Niere (2), full

What are the most important organs for eliminating metabolic waste from the blood?

The Nieren (kidneys), which also clear drugs from the body

From where do the kidneys receive blood?

The kidneys receive blood from the renal arteries, which branch from the abdominal aorta.

What is the kidney’s role in the homeostasis of water and electrolytes?

The kidney is the main organ that regulates the concentration of sodium, potassium, calcium, magnesium, phosphate, protons, and bicarbonate in the blood, and it regulates the water content of the body.

Renin

A protease that control the formation of the hormone angiotensin.

Calicrein

A protease that controls the vasodilating and thereby pain-causing hormone bradykinin.

What is the kidney’s role in metabolism

Kidneys can produce ammonia from circulating amino acids and can, under certain circumstances, become the main source for the production of glucose.

What is the glomerulus?

The glomerulus, which is about 200 µm in diameter, is formed by the invagination of a tuft of capillaries into the dilated, blind end of the nephron (Bowman’s capsule).

What happens to the distal ends of the capillaries of each glomerulus?

The distal ends of the capillaries of each glomerulus coalesce to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surround the renal tubules.

What is unique about renal circulation?

• Renal circulation has two capillary beds:

  • Glomerular capillaries

  • Peritubular capillaries

• These capillary beds are arranged in series and separated by the efferent arterioles

• The efferent arterioles help regulate the hydrostatic pressure in both capillary beds

• The peritubular capillaries empty into the venous system, which progressively forms:

  • Interlobular vein

  • Arcuate vein

  • Interlobar vein

  • Renal vein

• The renal vein leaves the kidney beside the renal artery and the ureter

What weight does a typical kidney have in males and females?

Approximately 150g in males and 120g in females

How many lobes does each human kidney consist of?

Approximately 14 Nierenlappen (renal lobes)

Which two main regions make up an individual lobe of the kidney?

The Nierenrinde (cortex) and the Nierenmark (medulla)

What funnel-like structure collects urine before it is drained to the ureter?

The Nierenbecken (renal pelvis), which is connected to the Kelche (calyces)

What percentage of cardiac output goes to the kidneys in a sedentary human?

Approximately 20%, which is about 1 liter of blood per minute

Name four specific waste products that the kidney clears from the blood.

Harnstoff (urea), Harnsäure (uric acid), Ammonium, and Kreatinin (creatinine)

What substance is a product of muscle metabolism and serves as a vital indicator of kidney function?

Kreatinin (creatinine)

Name three substances that the kidney must actively retrieve or reabsorb from the filtrate.

Glucose (sugar), Laktat (lactate), and Aminosäuren (amino acids)

Which kidney hormone controls the production of red blood cells?

Erythropoietin (EPO), with 85% produced in the kidney and 15% in the liver

Which kidney hormone is involved in controlling platelet production?

Thrombopoietin

What is the functional unit of the kidney called?

The Nephron, and there are about 1 million per human kidney

What are the three primary processes that form urine in a nephron?

Filtration (in the glomerulus), Reabsorption (tubular reabsorption), and Sekretion (tubular secretion)

What characterizes a “panel B substance”?

• It is freely filtered at the glomerular capillaries

• It is partly reabsorbed from the tubules into the blood

• Therefore, the rate of urinary excretion is less than the rate of filtration

• Excretion rate = Filtration rate − Reabsorption rate

• Examples: Electrolytes

What characterizes a “panel D substance”?

• It is freely filtered at the glomerular capillaries

• It is not reabsorbed from the renal tubules

• It is secreted from the peritubular capillary blood into the tubules

• Therefore it is rapidly cleared from the blood and excreted in large amounts

• Excretion rate = Filtration rate + Tubular secretion rate

What special structural characteristics contribute to the high filtration rate in the glomerulus?

• High filtration rate is partly due to special structural features:

  • Perforation of the endothelium with structures called fenestrae

  • (Fenestrated capillary endothelium)

What is the function of the glomerular filtration barrier?

• Selective based on the size and electrical charge of the molecules.

