BCH 450 Biochemistry of Specialized Tissues( Kidney)

Dr. Samina Hyder Haq

Dept of Biochemistry

King Saud University

Kidney structure and Function Location: Retroperitonial

Blood Flow: Renal artey &renal vein

Cardiac output: 25% Function:

1. Filter wastes such as urea and ammonium.

2. Regulates electrolyte balance, acid base balance and blood pressure

3. The production of hormones including vitamin D, renin and erythropoietin

Anatomical Location and Gross Structure

Kidney Cross section

How the Kidney Works

Nephron The functional unit of Kidney

Key words 1. Glomerulus: dense mass of very fine blood

capillaries at thenephron that act as a filter2. Bowman’s capusle:cup-shaped part of the nephron

that holds a glomerulus and collects the products of filtration from it

3. Glomerular filtrate: liquid removed from the blood by filtration in the kidney

4. An afferent arteriole delivers blood to a glomerulus

5. Efferent arterioles :The blood leaves the glomerulus through it.

Formation of urine The three processes of urine formation 1) glomerular filtration, 2) tubular reabsorbt ion and 3) tubular secretion.

Glomerular filteration1. Glomerulus brings a large surface

area of blood capillaries in close contact with Bowman’s capsule

2. Liquid filtered from blood under pressure (filtration)

3. Glomerular filtrate produced containing:-water-glucose-salts-urea

(Protein molecules and red bloodcells do not pass into tubule asthey are TOO BIG!!!!)

Tubuler Reabsorbion A lot of substance needs to

be reabsorbed such as water, glucose and some salts.

Final urine contains Water Waste urea Unneeded salts

Variable amounts of water and salts reabsorbed and filtrate gradually turning into urine

Glucose reabsorbed

More water absorbed

Summary of tubuler reabsorbtion

Tubular secretion Urine formation is completed as the fluid passes

from the proximal tubule flows through the loop of henle and distal tubules where the cells through special mechanism reabsorb most of water, electrolytes

The reabsorbtion of various electrolytes are under the control of adrenal cortical hormones, aldostrane, deoxycorticosterone

The reabsorbtion at distal tubule also under the control of antidiuretic hormone, vasopressin

Kidney act as a homeostatic organ

Histology of kidney

Hormones controlling water absorption Water reabsorption is controlled by the antidiuretic hormone

(ADH) in negative feedback. ADH is released from the pituitary gland in the brain. Dropping levels of fluid in the blood signal the hypothalamus to cause the pituitary to release ADH into the blood. ADH acts to increase water absorption in the kidneys. This puts more water back in the blood, increasing the concentration of the urine. When too much fluid is present in the blood, sensors in the heart signal the hypothalamus to cause a reduction of the amounts of ADH in the blood. This increases the amount of water absorbed by the kidneys, producing large quantities of a more dilute urine.

Aldosterone a hormone secreted by the kidneys, regulates the transfer of sodium from the nephron to the blood. When sodium levels in the blood fall, aldosterone is released into the blood, causing more sodium to pass from the nephron to the blood. This causes water to flow into the blood by osmosis.

Other hormones secreted by kidney Human kidney secretes

1. Calciteriol:Calcitriol acts on the cells of the intestine to promote the absorption of calcium from food and bone to mobilize calcium from the bone to the blood

2. Erythropoitin:Erythropoietin is a glycoprotein. It acts on the bone marrow to increase the production of red blood

cells.

3. Renin:

Renin One of the functions of the kidney is to monitor blood

pressure and take corrective action if it should drop. Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing

10 amino acids called angiotensin I.

angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme(ACE) — producing angiotensin II, which contains 8 amino acids. angiotensin II constricts the walls of arterioles closing down capillary beds. stimulates the proximal tubules in the kidney to reabsorb sodium ions; stimulates the adrenal cortex to release aldosterone. Aldosterone causes the

kidneys to reclaim still more sodium and thus water . increases the strength of the heartbeat; stimulates the pituitary to release the vasopressin.

All of these actions lead to an increase in blood pressure

Action of renin

Kidney clearanceAs the blood containing waste passes through the kidneys, a

certain proportion of these substances is removed per unit time.

Kidney clearance of a substance excreted in the urine in one minute.

Plasma rather than whole blood clearance are determined C = UV/P U =the conc of substance per milliliter of urine V= themilliliter of urine secreted per minute P= the conc of substance per milliliter of plasma. The polysaccharide inulin Mw 5000 is most commonly used

determination of glomeruler filtration

Kidney Clearance The clearance of many substances such as Na+,

K+,HCO3,Cl,SO4. HPO4. amino acid glucose, uric acid and ascorbic acid show clearance less than inulin are reabsorbed by the tubules.

