Renal System (Lectures 16-18) (copy)

A WET BED

A - Acid-base balance

W - Waste removal

E - Erythropoeitin

T - Toxin removal

B - Blood Pressure

E - Electrolytes

D - vitamin D (activation)

What are the 3 internal regions of the kidney, outside to inside?

1. Renal cortex (outer, light, granular — site of glomerular filtration)

2. Renal medulla (darker — contains medullary pyramids with collecting ducts)

3. Renal pelvis (funnel-shaped collecting space → drains into ureter)

What are the 3 supportive layers around the kidney, from outside to inside?

1. Renal fascia (outermost — dense fibrous CT, anchors kidney + adrenal)

2. Perirenal fat capsule (middle — cushions, anchors ureters in position)

3. Fibrous capsule / renal capsule (innermost — prevents infection spreading in)

Trace the path of urine from the collecting duct to leaving the kidney.

Collecting duct → papillary duct → papilla → minor calyx → major calyx → renal pelvis → ureter

Trace the arterial blood supply from the renal artery to the glomerulus.

Renal artery → segmental arteries → interlobar arteries (travel through renal columns) → arcuate arteries (arch along cortex-medulla junction) → cortical radiate arteries → afferent arterioles → glomerulus

What is the difference between renal columns and medullary pyramids?

Medullary pyramids = cone-shaped darker tissue in medulla; contain collecting ducts (give striped appearance).

Renal columns = extensions of lighter cortical tissue that dip DOWN between the pyramids; they carry blood vessels to/from cortex.

What is the trigone and why is it clinically important?

The trigone is the smooth triangular region on the bladder floor, outlined by the 2 ureteral openings and the 1 urethral opening. It's clinically important because urinary tract infections tend to persist in this region (some urine always remains there after voiding).

What are the components of the juxtaglomerular complex (JGC) and what does each do? (3)

Granular cells (JG cells): in wall of afferent arteriole; modified smooth muscle; mechanoreceptors; secrete renin.

Macula densa cells: in ascending limb / early DCT wall; chemoreceptors; monitor NaCl concentration in filtrate; regulate GFR.

Extraglomerular mesangial cells: between arteriole and tubule; gap junctions; pass signals between granular and macula densa cells.

Cortical vs. juxtamedullary nephrons — what are the key differences?

Cortical (85%): short nephron loop, glomerulus in outer cortex, efferent arteriole → peritubular capillaries, mainly salt handling.

Juxtamedullary (15%): long nephron loop dipping deep into medulla, glomerulus near cortex-medulla junction, efferent arteriole → vasa recta, critical for water conservation (osmotic gradient).

What is the difference between peritubular capillaries and vasa recta?

Both arise from efferent arterioles and are low-pressure.

Peritubular capillaries: associated with cortical nephrons; random network around PCT and DCT; reabsorb substances from tubule cells.

Vasa recta: associated with juxtamedullary nephrons only; long straight parallel vessels running alongside nephron loops into medulla; maintain the medullary osmotic gradient; critical for producing concentrated urine.

What are the two cell types in the collecting duct and what does each do?

Principal cells: sparse, short microvilli; maintain body's water and Na⁺ balance (respond to ADH and aldosterone).

Intercalated cells: abundant microvilli; maintain acid-base balance (types A and B — secrete H⁺ or HCO₃⁻).

Why is the glomerulus different from every other capillary bed in the body?

Every other capillary bed is fed by an arteriole and drained by a VENULE. The glomerulus is fed by an afferent arteriole AND drained by an EFFERENT arteriole. This arteriole-to-arteriole arrangement maintains high pressure (~55 mmHg) needed for filtration.

What are the 3 layers of the filtration membrane, from blood side to capsule side?

1. Fenestrated capillary endothelium (pores let all pass except blood cells)

2. Basement membrane (negatively charged — repels plasma proteins; keeps them in blood)

3. Podocyte visceral layer of glomerular capsule (filtration slits between foot processes/pedicels)

Calculate net filtration pressure: HPg = 55, OPg = 30, HPc = 15 (all in mmHg).

GFR (glomerular filtration rate) = total filtrate formed per minute by both kidneys = 125 ml/min.Determined by: (1) total surface area of filtration membranes, (2) permeability of filtration membrane, (3) net filtration pressure (NFP).

What is the difference between filtrate and urine?

 Filtrate = plasma minus proteins (everything small enough passes through the filtration membrane; enters Bowman's capsule).

