Pathophysiology Exam 4 (Chapters 26+27+28+29)

What are the main functions of the kidneys?

• Maintain fluid & electrolyte balance

• Remove water-soluble wastes

Where are the kidneys located?

Posterior part of the abdomen on either side of the vertebral column.

*Right kidney is slightly lower than left kidney.

Function unit of the kidney?

Each kidney is made of nearly 1 million functional units called nephrons.

What are the main nephron functions?

• Filtration

• Reabsorption

• Secretion

How much fluid do kidneys filter per hour, and how much is reabsorbed?

• Filter: >7 liters/hour

• Reabsorb: ~99%

What is the end product of kidney filtration?

A small volume of urine that contains high concentrations of waste

What happens when 50% of nephrons are lost?

Renal reserve is reduced, but no major symptoms appear yet.

What percentage of nephron loss causes serious renal impairment?

75%–90% nephron loss = significant kidney damage

When do clinical signs of chronic kidney disease (CKD) appear?

Not until late stages, when most nephrons are already damaged.

Urinary system is composed of what?

Kidneys, ureters, and bladder urethra.

What is the costovertebral angle (CVA) used for?

It’s an external landmark to locate kidneys; tenderness here can indicate kidney infection.

What is the hilum of the kidney?

The entry/exit point for lymphatic vessels, blood vessels, and nerves.

What covers each kidney?

A thin fibrous capsule

What are the three main areas of the renal parenchyma?

• Cortex – outer layer

• Medulla – middle layer

• Pelvis – inner collecting area

What does the renal pelvis do?

It’s the inner collecting area, made up of calyces, where urine drains before entering the ureter.

What’s found in the renal medulla?

The middle portion that contains the renal pyramids, which help concentrate urine

What’s found in the renal cortex?

The outer portion that holds the glomeruli and nephron tubules where filtration begins.

What are the main parts of the nephron?

• Glomerulus (capillary tuft + Bowman capsule)

• Tubule (Proximal convoluted → Loop of Henle → Distal convoluted)

What happens in the glomerulus?

Blood gets filtered; large molecules (like proteins) stay in the blood, small ones go into Bowman’s capsule.

What’s special about the tubule cells?

The epithelial cells in each segment are specialized for specific transport functions (some reabsorb, others secrete).

Nephron Cell Cilia and Their Role

• Nearly all nephron cells have a single cilium (tiny hair-like projection).

• These cilia act as mechanoreceptors and chemoreceptors —
  -Mechanoreceptors = sense flow rate
  -Chemoreceptors = sense composition (what’s in the filtrate).

• They trigger signaling cascades that regulate how kidney cells behave:

  • Proliferation (growth)

  • Differentiation (specialization)

  • Apoptosis (cell death)

When these signaling pathways are abnormal, it can lead to polycystic kidney disease (PKD) — where cysts form and damage kidney tissue.

What do nephron cell cilia do?

They act as mechanoreceptors (detect flow) and chemoreceptors (detect composition), sending signals to control cell growth, specialization, and death.

Think: Cilia Feel & Deal

What happens if cilia signaling is defective?

It can cause polycystic kidney disease (PKD) due to abnormal cell signaling.

Proximal Convoluted Tubule (PCT)

Function:

• Made of cuboidal epithelial cells (lots of mitochondria = active reabsorption)

• Reabsorbs:

  • ~2/3 of filtered water and electrolytes

  • All glucose, amino acids, proteins, vitamins

• Water reabsorption is passive (follows solute movement)

Think: PCT = Pick up Clean Treasures

Loop of Henle

Thin Descending Limb:

• Permeable to water → water leaves → filtrate becomes more concentrated

Thick Ascending Limb:

• Na⁺-K⁺-2Cl⁻ cotransporters pump ions out into interstitial fluid

• Impermeable to water → water stays, ions leave → filtrate becomes diluted

Think: Down loses water, Up loses salt

Distal Convoluted Tubule (DCT)

• Filtrate is hypo-osmotic (diluted) → ions were already removed in the Loop of Henle.

• Main jobs:

  • Fine-tune electrolyte levels.

  • Respond to hormones for sodium, water, and acid control.

Hormonal actions:

• Aldosterone & Angiotensin II:
  → “Hold onto salt & sip water” (reabsorb Na⁺ + water).