• The filtration barrier allows small molecules to freely diffuse through

• It retains high molecular weight molecules, such as proteins, in the blood plasma

What drives glomerular filtration and how can glomerular filtration rate (GFR) be measured?

• The driving force for filtration is the pressure difference between the plasma and the proximal tubule

• The glomerular filtration rate (GFR) can be experimentally measured by determining the clearance of a particular substance

What happens to clearance when a substance is completely extracted from plasma in one renal passage, and what is an example?

• If a substance is completely extracted from plasma in one passage through the kidney:

  • A portion is removed by filtration (e.g., 20%)

  • The remaining is removed by secretion (e.g., 80%)

• Its clearance depends only on renal plasma flow

• This is called “flow-limited” clearance

• Example: para-amino hippurate (PAH)

What forces determine net filtration pressure in the glomerulus?

• Net filtration pressure is the sum of hydrostatic and colloid osmotic forces

• These forces include:

  • Glomerular capillary hydrostatic pressure → promotes filtration

  • Bowman’s capsule hydrostatic pressure → opposes filtration

  • Glomerular capillary colloid osmotic pressure (oncotic pressure) → opposes filtration

  • Bowman’s capsule colloid osmotic pressure → promotes filtration

• Under normal conditions, the colloid osmotic pressure in Bowman’s capsule is zero

How do colloid osmotic pressure and hydrostatic pressure behave in glomerular capillaries?

• The colloid osmotic pressure in the capillary is largely determined by the concentration of albumin in the blood plasma and remains rather constant

• The hydrostatic pressure in the capillary is determined by blood pressure and varies

What happens to GFR if blood pressure changes are not compensated by the kidney?

• If changes in blood pressure are not compensated by the kidney:

  • The glomerular filtration rate (GFR) would change tremendously in response to blood pressure changes

What are the two mechanisms of glomerular autoregulation?

1. Myogenic autoregulation:

• Constriction of the afferent arteriole

• Lowers local blood pressure

• Leads to a decrease in GFR

2. Tubuloglomerular feedback (renin–angiotensin system):

• Based on macula densa cells in the distal tubule

• Macula densa measures NaCl concentration

• NaCl increases when GFR increases

• Increased NaCl leads to inhibition of the renin–angiotensin system

• This helps regulate arterial pressure

What is the role of different parts of the renal tubule in reabsorption and secretion?

• Different parts of the tubular system are responsible for specific reabsorption/secretion functions

• Proximal tubule:

  • Reabsorbs ~60% of water

  • Reabsorbs ~60% of NaCl

  • Reabsorbs ~90% of bicarbonate

  • Reabsorbs ~99% of glucose

  • Reabsorbs almost 100% of amino acids

• Ion handling (K⁺, Ca²⁺, Mg²⁺):

  • Cations are removed from the primary urine in specific tubular compartments (as shown in Figure 2.15)

• Reabsorption and secretion processes involve both:

  • Active transport

  • Passive transport

• This represents functional compartmentalization along the nephron

What are the main processes for sodium transport in the proximal tubule?

• Sodium is transported across the proximal tubule by at least 3 processes:

  • 1. Co-transport with organic solutes:

    • Na⁺ is co-transported with glucose or amino acids

  • 2. Na⁺/H⁺ exchange:

    • Exchange of protons (H⁺) with sodium (Na⁺)

    • Linked to bicarbonate (HCO₃⁻) reabsorption

    • H⁺ is produced from H₂CO₃ / HCO₃⁻ system

  • 3. Co-transport of Na⁺ and Cl⁻:

    • Entry of Na⁺ and Cl⁻ into epithelial cells

    • Called “solvent drag”

What are the structural and functional characteristics of the thin descending and thin ascending limbs of the loop of Henle?

• The thin descending and thin ascending segments have:

  • Thin epithelial membranes

  • No microvilli

  • Few mitochondria

  • Minimal metabolic activity

• In the loop of Henle:

  • Most water reabsorption occurs

  • Almost all of this reabsorption occurs in the thin descending segment

What are the structure and function of the thick ascending limb of the loop of Henle?