Urine = filtrate minus nutrients (glucose, amino acids), essential ions, and 99% of water (all reabsorbed as filtrate travels through tubules). 180 L filtrate/day → only ~1.5 L urine.

Describe the myogenic mechanism for GFR autoregulation.

When systemic BP rises, increased pressure stretches the smooth muscle of the afferent arteriole → it contracts (vasoconstriction) → restricts blood entering glomerulus → prevents ↑ GFR.When BP falls → smooth muscle relaxes (vasodilation) → more blood enters → maintains GFR.This is an intrinsic property of vascular smooth muscle.

Describe the tubuloglomerular feedback mechanism.

Directed by macula densa cells in ascending limb/early DCT.High NaCl (fast flow = GFR too high): macula densa releases ATP → vasoconstriction of afferent arteriole → ↓ GFR → slows flow → more time for reabsorption.Low NaCl (slow flow = GFR too low): less ATP released → vasodilation → ↑ GFR.

What are the 3 triggers for renin release from granular cells?

1. Sympathetic nervous system stimulation (baroreceptor reflex activates β₁-adrenergic receptors on granular cells)

2. Macula densa cells sense low NaCl in filtrate (slow-flowing filtrate from ↓ GFR) → signal granular cells

3. Reduced stretch of granular cells (low arterial BP directly detected as less membrane stretch)

What happens to GFR and kidney function when systemic BP drops below 80 mmHg?

Renal autoregulation fails below 80 mmHg (hypovolemic shock territory). Extrinsic controls take over — sympathetic nervous system shunts blood to heart and brain, drastically reducing renal blood flow. GFR can drop to near zero → risk of acute renal failure / anuria if prolonged.

Internal vs. external urethral sphincter — what type of muscle? What type of control?

Internal urethral sphincter: smooth muscle (thickening of detrusor); involuntary; controlled by autonomic NS.

External urethral sphincter: skeletal muscle; voluntary control; located at level of urogenital diaphragm.

What 3 things must happen simultaneously for micturition to occur?

1. Detrusor muscle must contract

2. Internal urethral sphincter must open

3. External urethral sphincter must open

Bladder stretch receptors → sacral spinal cord → parasympathetic excitation (1+2) + somatic inhibition (3).

What drives secondary active transport in tubular reabsorption, and what substances does it reabsorb?

The Na⁺-K⁺ ATPase on the basolateral membrane pumps Na⁺ out of the tubule cell, keeping intracellular Na⁺ low. This creates a gradient that pulls Na⁺ into the cell from the filtrate via apical cotransporters. These cotransporters simultaneously carry glucose, amino acids, vitamins, lactate, and some ions into the cell. This accounts for 80% of all active transport ATP usage in the kidneys.

What is the transport maximum for glucose, and what happens when it is exceeded?

The transport maximum (Tm) for glucose is 375 mg/min. This means all carriers are saturated and cannot reabsorb more than 375 mg/min. The plasma concentration at which this occurs (renal threshold) is ~300 mg/100 mL. Above this, filtered glucose exceeds the Tm, and the excess appears in urine (glycosuria). Every mg/min above 375 stays in the filtrate and is excreted.

Why is creatinine useful for estimating GFR?

Creatinine is freely filtered at the glomerulus and is NOT reabsorbed by the tubules. Because 100% of filtered creatinine stays in the filtrate and is excreted, measuring plasma and urine creatinine concentrations lets you back-calculate the GFR without needing to infuse inulin.

Distinguish obligatory vs. facultative water reabsorption. Where does each occur?

Obligatory: always occurs regardless of hydration status; aquaporins are permanently present in PCT and descending limb of loop — water MUST follow solutes; not regulated by hormones.

Facultative: occurs in DCT and collecting duct; regulated by ADH; variable depending on body's need to conserve or excrete water. ADH inserts aquaporins into principal cell apical membranes → more water reabsorbed when needed.

Why is the descending limb permeable to water but not salt, while the ascending limb is permeable to salt but not water? What is the net result?

Descending limb: has aquaporins (water channels) but no NaCl transporters → water leaves by osmosis as filtrate descends into the increasingly hypertonic medulla → filtrate reaches up to 1200 mOsm at the bend.

Ascending limb: has Na⁺-K⁺-2Cl⁻ cotransporters but NO aquaporins → NaCl is actively pumped out into the medullary interstitium, but water cannot follow → filtrate becomes dilute (as low as 100 mOsm at the top).

