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Glomerular and tubular Glomerular and tubular dysfunctions dysfunctions Tatár M. Tatár M.

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Page 1: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Glomerular and tubular Glomerular and tubular dysfunctionsdysfunctions

Tatár M.Tatár M.

Page 2: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Basic kidney functionsBasic kidney functions

• Water and electrolyte homeostasis

• Acid – base balance

• Elimination of waste products and ingested chemicals

• Hormone production

Page 3: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 4: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Mechanisms of renal excretionMechanisms of renal excretion

• 180 l glomerular filtrate per day (2 ml/s)

• 99% - back reabsoption

• Renal perfusion at rest = 20% of cardiac output (this is higher than in heart, brain and liver

Page 5: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 6: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 7: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Glomerular filtration rate

• Balance of hydrostatic and osmotic pressures acting across diffusion barrier (endotelium fenestrae, basement nenbrane, slit diaphragms betweens the podocytes)

• Factors determining GFR:– Surface area (1 milion nephrons within each

kidney)– Permeability – Net filtration pressure (NFP) across diffusion

barrier

Page 8: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Factors determining GFR

filtration koefficient (Kf)surface area

permeability

GFR = Kf x NFP

NFP = PGC – PT – GC

24 = 60 - 15 - 21 mmHg

Page 9: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 10: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Disturbances of glomerular function (1)

A. Decrease of glomerular filtration

renal blood flow stenosis of renal artery

glomerular capillary hydrostatic pressure (PGC)hypovolemia, circulatory shock

hydrostatic pressure in Bowman´s capsule (PT)block of fluid flow ( intra- and extrarenal)

concentration of plasma proteins (GC)

Kf

effective filtration surface area

Page 11: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Disturbances of glomerular function (2)

B. Increase of glomerular permeability

Proteinuria

• Glomerular proteinuria

– Size-selective properties of the glomerulus– Charge-selective propeties of the glomerulus– Hamodynamic forces operating across the

glomerulus

Page 12: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 13: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 14: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Glomerular proteinuria

• Selective proteinuria– Albumin– Small amount of low-molecular

globulins

• Non-selective proteinuria– Albumin– Globulins of various molecular

weight

Page 15: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Tubular reabsorption of proteins

Page 16: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Tubular proteinuria

excretion of low molecular proteins

1-microglobulin, 2-microglobulin

Page 17: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Overload (prerenal) proteinuria

• Small molecular weight proteins can rise when are synthetised in excess

– Tissue degraded products– Proteins of acute phase (pyretic

proteinuria)– Myoglobin (rhabdomyolysis)– Ligfht immunoglobulin chains (myeloma)

Page 18: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Proteinuria

• Healthy adult subject– No more than 150 mg/day

• Small proteinuria– 1 g/day

• Haevy proteinuria– 3,5 g/day and more– Nephrotic syndrome (10 – 30 g/day)

Page 19: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Renal hematuria

• Glomerular– Abnormally increased permeability

• Non-glomerular – Rupture of tumor or cyst vessels

• Bleading from urinary tract

Page 20: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Relation between the reduction of GFR and excretion function of kidneys

GF GF retention of substratesretention of substrates

1.1.urea, urea, ccreatinínreatinín

2.2.phosphatesphosphates, K, K++, H, H++

3.3.NaClNaCl

Page 21: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products
Page 22: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Tubular reabsorption and secretion

Page 23: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Active transport

Page 24: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Reabsorption of glucose, amino acids, Na, K, Cl, H2O

Proximal tubule Thick ascending limbof loop of Henle

Distale tubule

Page 25: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Disturbances of tubular functions

• Tubular proteinuria• Glucosuria • Aminoaciduria

• Diabetes insipidus– Neurogenic ( ADH)– Nephrogenic (insensitivity of the renal tubule to ADH)

• Osmotic diuresis– Pressure of large quantities of unreabsorbed solutes

in the renal tubules increase in urine volume– Unreabsorbed solutes in the proximal tubules „hold

water in the next tubules“

Transport maximum

Page 26: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Hydrogen ion secretion and bicarbonate reabsorption

Renal tubular acidosis - impairment of the ability to make the urine acidic - chronic renal disease – reduction of secreted hydrogen ion because of impaired renal tubular production of NH4

+

Page 27: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Loop of Henle and production of concentrated urine

- Permeability for water and NaCl

- ADH

Page 28: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Counter-current exchange in the vasa recta

Page 29: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Disturbances of kidney ability to concentrate urine

A. Disturbances of water reabsorption- diabetes insipidus

B. Disturbances of the production of medullar hyperosmolarity

- osmotic diuresis- blood flow in vasa recta- morphologic deformations of medulla

Page 30: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Nephrotic syndrome

• Proteinuria: 3.5 g or more of protein in the urine per day– Minimal changes of glomerular membrane: 90%

albumin (selective proteinuria)

• Hypoproteinemia (hypoalbuminemia)– Mechanisms: proteinuria +

– Protein loss by stool– Plasma proteins are shifted to extravascular space– Increased albumin katabolism– Inadequately increase albumin synthesis in liver

• Hyperlipidemia– Incresed lipoprotein synthesis in liver

• Generalised edema

Page 31: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Mechanisms of edema in nephrotic syndrome (NS)

• Classis theory– Hypoalbuminemia plasma oncotic pressure

hypovolemia R-A-A + ADH Na + water retention

• !!! But hypovolemia is present only in 30% of patients suffering from NS; plasma renin activity and aldosteron are decreased

• Two groups of patients with NS:1. Hypovolemia and R-A-A activity

- small glomerular abnormalities

2. Hypervolemia without R-A-A activation- more serious morphological abnormalities

Page 32: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Pathophysiology of edema formation

• Extracellular fluid volume is determined by the balance between Na intake and its renal excretion

• Common feature: renal salt retention despite progressive expaansion of ECF volume

– Primary abnormality of the kidney– Secondary response to some disturbances in the

circulation

Page 33: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Primary edema (overfill)

• Primary defect in renal sodium excretion

– Hyperevolemia leads to high cardiac output

R-A-A, ADH, sympathetic activity

Examples: blomerulonephritis, renal failure

Page 34: Glomerular and tubular dysfunctions Tatár M.. Basic kidney functions Water and electrolyte homeostasis Acid – base balance Elimination of waste products

Secondary edema (underfill)

• Response of normal kidnay to actual or sensed underfilling of the circulation

– Primary disturbances within the circulation secondary triggers renal sodium retention

R-A-A, ADH, sympathetic activity

– Effective arterial blood volume