VISHNU DENTAL COLLEGE DEPARTMENT OF PERIODONTICS AND IMPLANTOLOGY SEMINAR ON STRUCTURE AND FUNCTION OF LIVER AND KIDNEY

2014-2017

GUIDED BY: H.D.MANASA PRESENTED BY: R.UDAY BHASKAR

CONTENTS : KIDNEY Introduction

Anatomy

Blood and nerve supply

Nephron

Functions

Formation of urine

Excretion of metabolic waste products and foreign chemicals

Regulation of water and electrolyte balances

Regulation of arterial pressure

Regulation of acid base balanc

Glucose synthesis

LIVER Introduction

Anatomy

Blood and nerve supply

Functions

The Liver Stores Iron as Ferritin

Coagulation

Excretion of drugs and other hormones

Measurement of Bilirubin

Jaundice

Drugs

Clinical significance

conclusion

KIDNEY ANATOMY The kidneys are bean shaped organs that serve several essential regulatory roles in vertebrate animals

Two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity.

Weighs 150 gm

Medial side of each kidney contains an indented region called the hilum

The kidney is surrounded by a tough, fibrous capsule

Outer cortex and inner medulla.

Medulla is divided into multiple cone-shaped

masses of tissue called renal pyramids. The base of each pyramid originates at the border between the cortex and medulla and terminates in the papilla..

The outer border of the pelvis is divided into open-ended pouches called major calyces that extend downward and divide into minor calyces, which collect urine fromthe tubules of each papilla

NEPHRON: Functional Unit of the Kidney

Each kidney -1 million nephrons, each capable of forming urine.

The kidney cannot regenerate new nephrons.

Therefore, with renal injury, disease, or normal aging, there is a gradual decrease innephron number.

2 parts : a renal corpuscle and renal tubule

Renal corpuscle has two components - glomerulus and glomerular capsule (Bowans capsule)

Fluid filtered from the glomerular capillaries flows into Bowmans capsule and then into the proximal tubule, which lies in the cortex of the kidney.

From the proximal tubule, fluid flows into the loop of Henle, which dips into the renalmedulla. Each loop consists of a descending and an ascending limb. The walls of the descending limb and the lower end of the ascending limb are very thin and therefore are called the thin segment of the loop of Henle.

After the ascending limb of the loop has returned partway back to the cortex, its wall becomes much thicker, and it is referred to as the thick segment of the ascending limb.

At the end of the thick ascending limb is a short segment, which is actually a plaquein its wall, known as the macula densa.

Beyond the macula densa, fluid enters the distal tubule, that lies in the renal cortex.

This is followed by the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct.

The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct.

The collecting ducts merge to form progressively larger ducts that eventually emptyinto the renal pelvis through the tips of the renal papillae. In each kidney, there are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons.

FUNCTIONS: Excretion of metabolic waste products and foreign chemicals

Regulation of water and electrolyte balances

Regulation of body fluid osmolality and electrolyte concentrations

Regulation of arterial pressure

Regulation of acid-base balance

Secretion, metabolism, and excretion of hormones

Gluconeogenesis

URINE FORMATION: 3 basic processes 1. glomerular filtration 2. tubular reabsorption 3. tubular secretion

GLOMERULAR FILTRATION: Urine formation begins with filtration of large amounts of fluid through the glomerular capillaries into Bowmans capsule.

Like most capillaries, the glomerular capillaries are relatively impermeable to proteins, so that the filtered fluid (called the glomerular filtrate) is essentially protein-free and devoid of cellular elements, including red blood cells.

The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma.

In the average adult human, the GFR is about 125 ml/min, or 180 L/day.

About 20% of the plasma flowing through the kidney is filtered through the glomerular capillaries.

The filtration fraction is calculated as follows:

Filtration fraction = GFR/Renal plasma flow Even with this high rate of filtration, it is the glomerular capillary membrane that normally prevents filtration of plasma proteins.

The glomerular capillary membrane is similar to that of other capillaries, except thatit has three (instead of the usual two) major layers:

(1) the endothelium of the capillary, (2) a basement membrane, (3) a layer of epithelial cells (podocytes) surrounding the outer surface of the capillarybasement membrane All the layers are richly endowed with fixed negative charges that hinder the passage of plasma proteins. Filterability of solutes is inversely related to their size.

In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition referredto as minimal change nephropathy.

As a result of this loss of negative charges on the basement membranes, some of the lower-molecular-weight proteins, especially albumin, are filtered and appear in the urine, a condition known as proteinuria or albuminuria.