• Atrial Natriuretic Peptide (ANP) & Urodilatin:
  → “Flush the salt” (inhibit Na⁺ & water reabsorption).

• Also: Secretes acid (H⁺) to regulate pH.

Collecting Duct

Structure & cells:

• Forms the medullary pyramids.

• Contains two main cell types:

  1. Principal (P) cells → respond to ADH (antidiuretic hormone).

     • ADH makes ducts permeable to water, so water is reabsorbed → concentrated urine.

  2. Intercalated (I) cells → control acid-base balance by secreting H⁺ or reabsorbing HCO₃⁻.

Think: P for Pee control, I for pH control

Glomerular Filtration Rate (GFR)

• The volume of plasma filtered by the glomeruli per unit time.

• Determined by filtration pressure and surface area/permeability of the glomerular membrane.

Forces that Favor Filtration (Push fluid out of glomerulus)

• Capillary hydrostatic pressure (HPc) – pushes water out of glomerular capillaries into Bowman’s capsule.

• Bowman capsule oncotic pressure (πBc) – very small, but can slightly favor filtration.

Forces that Oppose Filtration (Keep fluid in capillaries)

• Plasma/capillary oncotic pressure (πc) – proteins in plasma pull water back into capillaries.

• Bowman capsule hydrostatic pressure (HPbc) – pressure inside the capsule resists incoming filtrate.

Net Filtration Pressure (NFP)

• NFP = (HPc + πBc) − (πc + HPbc)

• Varies along the glomerular capillary (higher at afferent end, lower at efferent end).

• Normal GFR= 125 mL/min

Think of it like a tug-of-war:

• Filtration forces push the water out → into urine formation.

• Opposing forces pull water back → into blood.

Factors Affecting GFR— Blood Volume

• Increase in blood volume → ↑ GFR → extra fluid excreted.

• Decrease in blood volume → ↓ GFR → fluid conserved.

Factors Affecting GFR— Autoregulation

• Purpose: Protects glomerular capillaries from wide fluctuations in blood pressure.

• Myogenic mechanism: Arterioles respond to stretch (effective for arterial pressure 75–160 mmHg).

• Mechanism:

  • High pressure → afferent arteriole constricts → prevents excess filtration.

  • Low pressure → afferent arteriole dilates → maintains filtration.

Factors Affecting GFR—Pressure in Bowman Capsule

Obstruction in tubules (like stones or high tubular pressure) reduces GFR

Factors Affecting GFR—Plasma Oncotic Pressure

• Determined by plasma proteins (mainly albumin).

• Low plasma protein → ↓ oncotic pull → ↑ GFR

Think: Less protein, more pee

Factors Affecting GFR—Mesangial Cell Contraction

• Specialized cells around glomerular capillaries regulate surface area for filtration.

• Contraction → ↓ GFR

• Relaxation → ↑ GFR

Glomerulus

• Afferent arteriole constriction + efferent arteriole dilation → ↓ GFR

• Afferent arteriole dilation + efferent arteriole constriction → ↑ GFR

Macula Densa

• Cells in distal tubule sensing sodium (Na⁺) levels.

• High Na⁺ at macula densa → indicates high GFR → signals afferent constriction → ↓ GFR

• Low Na⁺ at macula densa → indicates low GFR → signals afferent dilation → ↑ GFR

Juxtaglomerular Cells

• Specialized smooth muscle cells in afferent arteriole.

• Produce and release renin → activates renin-angiotensin-aldosterone system (RAAS) → ↑ Na⁺ & water reabsorption → restores blood volume → indirectly affects GFR.

Think: JG cells are the body’s renin factories

Effect of Glucose and Amino Acids

• ↑ Glucose or amino acids in filtrate → ↑ Na⁺ reabsorption in proximal tubule → less Na⁺ reaches macula densa → signals increase in GFR (tubuloglomerular feedback).

Think: Sugar and protein steal sodium → JGA thinks flow is low → opens the gates → ↑ GFR.

Transport Across Renal Tubules

1. Transcellular Transport

2. Paracellular Transport

3. Reabsorption of Glucose

4. Regulation of Acid-Base Balance

5. Secretion of potassium

Transcellular Transport

• Route: Through the tubular epithelial cells.

• Mechanism: Uses specific transporter proteins in membranes.

• Dependency: Often Na⁺ reabsorption-dependent (powered by Na⁺-K⁺ pump on basolateral membrane).

