Homeostasis

By Dr Kirtish Acharya
PG Resident
Department Of Physiology
MKCG Medical College Berhampur
Contents

• Introduction
• Brief history
• Components
• Homeostasis at systemic Levels
Introduction
Defined as maintenance of Nearly constant conditions in the internal
environment.
Internal environment – it consists of blood and tissue fluids.
Hence homeostasis keeps composition of blood and body fluids in normal
limits
This maintenance of constant internal environment is independent of
changes in external environment.
History
• In 1929 , Walter Cannon(1871-1945) coined the term Homeostasis
• In 1849, Claude Bernard described the concept of ‘internal environment’
as Mileu interior
• In 1932, Joseph Barcroft  British physiologist, was the first to say that
higher brain function required the most stable internal environment.
Components

• Temperature Regulation
• Feedback mechanism
• Fluid Balance
• Acid Base Balance
 Temperature Regulation
• Thermoregulation is an important component of homeostasis.
• There are primarily two modes of thermoregulation in nature, ectotherms and
endotherms. Humans are primarily endotherms.
Normal Core temperature
The anterior portion of the
hypothalamus, especially the preoptic
area, is concerned with regulation of
body temperature. An increase in
temperature of the blood flowing
through this area increases activity of
temperature-sensitive neurons, whereas
a decrease in temperature decreases
their activity.
 Mechanism of Thermoregulation
Heat is gained by
• Shivering
• Exercising
• Increased calorie intake
Heat is lost by
• Perspiration (major )
• Radiation into surroundings
• Conduction and convection (rarely)
• Small amount also lost through expiratory warm air
 Feedback Mechanism

• One of most important modes of

homeostasis operating. Operates in various
systems like oxygen and carbon dioxide
concentration in ECF, regulation of arterial
blood pressure.
 Types

• Negative Feedback- Negative feedback is a type of regulation in

biological systems in which the end product of a process in turn
reduces the stimulus of that same process.
• Positive Feedback- Positive feedback is a process in which the end
products of an action cause more of that action to occur in a feedback
loop.
Negative feedback
Positive Feedback
 Clinical Implications
• Disorder Of HPA axis- HPA axis dysfunction
symptoms can occur as a result of damage or
disease in the hypothalamus, pituitary gland,
and adrenal glands. Eg Cushing’s Syndrome.
• Cushing’s syndrome is the result of too much
ACTH produced in the pituitary gland (usually
by a benign tumor) over longer periods – this
increases cortisol levels. Cushing’s syndrome
can also be due to adrenal gland pathology that
leads to cortisol overproduction.
 Fluid Balance
• Normal constituents are enlisted below
 Thirst regulation
Decrease in ECF volume stimulates thirst by a
pathway independent of that mediating thirst in
response to increased plasma osmolality Thus,
hemorrhage causes increased drinking even if there
is no change in the osmolality of the plasma. The
effect of ECF volume depletion on thirst is mediated
in part via the renin–angiotensin system Renin
secretion is increased by hypovolemia and results in
an increase in circulating angiotensin II. The
angiotensin II acts on the subfornical organ, a
specialized receptor area in the diencephalon to
stimulate the neural areas concerned with thirst.
Related Clinical conditions

• Polydipsia- Excessive thirst. Physiological causes

Hypokalaemia, Hypovolemia. Pathological causes Diabetes
Mellitus (most common), Diabetes insipidus, drug induced (like
antipsychotics) , organophosphorus poisoning, mineral
deficiency (like zinc).
 Acid Base Balance

• The pH of the arterial plasma is normally 7.40 and that of venous plasma
slightly lower. A decrease in pH below the norm (acidosis) is technically
present whenever the arterial pH is below 7.40 and an increase in pH
(alkalosis) is technically present whenever pH is above 7.40.
• Acid–base disorders are split into four categories: respiratory acidosis,
respiratory alkalosis, metabolic acidosis, and metabolic alkalosis.
Normal acid-base concentrations and related clinical
conditions resulting from its alteration
 Clinical implications
• Diabetic Ketoacidosis (DKA)- A life threatening complication of Diabetes mellitus,
characterised by polyuria, deep gasping breathing (Kussmaul’s breathing) , vomiting and loss
of consciousness.
• Clinically diagnosed by high serum osmolarity and detection of ketone bodies in blood. This is a
major cause of metabolic acidosis.
Important Homeostatic mechanisms

• Control Of Blood Pressure

• Control of Fluid Balance
• Acid base Balance
• Endocrine control
Control Of Blood Pressure

• At Cardiac Level
• At Renal Level
 At Cardiac Level

• Control is primarily short term regulation.

• Primarily consists of Baroreceptor system.
• Baroreceptors are present at bifurcation of common carotid artery, and also arch of
aorta.
• When BP increases , they are stimulated by stretching of arterial wall, send impulse
via the medulla. This leads to inhibition of vasomotor centre, which as a result
inhibits sympathetic discharge to heart and blood vessels, hence reducing the BP.
 Renal Control of Blood pressure

At renal level 2 mechanisms primarily work for regulating BP

• Renin Angiotensin Aldosterone System- For increasing BP during
lowering of Renal perfusion and reduced GFR
• Fluid excretion in response to hypervolemia leading to high BP- For
reducing the BP
Renin angiotensin aldosterone system
 Renal Fluid control

• This mechanism works primarily in response to increased blood pressure.