DETERMINANTS OF GFR: The GFR is determined by (1) the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure, and

(2) the glomerular capillary filtration coefficient, Kf.

Expressed mathematically, the GFR equals the product of Kf and the net filtration pressure:

GFR = Kf Net filtration pressure

Net filtration pressure: (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration; (2) the hydrostatic pressure in Bowmans capsule (PB) outside the capillaries, which opposes filtration; (3) the colloid osmotic pressure of the glomerular capillary plasma proteins (pG), which opposes filtration; and (4) the colloid osmotic pressure of the proteins in Bowmans capsule (pB), which promotes filtration. REGULATION OF GFR RATE: Renal autoregulation

Myogenic mechanism Tubuloglomerular feedback Neural regulation

Hormone regulation

Angiotensin II Atrial natriuretic peptide (ANP) TUBULAR REABSORPTION: Reabsorption of filtered water and solutes from the tubular lumen across the tubularepithelial cells, through the renal interstitium, and back into the blood.

Solutes are transported through the cells (transcellular route) by passive diffusion oractive transport, or between the cells (paracellular route) by diffusion.

Water is transported through the cells and between the tubular cells by osmosis. Transport of water and solutes from the interstitial fluid into the peritubular capillariesoccurs by ultrafiltration (bulk flow).

PRIMARY ACTIVE TRANSPORT: The sodium-potassium pump transports sodium from the interior of the cell across the basolateral membrane, creating a low intracellular sodium concentration and a negative intracellular electrical potential.

The low intracellular sodium concentration and the negative electrical potential cause sodium ions to diffuse from the tubular lumen into the cell through the brush border.

SECONDARY ACTIVE TRANSPORT: The upper cell shows the co-transport of glucose and amino acids along with sodium ions through the apical side of the tubular epithelial cells, followed by facilitated diffusion through the basolateral membranes.

The lower cell shows the counter-transport of hydrogen ions from the interior of the cell across the apical membrane and into the tubular lumen; movement of sodium ions into the cell, down an electrochemical gradient established by the sodium-potassium pump on the basolateral membrane, provides the energy for transport of the hydrogen ions from inside the cell into the tubular lumen.

For most substances that are actively reabsorbed or secreted, there is a limit to the rate at which the solute can be transported, often referred to as the transport maximum.

This limit is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule (referred to as tubular load) exceeds the capacity of the carrier proteins and specific enzymes involved in the transport process.

PRIMARY TRANSPORT CHARACTERISTICS OF THE PROXIMAL TUBULE: The proximal tubules reabsorb about 65% of the filtered sodium, chloride, bicarbonate, and potassium and essentially all the filtered glucose and amino acids.

The proximal tubules also secrete organic acids, bases, and hydrogen ions into thetubular lumen.

TRANSPORT CHARACTERISTICS OF THE THIN DESCENDING LOOP OF HENLE AND THE THICK ASCENDING SEGMENT OF THE LOOP OF HENLE: The descending part of the thin segment of the loop of Henle is highly permeable towater and moderately permeable to most solutes but has few mitochondria and little or no active reabsorption.

The thick ascending limb of the loop of Henle reabsorbs about 25 per cent of the filtered loads of sodium, chloride, and potassium, as well as large amounts of calcium,bicarbonate, and magnesium.

This segment also secretes hydrogen ions into the tubular lumen.

TRANSPORT CHARACTERISTICS OF THE EARLY DISTAL TUBULE AND THE LATEDISTAL TUBULE AND COLLECTING TUBULE The early distal tubule has many of the same characteristics as the thick ascending loop of Henle and reabsorbs sodium, chloride, calcium, and magnesium but is virtually impermeable to water and urea.

The late distal tubules and cortical collecting tubules are composed of two distinct cell types, the principal cells and the intercalated cells.

The principal cells reabsorb sodium from the lumen and secrete potassium ions into the lumen.

The intercalated cells reabsorb potassium and bicarbonate ions from the lumen and secrete hydrogen ions into the lumen. The reabsorption of water from this tubular segment is controlled by the concentration of antidiuretic hormone.

TRANSPORT CHARACTERISTICS OF THE MEDULLARY COLLECTING DUCT: The medullary collecting ducts actively reabsorb sodium and secrete hydrogen ions and are permeable to urea, which is reabsorbed in these tubular segments.

The reabsorption of water in medullary collecting ducts is controlled by the concentration of antidiuretic hormone.

REGULATION OF TUBULAR REABSORPTION: Regulation of sodium, k balance:

High-sodium diet decreases plasma aldosterone, which tends to decrease potassium secretion by the cortical collecting tubules. However, the high-sodium diet simultaneously increases fluid delivery to the cortical collecting duct, which tends to increase potassium secretion.

