Lecture 1-2: Role of Kidney Homeostasis and Clinical Cases

Flashcards covering key concepts from the PY511 Renal case notes: glomerular physiology, GFR regulation, transporters, hormones, urine concentration, acid-base regulation, and clinical scenarios.

What clinical condition could these symptoms indicate?

Acute kidney injury/acute renal failure (possible uremia); requires evaluation of kidney function and history.

Net filtration pressure in the glomerulus (as given in the notes)

Net pressure = 55 mmHg (blood hydrostatic) − [15 mmHg (filtrate hydrostatic) + 30 mmHg (oncotic)] = 10 mmHg.

What is the normal mean arterial pressure (MAP) range to ensure safe organ perfusion?

Approximately 70–100 mmHg.

GFR is regulated by two main pathways. Name them.

Intrinsic (autoregulation: myogenic response and tubuloglomerular feedback) and Extrinsic (neural and hormonal—RAAS/ANP).

Describe the myogenic response.

Increased blood pressure stretches the afferent arteriole, activating stretch-activated Na channels, causing vasoconstriction to protect the glomeruli and maintain GFR.

Describe tubuloglomerular feedback (TGF).

Increased NaCl delivery to the macula densa triggers signaling (ATP → adenosine) causing afferent arteriolar vasoconstriction to reduce GFR.

What triggers adenosine release in TGF and what is its effect?

Increased NaCl delivery to macula densa leads to ATP/adenosine release, which constricts the afferent arteriole via A1 receptor signaling.

What is the extrinsic neural regulation of renal blood flow during reduced blood volume?

Sympathetic activation releases noradrenaline, constricting afferent/efferent arterioles and reducing filtration to preserve volume.

What are the major hormonal components of the RAAS pathway?

Renin converts angiotensinogen to Angiotensin I; ACE converts Ang I to Ang II; Ang II promotes vasoconstriction and stimulates aldosterone release.

What is the effect of atrial natriuretic peptide (ANP) on the kidney?

Vasodilates the afferent arteriole, inhibits renin, increases GFR, and promotes salt and water excretion—opposes RAAS.

How does ADH affect the collecting duct?

ADH increases water reabsorption by inserting aquaporin-2’s into the apical membrane of collecting duct cells.

Which receptor mediates ADH signaling in the collecting duct?

V2 receptor (Gs → cAMP → PKA pathway).

Name key transporters in the proximal tubule for reabsorption.

SGLT2 and SGLT1 (glucose/Na+ cotransport), Na+/H+ exchanger, Na+/K+-ATPase; water reabsorption via aquaporins; general paracellular transport with Na+.

Which transporter is the NKCC2 transporter and where is it located?

NKCC2 is the Na+-K+-2Cl− cotransporter in the thick ascending limb responsible for Na+, K+, and Cl− reabsorption.

Which transporter reabsorbs Na+ and Cl− in the distal convoluted tubule?

Na+-Cl− cotransporter (NCC).

Which channel mediates Na+ reabsorption in the collecting duct?

ENaC (epithelial Na+ channel).

What is the effect of aldosterone on nephron transporters?

Upregulates Na+/K+-ATPase and ENaC, increasing Na+ reabsorption and K+ secretion.

What are the effects of ANP on renal function and blood pressure regulation?

Vasodilation of the afferent arteriole, inhibition of RAAS, increased GFR, increased Na+/water excretion, and lowered blood volume/pressure.

List the three main mechanisms contributing to urine concentration.

Countercurrent multiplier, urea recycling, and ADH-mediated water reabsorption.

What are normal ranges for urine osmolarity and urine specific gravity?

Urine osmolarity: 300–900 mOsm/kg (24-hour typically 500–800; after restriction >850 mOsm/kg). Specific gravity: 1.005–1.03 (dehydration ≥ 1.035).

What does a urine osmolarity > 850 mOsm/kg after fluid restriction indicate?

Concentrated urine indicating effective renal concentrating ability (often dehydration).

What is the first step of urine formation?

Glomerular filtration in the renal corpuscle, filtering unbound small molecules.

What is the Glomerular Filtration Rate (GFR) a measure of?

The rate at which plasma is filtered into the nephron; normal GFR is about 90–120 mL/min/1.73 m2.

What is the Cockcroft-Gault equation used for and what is the sex factor as given in the notes?

Used to estimate creatinine clearance (CrCl). CrCl = (140 − age) × weight × F / Creatinine; F = 1.04 for females, 1.23 for males (creatinine in micromol/L in these notes).

Where does protein reabsorption occur and how is it processed?

In the proximal tubule via pinocytosis; proteins in small amounts are reabsorbed and amino acids returned to blood; proteinuria indicates glomerular damage.

How do the kidneys participate in acid-base balance (pH homeostasis)?

Filter/reabsorb HCO3−, excrete H+, interact with respiratory CO2 exchange; plasma buffers (proteins, phosphate, bicarbonate) maintain pH in 6.8–7.8.

Describe the renal compensatory response to metabolic acidosis (e.g., ketoacidosis).

Hyperventilation to blow off CO2; kidneys excrete H+ and reabsorb HCO3− to raise pH.

Describe the renal compensatory response to metabolic alkalosis (e.g., vomiting).

Hypoventilation to retain CO2; kidneys reabsorb H+ and excrete HCO3− to lower pH.

Describe the renal compensatory response to respiratory alkalosis (e.g., panic attack with hyperventilation).

Renal compensation: excrete HCO3− and reabsorb H+ to decrease pH and restore balance.

Describe the renal compensatory response to respiratory acidosis (e.g., opioid overdose, COPD).

Renal compensation: increase HCO3− reabsorption and H+ secretion to raise pH.

What general nephron sequence should you know from the afferent arteriole to the collecting duct?

Afferent arteriole → glomerulus (capillaries) → Bowman's capsule → efferent arteriole → proximal tubule → descending limb → loop of Henle → ascending limb → distal tubule → collecting duct.

What are the three main steps of urine formation mentioned in the notes?

Filtration (glomerular), Reabsorption (tubular), Secretion (into tubule).

ADH stands for

Anti-diuretic hormone

Vasopressin and AVP or 8-arginine-vasopressin are alternative names for what hormone?

ADH

Actions of Antidiuretic Hormone

ADH interacts with V2 receptors on basolateral surface of principle cells in collecting duct of tubule

Permeability to water is now increased, water enters via aquaporin-2 channels on apical surface

(salt does not follow)

Why is aquaporin-2 phosphorylated?

IT will cause the aquaporin channel to stay open (check)

Alcohol affects ADH how?

Inhibits causing you to pee more

ADH is released in response to changes in plasma osmolality and effective circulating volume or ECV. What detect these changes?

Osmoreceptors and baroreceptors