• Function: Moves substances actively or passively between tubular filtrate and interstitial fluid.

Think: Transcellular = through the cell, like going through a door

also Na⁺ is the power source for many transporters here

Paracellular Transport

• Route: Between tubular epithelial cells through tight junctions.

• Mechanism: Passive movement, driven by electrochemical gradients or solvent drag.

• Function: Moves water, ions, or small solutes without entering the cell.

Think: Paracellular = pass between the cells, like taking a shortcut along the fence

Where is all glucose normally reabsorbed?

Proximal tubule (100% under normal conditions)

Think: Glucose goes Proximal or it goes Pee

What transporter reabsorbs glucose?

SGLT2 (Sodium-Glucose Linked Transporter 2)

Think: SGLT2 SUCKS sugar in.

What is the “renal threshold” for glucose?

The blood glucose level at which glucose starts appearing in urine because SGLT2 transporters are maxed out.

Why is sodium needed for glucose reabsorption?

SGLT2 is sodium-dependent — it uses the Na⁺ gradient created by Na⁺/K⁺ pump.

Think: Na⁺ is the ‘Uber’ that drives glucose into the cell.

What are the kidney’s two main acid-base functions?

• Excrete H⁺

• Reabsorb / regenerate HCO₃⁻

Think: Kidneys do the H’s: kick out H⁺, hold onto HCO₃

Is bicarbonate directly reabsorbed in the tubule?

No. It must be converted first.

How is HCO₃⁻ reabsorbed?

It combines with secreted H⁺ → forms H₂CO₃ → breaks into CO₂ + H₂O

Think: Bicarb + Hydrogen → CO₂ + H₂O (the magic trick)

What enzyme drives both directions of the bicarbonate/CO₂ reaction?

Carbonic anhydrase (CA)

Think: CA = Can Accelerate the reaction

What occurs inside the tubular epithelial cell?

CO₂ diffuses in → CA converts it back to H₂CO₃ → HCO₃⁻ + H⁺

Think: CO₂ slips in, CA flips it

How does HCO₃⁻ return to the blood?

It is transported out the basolateral membrane into circulation.

Think: Bicarb exits BACK to the BLOOD (B → B)

What does the cell do with the H⁺ made inside?

It’s secreted into the tubule again to continue the process.

Think: H⁺ recycles to rescue more bicarb

Acid–Base Regulation in the Kidney

FILTER → FIX → FLIP → RETURN

1. Filter HCO₃⁻

2. Fix it by combining with H⁺

3. Flip it to CO₂ (crosses membrane), then flip back to HCO₃⁻

4. Return it to the blood

Potassium secretion in the kidney depends on several key regulators:

1. Activity of the Na⁺–K⁺ pump (on the basolateral membrane)

• This pump pulls K⁺ into the cell and pushes Na⁺ out, creating the gradient that allows K⁺ to secrete into the tubular lumen.

2. In the distal tubule, these pumps are regulated by:
    Aldosterone

• Aldosterone increases Na⁺–K⁺ pump activity.

• It also increases the number of K⁺ channels on the luminal membrane, which promotes K⁺ secretion.

3. Also affected by:
   Plasma K⁺ concentration

• High plasma potassium directly stimulates aldosterone release.

• It also increases the gradient for K⁺ secretion.

4. Activity of the K⁺–H⁺ exchanger

• When H⁺ is secreted more, K⁺ secretion decreases (and vice-versa).

• This explains why acidosis decreases K⁺ secretion and alkalosis increases K⁺ secretion.

How the kidneys regulate blood volume & osmolality

The kidneys maintain balance by adjusting:

1. GFR (glomerular filtration rate)

2. Reabsorption of water and solutes from the filtrate

Antidiuretic Hormone (ADH / Vasopressin)

• Makes the collecting tubules more permeable to water

• More water is reabsorbed back into the blood

• Result:
  Increased blood volume
  Decreased blood osmolality (more diluted blood)

Aldosterone, Angiotensin II, Natriuretic Peptides, Urodilatin, Uroguanylin, Guanylin

These hormones affect blood volume, but not osmolality.

Aldosterone & Angiotensin II

• Increase sodium reabsorption

• Water follows sodium → blood volume increases

Natriuretic Peptides & Urodilatin

• Inhibit sodium and water reabsorption

• Result: Decrease blood volume

Diuretic Agents

Drugs that change the osmolality of the filtrate and block water reabsorption, causing more urine output.