• The thick segment of the loop of Henle begins about halfway up the ascending limb

• It has:

  • Thick epithelial cells

  • High metabolic activity

• Functions:

  • Actively reabsorbs sodium (Na⁺), chloride (Cl⁻), and potassium (K⁺)

  • About 25% of Na⁺, Cl⁻, and K⁺ are reabsorbed in the loop of Henle, mostly in this segment

  • Also reabsorbs calcium, bicarbonate, and magnesium

• Transport mechanism:

  • Specific transporters move Na⁺, Cl⁻, and K⁺ into the interstitial fluid

  • Main driving force is the Na⁺/K⁺-ATPase

• Functional result:

  • No water permeability (selective water impermeability implied)

  • Increases salt concentration of urine

  • Decreases urine volume

What are the major factors contributing to the high osmolarity of the renal medulla?

The kidneys concentrate urine by building up solutes in the renal medulla through:

• 1. Active transport from thick ascending loop of Henle:

  • Na⁺ is actively transported

  • Co-transport of K⁺, Cl⁻, and other ions into the medullary interstitium

• 2. Active transport from collecting ducts:

  • Ions are transported from the collecting ducts into the medullary interstitium

• 3. Urea recycling:

  • Facilitated diffusion of urea from inner medullary collecting ducts into the medullary interstitium

• 4. Limited water diffusion:

  • Only small amounts of water diffuse from medullary tubules into the interstitium

What features help preserve the high ion concentration in the renal medulla?

• Two important features maintain the high ion concentration in the renal medulla:

  • Low medullary blood flow

  • The vasa recta acts as a countercurrent exchanger

How does the countercurrent exchange mechanism in the vasa recta operate?

• Plasma flowing down the descending limb of the vasa recta becomes more hyperosmotic due to:

  • Diffusion of water out of the blood vessel

  • Diffusion of solutes into the blood from the renal interstitial fluid

• In the ascending limb of the vasa recta:

  • Solutes diffuse back into the interstitial fluid

  • Water diffuses back into the vasa recta

What is the mathematical formula for the Harnausscheidung (urinary excretion rate)?

Excretion rate = filtration rate - reabsorption rate + secretion rate

Describe the renal handling of a "Panel A" substance like Inulin or Kreatinin.

It is freely filtered but neither reabsorbed nor secreted, meaning its excretion rate equals its filtration rate

Describe the renal handling of Glucose or Aminosäuren in a healthy kidney.

They are freely filtered but 100% rückresorbiert (reabsorbed) into the blood, so their excretion rate is zero

What are the three major layers of the glomerular filter?

The capillary Endothel (endothelium), the Basalmembran (basement membrane), and the Podozyten (podocytes)

What are the perforations in the glomerular capillary endothelium called?

Fenestrae (fenestrations)

What proteins primarily make up the Glomeruläre Basalmembran (glomerular basement membrane)?

Laminine and Kollagene (specifically type IV collagen)

What are the foot-like processes of Podozyten called and what do they form?

Podozytenfortsätze (foot processes), which are separated by gaps called Schlitzdiaphragma (slit diaphragms)

On what two physical properties is glomerular filtration selectivity based?

Größe (molecular size) and Ladung (electrical charge)

Why do negatively charged particles pass through the glomerular filter more with more difficulty?

The basement membrane contains negative Heparansulfat (heparan sulfate), which repels negative particles

What is the definition of Clearance?

The volume of blood plasma (in ml) that is completely freed of a specific substance by the kidneys per minute

What is the mathematical formula for Clearance?

Cl = (Ux / Px) * V, where Ux is concentration in urine, Px is concentration in plasma, and V is urine volume

What is the average Glomeruläre Filtrationsrate (GFR) in a healthy adult male?

Approximately 125 ml/min, which totals about 180 liters of primary urine per day

What substance is the "gold standard" for measuring GFR because it is neither reabsorbed nor secreted?