The opposing effects of a high sodium diet counterbalance each other, so that thereis little change in potassium excretion.

Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites. urea(from the metabolism of amino acids),

creatinine (from muscle creatine),

uric acid (from nucleic acids),

end products of hemoglobin breakdown (such as bilirubin),

and metabolites of various hormones.

Regulation of Water and Electrolyte Balances. maintenance of homeostasis,

If intake exceeds excretion, the amount of that substance in the body will increase.

If intake is less than excretion, the amount of that substance in the body will decrease.

Regulation of Arterial Pressure. kidneys play a dominant role in long-term regulation of arterial pressure by excreting variable amounts of sodium and water.

The kidneys also contribute to short-term arterial pressure regulation by secreting vasoactive factors or substances, such as renin, that lead to the formation of vasoactive products

Regulation of Acid-Base Balance. The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores.

sulfuric acid

phosphoric acid

REGULATION OF ERYTHROCYTE PRODUCTION. The kidneys secrete erythropoietin, which stimulates the production of red blood cells

stimulus for erythropoietin secretion by the kidneys is hypoxia.

In people with severe kidney disease or who have had their kidneys removed and have been placed on hemodialysis, severe anemia develops.

Regulation of 1,25Dihydroxyvitamin D3 Production.: kidneys produce the active form of vitamin D, 1,25- dihydroxyvitamin D3 (calcitriol)

Calcitriol is essential for normal calcium deposition in bone and calcium reabsorption by the gastrointestinal tract.

calcitriol plays an important role in calcium and phosphate regulation.

GLUCOSE SYNTHESIS. The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis.

With complete renal failure, enough potassium, acids, fluid, and other substances accumulate in the body to cause death within a few days, unless clinical interventionssuch as hemodialysis are initiated to restore, at least partially, the body fluid and electrolyte balances.

Less known facts about kidneys Fit kidney works 24 hours a day /7 days a week to fresh the blood.

Kidney will continue performing till they have mislaid 75-80% of their function.

Just one donated Kidney is required to substitute two failed Kidneys.

LIVER The liver is a discrete organ .

Heaviest gland

Weighs about 1.4 kgs

Occupies most of right hypochondrium

ANATOMY OF THE LIVER: The liver is almost completely covered by visceral peritoneum and is completely covered by a dense irregular connective tissue The liver is divided into two principal lobesa large right lobe and a smaller left lobeby

the falciform ligament, a fold of the mesentery Although the right lobe is considered by many anatomists to include an inferior quadrate lobe and a posterior caudate lobe based on internal morphology, the quadrate and caudate lobes more appropriately belong to the left lobe. The falciform ligament extends from the undersurface of the diaphragm between the two principal lobes of the liver to the superior surface of the liver, helping to suspend the liver in the abdominal cavity. In the free border of the falciform ligament is the ligamentum teres (round ligament), a remnant of the umbilical vein of the fetus

HISTOLOGY OF THE LIVER The basic functional unit of the liver is the liver lobule

contains 50,000 to 100,000 individual lobules

HEPATOCYTES : major functional cells of the liver

80% of the volume of the liver

hepatic laminae

Hepatocytes secrete bile

BILE CANALICULI : These aresmall ducts between hepatocytes that collect bile produced bythe hepatocytes . From bile canaliculi, bile passes into bileductules and then bile ducts. The bile ducts merge and eventuallyform the larger right and left hepatic ducts, whichuniteand exit the liver as the common hepatic duct The common hepatic duct joins the cystic duct from the gallbladder to form the commonbile duct.

HEPATIC SINUSOIDS highly permeable blood capillaries between rows of hepatocyte

Hepatic sinusoids converge and deliver blood into a central vein

From central veins the blood flows into the hepatic veins

drain into the inferior vena cava

stellate reticuloendothelial (Kupffer) cells

PORTAL TRIAD a bile duct,

branch of the hepatic artery,

branch of the hepatic vein

HEPATIC LOBULE hepatic lobule is shaped like a hexagon

central vein, and radiating out from it are rows of hepatocytes and hepatic sinusoids.

hepatic lobules surrounded by thick layers of connective tissue

PORTAL LOBULE portal lobule is triangular in shape

three imaginary straight lines that connect three central veins that are closest to the portal triad

HEPATIC ACINUS Each hepatic acinus is an approximately oval mass that in- cludes portions of two neighboring hepatic lobules

short axis-portal triad

long axis two imaginary curved lines, which connect the two central veins

Hepatocytes in the hepatic acinus are arranged in three zones

zone 1

Zone 2

Zone 3

Blood Supply of the Liver The Liver Has High Blood Flow and Low Vascular Resistance.