• If BP increases and capacitance of vessels is unchanged, arterial pressure
increases. This leads to excretion of excess fluids, to bring arterial down
to normal. This is called pressure diuresis.
 Applied aspects

• Reduction of BP is achieved by using pharmacological agents which block

the RAAS system. ACEIs like Enalapril, Ramipril, ARBs like Olmesartan,
Telmisartan are commonly used.
• Diuretics like loop diuretics ( Furosemide, Budesonide) and thiazides
( chlorthalidone etc) reduce BP by promoting diuresis.
 Acid Base Balance
• Most important organs maintaining acid base balance are kidney and lungs.
• Acid base balance is primarily dependent on buffer system

• A buffer is any substance that can reversibly bind H . The general +

form of the buffering reaction is as follows:

Buffer +H Hbuffer
• Most important buffer acting in blood is bicarbonate buffer. HCO : 3−

H CO
2 3 HCO + H3 +
Regulation by Kidney

Kidney regulates acid base concentration by three major mechanisms

(1) secretion of H ; +

(2) reabsorption of filtered HCO ; 3−

(3) production of new HCO 3−

In case of acidosis, there is secretion of H+ in urine and reabsorption of

bicarbonate , while in alkalosis there is excess secretion of bicarbonate in urine.
 Regulation by Lungs
• Lungs regulate acid base balance by altering partial pressure of alveolar CO2 and O2.
• An increase in ventilation eliminates CO2 from extracellular fluid, which, by mass
action, reduces the H+ concentration. Conversely, decreased ventilation increases CO2
and H+ concentrations in the extracellular fluid.
• Feedback Control of H Concentration by the Respiratory System.
+

Because increased H concentration stimulates respiration and

+

because increased alveolar ventilation decreases H concentration, +

the respiratory system acts as a typical negative feedback

controller of H concentration:
+
Negative Feedback control of H+ by
respiratory system
 Applied aspect
Altitude Sickness - Even at high altitudes, carbon dioxide (CO2) is continually
excreted from the pulmonary blood into the alveoli. In addition, water vaporizes into
the inspired air from the respiratory surfaces. These two gases dilute the O2 in the
alveoli, thus reducing the O2 concentration.
In the case of CO2, during exposure to very high altitudes, the alveolar partial pressure
of CO2 (Pco2) falls from the sea level value of 40 mm Hg to lower values. In the
acclimatized person, who increases ventilation about fivefold, the Pco2 falls to about 7
mm Hg because of increased respiration.
Endocrine Control

Hormones have a major role to play in maintaining homeostasis.

Most important of them to be discussed are
• Parathyroid and calcium/Vit D3 metabolism
• Pancreas and insulin (glucose metabolism)
 Parathyroid and Ca++ metabolism

Calcium is absorbed from GIT ( promoted by Vitamin D3). Vit D3 also promotes Ca++ in bones (also
promoted by calcitonin).
Parathyroid (PTH) is released in response to decreased serum Ca++ levels.
1) PTH stimulates bone resorption, causing release of calcium into the extracellular fluid;
2) PTH increases calcium reabsorption and decreases phosphate reabsorption by the renal tubules, leading
to decreased excretion of calcium and increased excretion of phosphate;
3) PTH is necessary for conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol,which,
in turn, increases calcium absorption by the intestines. These actions together provide a powerful means
of regulating extracellular fluid calcium concentration.
4) Increased Ca++ in serum acts as negative feedback response to reduce secretion of PTH
Effect of PTH on calcium and phosphate
concentration
Applied aspects

• Hyperparathyroidism- cause of hypercalcemia, osteopenia,

osteoporosis, renal stones etc.
• Increased bone resorption.
• Clinical findings – Racquet Nails
• Radiological finding- Rugger Jersey Spine on Xray spine
Pancreas and Glucose Metabolism

• Insulin from beta cells of islets of Langerhans , along with Glucagon

paly chief role in regulating glucose concentration.
• Insulin promotes storage of glucose in liver , muscles ettc and also
promotes storage in adipose tissues, while glucagon, cortisol and
growth hormone act opposite.
• Hypoglycaemia is a strong stimulation for hunger while
hyperglycaemia is strong stimulus for insulin release
 Applied aspect
• Diabetes Mellitus Type 2 – one of most common metabolic condition as well as
non communicable disease.
• Primary cause – Insulin resistance with normal beta cell count.
• Diagnosed by increased FBS > 140 mg/dl, prolonged oral glucose tolerance
• Complications – Diabetic neuropathy, nephropathy, retinopathy
• Treatment – Lifestyle modification, dietary modifications, synthetic insulin =/- oral
hypoglycaemics ( sulfonylureas , metformin, SGLT 2 Inhibitors, DPP 4 inhibitors
etc)