Part I

General Principles
and Cellular Basis
of Medical
Physiology

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Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) ress.com Universities Press
 INTRODUCTION TO
PHYSIOLOGY AND ITS
GENERAL PRINCIPLES

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 LAWS OF NATURE THAT GOVERN
VITAL FUNCTIONS

Vital processes (life processes):

essentially are biomechanical and
biochemical processes, e.g.,
• nutrient and gas intake,
• their distribution,
• waste disposal,
• propagation of species etc.

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 HOMEOSTASIS AND EQUILIBRIUM STATE

• Definition of Homeostasis:

The physiological process by which the internal

systems of the body are maintained at
equilibrium despite variations in the external
conditions

• Equilibrium State:
Claude Bernard,
 Opposing forces across fluid compartments 1840
are balanced
 No net transfer of any substance across the
barrier
 Undisturbed equilibrium state remains as a
stable state—homeostasis

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 FACTORS AFFECTING HOMEOSTASIS

Examples:
• O2 and CO2 tensions
• Concentrations of glucose/metabolites
• Osmotic pressure
• Ionic (H+, K+, Ca2+ and Mg2+ etc.)
concentration
• Body-temperature etc.

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 HOMEOSTATIC REGULATION

Components in a Control System:

• Variable, centre (set-point) and executor(s) or effector(s)

Types of Feedback Systems:

• Negative Feedback: Promotes stability

• Positive Feedback: Promotes change and may have

destabilising effect (disease/death)

• Feed Forward: Anticipates a change and brings advance

adjustments

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 NEGATIVE FEEDBACK SYSTEM

• Definition: A change in the known variable in the

direction opposite to the initial change
• Most common type of control system
• Promotes stability

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 POSITIVE FEEDBACK SYSTEM
Definition: A change in the
known variable in the same
direction as the initial change
• Creates biological
momentum
• Less common mode of
feedback control, e.g.,
 Ovulation
 Micturition
 Uterine contractions
during parturition etc.
• Has a destabilising effect,
may result in disease/death

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 FEED FORWARD SYSTEM
• Definition: The process when the body anticipates a
change and compensates before the variable has changed
too much

• Benefits:
Ensures minimal deviation of the variables
Reduces/eliminates the ‘response-time’

• Examples:
Putting on some warm clothes before leaving the house
on a cold day, rather than getting cold first and then
putting on the thermals
Pre-exercise adjustments in cardio-pulmonary function

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 EVOLUTION AND ITS INFLUENCE
• Evolution led to:
 Division of labour
 Development of specific cell groups called ‘systems’ for each
specific vital function

• Cell: A basic structural and functional unit

• Tissues: A group of cells performing a particular life-activity, e.g.,

 Muscle contraction
 Nerves communication etc.

• Organ: A discrete structure of different tissues with a specific

function, e.g., digestive system for food digestion and absorption

• Organism: Combination of all of these things as a discrete and

separate entity

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 DEFINITION OF PHYSIOLOGY

Physiology is a branch of biology that

deals with:
• Functions and activities of life or of
living matter, e.g., organs, tissues or
cells, and
• physical and chemical phenomena
involved in these functions.

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 BRANCHES OF PHYSIOLOGY

• Subdivisions:
 Systemic
 Cellular
 Comparative
 Regional
 Applied
 Human
 Medical
 Clinical etc.

• Pathophysiology: A study of disordered body

function (disease)
 Basis of clinical medicine.

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 CELL: FUNCTIONAL MORPHOLOGY

• ˜ 100 trillion in
human body
• Types:
 Eukaryotic: nuclear
membrane (+)
 Prokaryotic: nuclear
membrane (-)
• Major Components:
 Cytoplasm/ protoplasm
with its inclusions
 Covering: cell wall
(plasma membrane)

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 CELL/PLASMA MEMBRANE
• Components:
 Bilayer of Proteins (≈50%) and
Phospholipids (Ratio 1:50 moles)
 Fluid mosaic model (Singer and Nicolson)

• Proteins: ˜100 different types

 Structural: Integral and peripheral
 Functional: e.g., enzymes, transporters,
receptors etc.

• Lipids: Mainly phospholipids (also

glycolipids etc.)
 Amphipathic property:
 Hydrophilic head: Peripherally
 Hydrophobic tail: Towards core
 Functions: Semipermeability, act as
messengers and blood group antigens

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 FUNCTIONS OF THE CELL MEMBRANE

• Provide exclusive domain to the cell and its inclusions

• Protective

• Semipermeable, dynamic structure

• Membrane proteins:
 Stability
 Regulation of transmembrane transport
 Act as Receptors and enzymes
 Participate in immunity

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 CELL INCLUSIONS/ORGANELLES

• Cytoplasm: Cytosol stores organelles and substances

• Nucleus: Custodian of genetic information

• Endoplasmic Reticulum: Build molecules and help their

intracellular movement

• Golgi Complex: Cell-wall synthesis, packaging and shipping

station

• Mitochondria: Powerhouse of cell, provide energy for life

processes

• Vacuoles: Storage sacs, some contain digestive enzymes (e.g.,

lysosomes)

• Cytoskeletal Structures: Mechanical support, also help

intracellular movement and cell movement

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 MITOCHONDRIA: ENERGY TO CELLULAR
LIFE PROCESSES
• Mitochondrial number ∞ cellular activity

• Structure:
 Double-layered membrane covering
 Inner membrane pleated (crystae), contain oxidative enzymes
 DNA and ribosomes in the matrix

• Functions:
 Oxidation of body fuels
 Role in synthesis of steroid hormones
 Regulation of intracellular Ca2+

• Energy to the cell:

 Solar radiation energy Plants Metabolic oxidation Human cells
(ADP ATP)
 Involves combination of nutrients (glucose) with oxygen, releasing the
stored energy (ATP)
 ATP provides energy for cellular processes, e.g., transport, synthesis
etc.
 Similarly cyclic nucleotides (e.g., GTP) also provide energy.

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 TYPES & FUNCTIONS OF
CYTOSKELETAL STRUCTURES
• Microtubules
 Tubular, cylindrical or rod-like
 Tubulin (actin-like) and dynein (myosin-
like)
 Spirally arranged, form hollow
microtubules
 Assist fast intracellular transport
• Microfilaments
 Role in muscle contraction (actin and
myosin)
• Cilia and flagella
 ‘Movers and shakers’ of the luminal
content, sperm motion
• Centrioles
 Modified microtubules
 Located close to the nucleus
 Play an important role during cell division
(in cell cleavage, form mitotic spindles,
etc.)
Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press
 CELL-TO-CELL LINKAGES
Types:
• Tight Junctions (Zona occludens):
 Found in choroid plexus, renal tubules, intestinal mucosa
etc.
 Regulate transmembrane transport
• Gap Junctions (Nexus):
 Found in smooth and cardiac muscles
 Permit rapid movement of small molecules and ions across
adjacent cells
 Channel patency regulated by Ca2+
• Desmosomes (Zona adherens):
 Found in cell groups subjected to stretch (e.g., skin).
Proteinacious thickenings (tonofilaments) of adjacent cell
walls
 Hemidesmosomes: Found in the basement membrane
Cell Adhesion Molecules (CAMs):
• Proteins having special structural and signalling functions
• Broad families:
 Integrins that bind to various receptors
 Adhesion molecules of the immunoglobulin-G
 (IgG) family
 Cadherins
 Selectins

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 CELL ADAPTATIONS
• Hypertrophy:
 e.g., stressed muscle cells (stress
within limit) enlarge, and function
improves
• Atrophy:
 Shrinking associated with
inefficiency, e.g., in disused muscles
• Inflammation:
 Severe stress activation of immune
response body’s defence reaction
• Necrosis:
 Cell-collapses due to uncopable
stress, e.g., Duchenne muscle
paralysis
• Apoptosis (programmed cell-death):
 Clinical significance:
 Renovation of cells
 Excessive atrophy
 Defective/uncontrolled
growth Diseases, e.g., cancer

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 MODE OF CELL-TO-CELL
SIGNALLING
• Cells ‘speak’ to each other
• Communication is essential for homeostatic
regulation
• Types of messengers: Physical and chemical
(predominant)

• Factors affecting Signalling:

 Distance
 Speed required

• Types of Pathways:
 Gap junction pathway
 Paracrine pathway
 Endocrine pathway
 Neurocrine and neuroendocrine pathways

• Signal Transduction:
 Receptors
 Second messenger system
 Categories of second responses

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 SIGNAL TRANSDUCTION (1)

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press

 SIGNAL TRANSDUCTION (2)

Mrutyunjay Guttal. MD : Textbook of Physiology (1st Edn) Universities Press