PHYSL

Important notes , tutorial 1st 5 lecs

mid1

LEC 1

Function of kidney “ slide 4+5” :• Excretion• Homeostatic function• Biosynthesis/Metabolism

Type of nephron :

THE FILTRATION MEMBRANE:1. Capillary Endothelium: negative charges that

restrict the passage of plasma proteins2. Basement Membrane: mesangial cells are located

between the basal lamina and the endothelium. 3. Podocytes (Epithelium) : foot-like processes

all layers of glomerular capillary membrane have negative charge provide a barrier to the filtration of plasma proteins.

Juxtaglomerular Apparatus: “ slide 23 “• The Macula Densa: Detect & respond to changes in

the sodium chloride levels in the distal tubule of the kidney.

• Juxtaglomerular Cells : secrete renin

LEC 2

Glomerular Filtration:The first step in urine formation is the Glomerular filtration during which, large quantity of water and solutes pass through the filtration membrane from the blood into the Bowman’s Capsule due to pressure gradient.

Abnormal value :Microalbuminuria is 30–300 mg/24 hours Macroalbuminuria is 300mg/24 hours

Factors affecting GFR:• Changes in renal blood flow• Changes in glomerular capillary hydrostatic pressure– Changes in systemic blood pressure– Afferent or efferent arteriolar resistance

• Changes in hydrostatic pressure in Bowman’s capsule– Ureteral obstruction– Edema of kidney inside tight renal capsule

• Changes in concentration of plasma proteins:– Dehydration– Hypoproteinemia, etc.

• Changes in Kf

– Changes in glomerular capillary permeability– Changes in effective filtration surface area

Glomerular Capillary Hydrostatic Pressure (PG): “slide 15”

It is the primary means for physiologic regulation of GFR.

Increase PG raises GFR, and vice versa. It is determined by three variables:

Arterial PressureAfferent Arteriolar ResistanceEfferent Arteriolar Resistance.

LEC 3

Remember

• Loop of Henle ascending : electrolyte • Loop of Henle descending : only water• Proximal convoluted tubule PCT: glucose and

amino acid 100% reabsorped

LEC 4

Remember

• Level of glucose in blood will cause TM and it’ll cause threshold

• Threshold = 180-200• The main function of urea is controlling water

balance and concentration of urine • Ca and phosphate influenced by PTH

Lec 5

Most important substances secreted by the tubules

Is H+and K+

• H+

• Important in regulating acid-base balance• Secreted in proximal, distal, and collecting tubules

• K+

• Keeps plasma K+ concentration at appropriate level to maintain normal membrane excitability in muscles and nerves

• Secreted only in the distal and collecting tubules under control of aldosterone

During acidosis H+ secretion is increase lead to retention of K+.

small increase in plasma potassium will cause cardiac arrhythmias, and higher concentrations can lead to cardiac arrest or fibrillation.

small loss of potassium from the extracellular fluid could cause severe hypokalemia.

rapid and appropriate compensatory response mechanism is vital to avoid dangerous Hyperkalemia(with bradycardia)

or Hypokalemia (with tachycardia )

Factor effecting secretion : slide 13+14+17• Diet• Aldosterone • Acid base balance • RAAS will reabsorb Na+ and excrete K+ –Renin–Angiotensin–Aldosterone system (RAAS)–Increase of RAAS cause hypertension.–RAAS is also responsible for fluid retention and EDEMA occurring in

congestive heart failure. –Angiotensin Converting Enzyme inhibitor – ACE inhibitor drugs are used for

hypertension and congestive heart failure• diuretics will block the Na+\K+ pump• PAH is used to diagnose renal blood flow , cus it’s not reabsorbed• NSAID + Aspirin cause tubular damage, will cause in large dose

acute renal failure

Tutorial

For all the 5 lecs

Lec1 1-Biosynthesis/Metabolism FUNCTIONS OF KIDNEYS?– Renin secretion – Erythropoietin– Activation of Vitamin D> Calcitriol (1,25 DHCC)– Other substances: • Prostaglandin,• Adenosine… etc ..

But the 1st 3 are most important

2-Homeostatic function of kidney ?– acid-base balance – Osmolality and volume of ECF– blood pressure.– water and electrolyte balances.– Plasma ions concentration.

3-Excretion function of kidney ?– metabolic end product, e.g. urea– foreign substances, e.g. drugs, toxins

Parts of Nephron?

4-What is peritubular capillaries?Around the tubules and its function is to reabsorb

substances from tubules 5-What is vasa recta ?

straight capillaries in the medulla

6-Difference b\w cortical and juxta medullary nephrons ?

