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What is homeostasis?
The maintenance of a relatively stable internal environment despite external or internal change. The internal environment = extracellular fluid (plasma + interstitial fluid).
What are the three components of a homeostatic control system?
Detector (monitors variable and detects deviation), Controller/Integrating Centre (compares to set point and generates error signal), Effector (carries out corrective response).
Give examples of detectors in homeostatic systems.
Thermoreceptors, baroreceptors, pancreatic B cells.
Give examples of controllers in homeostatic systems.
Hypothalamus, brainstem, pancreas.
Give examples of effectors in homeostatic systems.
Sweat glands, skeletal muscle, blood vessels, endocrine glands.
What is negative feedback control?
A mechanism where deviation from the set point triggers responses that oppose the original change, returning the variable toward the normal range.
Describe the negative feedback response to a rise in body temperature.
Thermoreceptors detect increase → hypothalamus compares to set point → vasodilation and sweating activated → temperature falls back toward normal.
Describe the negative feedback response to a fall in body temperature.
Thermoreceptors detect decrease → hypothalamus activates → vasoconstriction, shivering and increased metabolic heat production.
Describe the negative feedback response to a rise in blood glucose after a meal.
Pancreatic B cells detect rise → insulin released → cells take up glucose → glucose returns to set point.
What is dynamic constancy in homeostasis?
Variables fluctuate over short periods but remain stable long term; complete constancy is impossible — small variation is normal.
How does homeostasis achieve stability?
By matching input and output rates, not by maintaining absolute constant values. Requires continuous energy expenditure.
What is the ICF and why does it differ from the ECF?
The intracellular fluid (ICF) is the fluid inside cells; it is kept distinct from the ECF to support enzyme function, electrical excitability, metabolism and osmotic balance.
What is the role of the phospholipid bilayer in maintaining the cellular internal environment?
It forms a selective barrier; hydrophobic core limits movement of polar/charged molecules while lipid-soluble substances (O2, CO2) diffuse freely. Ions and polar solutes require transport proteins.
What is facilitated diffusion?
Passive transport via channel or carrier proteins, down the concentration gradient — no energy required. Examples: GLUT1, ion channels.
What is primary active transport? Give an example.
Direct use of ATP to move substances against their gradient. Example: Na+/K+ ATPase — pumps 3 Na+ out and 2 K+ in.
What does the Na+/K+ ATPase pump maintain?
Low intracellular Na+, high intracellular K+, resting membrane potential and osmotic balance.
What is secondary active transport? Give an example.
Uses the energy stored in ion gradients (not direct ATP) to transport another substance. Example: Na+-glucose cotransporter.
What is the normal intracellular ionic environment?
High K+ intracellularly; high Na+ and Cl- extracellularly. This creates a resting membrane potential and electrical excitability in neurons and muscle.
How do cells regulate osmotic balance and volume?
Na+/K+ pump reduces intracellular Na+; regulation of aquaporins; adjustment of intracellular osmolytes. If Na+ accumulates inside, water follows causing cell swelling.
What is intracellular compartmentalisation and why is it important?
Membrane-bound organelles create specialised internal environments (e.g. lysosomes = acidic pH; mitochondria = proton gradient for ATP). Allows separation of incompatible reactions and efficient metabolic regulation.
How do cells regulate intracellular pH?
Buffer systems, H+ pumps, Na+/H+ exchangers and CO2 regulation maintain cytosolic pH at ~7.2.
How is intracellular Ca2+ regulated?
Kept extremely low compared to extracellular levels via Ca2+ ATPases, Na+/Ca2+ exchangers and storage in ER/SR.
What is the role of nucleic acids as building blocks?
DNA forms chromatin/chromosomes (with histones); rRNA forms ribosome structure; DNA encodes all signalling molecules, receptors and enzymes; miRNA/siRNA regulate gene expression; nucleotide derivatives (cAMP, cGMP) act as second messengers.
What is the role of proteins as building blocks?
Cytoskeleton (actin, microtubules, intermediate filaments); membrane channels and carriers; extracellular matrix (collagen, elastin); cell adhesion (cadherins, integrins); immune recognition (antibodies, MHC); signalling (enzymes, G-proteins, ion channels, peptide hormones).
What is the role of lipids as building blocks?
Phospholipid bilayer forms plasma membrane; cholesterol regulates membrane fluidity; glycolipids contribute to membrane asymmetry; steroid hormones (cortisol, oestrogen, testosterone); eicosanoids (prostaglandins); second messengers DAG and IP3.
What is the role of carbohydrates as building blocks?
Glycoproteins and glycolipids form the glycocalyx; structural polysaccharides in ECM; cell recognition (blood group antigens); adhesion and immune recognition; glycosylation modifies receptor function; glucose is an energy source.
How are polymers formed and broken down?
Formed by dehydration (condensation) reactions; broken down by hydrolysis of polymers.
What are the two types of sweat glands?
Eccrine (simple coiled tubular glands in deep dermis; important for thermoregulation) and Apocrine (larger glands opening into hair follicles; found in axilla/groin; not important for thermoregulation).
Describe the structure of eccrine sweat glands.
Simple coiled tubular glands in deep dermis/upper hypodermis; secretory coil + duct to skin surface; secretory cells produce isotonic fluid; duct cells reabsorb Na+ and Cl-; myoepithelial cells help expel sweat.
How many eccrine glands do humans have and where are they most dense?
2–4 million; highest density on palms, soles and forehead.
What neurotransmitter controls eccrine sweat glands?
Acetylcholine, released by postganglionic sympathetic fibres.
Describe the composition of sweat.
Water, Na+, Cl- and small amounts of K+. Initial sweat is isotonic to plasma; after duct reabsorption of Na+ and Cl-, final sweat is hypotonic.
What happens to sweat composition during heat acclimatisation?
Aldosterone increases → enhanced Na+ reabsorption in sweat ducts → sweat becomes more dilute → reduced sodium loss. Also: earlier onset of sweating, higher sweat rate, improved cardiovascular stability.
What is the difference between thermoregulatory and emotional sweating?
Thermoregulatory: triggered by increased core temperature, generalised distribution. Emotional: triggered by stress, localised to palms, soles and axillae; mediated by limbic system.
What are the consequences of impaired or excessive sweating?
Impaired: reduced evaporative cooling and risk of hyperthermia. Excessive without fluid replacement: hypovolaemia, hyperosmolar dehydration and reduced sweating capacity.
Where are peripheral thermoreceptors located and what do they detect?
In the skin; detect environmental temperature changes via TRP channels; signals travel to the brainstem and hypothalamus via the lateral parabrachial nucleus then to the preoptic area.
Where are central thermoreceptors located?
Warm-sensitive neurons in the hypothalamus detect blood temperature directly.
What is the primary integrative centre for thermoregulation?
The preoptic area (POA) of the hypothalamus — receives peripheral and central thermal input and activates effector pathways.
Describe the cutaneous vasodilation response to heat.
Sympathetic vasoconstrictor tone is withdrawn → arterioles and AV anastomoses dilate → skin blood flow increases (from 5% to up to 60% of cardiac output) → active cholinergic vasodilation (ACh + nitric oxide) → heat transferred from core to skin surface.
Why is evaporation the only effective cooling mechanism when ambient temperature exceeds body temperature?
Radiation, convection and conduction all require a temperature gradient between body and environment; when ambient temperature is higher, only evaporation (via latent heat of vaporisation) can remove heat.
Describe the cutaneous vasoconstriction response to cold.
Increased sympathetic outflow → noradrenaline released → vasoconstriction → reduced skin blood flow → AV anastomoses constrict → reduced surface heat loss.
Describe the shivering response to cold.
Hypothalamic shivering centre activates anterior motor neurons → rapid oscillatory skeletal muscle contractions → ATP hydrolysis without external work → heat production.
What is the heat balance equation?
M − W ± R ± C ± K − E. (M=metabolic heat, W=external work, R=radiation, C=convection, K=conduction, E=evaporation). If = 0: balanced; < 0: net heat loss; > 0: net heat gain.
What triggers ADH release and what does ADH do?
Triggered by increased plasma osmolality (detected by hypothalamic osmoreceptors). ADH acts on kidney collecting ducts → increases aquaporin insertion → increased water reabsorption → concentrated urine → minimises water loss.
What triggers RAAS activation and what does it achieve?
Triggered by reduced plasma volume (detected by baroreceptors and renal perfusion sensors). Renin → Angiotensin II → Aldosterone → Na+ reabsorption in kidney → water follows sodium.
What are the early signs of heat illness from inadequate fluid intake?
Profuse sweating, thirst, tachycardia, warm flushed skin.
What are the late signs of heat illness from inadequate fluid intake?
Reduced sweating, hypotension, confusion, hyperthermia, risk of heat stroke.
Why does thermoregulation fail in severe dehydration?
Heat gain exceeds heat loss; circulatory collapse limits skin blood flow and dehydration limits sweating capacity.
What is Mendel's Law of Dominance?
In a heterozygote, one allele masks the other; the dominant phenotype is expressed.
What is Mendel's Law of Segregation?
Two alleles separate during gamete formation (meiosis I); each gamete carries only one allele.
What is Mendel's Law of Independent Assortment?
Alleles of different genes on different chromosomes assort independently during gamete formation (e.g. BbJj → gametes BJ, Bj, bJ, bj).
What are the 3 main steps of DNA replication?
Initiation, Elongation and Termination.
What happens during initiation of DNA replication?
Initiator proteins bind AT-rich regions at the Origin of Replication Complex (ORC). DNA helicase unwinds the double helix creating a replication fork. Topoisomerase relieves supercoiling ahead. Single-stranded binding proteins stabilise separated strands.
Why do initiator proteins bind AT-rich regions?
AT pairs have only 2 hydrogen bonds (vs 3 for GC) so they separate more easily.
What happens during elongation of DNA replication?
RNA primase synthesises a short RNA primer (5–20 bases) providing a 3'-OH starting point. DNA polymerase adds complementary nucleotides 5' to 3'. Leading strand synthesised continuously; lagging strand synthesised as Okazaki fragments. RNA primers removed, gaps filled by DNA polymerase, fragments joined by DNA ligase.
What does DNA ligase do?
Seals nicks in the DNA backbone by forming phosphodiester bonds, connecting Okazaki fragments.
What happens during termination of DNA replication?
Replication forks meet; RNA primers removed by RNase; DNA polymerase fills gaps; DNA ligase seals final nicks. Result: two identical DNA molecules.
Describe the structure of DNA.
Polymer of nucleotides (phosphate group + deoxyribose sugar + nitrogenous base). Bases: A, T, G, C. Nucleotides joined by phosphodiester bonds. Two antiparallel strands (5'→3' and 3'→5'). A-T (2 H-bonds), G-C (3 H-bonds). Right-handed double helix, one turn every 10 base pairs. Major and minor grooves allow protein binding and gene regulation. Packed around histones (8 histones per nucleosome) into chromosomes.
What is epithelium?
Tissue composed of closely packed cells that covers body surfaces, lines internal cavities/hollow organs, and forms glands. Avascular, rests on a basement membrane, exhibits polarity, high regenerative capacity, minimal ECM.
What are the three surface domains of an epithelial cell?
Apical (faces lumen/external environment), Lateral (contacts neighbouring cells), Basal (attached to basement membrane).
What are the functions of the basement membrane?
Structural support, filtration, guides cell regeneration, and acts as a barrier to tumour invasion.
What are the four types of cell junctions in epithelium and their roles?
Tight junctions (prevent leakage), Adherens junctions (mechanical strength), Desmosomes (mechanical strength), Gap junctions (communication).
How is epithelium classified by number of layers?
Simple (one layer, all cells contact basement membrane), Stratified (multiple layers, protective), Pseudostratified (appears multilayered but all cells touch basement membrane, often ciliated).
How is epithelium classified by cell shape?
Squamous (flat, rapid diffusion), Cuboidal (cube-shaped, secretion/absorption), Columnar (tall, absorption/secretion/transport), Transitional/Urothelium (specialised for stretching, urinary tract).
What are the 6 major roles of epithelia?
Protection (barrier), Absorption (intestine, kidney), Secretion (mucus, enzymes, hormones), Filtration (renal corpuscle), Diffusion/Gas exchange (lungs), Sensory reception (taste buds, olfactory epithelium).
What is the difference between exocrine and endocrine glands?
Exocrine glands secrete via ducts (e.g. sweat glands); Endocrine glands secrete hormones directly into the bloodstream.
What is connective tissue and how does it differ from epithelium?
Supporting tissue that connects, supports, protects and binds other tissues. Unlike epithelium, it has few cells, abundant extracellular matrix (ECM), and is usually vascular.
What are the resident (fixed) cells of connective tissue?
Fibroblasts (produce collagen, elastin, ground substance), Adipocytes (fat storage), Macrophages (phagocytosis, immune surveillance), Mast cells (release histamine, inflammation).
What are the three types of fibres in connective tissue?
Collagen fibres (tensile strength, resist pulling), Elastic fibres (stretch and recoil, lungs/large arteries), Reticular fibres (fine branching network, support lymphoid organs).
What is ground substance in connective tissue?
Gel-like material composed of water, proteoglycans, glycosaminoglycans (GAGs) and adhesive glycoproteins. Functions: diffusion medium, shock absorption, structural support.
What are the major functions of connective tissue?
Structural support, binding/connecting (tendons, ligaments), protection (bone, fat), transport (blood), immune defence, energy/mineral storage.
Compare the three types of muscle tissue.
Skeletal: striated, multinucleated, voluntary, attached to bone, somatic control. Cardiac: striated, single central nucleus, intercalated discs, involuntary, heart wall, intrinsic pacemaker. Smooth: non-striated, single nucleus, involuntary, hollow organs, autonomic/hormonal control.
What are the main structural components of a neuron?
Cell body/soma (metabolic centre, protein synthesis), Dendrites (input region, graded potentials), Axon (output region, conducts action potentials), Synapse (junction for neurotransmitter release).
What are the three structural variations of neurons?
Multipolar (many dendrites, one axon; motor neurons), Bipolar (one dendrite, one axon; retina), Pseudounipolar (single process splits into two; sensory neurons/dorsal root ganglia).
What is the role of myelin and nodes of Ranvier?
Myelin is a lipid-rich insulating layer that increases conduction speed via saltatory conduction. Nodes of Ranvier are gaps where action potentials "jump" from node to node.
What are the four types of CNS glial cells and their functions?
Astrocytes (structural support, BBB, ion regulation, neurotransmitter uptake), Oligodendrocytes (CNS myelination, one cell → multiple axons), Microglia (immune surveillance, phagocytosis), Ependymal cells (produce/circulate CSF).
What are the two types of PNS glial cells and their functions?
Schwann cells (PNS myelination, one cell → one axon segment; support axon regeneration), Satellite cells (surround neuron cell bodies in ganglia, regulate microenvironment).
What is a stem cell?
An undifferentiated cell with the ability to self-renew and differentiate into specialised cell types.
What are pluripotent stem cells?
Stem cells that can differentiate into all cell types of the three germ layers (ectoderm, mesoderm, endoderm). High proliferative capacity, can form teratomas if uncontrolled. Examples: Embryonic stem cells (ESCs) and Induced pluripotent stem cells (iPSCs).
What are ESCs and iPSCs?
ESCs: derived from the inner cell mass of a blastocyst (5–7 days old), naturally pluripotent. iPSCs: adult somatic cells reprogrammed using Yamanaka transcription factors to behave like ESCs; avoids ethical concerns of embryo use.
What are tissue-specific (adult) stem cells?
Multipotent or unipotent stem cells restricted to generating cell types within their resident tissue. Maintain tissue homeostasis and repair; lower tumour risk than pluripotent cells.
Give two examples of tissue-specific stem cells.
Haematopoietic stem cells (HSCs): in bone marrow, generate all blood cell lineages, used in bone marrow transplantation. Mesenchymal stem cells (MSCs): found in bone marrow/adipose tissue, act mainly via paracrine signalling.
Compare totipotent, pluripotent, multipotent and unipotent stem cells.
Totipotent: all cell types including extra-embryonic (e.g. zygote). Pluripotent: all 3 germ layers, not placenta (ESCs, iPSCs). Multipotent: multiple related types within one lineage (HSCs, MSCs). Unipotent: only one cell type, still self-renew (epidermal stem cells, muscle satellite cells).
How do intestinal stem cells maintain GI homeostasis?
Lgr5+ stem cells in crypt bases → transit-amplifying cells → specialised epithelial cells (enterocytes, goblet cells, Paneth cells, etc.) → migrate up villus → apoptosis/shedding at tip. Maintains barrier integrity, nutrient absorption and mucosal defence.
