Fundamentals of Physiology & Pharmacology PDF

Fundamentals of Physiology & Pharmacology Homeostasis – maintaining physiological variables Dr. Greg Knock [email protected] After studying this lecture, you should be able to: Explain the u...

Fundamentals of Physiology & Pharmacology Homeostasis – maintaining physiological variables Dr. Greg Knock [email protected] After studying this lecture, you should be able to: Explain the underlying principles of physiological homeostasis, including the importance of negative feedback Describe the role of the autonomic nervous system in physiological control Describe the role of endocrine systems in physiological control Describe the role of paracrine homeostatic signalling in physiological control Describe feed-forward and positive feedback control mechanisms Physiology (/ˌfɪziˈɒlədʒi/; from Ancient Greek φύσις (phúsis) 'nature, origin', and -λογία (-logía) 'study of') is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out chemical and physical functions in a living system. According to the classes of organisms, the field can be divided into medical physiology, animal physiology, plant physiology, cell physiology, and comparative physiology. Central to physiological functioning are biophysical and biochemical processes, homeostatic control mechanisms, and communication between cells. Physiological state is the condition of normal function. In contrast, pathological state refers to abnormal conditions, including human diseases.  What is Physiology? The study of how organisms function and how function is controlled and maintained in order to keep us alive and healthy Physiology Normal Function Abnormal Function = Pathophysiological Function = Physiological = illness & disease = Health Control of function Homeostasis  PART 1 Basic concepts  Important terms Physiological variable A measure of a bodily condition or bodily function Homeostasis ‘The dynamic maintenance of physiological variables within a predictable range’ Set-point The normal ‘basal’ or ‘at rest’ value for a physiological variable E.g. Core temperature = 37°C, arterial carbon dioxide = 5.3 KPa Set-points may be temporarily over-ridded or may need to be adjusted to suit changing circumstances Negative Feedback The most common mechanism for the maintenance of physiological variables  Why do we need homeostasis? Short term Immediate survival  Medium-long term health and well-being, reproductive capability  If a physiological variable strays too far out of its normal range for too long? Hyperthyroidism Hypertension (Grave’s disease) Illness, disease or death Excess Cortisol Hypoxemia (Cushing Syndrome) Acidosis/Alkalosis Hyperglycemia (Diabetes) Example physiological variable: blood glucose concentration Rises after a meal, then is brought back towards the set-point of ~90 mg/ml through homeostatic control 140 Breakfast Lunch Dinner Blood glucose (mg/ml) 120 100 80 60 24:00 06:00 12:00 18:00 Time of day  Example physiological variable: blood pressure 140 Arterial pressure (mmHg) systolic 100 60 diastolic Mean (at rest, awake): 20 diastolic = 80 mmHg Sleep systolic = 120 mmHg 09:00 12:00 15:00 18:00 21:00 24:00 03:00 06:00 09:00 Time (hrs) Physical activity, mood etc – all influence BP, but only in the short-term BP is predictable over the long-term Set-point is lower during sleep  Physiological variables are often inter-dependent Temperature Metabolic rate Optimal Growth rate functioning of all cells of the body Blood Glucose Breathing rate Tissue CO2 and pH Healthy human Blood Blood Tissue O2 pressure flow rate Water Plasma volume content Sodium Plasma osmolality content  Physiological variables are often inter-dependent Temperature Metabolic rate Optimal Growth rate functioning of all cells of the body Blood Glucose Breathing rate Tissue CO2 and pH Healthy human Blood Blood Tissue O2 pressure flow rate Water Plasma volume content Sodium Plasma osmolality content Important term: Hierarchy of importance of physiological variables Example: Osmolality (salt/water balance) is more important to immediate survival than blood pressure - BP can go too high so to maintain osmolality Excessive salt in diet Plasma osmolality Increased plasma osmolality (could be fatal) Plasma volume Water intake increased to compensate Plasma osmolality maintained High BP is dangerous But blood volume is increased in the long-term = Hypertension Blood pressure Blood pressure is increased  Key features of all negative feedback loops >START HERE< Effectors A physiological Negative Produce variable drifts feedback responses that away from it’s tend to bring the normal set-point variable back Sensors towards its set- detect the point change in the variable Efferent pathway Afferent pathway carries signals from carries signals from sensors to integrating integrating centre to centre effectors Integrating centre Compares inputs from sensors against physiological set-point and elicit a response  Three main types of negative feedback Neuronal Endocrine Paracrine  PART 2 Neuronal feedback control Many neuronal integrating centres are in the midbrain or brain stem Hypothalamus Pons medulla Essential for: Temperature control Osmolality control Blood pressure/flow control Blood gas/breathing control Communication with effectors is usually via the sympathetic and parasympathetic nervous systems They tend to have opposing actions on bodily functions Parasympathetic (acetylcholine) (noradrenaline) Sympathetic This results in a fine-tuning of physiological variables Examples: Cardiac output & blood pressure Lung ventilation GI tract motility & bladder control Exocrine secretions Endocrine secretions Example of neuronal control: body temperature Normal core body temp = 37°C When core temp maintained at 37°C and is in equilibrium with ambient temperature (typically 20°C), system is in steady state If room temp is lowered, If room temp is raised, body body temp also begins to temp also begins to rise drop Responses activated to raise Responses activated to lower body temp back to set-point body temp back to set-point Negative feedback How does this work?  