Inulin, a starch-like polymer of fructose

What value represents the effective renal plasma flow in humans?

Approximately 625 ml/min, which can be measured using PAH (para-amino hippurate)

What pressure "pushes" fluid from the capillary into the Bowman capsule?

Hydrostatischer Druck (hydrostatic pressure), which is roughly 60 mm Hg

What pressure acts as the main counter-pressure to filtration due to proteins in the plasma?

Kolloidosmotischer Druck or onkotischer Druck (colloid osmotic/oncotic pressure), which is about 32 mm Hg

What is the calculated Nettofiltrationsdruck (net filtration pressure) under normal conditions?

Approximately 10 mm Hg

What is the Bayliss-Effekt (Bayliss effect)?

A myogenic mechanism where the afferent arteriole undergoes Vaskokonstriktion (vasoconstriction) in response to high blood pressure to keep GFR constant

Within what range of mean arterial pressure does Autoregulation effectively maintain GFR?

Between 80 and 160 mm Hg

What specialized cells in the distal tubule measure NaCl concentration as part of autoregulation?

The Macula densa

How does the Renin-Angiotensin-System respond to a decrease in GFR sensed by the Macula densa?

It increases Renin and Angiotensin II, causing vasoconstriction of the efferent arteriole to raise filtration pressure

What percentage of filtered water and NaCl is reabsorbed in the Proximaler Tubulus (proximal tubule)?

Approximately 60% to 70%

What is the structural feature of proximal tubule cells that increases their surface area 30-60 times?

The Bürstensaum (brush border), consisting of many microvilli

Why do proximal tubule cells contain a high number of Mitochondrien?

They require massive amounts of ATP to power the Na+/K+-ATPase for active transport

Through what two pathways does water penetrate the epithelial layer in the proximal tubule?

The Parazellulär (paracellular) and Transzellulär (transcellular) pathways

What is the specific transporter responsible for reabsorbing glucose in the proximal tubule?

SGLT-2 (Sodium-Glucose Linked Transporter 2)

What clinical side effect occurs if SGLT-2 Hemmer (inhibitors) are used?

Glukosurie (glucose in the urine), which leads to increased urine volume and thirst

What is Solvent Drag?

A process where the flow of water "drags" dissolved solutes like sodium and chloride between cells into the blood

In what fashion is water reabsorbed in the proximal tubule regarding osmolarity?

In an iso-osmolar (iso-osmotic) fashion, meaning the osmolarity of the remaining urine does not change

Name the three functionally distinct segments of the Henle’sche Schleife (loop of Henle).

The thin descending limb, the thin ascending limb, and the thick ascending limb

Is the absteigender Ast (descending limb) of the loop of Henle permeable to water?

Yes, it is highly wasserdurchlässig, but it is impermeable to ions

Is the aufsteigender Ast (ascending limb) of the loop of Henle permeable to water?

No, it is virtually wasserundurchlässig, but it actively transports ions out

What is the Gegenstromprinzip (countercurrent principle)?

A multiplier system in the loop of Henle that traps solutes to create a high osmotic gradient in the medulla

What is the maximum osmolarity the human kidney can reach in the inner medulla?

Approximately 1,200 to 1,400 mosmol/l

What percentage of the medullary osmolarity is contributed by Harnstoff (urea) during maximum concentration?

Approximately 40% to 50%

How does urea contribute to urine concentration?

It recirculates between the Sammelrohr (collecting duct) and the loop of Henle to maintain medullary hyperosmolarity

What is the role of the Vasa recta in the kidney?

A specialized capillary network that removes reabsorbed water without washing out the medullary salt gradient

Which hormone, also known as Vasopressin, is the main control for water excretion volume?

ADH (Anti-Diuretic Hormone)

Where is ADH produced and what triggers its release?

It is secreted by the Hypophyse (pituitary gland) in response to high plasma osmolarity sensed by receptors in the brain

What receptors does ADH activate in the kidney, and what channels are incorporated as a result?

