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PY1.1-7 | General Physiology — Part 3

Homeostasis — The Body's Autopilot (PY1.4)

Homeostasis is the maintenance of a stable internal environment despite changing external conditions. The concept was introduced by Claude Bernard (who called it the milieu intérieur) and later named by Walter Cannon.

Your body maintains dozens of variables within narrow ranges:
• Body temperature: 36.5–37.5°C
• Blood pH: 7.35–7.45
• Blood glucose: 70–110 mg/dL (fasting)
• Plasma osmolarity: 280–295 mOsm/L
• Blood pressure: ~120/80 mmHg

The homeostatic control loop has three components:

1. Sensor (receptor) — detects a change in the variable. Example: baroreceptors in the carotid sinus detect a drop in blood pressure.
2. Control centre (integrator) — receives the signal, compares it to the set point, and sends a command. Usually the brain (hypothalamus, medulla) or an endocrine gland.
3. Effector — carries out the corrective action. Example: the heart increases its rate and force of contraction.

Negative feedback — the response OPPOSES the stimulus, bringing the variable back toward the set point. This is the most common homeostatic mechanism.
• Example: Blood glucose rises after a meal → pancreatic beta cells (sensor/control) release insulin (signal) → liver and muscle cells (effectors) take up glucose → blood glucose falls back to normal.
• Think of a thermostat: when the room gets too hot, the AC turns on. When it cools down enough, the AC turns off.

Positive feedback — the response AMPLIFIES the stimulus. This is rare and always has an endpoint.
• Example: During childbirth, oxytocin stimulates uterine contractions → contractions push the baby's head against the cervix → the cervix sends more signals → more oxytocin → stronger contractions → delivery (endpoint) → the cycle stops.
• Another example: Blood clotting — each activated clotting factor activates more of the next factor in a cascade.

Why homeostasis matters to you: Almost every disease can be understood as a failure of homeostasis — diabetes (glucose homeostasis fails), hypertension (blood pressure homeostasis fails), fever (temperature set point shifts), acidosis (pH homeostasis fails).

Blood and Body Fluids — Composition and Functions (PY1.5)

Blood is a specialised connective tissue — a fluid tissue that circulates through the cardiovascular system. An adult has about 5 litres of blood.

Figure: Blood and Body Fluids — Composition and Functions (PY1.5)

Blood has two components:

• Plasma (55% of blood volume) — the liquid portion. It's ~90% water + dissolved solutes:
• Proteins (~7 g/dL): Albumin (60% — maintains oncotic pressure, binds drugs), Globulins (35% — includes antibodies/immunoglobulins), Fibrinogen (4% — clotting)
• Electrolytes: Na⁺, K⁺, Cl⁻, HCO₃⁻, Ca²⁺
• Nutrients: glucose, amino acids, lipids
• Waste products: urea, creatinine, bilirubin
• Gases: dissolved O₂, CO₂
• Hormones, vitamins

• Formed elements (45% — the haematocrit) — cells and cell fragments:
• Red blood cells (RBCs/erythrocytes) — ~5 million/μL in males, ~4.5 million/μL in females. Carry O₂ (via haemoglobin) and CO₂. Biconcave disc shape maximises surface area for gas exchange. No nucleus in mature RBCs (more room for haemoglobin).
• White blood cells (WBCs/leukocytes) — 4,000–11,000/μL. Types: neutrophils (60–70%, bacterial infection), lymphocytes (20–30%, viral/immune), monocytes (3–8%), eosinophils (1–4%, parasites/allergy), basophils (<1%).
• Platelets (thrombocytes) — 1.5–4 lakh/μL. Cell fragments from megakaryocytes. Essential for clotting.

Functions of blood:
1. Transport — O₂, CO₂, nutrients, waste, hormones
2. Regulation — body temperature (distributes heat), pH (buffer systems), fluid balance (oncotic pressure from albumin)
3. Protection — WBCs fight infection, platelets and clotting factors prevent blood loss

Plasma vs Serum: Plasma contains fibrinogen and clotting factors. Serum is plasma MINUS fibrinogen and clotting factors (i.e., what remains after blood clots). When you send blood in a plain tube (red top), you get serum. When you send it in an EDTA/citrate tube (purple/blue top), the anticoagulant preserves plasma.

In Biochemistry, you're studying proteins right now — albumin, globulins, and enzymes. These plasma proteins are made by the liver (except immunoglobulins, made by plasma cells). Understanding their structure (BI) explains their function (PY).

pH Regulation and Buffer Systems (PY1.6)

pH is a measure of hydrogen ion concentration. Normal blood pH is tightly regulated between 7.35 and 7.45 — slightly alkaline.

Figure: pH Regulation and Buffer Systems (PY1.6)

• pH < 7.35 = acidosis (too many H⁺ ions)
• pH > 7.45 = alkalosis (too few H⁺ ions)
• pH < 6.8 or > 7.8 is incompatible with life

Why is pH so critical? Proteins (including enzymes) change their 3D shape when pH changes. Since enzymes drive every biochemical reaction, even a small pH shift can disrupt metabolism, neuromuscular function, and cardiac rhythm.