Temperature control uses negative feedback Reduced Heat >START HERE< Sensors blood loss from flow to A drop in ambient Hypothalamus body skin Negative temperature senses the feedback causes a drop in change Heat core temperature shivering production Effectors Afferent Skin blood vessels pathway and muscle Neurons communicate within Integrating centre hypothalamus Hypothalamus compares Efferent against set-point for pathway(s) temperature Nerve signals from hypothalamus to effectors  PART 3 Endocrine and Paracrine feedback control  Human endocrine organs Hypothalamus Posterior Thyroid pituitary gland Anterior pituitary Adrenal gland Pancreas Kidney Testes Ovaries There are others. Can you name them?  Class of hormone: tyrosine derivatives H H HO C C COOH H NH3+ Tyrosine Thyroxine (T4) Adrenaline I I H H HO HO H H HO O C C COOH Adrenal N HO C C H NH3+ medulla CH3 Thyroid I I H H No need to learn the exact hormone structures for this module, just the key features  Class of hormone: peptides, polypeptides, glycopeptides Peptides Anti-diuretic hormone (posterior pituitary) Oxytocin (posterior pituitary) Polypeptides Insulin (pancreas) Growth hormone (anterior pituitary) Glycopeptides Luteinizing hormone (anterior pituitary) Follicle-stimulating hormone (anterior pituitary) Insulin Thyroid-stimulating hormone (anterior pituitary) (a polypeptide)  Class of hormone: steroids Liver Ovaries Testes Cholesterol Estradiol Testosterone Adrenal cortex Aldosterone Cortisol No need to learn the exact hormone structures for this module, just the key features  Features of simple endocrine negative feedback Example: control of blood glucose concentration Integrating centre Within the b-cell, change is compared against set-point Efferent pathway Pancreas secretes more of the hormone insulin into the blood Afferent pathway Intracellular pathway within the b-cell Effectors Other tissues Sensor (E.g. liver) Pancreatic b-cells absorb more glucose from blood Eating a meal causes Negative Blood glucose concentration blood glucose feedback decreases back to set-point value concentration to increase >START HERE< Note: hormones act on target cells by binding to receptors  Hormone Receptors Type of hormone Receptor location Mechanism of action peptides, proteins second messengers to change enzyme activity Glycoprotein Cell surface: plasma membrane Rapid, often transient catecholamines response Steroids Alter gene transcription Intracellular: thyroid hormones cytoplasm or nucleus Slow, prolonged response Note: Response of a target tissue may depend on the type of hormone receptor expressed  Paracrine homeostatic control Negative feedback loops operating locally Sensors, integrating centres and effectors are all located in the same tissue Efferent pathway usually involves secretion of diffusible substances from one group of cells to act on another group of cells nearby Stimulus Effect May operate in Diffusible substances parallel or may act on cell independently of surface receptors or neuronal and intracellular targets of endocrine control effector cells  Example of paracrine negative feedback: Skeletal muscle blood flow during exercise >START HERE< Increased metabolic O2, CO2, lactic Sensor: endothelium of arterioles demand during exercise acid in muscle supplying blood to the muscle Negative feedback Endothelium: Afferent pathway and Sensor integrating centre in Muscle O2 supply afferent pathway endothelial cell, compares increased integrating centre against set-point CO2 & lactic acid washed away Increased secretion of vasodilators by Smooth endothelium Muscle blood flow increases muscle: Effector Efferent pathway Vasodilators diffuse from endothelium Arterioles dilate Smooth muscle relaxes to adjacent smooth muscle  Feed-forward and Positive Feedback Feed-forward Anticipation of a change brings about the response to that change before the change can be detected by negative feedback sensors Positive feedback A change in a variable triggers a response that causes further change in that variable The effect is therefore amplification of the change rather than normalisation  Feed-forward control mechanisms are usually neuronal Two Examples: Anticipation of physical exertion Anticipation of a meal Increased heart Increased blood flow rate in muscles Stimulation of saliva and gastric juice production Preparation for increased demand for O2 and fuel by muscles Preparation for food intake Positive Feedback is rare but required under special circumstances Example: Parturition (contraction of uterus to expel fetus) >START HERE< Pregnancy shifts maternal estrogen/progesterone balance Increased excitability of uterus Uterine contractions Birth of baby terminates positive feedback +ve feedback Fetus presses on cervix Signals to hypothalamus Oxytocin secretion from pituitary gland Any questions?