It activates V2-Rezeptoren, leading to the insertion of Aquaporine (water channels/AQP2) into the collecting duct membrane

What is the osmolarity of urine in a state of excess water (low ADH)?

Approximately 15 to 50 mosmol/l, resulting in large volumes of dilute urine

Which hormone produced in the adrenal gland increases NaCl reabsorption and potassium secretion?

Aldosteron (aldosterone), acting on the collecting tubule and duct

Which peptide hormone decreases NaCl reabsorption in the distal tubule and duct?

Atriales natriuretisches Peptid (ANP)

Which hormone decreases phosphate reabsorption and increases calcium reabsorption?

Parathormon (PTH), acting on the proximal tubule and loop of Henle

What is the primary indicator of a damaged glomerular filter found in urine?

Proteinurie (proteinuria), the appearance of proteins like albumin.

• Prognostic marker of the kidney disease

• Independent risk factor for cardiovascular mortality

• Can progress in 10-50% of patients to chronic kidney disease, which ultimately requires dialyses or transplantation.

What are the general consequences of conditions that affect protein filtration in the kidney?

• Many causes can affect protein filtration (besides genetic diseases)

• Most of these conditions are:

  • Reversible

  • Usually do not cause permanent disease

• If not treated:

  • They can become chronic and progressive

  • May eventually lead to renal failure

What is amino aciduria and what causes it?

• Amino aciduria = failure of the kidneys to reabsorb amino acids

• Amino acids are normally reabsorbed by the tubular system

• Some amino acids share the same transport systems

• Types:

  • Generalized amino aciduria:

    • Very rare

    • Deficient reabsorption of all amino acids

  • Specific amino acid transport defects:

    • More common

    • Affect individual transport systems

    • Examples:

      • Cystinuria (affects cystine reabsorption)

      • Glycineuria (affects glycine reabsorption)

What is renal hypophosphatemia and what are its consequences?

• Renal hypophosphatemia = failure of the kidneys to reabsorb phosphate

• Usually not very severe initially

• Over longer periods can cause:

  • Reduced bone calcification

  • Development of rickets (rachitis)

  • Resulting in soft bones

What is renal tubular acidosis and what causes it?

• Renal tubular acidosis = failure of the renal tubules to secrete hydrogen ions (H⁺)

• Consequences:

  • Inability to secrete adequate amounts of H⁺

  • Continuous loss of sodium bicarbonate (NaHCO₃) in urine

  • Leads to a persistent metabolic acidosis

• Causes:

  • Hereditary disorders

  • Widespread injury of the renal tubules

What genetic disease is caused by mutations in Kollagen 4 and affects the basement membrane?

Alport-Syndrom (Alport syndrome)

What genetic disease involves mutations in Laminin beta-2 and causes nephrosis and microcoria?

Pierson-Syndrom (Pierson syndrome)

What condition describes glucose in the urine despite normal blood sugar levels?

Renale Glukosurie (renal glycosuria), often due to defective tubular transporters

What defines Diabetes insipidus in the context of tubular function?

A failure to respond to ADH (brain problem, receptor defect, or non-functional aquaporins), leading to massive water loss

What is Fanconi’s Syndrom?

A generalized defect in the proximal tubule's ability to reabsorb amino acids, glucose, and phosphate

What treatment is necessary if a patient suffers from irreversible Nierenversagen (renal failure)?

Hämodialyse (hemodialysis) or a kidney transplant

How do Schleifendiuretika (loop diuretics) like Furosemid work?

They block the Na+, K+, 2Cl- Symport in the thick ascending loop of Henle to increase ion and water excretion

Which diuretic group acts on the proximal tubule by inhibiting Karboanhydrase?

Proximale Diuretika (e.g., Acetazolamid)

Which diuretics act on the Frühdistaler Tubulus (early distal tubule) and block NaCl-Symport?

Thiazide (e.g., Hydrochlorothiazid)

What is the target of Kalium-sparende Diuretika (K-sparing diuretics)?

They block Na-Kanäle (sodium channels) or act as Aldosteron-Antagonisten (e.g., Spironolakton)