Animal Phys

  • Created by: Alex
  • Created on: 03-06-13 12:09
purpose of a heart
Delivers 02 to the body by aqueous medium. (water has low O2 solubility so plasma solution needed)
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Open system
Heart pumps blood into open ended vessels
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Fluid that bathes tissues of an animal with an open circulatory system
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Closed System
Blood flows through continuous circuit of blood vessels.
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Purpose of closed system
Transports nutrients, 02, metabolic wate, hormones, metabolic heat, maintains ph & defends against microorganisms
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Vertebrate circulatory system components
Heart, blood vessels, blood, lymph and lymph vessels
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How many circuits in typical closed system
2, one thorugh heart, one through body. allow low pressure in lungs and high in remainder of body
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Features of evolution
Single central pump, unidirectional flow and one way valves to maintian pressure
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Location of heart
Between sternum and vertebre in upper part of throax
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Size and weight of heart
12cm long, 8cm diameter, 250-300g in weight
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4 chambers of heart
Left and right ventricle and atrium
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4 vessels of heart
Pulmonary artery, pulmonary vein, aorta and vena cava
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4 valves of heart
left and right AV valve, pulmonary valve and aortic valve
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Whats's the tricuspid valve
The three-segmented valve of the heart that keeps blood in the right ventricle from flowing back into the right atrium. - right AV valve
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What's the bicuspid valve
two segmented valve - 2 flaps/cusps. between the left atrium and the left ventricle. It permits blood to flow one way only, from the left atrium into the left ventricle (Left AV valve)
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what are chordae tendineae
Heart strings - cord-like tendons that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart. Prevent Eversion (turning inside out)
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Purpose of semi-lunar valves
Prevent backflow. forced open when pressure is greater on non-lunar side. close when pressure changes. on at opening of aorta,, on at opening of pulmonary artery
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Type of muscle is cardiac?
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When heart muscle relaxes and allows chambers to fill with blood - expansion
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The phase of the heartbeat when the heart muscle contracts and pumps blood from the chambers into the arteries.- Relaxation
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What makes the Heart beat (lub-dub)
1. Upper &lower chambers fill & the pulmonary & aortic valves close. 2. upper chambers contract and prime lower chamber. 3. lower chamber contracts, the AV valve closes (1st sounds) blood ejects through the semi-lunar valve which then closes (2nd sou
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What system controls heart beat
Autonomic nervous system combined with an internal pace maker
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Pathway of Conduction
1.Stimulus initiated in SAN 2.atrial muscle fibres contract 3.conduction via AVNode 4.spreads down AV bundle to right and left branch bundle eventually forming purkinje fibres 5.fibres conduct impulses to muscle fibres of both ventricles 6.contractio
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Two types of muscle in heart
Pacemaking and contractile
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Excitation-contraction coupling definition
physiological process of converting an electrical stimulus to a mechanical response
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Cardiac muscle is excited by spread of depolarizing current through gap junctions. triggers the opening of ca2+ channels. ca2+ binds to troponin enabling crossbridge cycle to occur. to terminate ca2+ is pumped out cytosol
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What controls heart function
Heart muscle itself and the AutonomicNS
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Cardiac output (equation)
Heart rate x stroke volume
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How much blood pumped in a minute
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Starlings law of the heart
Stroke volume of the heart increases with increase in volume of blood filling the heart. -ventricular wall stretches causing cardiac muscle 2 contract more forcefully. increase in load experienced by each muscle fiber = greaterheart contraction &beat
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Heart beat at rest
SAN at 70bpm
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Neuronal activity during exercise
Parasympathetic activity falls, sympathetic activity increases - increase heart beat and contractile force
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Neurotransmitter parasympathetic NS
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Neurotransmitter for Sympathetic NS
Norepinephrine (post ganglionic) Acetylcholine (pre ganglionic)
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Parts of the circulatory system
Carrier & mediium, pump & contributory flow mechanisms, Distribution system & a surface for exchange - facilitate diffusion from carrier to tissues
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Function of arterioles
Control vessels by changing diameter & therefore also flow and pressure in the system
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How Homeostasis is helped maintained by circulatory system
transport of O2, nutrient, waste, products, metabolic heat and hormones
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Arteries deliver...
Oxygenated blood and nutrients
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Veins remove
De-oxygenated blood and waste products
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Major arteries
Aorta, carotid, brachial, radial iliac, femoral, gastric, hepatic and renal
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Major veins
vena cava, jugular, brachial, basilic & cephalic, common iliac and femoral
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Arteries divide into...
arterioles then capillaries
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Where does blood and tissue exchange occur?
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What do capillaries reform to join?
