Introduction and Homeostasis

J. AgugliaroHuman Physiology

BIOL 2213-001

Some Definitions

• Physiology = how living organisms work– physis + logia = “study of nature”– relationship between the regulated internal

environment and the external env’t• Pathophysiology

– physiology “gone wrong”– study of how homeostasis is perturbed by a

disease state

Organization of the Human Body

• cells → tissues → organs → organ systems

• cells = the simplest structural units into which a complex multicellular organism can be divided and still retain the functions characteristic of life

• cell differentiation = transformation of unspecialized cells into specialized cell types during development

4 major functional categories of specialized cell types

1) Epithelial cells– skin, lining of GI tract and body cavities, respiratory

tract, kidney tubules, classic endocrine glands– endothelial cells → line the inside of blood vessels

2) Connective tissue cells– tendons, ligaments, fat, bone cells, RBCs, WBCs

3) Nerve cells– neurons → initiate and propagate electrical signals

4) Muscle cells– skeletal, cardiac, smooth

Fig. 1−1

A tissue is an aggregate of a single specialized cell type

An organ is an aggregate of different tissue types

Organ systems are groups of organs that work together

Compartmentalization of TBW

1) Extracellular Fluid (ECF)= plasma + interstitial fluid= “internal environment”− plasma and interstitial fluid have very similar

concentrations of dissolved substances *exception: [protein] is higher in the plasma

− interspersed w/in the extracellular matrix

2) Intracellular Fluid (ICF)

Total body water (TBW) is 55-60% of body weight in adult males

Fig. 1−2

ECF

TBW amounts to 42 L in an average (70 kg, 154 lb) person

Concentration differences between the ECF and ICF are the result of differential regulation of the two compartments

Normal ranges of some variables in the ECF

From Guyton and Hall’s Textbook of Medical Physiology (see also back inside cover of your textbook for an extensive list of blood variables)

Homeostasis

• Definition:– the dynamic mechanisms that detect and

respond to deviations in physiological variables from their “set point” values by initiating effector responses that restore the variables to the optimal physiological range

– dynamic constancy

Homeostasis

• History:– Claude Bernard’s (1878) milieu intérieur: “The

constancy of the internal environment implies a level of organization of the organism such that external variations are continually being buffered and equilibrated. Even though it may appear as if the animal is quite independent from and insensitive to the external environment, this is far from the case as its state of equilibrium results from constant and delicate adjustments, as with the most sensitive of balances.”

– Walter Cannon (1929)

Homeostatic Control Mechanisms

1) Negative feedback

2) Positive feedback

3) Feedforward regulation

Homeostatic Control Mechanisms

1) Negative feedback= regulation of some variable around a set point− ex: blood pH, pO2, pCO2, BP− ex: blood [glucose]− ex: Tb

− ex: enzyme pathways

Fig. 1−3

Negative Feedback: Blood Glucose

Negative Feedback: Blood GlucoseFig. 16−7

Fig. 1−4

Negative Feedback: Thermoregulation

Fig. 1−6 Negative Feedback Control System: The Reflex Arc

A reflex is an involuntary response to a stimulus

A reflex arclinks an involuntary response to a particular stimulus

Basic Components of the Reflex Arc

1) Receptor = monitors response variable2) Afferent pathway = carries sensory info to IC3) Integrating center = compares measured

value to regulated set point→ usually some aspect of the CNS

4) Efferent pathway = carries info to effector5) Effector = restores variable to w/in set-point

range→ endocrine glands and muscles (skeletal, smooth,

cardiac) are the body’s major effectors

Fig. 1−7

Reflex Arc: Thermoregulation

Fig. 16−18

Reflex Arc: Thermoregulation

(stimulus) (stimulus)

(receptor) (receptor)

(IC)

(IC)

Effectors:

Non-shivering thermogenesis

Evaporative cooling Vasoconstriction Shivering thermogenesis

(afferent) (afferent)

(efferent)(efferent)

Fig. 1−5

Negative Feedback: Enzyme Pathways

ATP

Glucose

Glycolysisenzymes and intermediates

Homeostatic Control Mechanisms

2) Positive feedback→ accelerates some physiological process− ex: opening of Na+ channels during an

action potential− ex: effect of oxytocin secretion on uterine

contractions during labor− ex: blood clotting

Homeostatic Control Mechanisms

3) Feedforward regulation= anticipatory regulation of a variable→ improves speed and reduces deviation

from set point

Feedforward Regulation

• Examples:– peripheral thermoreception– glucose-dependent insulinotropic peptide

(GIP) in response to feeding– melatonin and control of circadian rhythms

Fig. 1−9

Circadian Rhythms

Anticipated higher K+

ingestion during day

Anticipatory rise in Tb as morning approaches

Entrainment of melatonin secretion to a particular night length causes jet lag following transfer to a novel photic environment

From Nelson et al.’s Seasonal Patterns of Stress, Immune Function, & Disease

Note anticipatory decrease in [melatonin]

Rheostasis

• Mrosovsky (1990):– “Rheostasis refers to a condition or state in

which, at any one instant, homeostatic defenses are still present but over a span of time there is a change in the regulated level.”

– “The body does not always seek constancy of its internal environment. It does not always react in ways that prevent change. On the contrary, sometimes physiological mechanisms actively promote change.”

Rheostasis

• Examples:– fever– decreased Tb during sleep

Fig. 16−19

The regulated elevation of set-point Tb during fever in response to an infection is an example of rheostasis

Categories of Chemical Messengers1) Hormones – released into bloodstream,

produce specific action by binding to target tissue receptors

2) Neurotransmitters – released by neurons into interstitial fluid to act on target post-synaptic cells (other neurons, muscle cells)

3) Paracrine agents – act locally on neighboring cells

4) Autocrine agents – act on the cell itself that released the agent

All of the above (esp. hormones and NTs) may serve as important components of reflex arcs, particularly in eliciting effector responses

Fig. 1−8

Categories of Chemical MessengersIntercellular messengers Intracellular

Concept of steady state

Variance is a necessary component of regulation

Rheostasis = resetting of set points

Clashing demands

Negative feedback is most common

6) Importance of redundancy (e.g., Tb and BP regulation)

Acclimatization

• Definition: environmentally-induced change in a physiological function

• Usually reversible• Involves a change in the number, size, or

sensitivity of one or more of the cell types that participate in a homeostatic control system

• Ex: effect of altitude or exercise training on hematocrit → due to effect of erythropoietin on RBC count