There are no of substances which have clearance greater than inulin which means that these substances are secreted into tubular fluid by the tubular cells

Renal Clearance: If a substance is not reabsorbed or secreted, then the amount excreted = amount filtered

Quantity excreted (mg/min) = V x U

V = rate of urine formation;

U = inulin concentration in urine

Renal Threshold Tm Tm represent the maximum rate at which the tubule

can reabsorb or excrete a substance. At normal blood sugar level 100mm/100ml of plasma. Urine contains essentially no glucose

The amount appearing in the urine per minute when the plasma level exceeds the excretory capacity represent the excretory Tm.

Similarly various substances such as glucose, ascorbic acid, Na, Cl do not appear in urine until their plasma concentration rise to certain values called threshold substances

Tubular Function The quantity of glomerular fluid formed in the kidney is enormously

greater than the amt of urine excreted due to reabsorbtion of most of the water as the fluid passes the tubules

The solute concentration in plasma and glomerular fluid is normally around 0.3osmolar/litter in urine the solute concentration may rise to 1.4osmolar/litter

The pH of glomerular filtrate is about the same as that of plasma and filtrate as 7.4

As the glomerular filtrate passes through the proximal tubule 80-85%of the electrolyte Na, k, Cl, HCo3, HPO4, SO4. practically all of glucose, amino acid and ascorbic acids are reabsorbed.

125ml of glomerular filtrate passing through the proximal tubule only some 20-25ml reaches the loop of Henley and distal tubule.

About 80% of water is absorbed into the plasma by the proximal tubules 20% passes to the distal tubule.

Kidney as acid-base balance

The acid –base balance of the body is concerned with the metabolism of H ions or protons their excretion and handling pH7.4

Normal urine normally is slightly acidic because the kidneys reabsorb almost all HC03-and excrete H+.

The chief acids are H2CO3,HHb, HHb,HHbO2, protein-,HPO4

Proton added to body fluids are taken by the buffer basis(anions)to form the buffer acids when there is deficiency they are given to body fluid by the buffer acid H+ buffer bases __H+ increases

Buffer acids _H +decreases_ Kidney regulates {H+} The total cation equivalence to the total anions in your plasma

Acid base Balance A buffer is a mixture of a weak acid and a

salt of its conjugate base that resist changes in pH. No of buffer system in our body

1. HCO3/CO3 acid buffer system

2. Phosphate buffer system

3. Plasma protein and haemoglobin buffer system

Renal Buffer

Renal excretion of acid and conservation of HCO3 occur through several mechanism

1. The Na H+exchange

2. Production of ammonia and excretion of NH4

3. Reclamation of bicarbonate

Na+ H+ exchange All mammalian cells contain ATP-hydrolyzing

protein capable of exchanging Na+ions for protons the so called Na,H exchanger,

In renal tubules the exchanger extrudes H ions into the tubular fluid in exchange for Na ions.it enhances in estate of acidosis and inhibited in alkalotic states.

The proximal tubule cannot maintain an H gradient of more than pH=1,wheras the distal tubules cannot maintain more than pH=3max acidity =4.4

K ions compete with H in the renal tubular Na,-H+ exchanger.

Renal production of ammonia and excretion of ammonium ionsRenal tubular cells are able to generate ammonia from glutamine and

other amino acids derived from muscles and liver cells.

L-Glutamine + H2O glutaminase L-Glutamate + NH4.............(reaction 1) Glutamate + NH3 + ATP (Glutamine synthetase) Glutamine + ADP + Pi.......(reaction 2)

NH4 + 2-oxoglutarate + NADPH glutamate dehydrogenase L-glutamate + NADP+ H2O.....(reaction 3) NH4 NH3 + H

NH4 ions transported to tubular lumen without dissociation in NH3 and H. At normal pH the ratio of NH3 to NH4 is about 1 to 100. NH3 is a gas diffuses quickly through the cell membrane into the tubular lumen where it combines with H to form NH4 . In individual with critical acidosis NH3 production is not achieved to buffer the non-volatile acids.

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H+ secreted by Na+ H+ exchanger may react with HPO4. to form H2PO4 . In renal disease less excretion of H2PO4

Strong acids like sulfuric,hydrochloric and phosphoric ionized freely at pH of urine and excreted only when H reacts with the buffer base, excretion of these anions is accompanied by simultaneous removal of cations Na, k, NH+ to provide electrolytic balance.

Reclamation of filtered bicarbonate. For each H+ secreted into the tubular fluid one Na+ and one HCO3 absorbed. When concentration exceed 26mmol it is excreted out.

In increase acidosis of proximal tube, urine CO2 increases and HCO3 decreases

Ammonia Toxicity Brain tissue very sensitive to ammonia. High conc

of ammonia causes Coma. Cells get rid of ammonia by Reaction 2

High concentration of ammonia shifts the reaction towards glutamine, Glutamine synthetase uses ATP, this depletes the brain cell of ATP hence essential for vital function

Glutamate is a precursor of GABA. High concentration of ammonia deplete glutamate, in turn

deplete GABA which is a basic neurotransmitter.

Conditions associated with abnormal Acid base balance Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis