Tracts of Goll and Burdach (Posterior Columns / Dorsal Columns)

Names and Eponyms

Location in the Spinal Cord

• Fasciculus gracilis (Goll) - medial position
• Fasciculus cuneatus (Burdach) - lateral position (lateral to gracilis)

Somatotopic Organization

Key point: The fasciculus cuneatus is only present above T6 because below that level, there is no upper limb input. So at lumbar and sacral levels, only the gracilis exists; the cuneate fasciculus appears from mid-thoracic levels upward.

Neurons and Course (3-Neuron Pathway)

1st Order Neuron (Peripheral to Spinal Cord)

• Cell body in the dorsal root ganglion (DRG)
• Large-diameter, heavily myelinated A-alpha and A-beta fibers
• Enter the spinal cord via the medial dorsal root entry zone
• Axons ascend ipsilaterally in the posterior column (do NOT synapse in the cord)
• Some collaterals enter the dorsal horn gray matter to synapse on interneurons/motor neurons (contributes to spinal reflexes)

2nd Order Neuron (Spinal Cord to Thalamus)

• 1st order fibers synapse at the posterior column nuclei in the medulla:
  • Gracilis → Nucleus gracilis
  • Cuneatus → Nucleus cuneatus
• 2nd order axons then cross as internal arcuate fibers (decussation in the lower medulla)
• Form the medial lemniscus on the contralateral side
• The medial lemniscus initially has a vertical orientation in the medulla (feet ventral, "little person stands up"), then becomes horizontal in the pons and midbrain (legs lateral, arms medial - "little person lies down")
• Terminate in the ventral posterior lateral (VPL) nucleus of the thalamus

3rd Order Neuron (Thalamus to Cortex)

• VPL neurons project via the posterior limb of the internal capsule
• Reach the primary somatosensory cortex (S1) in the postcentral gyrus (Brodmann areas 3, 1, and 2)

Sensory Modalities Carried

Key Features to Remember

Clinical Relevance - Posterior Column Syndrome

• Proprioception (positive Romberg's sign)
• Vibration sense
• Fine touch and 2-point discrimination
• Sensory ataxia

• Tabes dorsalis (neurosyphilis)
• Subacute combined degeneration (Vitamin B12 deficiency)
• Friedreich's ataxia
• Multiple sclerosis
• Cervical spondylosis
• Posterior spinal artery infarct

Artificial Kidney (Haemodialysis)

Definition

Indications for Use

1. Acute Kidney Injury (AKI) - to support the patient until kidneys recover
2. End-Stage Renal Disease (ESRD) / Chronic Kidney Disease (CKD) - used chronically to maintain life when loss of kidney function is irreversible
3. Certain poisonings (barbiturates, salicylates, methanol, etc.)

Over 800,000 patients in the United States currently receive some form of ESRD therapy. The vast majority are treated with dialysis due to the shortage of donor kidneys.

Basic Principle

• Blood flows through minute channels bounded by a thin semipermeable membrane (e.g., cellophane/cuprophane)
• On the other side of the membrane flows the dialysate (dialyzing fluid)
• Waste substances in the blood (urea, creatinine, urate, phosphate, sulfate, excess K+) diffuse down their concentration gradient from blood into the dialysate
• Useful substances (glucose, bicarbonate) can be added to the dialysate to diffuse back into the blood if needed
• The membrane is porous enough to allow passage of all plasma constituents EXCEPT plasma proteins (too large to cross)

Components of the Artificial Kidney

Factors Affecting Rate of Solute Transfer

1. Concentration gradient - the greater the gradient, the faster the diffusion (maximum at start of dialysis)
2. Permeability of the membrane to that particular solute
3. Surface area of the dialyzing membrane (0.6 to 2.5 m²)
4. Duration of contact between blood and dialysate
5. Flow rates - increasing blood flow rate OR dialysate flow rate maintains a high concentration gradient and optimizes diffusion (this is why a flowing/continuous system is used)

In a flowing (continuous) system, the concentration gradient is not easily dissipated, making hemodialysis far more efficient than a static system.

The Dialyzing Fluid (Dialysate)

Operational Details

Effectiveness - Clearance

• The artificial kidney clears urea at 100-225 mL/min - about twice as fast as two normal kidneys (70 mL/min)
• However, because it is used only 4-6 hours, 3 times/week, the overall cumulative clearance is still considerably less than normal kidneys functioning continuously

Limitations of the Artificial Kidney

1. Cannot secrete erythropoietin → anaemia persists (chronic dialysis patients need EPO injections)
2. Cannot perform endocrine functions (activation of Vitamin D, renin secretion)
3. Cannot fully maintain fluid-electrolyte balance around the clock
4. Patients still have significantly impaired overall health
5. Patients on dialysis have higher risks of infections, cardiovascular disease

Hemofiltration (Additional Mechanism)

• A hydrostatic pressure is applied to force fluid and solutes across the membrane
• Used when ultrafiltration (removal of excess water) is needed

Peritoneal Dialysis vs Haemodialysis

Summary Box (Exam Points)

• Principle: Diffusion across semipermeable membrane down concentration gradient
• Membrane: Cellophane - allows small solutes, blocks plasma proteins
• What is removed: Urea, creatinine, K+, phosphate, sulfate, urate, excess water
• Anticoagulant used: Heparin
• Urea clearance: 100-225 mL/min (> normal kidneys' 70 mL/min)
• Schedule: 4-6 hrs, 3×/week
• Cannot replace: Erythropoietin secretion, Vitamin D activation

Dietary Fiber in IBS - Health Benefits Beyond Basic Nutrition

1. What is Dietary Fiber?

Classification

2. Mechanisms of Action - How Fiber Provides Health Benefits

A. Stool Bulking and Regulation of Transit

• Insoluble fiber like cellulose attracts water and increases stool bulk directly (physical water-binding)
• Fiber that is not fermented retains water in the colon, softening stool
• This reduces intracolonic pressure, which is why fiber is beneficial in diverticular disease - it softens stool, reduces pressure on the colonic wall and enhances expulsion of feces
• Every gram of wheat fiber ingested yields approximately 2.7 g of stool expelled
• Increased stool bulk reduces colonic transit time, decreasing mucosal contact with irritants

B. Fermentation to Short-Chain Fatty Acids (SCFAs) - Key Metabolic Benefit

• Acetate (2 carbons)
• Propionate (3 carbons)
• Butyrate (4 carbons) - the most biologically active

• SLC16A1 (MCT1) - proton-coupled monocarboxylate transporter
• SLC5A8 (SMCT1) - sodium-coupled monocarboxylate transporter

We may obtain as much as 10% of our total calories from compounds produced by bacterial digestion of substances in our digestive tract.

1. Production of SCFAs that are trophic for colonic epithelium
2. Increase in bacterial mass - contributing to increased stool volume

C. Gut Microbiome Modulation (Prebiotic Effect)

• Dietary fiber acts as a prebiotic - it selectively feeds beneficial colonic bacteria
• This promotes growth of health-promoting bacteria (Lactobacillus, Bifidobacteria)
• Butyrate from bacterial fermentation inhibits histone deacetylases (HDACs) - modulating the epigenetic profile and transcription of:
  • Cell-cycle regulator p21
  • G1-selective transcription factor CDX2
  • Intracellular signaling kinase p38
• Butyrate also blocks development of dendritic cells, contributing to immune tolerance in the gut lamina propria - important for mucosal immunity in IBS

D. Cholesterol and Cardiovascular Benefit

• Soluble fiber (pectins, β-glucan from oats) lowers blood cholesterol by binding bile acids in the intestine
• Bound bile acids are excreted in feces instead of being reabsorbed via the enterohepatic circulation
• β-glucan from oats has been shown in studies to reduce cholesterol through reduction in bile acid reabsorption
• Dietary fiber is associated with a reduced incidence of coronary heart disease

E. Blood Glucose Regulation

• Fiber slows the absorption of glucose, reducing the glycemic index of meals
• Soluble fiber forms a viscous gel in the small intestine, physically slowing glucose absorption
• This blunts postprandial blood glucose spikes - beneficial in insulin resistance and type 2 diabetes prevention

F. Colorectal Cancer Protection

• Epidemiological, case-control, and animal studies suggest dietary fiber protects against colorectal cancer (CRC)
• Mechanisms include:
  1. Dilution of carcinogens by increased stool bulk
  2. Accelerated elimination by decreased transit time - reducing duration of mucosal contact
  3. Reduced concentration of secondary bile acids and fecal mutagens (wheat and rye fiber)
  4. Cellulose and hemicellulose decrease levels of bacterial metabolic enzymes (e.g., β-glucuronidase) - reducing activation of carcinogens
  5. Fiber components bind toxic and carcinogenic substances, reducing their contact with colonic mucosa
  6. SCFA production (especially butyrate) inhibits carcinogenesis by epigenetic mechanisms

G. Weight Management and Satiety

• Fiber increases satiety by slowing gastric emptying
• Reduces total caloric absorption
• Low-fiber, high-calorie "Western diets" are associated with obesity, colorectal disease, and metabolic syndrome

3. Relevance to IBS Specifically

• Soluble fiber consistently improves IBS symptoms in controlled trials; evidence for insoluble fiber is conflicting
• Fiber supplementation can cause abdominal distension, bloating, and flatulence especially in early weeks - gradual introduction over several weeks is advised
• Recommended daily intake: 25-30 g/day of soluble fiber for IBS/constipation patients
• Minimum effective dose to significantly alter bowel function: 12 g/day

Important clinical note: The prescription of cellulose (an insoluble fiber) in IBS should be monitored carefully. While it provides benefits via stool bulking, some IBS patients - particularly women with delayed colonic transit - may find insoluble fiber aggravates abdominal distension. In such cases, switching to soluble fiber supplementation (psyllium/ispaghula husk) may be more appropriate.

4. Recommended Daily Intake (2015 Dietary Guidelines)

Summary

1. GI motility - bulks stool, reduces transit time, treats constipation
2. SCFA production - nourishes colonocytes, modulates gene expression and immune function
3. Prebiotic effect - supports healthy gut microbiome
4. Cardiovascular - lowers LDL cholesterol via bile acid binding
5. Metabolic - reduces glycemic index, aids weight control
6. Oncologic - reduces colorectal cancer risk via multiple mechanisms
7. Anti-inflammatory - butyrate inhibits HDAC, promotes immune tolerance in the gut