &Hall,11th

edition• Robbins and Cotran-- Pathologic basis of

disease--eighth edition• Davidson’s Principles and Practices of

medicine 21st ed.

Documents

STRUCTURE AND FUNCTIONS OF NEPHRON