BIOL0800 Exam 3

6 major functions of the kidney

1. Regulate blood volume

2. Regulate osmolarity

3. Regulate pH

4. Excrete metabolic waste

5. Regulate extracellular fluid ions

6. Regulate/secrete hormones

Gross structures of renal system

Kidney, ureter, bladder, urethra

Blood supply of renal system

Renal artery → aferente arteriole → glomerulus → efferent arteriole

Nephron structure (renal corpuscle)

• glomerulus (capillary bed for filtration)

• Bowman’s capsule (surrounds glomerulus)

Nephron structure (Renal tube)

• proximal distal tubule (cortex) — folded for surface area

• Descending limb of the loop of Henle (medulla) — water permeable

• Ascending thin limb of the loop of Henle (medulla)

• Thick ascending limb of the loop of Henle (medulla) — water impermeable

• Distal convoluted tubule (cortex)

Collecting duct (cortex to medulla)

Nephron structure (vascular components)

• afferent arteriole → glomerulus → efferent arteriole

• Peritubular capillaries (wrap around tubule for reabsorption)

• Vasa recta (surrounds loop of Henle; maintains osmotic gradient)

Renal blood flow

1000 ml/min (20% of cardiac output)

Renal plasma flow (RPF)

500 ml/min (accounts for hematocrits)

Glomerular filtration rate

125 ml/min (normal); total filtered per day 180 L; per nephron: 62.5 nL/min (125 ml/min / 2 million nephrons)

Filtration fraction

GFR/RPF → 125/500 =0.25 (25% plasma filtered)

Filtration barrier (three layer barrier)

• fenestrated endothelium

• Basement membrane

• Podocytes with filtration slits

Fenestrated endothelium

• endothelial cells have holes

• Allows water and solutes through

• Blocks RBCs

Basement membrane (selective)

• negatively charged

• Size selective (blocks large molecules)

• Charge-selective (repels negative molecules like proteins)

Podocytes with filtration slits

• specialized epithelial cells from visceral layer of bowman’s capsule

• Have foot processes that bridge filtration slits

• Slit diaphragm prevents protein passage

• Negatively charged glycocalyx adds charge selectively

Resistance in glomerulus

• Afferent arteriole is about 2/3 total resistance

• Efferent arteriole is about 1/3 total resistance

• About 50mmHg pressure drop occurs at afferent arteriole

• About 50mmHg to about 20mmHg across glomerulus

Three mechanisms controlling GFR

1. Sympathetic nervous system

2. Autoregulation

3. Endocrine control

Moderate to high sympathetic stimulation

• Constricts BOTH afferent and efferent arterioles

• Decreases renal blood flow and GFR

• Protects kidney from hypotension during stress

Severe sympathetic stimulation

• Greater constriction of afferent arteriole

• Dramatic decrease in GFR

• Can lead to renal damage if prolonged

Myogenic Response

• Renal baroreceptors within kidney sense stretch

• Increased pressure → stretch → increase intracellular Ca++ → smooth muscle contraction

• Increased pressure leads to constriction of afferent arteriole

• Maintains stable GFR despite blood pressure changes (between 80-180 mmHg)

Juxtaglomerular Apparatus (JGA)

• Location: Distal tubule comes into contact with afferent arteriole

• Components:

  • Macula densa cells: In distal tubule, sample filtrate

  • Juxtaglomerular (JG) cells: In afferent arteriole wall, secrete renin

  • Mesangial cells: Support structure

Paracrine Signaling from Macula Densa to Afferent Arteriole

Release paracrine factors (afferent arteriole)

Inc. NaCl → purines (e.g. adenosine) → constr.

Dec. NaCl → Nitric Oxide → dilation

Release paracrines that release Renin from Juxtaglomerular cells, renin activates hormones in blood

Endocrine Control

• Renin Angiotensin Aldosterone System (RAAS)

• Atrial Natriuretic Peptide (ANP)

JG cells release renin in response to:

• Low blood pressure (high pressure baroreceptors signal low pressure)

• Low NaCl in distal tubule

• Sympathetic stimulation

Atrial Natriuretic Peptide (ANP)

• Released from atria in response to high blood volume

• Dilates afferent arteriole, constricts efferent arteriole → increases GFR

• Also decreases reabsorption in tubules

How does kidney handle solutes and water?

• Dump plasma & solutes outside body into lumen

• Reabsorb what you want to keep

• Leave undesired plasma & solutes in lumen → forms urine

• Secretes solutes from plasma into lumen of tubule

Increase resistance of afferent arteriole

• Decrease in GFR/glomerular capillary bp

• Decrease in RBF

• Filtration fraction stays the same

Increase resistance in efferent arteriole

• increase pressure in glomerular capillary/increased GFR

• Decrease in RBF

• Increase in filtration fraction

Dilation of afferent arteriole

• Increase in GRF/increase in GC bp

• Increase in RBF

• Filtration fraction stays the same

Dilation of efferent arteriole

• Decrease in glomerular capillary bp/decrease in GFR

• Increase in RBF

• Decrease in filtration fraction

Juxtaglomerular cells

• in kidney afferent arterioles, smooth muscle cells, regulate blood pressure and fluid balance

• Produce, store, and secrete enzyme renin

• Initiates renin-angiotensin-aldosterone system (RAAS) to increase bp and blood volume

Function of macula densa cells

Sense NaCl levels → signal JG cells to adjust renin secretion

Endocrine effects

1. RAAS detects low blood volume/bp→ will try to increase blood volume/bp

2. ANP detects high blood volume/bp → will try to decrease blood volume/bp

How does the sodium concentration in the tubular epithelial cells play a role in glucose reabsorption?  

low sodium concentration in the tubular epithelial cells leads to increased capacity for sodium/glucose cotransporter use

Renal Clearance

the volume of plasma that is completely cleared of a substance per minute

Renal Clearance of X = ([X]urine x urine flow) / [X]plasma

What is "free water"?

pure H2O that is separated from solutes

Respiratory Acidosis

Hypoventilation

Pattern: - pH LOW ↓ - PCO2 HIGH ↑ - [HCO3-] NORMAL (or slightly high if chronic)

Metabolic compensation for respiratory acidosis

Kidneys reabsorb MORE HCO3- - Increases [HCO3-] - Partially raises pH back toward normal - Takes hours to days

Respiratory alkalosis

Cause: Hyperventilation (too much CO2 blow-off) Pattern: - pH HIGH ↑ - PCO2 LOW ↓ - [HCO3-] NORMAL

Metabolic compensation for respiratory alkalosis

Kidneys excrete MORE HCO3- - Decreases [HCO3-] - Partially lowers pH back toward normal - Takes hours to days

Metabolic Acidsosis

Cause: ↑ H+ production or ↓ HCO3- in blood Pattern: - pH LOW ↓ - [HCO3-] LOW ↓ - PCO2 NORMAL (or low if compensation happening)

Respiratory compensation for metabolic acidosis

(FAST - minutes): - Chemoreceptors detect low pH - ↑ Ventilation - Blow off CO2 - PCO2 DECREASES - Helps raise pH back

Metabolic alkalosis

Cause: ↓ H+ or ↑ HCO3- in blood Pattern: - pH HIGH ↑ - [HCO3-] HIGH ↑ - PCO2 NORMAL (or high if compensation happening)

Respiratory compensation for metabolic alkalosis

(SLOW - hours): - Chemoreceptors detect high pH - ↓ Ventilation - Retain CO2 - PCO2 INCREASES - Helps lower pH back

Respiratory Alkalosis → Metabolic Acidosis (compensation)

Patient hyperventilates → PCO2 LOW, pH HIGH → Kidneys sense high pH → ↓ H+ secretion in distal tubule → Activate B cells (intercalated cells) instead of A cells → ↑ HCO3- secretion into urine (rare) → [HCO3-] decreases → pH starts falling back toward normal

Respiratory Acidosis → Metabolic Alkalosis (compensation)

Patient hypoventilates → PCO2 HIGH, pH LOW → Kidneys sense low pH → ↑ H+ secretion in proximal tubule and collecting duct → ↑ HCO3- reabsorption → [HCO3-] increases → pH starts rising back toward normal

Metabolic Acidosis → Respiratory Alkalosis (compensation)

Patient produces ketones or lactate → [HCO3-] LOW, pH LOW → Chemoreceptors in carotid/aortic bodies sense low pH → Ventilation increases → CO2 blown off → PCO2 decreases → pH starts rising back toward normal

Metabolic Alkalosis → Respiratory Acidosis (compensation)

Patient loses HCl from vomiting → [HCO3-] HIGH, pH HIGH → Chemoreceptors sense high pH → Ventilation decreases → CO2 retained → PCO2 increases → pH starts falling back toward normal

A cells (Acid-secreting)

- H+ ATPase pump (active)

- Secrete more H+ when needed

- Acidify urine

- Help excrete net acid

B cells (Base-secreting)

- HCO3- channels (rare)

- Secrete HCO3- when needed

- Alkalinize urine

- Help excrete base

If macula densa destroyed:

• Lose feedback inhibition

• Renin tends to rise

• BP rises

pH < 7.4

acidosis

pH > 7.4

alkalosis

Acetic acid/vinegar ingestion

→ metabolic acidosis

Compensation:
→ hyperventilation

Slow-twitch fibers

• ↑ mitochondria

• ↑ myoglobin

• ↑ capillaries

• oxidative metabolism

Fast-twitch fibers

Have:

• ↑ glycogen

• less mitochondria

LOW intensity exercise

• burns more fat

• uses more slow-twitch fibers

• higher pH

HIGH intensity exercise

• more glycolysis

• more lactate

• lower pH

Largest oxygen use after exercise

Largest oxygen use after exercise:
→ post-exercise protein synthesis

NOT restoring myoglobin.

FIRST thing to change during exercise

→ ATP demand rises
→ glycolytic enzyme activity increases FIRST

Cephalic phase

• vagus nerve

• smell/thought/taste

Damage to vagus:
→ cephalic phase most affected

Gastric phase

Stimulated by:

• stomach distension

• peptides

• ENS

• gastrin

Chief Cells

Secrete:

• pepsinogen

• gastric lipase

Stimulated by:

• parasympathetic activity

• gastrin

• acid

• peptides

Inhibited by:

• somatostatin

• GLP-1

• GIP

• sympathetic activity

Trypsinogen activated by:

enteropeptidase

If trypsin active INSIDE pancreatic duct:

→ autodigestion/destruction

Feeding centers inhibited by:

• insulin

• glucose

• CCK

• leptin

GLP-1

Acts on:

• pancreas → ↑ insulin

• brain/NTS → ↓ appetite

Why better than GIP:

• stronger appetite suppression

• GIP can increase glucagon

Post-absorptive state

FASTING: insulin LOW, glucagon HIGH, ghrelin HIGH, gluconeogenesis HIGH, glucose leaving liver, ketones increase

What is hyperkalemia?

Excessively high extracellular potassium levels.

How does injection of insulin and glucose help to correct the state of hyperkalemia?

Insulin stimulates the Na+/K+ ATPase pump which results in more K+ being pumped into cells and a lowering of extracellular K+

How does lacking insulin lead to metabolic acidosis in Type I diabetes?

Low insulin signals the liver to produce keytones which, when metabolized, leads to metabolic acidosis