7-What are the layers of Glomerulus?1. Capillary Endothelium2. Basement Membrane3. Podocytes (Epithelium)

8-What are the layers of Bowmans Capsule?– Visceral > Podocytes ( which is the last layer of Glomerulus)– Parietal

9-What is the specialty\feature of Capillary Endothelium?Fenestrations =pores

10-What is the specialty\feature of Basement Membrane?negatively charged

11-What is the specialty\feature of Podocytes ?foot-like processes which helps in interlocking with other cells (gaps) to

have a better surface area 12-What are the layers of Filtration Membrane?

1. Endothelium2. Basement Membrane3. Podocytes

13-What is Juxtaglomerular Apparatus\ or what is the purpose of them?

Regulatory center for nephron 14-What are the Cells in JG Apparatus?

The Macula DensaWhere located? DCT What are they ? modified cells of DCTWhat is the function? Detect & respond to changes in the sodium chloride levels in the distal tubule of the kidney.

Juxtaglomerular Cells: also called granular cells Where present? wall of afferent arteriole endotheliumWhat are they ? Modified cells of endothelium What is the function? secrete reninWhich cells have granules? Juxtaglomerular cells

Extra Glomerular Mesangial CellsB\W arteries and tubules

15 –Where’s the JG Apparatus Cells present?Wall of efferent artery

16-What is the 1st step in urine formation ?1.Glomerular filtration – GFThen the 2nd and 3rd steps .. 2. Tubular reabsorption - TR3. Tubular secretion - TS

Lec 2 17-What are the substances that are not filtered ?

– Blood cells– Protein– Protein-bound molecules (calcium, fatty aids, amino acids)

18-What is the Definition Glomerular Filtration Rate (GFR)?– It is the Volume of plasma filtered by all nephrons of both

kidneys per unit time.

19-What is Normal GFR value? 125ml/min or 180L/day.

20-What are the factors Determine the GFR? – NET FILTRATION PRESSURE which is : Sum of the hydrostatic

and colloid osmotic pressures across the glomerular membrane– Capillary Filtration Coefficient (Kf): Surface Area “Membrane

Permeability”= thickness

21-what is Net filtration Pressure value ?: 10mmHg

And it’s consisting of 4 pressures Glomerular hydrostatic pressureGlomerular colloid osmotic pressureBowman’s capsular hydrostatic pressure Bowman’s capsular colloid osmotic pressure

22- 2 pressures helps in filtration ?– Glomerular hydrostatic pressure– Bowman’s capsular colloid osmotic pressure

23-Which pressure is used by body primarily for physiological regulation of GFR? | What’s primary mean of physiological GFR?

Glomerular hydrostatic pressure

-Hydrostatic pressure could affected by ? Renal blood flow

24- 2 pressures Opposing filtration?– Glomerular colloid osmotic pressure– Bowman’s capsular hydrostatic pressure

• So all 7 factors affecting the GFR?1. Glomerular hydrostatic pressure2. Glomerular colloid osmotic pressure3. Bowman’s capsular hydrostatic pressure 4. Bowman’s capsular colloid osmotic pressure5. Surface Area6. “Membrane Permeability”= thickness 7. Renal blood flow

25-How the regulation of GFR is done?| the methods of regulation in GFR?

1. Extrinsic mechanisms2. Intrinsic mechanisms by Autoregulation

26-What are the Extrinsic mechanisms?• sympathetic nervous system(autonomic) • Baroreceptor reflex (mainly autonomic also)

27-What is the Intrinsic mechanisms ?• Myogenic mechanism• Tubuloglomerular feedback (TGF)

28-What is Myogenic mechanism?increase pressure in capillary, the capp will be stretched , the stretching will cause entry of ca into smooth muscle = constriction of capillary So stretch =

29-What is Tubuloglomerular feedback (TGF)?It’s the func of Juxtaglomerular Apparatus Detects how much Na+ loss or reabsorbed in blood ..will make it balanced

30- what is Effect of Afferent Arteriolar Constriction of FGR?

GFR, Renal Blood Flow

31-What is the Effect of Efferent Arteriolar Constriction of FGR?

GFR, Renal Blood Flow

32-What is the Filtration Fraction (FF) and how much is it ?ratio of the GFR to the renal plasma flow (GFR/TRPF).

33-How much of blood flow goes to kidney= renal blood flow ?– 20-25% of total cardiac output. = 1 L/min

34-Out of that how much plasma supply to kidney ?• 625 ml • Out of that 125 ml is filtered

35-So Filtration fraction normal value ? (GFR/TRPF) = 0.2( 20%)

Measurement of GFR:• Characteristic of substance used for measurement:

– 1- Freely filtered (not reabsorbed not secreted)– 2- Not metabolized by the kidney– 3- Not toxic and stable– 4- Not bound to plasma protein– 5- Does not change renal plasma flow

36-Substance used to Measurement of GFR?– Inulin

lec3

37-Transport mechanism used in reabsorption ?

active

Primary active

Sodium-potassium pumps in

basolateral

membrane.