Net result: the loop first concentrates, then dilutes the filtrate, reducing filtrate volume overall and building a steep medullary osmotic gradient.

What role do the vasa recta play in the countercurrent mechanism?

The vasa recta are straight capillaries associated with juxtamedullary nephrons. They passively equilibrate with the surrounding medullary interstitial fluid as blood flows down and back up. They pick up reabsorbed water and solutes and return them to the circulation WITHOUT washing away the osmotic gradient — because they equilibrate gently in both directions rather than flushing solutes out in one pass.

Why can't a severely malnourished person concentrate urine effectively?

The medullary osmotic gradient depends partly on urea recycling from the collecting duct into the medullary interstitium. Urea comes from protein catabolism. A severely malnourished person has very low protein intake → produces much less urea → the deep medullary gradient is weaker (maybe 800–900 mOsm instead of 1200 mOsm) → even with maximal ADH, less water can be pulled out of the collecting duct → urine cannot be concentrated as effectively.

What stimulates (2) ADH release, and what are its two mechanisms of action?

Stimuli:

(1) rise in plasma osmolarity above ~300 mOsm (detected by hypothalamic osmoreceptors — main day-to-day trigger),

(2) large drops in blood volume or pressure (baroreceptors + renin-angiotensin).

Actions:

(1) inserts aquaporins into apical membranes of principal cells in collecting ducts → water reabsorption → small, concentrated urine,

(2) at very high concentrations acts as vasopressin → arteriole constriction → ↑ BP.

Trace the RAAS pathway from low blood pressure to increased blood volume.

Low BP → granular cells of JGC release renin (triggered by sympathetic NS, macula densa sensing low NaCl in filtrate, or reduced stretch of granular cells) → renin converts angiotensinogen (liver protein) → angiotensin I → ACE (in lungs) → angiotensin II → (1) systemic vasoconstriction → ↑ BP, (2) adrenal cortex releases aldosterone → aldosterone acts on DCT/collecting duct principal cells → ↑ Na⁺ reabsorption + K⁺ secretion → water follows Na⁺ → ↑ blood volume → ↑ BP.

How does ANP oppose the RAAS? What triggers its release?

Trigger: heart atria are stretched by elevated blood pressure/volume. ANP then: inhibits Na⁺ reabsorption in collecting ducts, suppresses ADH, renin, and aldosterone release, causes vasodilation.

Net: ↑ Na⁺ and water excretion → ↓ blood volume and pressure. ANP is essentially the body's "release valve" that counteracts the RAAS when BP is too high.

Why does alcohol cause dehydration the morning after drinking?

Alcohol inhibits the secretion of ADH (antidiuretic hormone). Without ADH, aquaporins are not inserted into collecting duct principal cells → collecting ducts remain impermeable to water → filtrate passes through without water reabsorption → large volume of dilute urine is produced → body loses more water than was consumed → dehydration.

Define renal clearance and state the formula. Why is it expressed in mL/min and not mg/min?

Renal clearance = the volume of plasma from which a substance is COMPLETELY cleared per unit time. Formula: RC = (U × V) / P. When you work out the units: (mg/mL × mL/min) / (mg/mL) = mL/min.

It reflects HOW MUCH plasma is completely cleared of that substance — not the rate of removal in mass units. This is the tricky part of the definition to memorize.

Interpret these three renal clearance scenarios: RC = 0, RC < 125 mL/min, RC > 125 mL/min. Give an example of each.

RC = 0: substance is completely reabsorbed; none excreted. Examples: glucose and amino acids in healthy individuals.

RC < 125 mL/min (e.g. urea = 70 mL/min): substance is partially reabsorbed — some cleared but not all; the remaining plasma still contains the substance.

RC > 125 mL/min (e.g. creatinine = 140, drug metabolites): substance is filtered AND secreted into the filtrate — more is cleared than could come from filtration alone.

Why must urea and uric acid be secreted back into the filtrate after being reabsorbed in the PCT?

Urea and uric acid are lipid-soluble waste products that are reabsorbed in the PCT with water. Secreting them back into the filtrate is necessary for excretion in urine; otherwise, they could accumulate, leading to conditions like gout.

What does fruity/acetone-smelling urine indicate and why?

Indicates uncontrolled diabetes mellitus with ketoacidosis. Lack of insulin leads to glucose inability in cells, triggering massive lipolysis and ketone production, including acetone, which gives the urine a fruity odor.