Cirrhosis of the Liver Greatly Increases Resistance to Blood Flow.

The Liver Functions as a Blood Reservoir

The Liver Has Very High Lymph Flow

High Hepatic Vascular Pressures Can Cause Fluid Transudation

Into the Abdominal Cavity from the Liver and Portal CapillariesAscites.

Regulation of Liver Mass Regeneration The liver possesses a remarkable ability to restore itself

Partial hepatectomy, in which up to 70 per cent of the liver is removed, causes the remaining lobes to enlarge and restore the liver to its original size.

Control of this rapid regeneration of the liver is still poorly understood, but hepatocyte growth factor (HGF)

transforming growth factor-, a cytokine secreted by hepatic cells, is a potent inhibitor of liver cell proliferation and has been suggested as the main terminator of liver regeneration

Hepatic Macrophage System Serves a Blood-Cleansing Function. Blood flowing through the intestinal capillaries picks up many bacteria from the intestines.

Kupffer cell, in less than 0.01 second the bacterium passes inward through the wall of the Kupffercell to become permanently lodged therein until it is digested.

FUNCTIONS many of its functions interrelate with one another.

(1) filtration and storage of blood (2) Metabolism of carbohydrates, proteins, fats, hormones, and foreign chemicals (3) formation of bile (4) storage of vitamins and iron (5) formation of coagulation factors. Metabolic Functions of the Liver Carbohydrate Metabolism

1. Storage of large amounts of glycogen 2. Conversion of galactose and fructose to glucose 3. Gluconeogenesis 4. Formation of many chemical compounds from Fat Metabolism

1. Oxidation of fatty acids to supply energy for other body functions 2. Synthesis of large quantities of cholesterol, phospholipids, and most lipoproteins 3. Synthesis of fat from proteins and carbohydrates Protein Metabolism

1. Deamination of amino acids 2. Formation of urea for removal of ammonia from the body fluids 3. Formation of plasma proteins 4. Interconversions of the various amino acids and synthesis of other compounds from amino acids The Liver Stores Iron as Ferritin. greatest proportion of iron in the body is stored in the liver in the form of ferritin

The hepatic cells contain large amounts of a protein called apoferritin,

When the iron in the circulating body fluids reaches a low level, the ferritin releases the iron.

Apoferritin ferritin system of the liver acts as a blood iron buffer

The Liver Forms a Large Proportion of the Blood Substances Used in Coagulation. Fibrinogen

prothrombin

accelerator globulin

Factor VII

The Liver Removes or Excretes Drugs, Hormones, and Other Substances. liver is well known for its ability to detoxify or excrete into the bile many drugs, including sulfonamides, penicillin, ampicillin, and erythromycin.

several of the hormones secreted by the endocrine glands are either chemically altered or excreted by the liver

Liver damage can lead to excess accumulation of one or more of these hormones

Jaundice Excess Bilirubin in the Extracellular Fluid Jaundice refers to a yellowish tint to the body tissues, including a yellowness of the skin as well as the deep tissues.

cause of jaundice is large quantities of bilirubin in the extracellular fluids

normal plasma concentration of bilirubin, 0.5 mg/dl of plasma.

The common causes of jaundice are (1) increased destruction of red blood cells, with rapid release of bilirubin i

(2) obstruction of the bile ducts or damage to the liver cells

These two types of jaundice are called, respectively

hemolytic jaundice and obstructive jaundice.

Diagnostic Differences Between Hemolytic and Obstructive Jaundice. In hemolytic jaundice, almost all the bilirubin is in the free form

in obstructive jaundice, it is mainly in the conjugated form.

van den Bergh reaction

Total obstructive jaundice, tests for urobilinogen in the urine are completely negative.

severe obstructive jaundice, significant quantities of conjugated bilirubin appear in the urine.

Liver function tests ALKALINE PHOSPHOTASE Alkaline phosphatase is present in high concentration in growing bone, in bile, and in the placenta.

Normal level: 30 to 115 U/l.

Increased A. In children (growing bone).

B. Osteoblastic bone disease

C. Hepatic disease

D. Pregnancy.

Decreased: Hypophosphatasia

hypothyroidism

malnutrition Bilirubin Destruction of haemoglobin yields bilirubin,

Bilirubin accumulates in the plasma when liver insufficiency exists, biliary obstruction is present, or the rate of hemolysis increases.