Secondary activeco-

transport (glucose, amin

o acids

, fatty acid)

counter-

transport (K+, H+)

passive

38-What are the Substance utilize for co-transport for many substances in renal tubule ?

Na+ (sodium )-GLUT depends on ? Facilitated diffusion

39-Glucouse utilizes which type of transport? co-transport or 2ry active transport

40- H+ ion utilizes which type of transport ? mostly counter-transport

41-Common Substances Reabsorbed in PCT:– Sodium 65%– Chloride 50%– Glucose 100%– Water 65%– Amino acid 100%– Bicarbonate 90%– Phosphate– Urea

42-What is the specialty of Loop of Henle?descending limb: highly permeable to waterAscending limb: only permeable to electrolyte and impermeable to water.

43-What is the specialty Late DCT and Cortical Collecting Tubule?Hormone regulation - Which Hormone can control the Permeability of

substances in Water? Anti diuretic Hormone (ADH) or Vasopressin

44-What are the type of cells present in the segment ?Principal cells +Intercalated cells

45-What is the function of Principal cells ? Have receptors for hormones like aldosterone , help in

reabsorption of electrolytes 46-What is the function of Intercalated cells?

Acid base balance , control reabsorb and excretion of H+ ions and Bicarb

47-Medullary Collecting Duct importance?– Last step where any change can occur into the tubular

fluid , after that the tubular fluid is passed on as urine48-What are the factors or mech that help in reabsorption?– Mostly hormones (aldosterone, angiotensin II,(ADH)…

etc.)– Then same forces, pressures in GFR

49- What is pressure natriuresis ? blood pressure, loss of NA+

50- What is Pressure diuresis ? blood pressure , loss of H2O

Na+ sodium51-Where’s reabsorbed? in the tubule (including aescending limb of Loop of Henle) except descending limb of Loop of Henle 52-What’s the effect of aldosterone on Na+? NA reabsorption53-What’s the effect of aldosterone on K+?

K+ excretionAldosterone : البوتاسيوم طارد الصوديوم صائد54-What’s the effect of Na on urea and chloride ?

their reabsorption by passive transport

Just remember that

Tubular Reabsorption – Sodium:• Proximal convoluted tubule 65 - 67%• Loop of Henle (thick ascending limb) 25 %• Distal and Collecting Tubule 8 %

Tubular Reabsorption – Water:• Proximal convoluted tubule (PCT) – 60-70%. It is passive.• Loop of Henle(Descending Limb) – 15%.• DCT and CT – 20%. DCT – 5%. CT – 15%.• In DCT and CT, water is reabsorbed under the action of

ADH (Anti-Diuretic Hormone) or Vasopressin.

Lec 4 55-How’s glucose reabsorbed?

Co-transportation or 2ry active transport 56-Whare glucose is reabsorbed?

PCT57-How much of glucose is reabsorbed by PCT? 100% 58-What is Tubular Maximum (Tm) of glucose ?

the maximum amount of glucose which can be reabsorbed after that point glucose appears in

urine59-Normal value of Tm?

375 mg/minute.

60-What is the renal threshold concentration of glucose at which glucose will appear in the urine

61-Normal value or the renal threshold ? 180mg % - 200mg %.62-Urea reabsorbed?

proximal tubule63-Urea secreted ?

loop of Henle. 64-reabsorbed again in?

the medullary collecting duct65-Under the influence of?

Hormones

66-What is Obligatory Urine Volume?minimum amount of urine which has to be

formed in excretion of harmful substance each day 67-Normal value of Obligatory Urine Volume?

0.5 L/day

Lec 5 68-What are the substance important for secretion:

H+ and K+ 69-Factors affect secretion?

1. Diet 2. Aldosterone3. Acid base balance

70-What is the affect of H+ ion on K+ secretion ? – Whenever Acidosis (H+) , K+ retention occurs , so

hyperkalemia will occur

Normal values

GFR value: 125ml/min or 180L/dayNet filtration Pressure value: 10mmHgRenal blood flow : 20-25% of total cardiac output. = 1 L/miPlasma supply to kidney: 625 ml Filtration fraction normal value: 0.2( 20%)Tm: 375 mg/minute.Renal threshold: 180mg % - 200mg %.Obligatory Urine Volume: 0.5 L/day