Big idea:
More solute stays in the tubule → more water stays in the tubule → increased urine volume.

Osmotic Diuretics

• Increase the osmolality of the filtrate

• Water follows the solutes → water stays in the tubule

• Result: More water is excreted (↑ urine)

Classic example: Mannitol (IV)

Hormonal functions of the kidneys

- Vitamin D Metabolism

- Renin

- Erythropoietin

Erythropoietin (EPO)

• A growth factor for red blood cells

• Released when the body senses:

  • Hypoxia (low oxygen)

  • Low circulating RBC mass

• Function: tells the bone marrow to make more RBCs

Active Vitamin D (Calcitriol)

• Kidneys convert vitamin D into its active form

• Needed for calcium absorption in the intestine

• Without it → calcium can’t be absorbed well

When kidneys fail, they can’t produce enough EPO or active vitamin D.

• ↓ EPO → Anemia

  • Fewer red blood cells = tiredness, low energy

• ↓ Active Vitamin D → Renal osteodystrophy

  • Weak bones

  • Calcium imbalance

Intrarenal Disorders

Problems that occur inside the kidney itself.

These can lead to:

• Renal insufficiency

• Renal failure

5 Major Categories of Intrarenal Disorders

C — Congenital

• Conditions you’re born with
  (e.g., renal dysplasia)

N — Neoplastic

• Tumors
  (e.g., renal cell carcinoma)

I — Infectious

• Infections inside the kidney
  (e.g., pyelonephritis)

O — Obstructive

• Blockages in the kidney
  (e.g., stones, strictures)

G — Glomerular

• Diseases of the glomerulus
  (e.g., glomerulonephritis)

Common Manifestations of Kidney Disease

1. Pain

2. Abnormal Urinalysis Findings

3. Other Diagnostic Tests (Kidney)

Pain

Nephralgia (kidney/renal pain)

Where it’s felt:

• Costovertebral angle (CVA) → halfway between spine & 12th rib

  • Providers press here to check for CVA tenderness

• Flank pain (side of the back)

Why pain occurs:

• Stretching, distention, or inflammation of the renal capsule

How it feels:

• Dull, constant ache

Why it can spread:

• Pain signals travel through T10–L1 sympathetic afferent neurons

• This makes the pain radiate across the dermatomes
  (meaning pain can be felt in areas supplied by these nerves)

Abnormal Urinalysis Findings

Urinalysis gives important clues to intrarenal diseases and helps with differential diagnosis.

Types of Urinalysis

• Dipstick test – quick chemical screen

• Microscopic urinalysis – looks at cells, casts, crystals, bacteria

• Color and appearance

Color & Appearance Changes

• Dark, strong-smelling urine

  • Suggests decreased renal function (more concentrated urine)

• Cloudy, foul-smelling (“pungent”) urine

  • Suggests an infectious process (UTI or pyelonephritis)

Other Diagnostic Tests (Kidney)

KUB (Kidneys–Ureters–Bladder X-ray)

Identifies:

• Size

• Position

• Shape

• May show renal calculi (stones)

Renogram / Renal Scan

• Shows renal vasculature

• Helps detect tumors and blood flow problems

Ultrasonography (Renal Ultrasound)

• Differentiates tissue characteristics

• Great for identifying cysts, hydronephrosis, and obstructions

CT / MRI

• Gives detailed information about:

  • Vasculature

  • Tissue structure

• Used for masses, trauma, stones, tumors

Glomerulopathies

• Diseases affecting the glomeruli (filtration units)

• Examples:

  • Acute Glomerulonephritis

  • Nephrotic Syndrome

What factors mediate glomerular damage?

• Immune processes (antibodies, immune complexes)

• Inflammatory processes

Causes of glomerulopathies

• Metabolic disorders (e.g., diabetes)

• Infectious agents (bacteria, viruses)

• Hemodynamic changes (high blood pressure)

• Toxic exposures (drugs, chemicals)

• Genetic mutations

• Physical injuries

What urinary findings may indicate a glomerular disorder?

• Hematuria (blood in urine)

• Proteinuria (protein in urine)

• Abnormal casts (RBC or WBC casts)

What systemic effects may result from glomerular disorders?