Three defence lines against pH change (in order of speed):

1. Chemical buffer systems — act within SECONDS

• Bicarbonate buffer (most important in ECF):
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
If H⁺ increases → HCO₃⁻ (bicarbonate) combines with H⁺ to form H₂CO₃ → CO₂ + H₂O (the CO₂ is exhaled)
If H⁺ decreases → H₂CO₃ dissociates to release more H⁺
Normal ratio: HCO₃⁻ : H₂CO₃ = 20 : 1 (maintained by the kidneys and lungs together)

• Phosphate buffer (important in ICF and urine):
HPO₄²⁻ + H⁺ ⇌ H₂PO₄⁻

• Protein buffer (important in ICF and plasma):
Haemoglobin is the most important protein buffer in blood. Albumin also buffers.

2. Respiratory compensation — acts within MINUTES
• If blood becomes acidic → chemoreceptors detect the rising CO₂/H⁺ → respiratory centre increases breathing rate → more CO₂ is exhaled → H⁺ decreases → pH rises back toward normal
• Kussmaul breathing — deep, rapid breathing seen in diabetic ketoacidosis — is the body desperately trying to blow off CO₂ to compensate for metabolic acidosis

3. Renal compensation — acts over HOURS to DAYS (slowest but most powerful)
• Kidneys can excrete H⁺ in urine (acidify the urine)
• Kidneys can reabsorb or generate new HCO₃⁻ (bicarbonate)
• Kidneys can excrete HCO₃⁻ if there is alkalosis

The Henderson-Hasselbalch equation ties it together:
pH = 6.1 + log([HCO₃⁻] / [0.03 × pCO₂])
The lungs control pCO₂ (the denominator). The kidneys control HCO₃⁻ (the numerator). Together they maintain the 20:1 ratio and keep pH at 7.4.

In Biochemistry, you're studying enzymes and their kinetics. Every enzyme has an optimal pH — pepsin works best at pH 2 (stomach), trypsin at pH 8 (intestine). Buffer systems ensure each compartment maintains the right pH for its enzymes to function.

Bone Physiology and Calcium Metabolism (PY1.7)

Bone is not a dead scaffolding — it's a dynamic, living tissue that is constantly being remodelled. Understanding bone physiology means understanding calcium metabolism, because 99% of the body's calcium is in bone, and the remaining 1% in blood and cells is critical for nerve conduction, muscle contraction, blood clotting, and enzyme function.

Figure: Bone Physiology and Calcium Metabolism (PY1.7)

Normal plasma calcium: 8.5–10.5 mg/dL (total) or 4.5–5.5 mg/dL (ionised — the physiologically active form)

Calcium exists in three forms in plasma:
• Ionised (free) Ca²⁺ (~50%) — the active form, tightly regulated
• Protein-bound (~40%) — bound mainly to albumin (inactive, cannot cross membranes)
• Complexed (~10%) — bound to anions like phosphate and citrate

Three hormones regulate calcium:

1. Parathyroid hormone (PTH) — from the parathyroid glands. Secreted when blood Ca²⁺ FALLS. Actions:
• Increases bone resorption (osteoclasts break down bone → releases Ca²⁺)
• Increases renal reabsorption of Ca²⁺ (less calcium lost in urine)
• Increases renal production of active vitamin D (1,25-dihydroxyvitamin D₃)
• Net effect: RAISES blood calcium

2. Calcitonin — from thyroid C-cells (parafollicular cells). Secreted when blood Ca²⁺ RISES. Actions:
• Inhibits osteoclasts (reduces bone resorption)
• Increases renal excretion of Ca²⁺
• Net effect: LOWERS blood calcium (opposite of PTH)
• Clinically less important than PTH in adults

3. Vitamin D (calcitriol / 1,25-(OH)₂D₃) — a hormone, not just a vitamin:
• Synthesised in skin (UV light converts 7-dehydrocholesterol → cholecalciferol) → hydroxylated in liver (25-hydroxylase) → activated in kidney (1α-hydroxylase, stimulated by PTH)
• Increases intestinal absorption of Ca²⁺ and phosphate
• Supports bone mineralisation
• Deficiency → rickets (in children — soft, bowed bones) or osteomalacia (in adults — soft bones)

Bone cells:
• Osteoblasts — build bone (lay down osteoid matrix and mineralise it)
• Osteoclasts — break down bone (resorption — acid + enzymes dissolve mineral and matrix)
• Osteocytes — mature bone cells trapped in lacunae, sense mechanical stress and regulate remodelling

Mnemonic: OsteoBlasts = Build. OsteoClasts = Crush. OsteoCytes = Communicate.

In Anatomy right now, you're learning that bones have a periosteum, endosteum, and blood supply. The osteoblasts live on these surfaces. Every time your Anatomy teacher says 'this bone is remodelled after a fracture,' they're describing the osteoblast-osteoclast cycle you're learning here in Physiology.