How do HSCs maintain haematopoietic homeostasis?
HSCs in bone marrow self-renew and differentiate into myeloid lineage (RBCs, platelets, granulocytes) and lymphoid lineage (B and T cells). Regulated by EPO from kidneys and other systemic signals. Maintains oxygen transport, immune defence and haemostasis.
What are the key ethical and safety concerns around unproven stem cell therapies?
Lack of proven safety/efficacy; regulatory loopholes (autologous claim); patient vulnerability/marketing; scientific misrepresentation (MSCs act via paracrine not direct differentiation); safety risks (infection, immune reaction, tumour formation); ethical issues (ESC use, inadequate consent, high cost).
What are the phases of clinical trials for new therapies?
Preclinical studies → Phase I (safety) → Phase II (efficacy) → Phase III (large-scale comparison) → Phase IV (post-marketing surveillance).
What are the main constituents and functions of blood?
RBCs (O2 transport), WBCs (immune response), Platelets (clotting), Plasma (liquid medium, transports nutrients/waste), Proteins (osmotic pressure, immune function).
Give normal values for key haematological parameters.
Haematocrit: ~45% (M), ~40% (F). Haemoglobin: 130–180 g/L (M), 120–160 g/L (F). Blood volume: ~70 mL/kg (~5 L). Arterial O2 saturation: 97–100%. Mixed venous saturation: ~75%. Arterial PO2: 90–100 mmHg. O2 content (CaO2): ~20 mL O2/100 mL blood.
Why is haemoglobin necessary for oxygen transport?
Oxygen has very poor solubility in blood (k = 0.003 mL O2/100 mL/mmHg), so a carrier is required. Hb increases oxygen-carrying capacity ~70-fold.
Describe the structure of haemoglobin.
Tetramer of 2α + 2β globin chains. Each chain contains a protoporphyrin ring with a central Fe2+ ion (haem group). Each Hb molecule can bind 4 O2 molecules.
What is the Bohr effect?
Increased CO2 and H+ (lower pH) and higher temperature decrease Hb affinity for O2, causing a right shift of the oxyhaemoglobin dissociation curve and promoting O2 unloading in metabolically active tissues.
What is 2,3-BPG and what does it do?
2,3-Bisphosphoglycerate; produced in RBC glycolysis; binds deoxyhaemoglobin, stabilises the T state and promotes O2 release. Levels increase in chronic hypoxia, anaemia and high altitude.
Describe the structure and function of red blood cells.
Biconcave disc (~7–8 μm diameter), large SA:volume ratio, no nucleus/mitochondria/ribosomes. Contains haemoglobin for O2 transport. Cytoskeletal proteins (spectrin, ankyrin, actin) maintain flexibility and shape. Lifespan ~120 days.
Why do mature RBCs lack a nucleus and organelles?
To maximise space for haemoglobin; no mitochondrial O2 consumption means all O2 is delivered to tissues; inability to synthesise proteins limits lifespan to ~120 days.
How is oxygen transported in blood?
1–2% dissolved in plasma (determines PaO2); 98–99% bound to haemoglobin as oxyhaemoglobin.
What is cooperative binding in haemoglobin?
When the first O2 binds, Hb changes shape (T→R state), increasing affinity for subsequent O2 molecules. This produces the sigmoidal oxyhaemoglobin dissociation curve.
Describe erythropoiesis and its stages.
Production of RBCs in red bone marrow (~5–7 days). Stages: HSC → Myeloid stem cell → Pro-erythroblast → Basophilic erythroblast → Polychromatophilic erythroblast → Orthochromatic erythroblast → Reticulocyte → Mature RBC. Progressive Hb accumulation, nuclear condensation/expulsion, loss of organelles.
What regulates erythropoiesis?
Erythropoietin (EPO) produced by the kidneys in response to hypoxia. Stimulated by anaemia, blood loss, high altitude. Increases erythroid progenitor differentiation and reticulocyte release.
What nutritional requirements are needed for RBC production?
Iron (haem synthesis), Vitamin B12 (DNA synthesis; deficiency → megaloblastic anaemia), Folate/B9 (DNA synthesis; deficiency → megaloblastic anaemia), Amino acids (globin synthesis), functional bone marrow.