Describe the three requirements for micturition and which part of the nervous system controls each.

(1) Detrusor muscle contraction — smooth muscle; controlled by parasympathetic NS (pelvic nerves from sacral cord).

(2) Internal urethral sphincter opens — pulled open by detrusor contraction; smooth muscle; involuntary (parasympathetic/autonomic).

(3) External urethral sphincter opens — skeletal muscle; voluntary control by somatic NS. The external sphincter is the one you consciously relax to void or keep closed to delay urination.

Distinguish stress incontinence from urinary retention.

Stress incontinence: involuntary urine leakage caused by a sudden increase in intra-abdominal pressure (coughing, sneezing, laughing) that physically forces urine past the external sphincter — common in women with weakened pelvic floor muscles from pregnancy or childbirth. NOT caused by emotional stress.

Urinary retention: inability to expel urine from the bladder despite it being full — common after general anesthesia (detrusor muscle takes time to recover) or in males with prostate hypertrophy (enlarged prostate compresses the urethra).

What are the chief cation and anion in ECF vs. ICF?

ECF: chief cation = Na⁺; chief anion = Cl⁻. ICF: chief cation = K⁺; chief anion = HPO₄²⁻ (phosphate). Na⁺ and K⁺ are nearly opposite in distribution — maintained by the Na⁺-K⁺ ATPase pump. Electrolytes have greater osmotic power than nonelectrolytes because they dissociate into multiple ions in solution.

What is the key distinction between ADH and aldosterone in terms of what they regulate?

ADH regulates WATER ONLY — it inserts aquaporins into collecting duct principal cells to increase water reabsorption.

Aldosterone regulates SALT (Na⁺) — it acts on DCT/collecting duct to increase Na⁺ reabsorption and simultaneously increase K⁺ secretion.

To move both salt AND water, you need both hormones. Without ADH, water won't follow even if Na⁺ is being reabsorbed.

What triggers ADH release and what triggers thirst? Are they the same?

Both are triggered by

(1) a rise in plasma osmolality — even just 1–2% activates hypothalamic osmoreceptors; dry mouth also contributes.

(2) A large drop in plasma volume/pressure (5–10%) — sensed by baroreceptors and via angiotensin II from the RAAS.

So yes, both ADH and thirst share the same triggers. ADH acts quickly at the kidney; thirst prompts drinking for a more sustained fix.

How does ANP oppose the RAAS, and when is it released?

ANP (atrial natriuretic peptide) is released by heart atrial cells when they are stretched by high blood pressure/volume. It acts as the body's "relief valve" — inhibits Na⁺ reabsorption in the collecting duct, suppresses ADH/renin/aldosterone release, and causes vasodilation. Net effect: more Na⁺ and water excreted → ↓ blood volume and BP. Everything it does is the exact opposite of the RAAS.

Why is Addison's disease life-threatening without hormone replacement?

Addison's disease involves autoimmune destruction of the adrenal cortex, eliminating production of both aldosterone AND cortisol. Without aldosterone, the body cannot reabsorb Na⁺ properly → massive Na⁺ and water loss in urine → dangerously low blood volume and BP. Without cortisol, the body cannot mount the metabolic response to any long-term stress (illness, surgery, injury). Both are essential to life, so hormone replacement is required permanently.

What’s Dania’s last name?

Nour

What two factors control K⁺ secretion in the DCT/collecting duct?

(1) Plasma K⁺ concentration — high ECF K⁺ directly stimulates principal cells to secrete more K⁺ into the filtrate.

(2) Aldosterone — when aldosterone is present, it stimulates Na⁺ reabsorption AND K⁺ secretion simultaneously (Na⁺-K⁺ ATPase moves them in opposite directions).

Either elevated K⁺ or low Na⁺ can independently trigger aldosterone release from the adrenal cortex.

What are PTH's three targets and what does it do at each?

PTH is released when blood Ca²⁺ drops. (1) Bone: activates osteoclasts → bone matrix dissolved → Ca²⁺ and phosphate released into blood (fastest way to raise Ca²⁺). (2) Small intestine: stimulates kidney to activate vitamin D → active vitamin D promotes intestinal Ca²⁺ absorption (slowest). (3) Kidneys: INCREASES Ca²⁺ reabsorption AND DECREASES phosphate reabsorption (opposite effects). Excreting phosphate keeps Ca²⁺ free and bioavailable rather than precipitating as calcium phosphate.