Normal level: 0.2 to 1.2 mg/dl.

Increased Direct and indirect forms of serum bilirubin are elevated in acute or chronic hepatitis,biliary tract obstruction , toxic reactions to many drugs, chemicals and toxins ,and Dubin-Johnson and Rotors syndrome Aspartate aminotransferase (AST) Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), lactate dehydrogenase (LDH) are intracellular enzymes involved in amino acid or carbohydrate metabolism.

Normal: 5 to 25 U/l.

Increased:

Myocardial infarction (especially AST), acute infectious hepatitis ,cirrhosis of the liver and metastatic and primary liver neoplasm Decreased: Pyridoxine (vitamin B6), deficiency (often as a result of repeated hemodialysis), renalinsufficiency, and pregnancy Jaundice Excess Bilirubin in the Extracellular Fluid Jaundice refers to a yellowish tint to the body tissues, including a yellowness of the skin as well as the deep tissues.

cause of jaundice is large quantities of bilirubin in the extracellular fluids

normal plasma concentration of bilirubin, 0.5 mg/dl of plasma.

The common causes of jaundice are

(1) increased destruction of red blood cells, with rapid release of bilirubin (2) obstruction of the bile ducts or damage to the liver cells These two types of jaundice are called, respectively

hemolytic jaundice and obstructive jaundice

Drugs to be avoided in cirrhosis NSAIDs, ACE inhibitors : Reduced renal blood flow

Hepatorenal failure

Ulceration Bleeding varices

Codeine Narcotics Anxiolytics : Constipation

Hepatic encephalopathy

, drug accumulation

drug-induced hepatotoxicity Cholestasis - Chlorpromazine

High-dose oestrogens

Cholestatic hepatitis - NSAIDs

Co-amoxiclav

Statins

Acute hepatitis - Rifampicin

Isoniazid

Clinical significance Halitosis : in liver insufficiency such as cirrhosis, ammonium will be accumulated in blood and will be exhaled

In kidney insufficiency , primarly caused by chronic glomerularnephritis will lead to increased uric acid level in blood

Conclusion Kidney and liver the functions of these organs are so vast that they alone, are testaments to the ingenuity of the body.

The primary function of the liver, kidneys being expulsion of toxins that result from the body's metabolism of various dietary and other harmful chemicals and hence these organs play a major role in maintaining homeostasis in the body.

References Guyton And Hall, Textbook Of Medical Physiology, W b Saunders, 11th Edition

Tortora GJ ,Grabowsk, Textbook Of Medical Physiology, harper Collins, 8th Edition .

Davidsons principles and practice of medicine, 20th edition

1)Management of renal failure patient a) Periodontal disease was recently reported in 100% of all patients scheduled for renal dialysis co-ordination with the patient's physician.

infection control protocol may involve extraction of teeth with poor or hopeless prognosis, scaling and root planing, restoration of carious lesions and endodontic treatment where needed.

prophylactic antibiotics

Antimicrobial mouthrinses

2) SGOT, SGPT a) formerly SGOT- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), lactate dehydrogenase (LDH) . Elevation of concentrations of these enzymes in blood indicate necrosis or disease especially of these tissues. Normal: 5 to 25 U/I Increased: Myocardial infarction (especially AST), acute infectious hepatitis (ALT usually elevated more than AST), cirrhosis of the liver (AST usually elevated more than ALT), and metastatic and primary liver neoplasm Decreased: Pyridoxine (vitamin B6), deficiency (often as a result of repeated hemodialysis), renal insufficiency, and pregnancy. Decreased: Pyridoxine (vitamin B6), deficiency (often as a result of repeated hemodialysis), renalinsufficiency, and pregnancy. Alanine aminotransferase (ALT) a) (formerly SGPT) -Normal level: 5 to 30 U/l. Increased: Liver disease (more specific than AST), pancreatitis, biliary obstruction

3)Drug metabolism a) The primary site for drug metabolism is liver All orally adminnstered drugs are exposed to drug metabolizing enzymes in liver

Kidneys are responsible for excreting all water soluble substances.

The amount of drug present in the urine is sumtotal of glomerular filteration, tubular reabsorption, tubular secretion most common pathway for drug metabolism Cytochrome-P450 4) halitosis in liver and kidney disease a) in liver insufficiency such as cirrhosis, ammonium will be accumulated in blood and will be exhaled, pleasantly sweet smell in odor qualification. In kidney insufficiency , primarly caused by chronic glomerularnephritis will lead to increased uric acid level in blood, fishy smell in odor qualification.