• Decreased GFR → reduced kidney filtration

• Edema → fluid retention due to protein loss

• Hypertension → fluid overload and altered renal function

What is the difference between primary and secondary glomerular disorders?

• Primary: Only the kidney is involved.

• Secondary: Results from another disease, condition, or medication.
  Examples: Goodpasture syndrome, SLE, diabetic nephropathy.

How are glomerular disorders classified based on extent of glomeruli involved?

• Diffuse: All glomeruli affected.

• Focal: Some glomeruli affected, not all.

How are affected glomeruli further described?

• Global: All parts of the glomerulus affected.

• Segmental: Only certain parts of the glomerulus affected.

• Membranous: Thickening of glomerular capillary walls.

• Sclerotic: Scarring of glomeruli.

What distinguishes nephrotic syndrome from nephritic syndrome?

• Nephrotic syndrome: Proteinuria ≥3–3.5 g/24 hrs → hypoalbuminemia, edema, hyperlipidemia.

• Nephritic syndrome: Glomerular inflammation → hematuria, RBC casts, mild proteinuria.

Think: Nephro = Protein, Nephri = Red

Key clinical presentations of glomerulonephritis?

• Acute Glomerulonephritis: Sudden onset; hematuria, edema, hypertension, decreased GFR.

• Chronic Glomerulonephritis: Slowly progressive; proteinuria, hematuria, hypertension, eventual renal failure.

What lab findings reflect nephrotic syndrome?

• Proteinuria ≥3 g/day

• Hypoalbuminemia

• Edema

• Hyperlipidemia

• Lipiduria

What is Acute Glomerulonephritis?

Acute inflammation of the glomeruli, usually immune-mediated, causing impaired filtration.

Lab findings in Acute Glomerulonephritis

• ↑ BUN

• ↑ Serum creatinine

• ↓ GFR

Urine findings in Acute Glomerulonephritis

• Proteinuria → foamy urine

• Hematuria

• RBC casts

Key clinical signs of Acute Glomerulonephritis

• Oliguria (low urine output)

• Edema

• Hypertension

Main goal of Acute Glomerulonephritis treatment

Supportive care while kidneys recover + control of blood pressure and fluid overload.

Supportive measures for Acute GN

Supportive measures for Acute GN

Management of hypertension in Acute GN

Control systemic and renal hypertension with meds (ACE inhibitors, diuretics).

What happens in ESRD from GN?

• Dialysis required

• Kidney transplantation if eligible

Acute Glomerulonephritis

BEG FOR HELP

• BUN ↑

• Edema

• GFR ↓

• Foamy urine (protein)

• Oliguria

• RBC casts

• Hematuria

• Elevated creatinine

• Lots of pressure = hypertension

• Proteinuria

What is Postinfectious Acute Glomerulonephritis?

GN that occurs after a skin or throat infection, most commonly post-streptococcal.

Infections that commonly precede PIGN

• Skin: impetigo

• Throat: strep pharyngitis

Who is most affected by PIGN?

Common in children, especially in developing countries.

Common in children, especially in developing countries.

Smoky or coffee-colored urine (due to blood in urine).

Treatment for PIGN

Supportive care only (fluids, blood pressure, monitoring).

IgA Nephropathy

• Most common glomerulonephritis worldwide

• Typically affects adults

• Often follows an upper respiratory or gastrointestinal viral infection

• Hematuria appears quickly (within 1–2 days after infection)

• Prognosis: variable — can remain stable for years or progress to end-stage renal disease (ESRD)

Tubular Disease

• Disorders affecting renal tubules

• Impaired reabsorption or secretion of electrolytes, water, or solutes

Crescentic GN

• Also called: Rapidly Progressive Glomerulonephritis (RPGN)

• Lesion appearance: Crescent-shaped

• Etiology:

  • Primary renal disorder (no systemic disease)

  • Complication of acute/subacute infection

  • Part of multisystem disease

  • Drug exposure

• Clinical manifestations:

  • Acute onset

  • Hematuria, proteinuria, RBC casts

  • Rapid decline in renal function (<6 months)

Goodpasture Syndrome

• Type: Autoimmune disorder

• Combination of:

  • Glomerulonephritis

  • Alveolar hemorrhage

• Key Symptoms:

  • Kidney: Hematuria, proteinuria

  • Lung: Shortness of breath, hemoptysis