Why does PTH have OPPOSITE effects on Ca²⁺ vs. phosphate at the kidney?

If PTH caused the kidney to reabsorb both Ca²⁺ AND phosphate, the Ca²⁺ x phosphate product in the ECF would rise and they would precipitate together as calcium phosphate salts in soft tissues or bones — this defeats the purpose of raising free blood Ca²⁺. By reabsorbing Ca²⁺ but excreting phosphate, PTH keeps Ca²⁺ free and bioavailable for muscle contraction, neurotransmitter release, and second messenger functions.

Compare the three mechanisms of pH regulation by speed and capacity.

 Chemical buffers (bicarbonate, phosphate, proteins): fastest (seconds) but limited capacity — can only temporarily soak up H⁺. Respiratory system: minutes (1–3 min) — can shift pH by ~0.2 units by varying CO₂ elimination via ventilation rate/depth. Renal mechanisms: slowest (hours to days) but largest capacity — the only mechanism that can permanently eliminate nonvolatile (fixed) acids and generate brand new HCO₃⁻.

Why can't the kidneys simply reabsorb HCO₃⁻ directly from the filtrate?

The apical membranes of tubule cells have NO transporters for HCO₃⁻ — it cannot cross these membranes directly. Instead, the kidneys use a workaround: H⁺ is secreted into the filtrate → combines with filtered HCO₃⁻ → forms H₂CO₃ → splits into CO₂ + H₂O → CO₂ (lipid-soluble) diffuses into the tubule cell → regenerated into HCO₃⁻ inside the cell → HCO₃⁻ then enters the peritubular blood. One filtered HCO₃⁻ disappears; one new HCO₃⁻ enters the blood.

Distinguish the two ways the kidneys generate NEW HCO₃⁻ to handle acidosis.

Method 1 — Phosphate buffer: Type A intercalated cells of collecting duct secrete H⁺ via H⁺-ATPase → H⁺ combines with HPO₄²⁻ in filtrate → forms H₂PO₄⁻ → permanently excreted in urine. New HCO₃⁻ generated in the cell enters the blood. During acidosis, less phosphate is reabsorbed so more stays as buffer.

Method 2 — NH₄⁺ excretion (most important): PCT cells metabolize glutamine → produces 2 NH₄⁺ + 2 HCO₃⁻. NH₄⁺ excreted in urine (carries H⁺ out permanently). New HCO₃⁻ enters blood. Both generate new HCO₃⁻ AND permanently eliminate H⁺.

What is the 3-step approach to diagnosing acid-base disorders?

Step 1: Look at pH — below 7.35 = acidosis; above 7.45 = alkalosis.

Step 2: Look at PCO₂ (normal 35–45 mmHg) — if abnormal AND in the direction that explains the pH change → respiratory cause.

Step 3: Look at HCO₃⁻ (normal 22–26 mEq/L) — if abnormal AND in the direction that explains the pH change → metabolic cause. For compensation: the OTHER parameter is out of range but moving in the WRONG direction to cause the pH change — meaning it's the body's attempt to correct the problem.

What are causes of respiratory and metabolic acidosis?

Respiratory acidosis (↑PCO₂, ↓pH): caused by hypoventilation (e.g., COPD, chest injury, narcotics). Metabolic acidosis (↓HCO₃⁻, ↓pH): caused by diabetic ketoacidosis, starvation, diarrhea, renal failure, or excess alcohol.

How does the body compensate for metabolic acidosis, and what does the blood picture look like?

In metabolic acidosis, low HCO₃⁻ and low pH trigger the respiratory system to increase breathing, reducing CO₂ levels. This results in a low pH (or near normal if compensated), low HCO₃⁻, and low PCO₂.

Interpret: pH 7.25, PCO₂ 46 mmHg, HCO₃⁻ 33 mEq/L

Step 1: pH 7.25 = acidosis.

Step 2: PCO₂ 46 mmHg = HIGH (above normal 35–45) → elevated CO₂ would cause acidosis → this IS in the right direction → RESPIRATORY cause (hypoventilation, CO₂ retention).

Step 3: HCO₃⁻ 33 mEq/L = HIGH (above normal 22–26) → high HCO₃⁻ would cause alkalosis, not acidosis → this is in the WRONG direction → kidney is compensating by generating more HCO₃⁻ to buffer the excess H⁺.

Answer: Respiratory acidosis, with renal compensation (but incomplete, since pH still 7.25).