Venules then veins then they return the blood to the heart
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structure of arteries
Layers of elastin and lots of muscle
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Structure of arterioles
Lack elastin
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Structure of capillaries
no elastin of muscle - only thin endothelium and basement membrane
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'structure of veins
Less muscle and elastin that arteries
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Types of capillary
Continuous, fenestrated and discontinuous
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Continuous capillaries have a sealed endothelium and only allow small molecules, like water and ions to diffuse.
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have pores in the endothelial cells (60-80 nm in diameter) that are spanned by a diaphragm of radially oriented fibrils and allow small molecules [2][3] and limited amounts of protein to diffuse.
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pecial fenestrated capillaries that have larger openings (30-40 μm in diameter) in the endothelium to allow red and white blood cells (7.5μm - 25μm diameter) and various serum proteins to pass, a process that is aided by a discontinuous basal lamina
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effect of pre-capillary sphincters
(band of smooth muscle) effectively shuts down capillaries at rest - sympathetic tone
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Effect of noradrenaline on circulatory system
causes vasoconstriction
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Efffect of adrenaline on circulatory system
dilates blood vessels in heart& skeletal muscle
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Function of valve system
Blood in veins pumped against gravity. Valves prevent backflow of blood. contracted muscle pushes blood through valves. venous valve prevents backflow.
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Blood pressure
The pressure exerted by the blood on the inside wall of an artery - measures diastolic, systolic nd mean pressure
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BP equation
cardiac output x total peripheral resistance - measured mmHg
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Peripheral resistance
resistance caused by blood viscosity + friction between blood and vessel wall
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High BP
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Short term BP maintence
Kept within limit by baroreceptor reflex - a homeostatic negative feedback system - vagus NF slow heart rate & velocity with Ach at SA & VA nodes
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Funciton of mechanoreceptors
Protect brain from excess presser - in aortic arch and carotid sinus - fire if BP increases
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Systolic BP
When the heart is beating - increases during exercise
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Diastolic BP
When the heart is relaxed
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Whats the cytoskeleton
A microscopic network of protein filaments and tubules in the cytoplasm of many living cells, giving them shape and coherence.
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Part of the cytoskeleton
Microfilaments, Neurofilaments/intermediate filaments, microtubules
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Function & structure of microfilaments
3-7nm Diam. polymer (built of) G-actin. Strands intertwine to form F-actin filaments. prevalent at edge of cell-cortex. generate cell movement by rapid assembly & dissasembly. Support, strengthen & shape cells
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Function and structure of Neurofilaments (intermediate filaments)
7-11nm Diam. Protein composition -cell type dependent. mechanical strenngth & stabalise cell - prevent excessive stretching from outside forces. stabalise & strengthen axon. organise internal structure. in only some animals.
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What are mutations of neurofilametns associated with
Neurodegenerative diseases
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Microtubules diameter
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structure of microtubules
long hollow unbranched tubes, primarily composed of tubulin (globular protein)
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Function of microtubules
position organelles in cytoplasm. maintain asymmetric cell shape(needed in e.g. nerves). coorinate complex cell movement. transport of secretory vesicles (highway for movement-ATP dirven) movement of speciaised cell projections-cilia and flagella
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Orthograde Axonal transport
Movement of organelles towards synaptic terminal from cell body. moved by kinesin
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Cellular components transported orthograde
fast - vesicles and organelles. slow - cytoskeleton and soluble enzymees
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Protein used for orthograde transport
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Motor protein. move along microtubule filaments, powered by hydrolysis of ATP. movement supports cellular functions including mitosis, meiosis & transport of cellular cargo, - axonal transport. kinesins walk to + end of microtubule, transporting carg
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Movement of organelles away from synaptic terminal towards cell body
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retrograde transport function
movement of trophic factors from neighboring cells to stroma - give information regarding the state of nerve terminal
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cellular components travel retorograde
fast - vesicles, organelles, & membranes. Some viruses and toxins also transported
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Protein used for retrograde transport
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converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by "walking" along cytoskeletal microtubules towards the minus-end of the microtubule, which is towards the cell centre
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sustentacular tissue that surrounds and supports neurons in the central nervous system;
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Neuroglia types in CNS
Astrocytes, oligodendrocytes, microglia & ependymal cells
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Neuroglia in PNS
Schwann and satellite cells
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Role of neuroglia
Support, insulate and protect neurons. glia to glia communication. Receptors for neurotransmission. connective tissue of CNS, Homeostatically maintain composition of extracellular environment
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Star shaped glial cells
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Role of Astrocytes
support & nourish neurones. regulate composition of CNS. guide neurones during development, glue of CNS-hold neurons together. repair of brain injuries & form neural scars. participate in formation of Blood,brain,barrier
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How astrocytes regulate composition of CNS
Remove excesse potassium ions - maintains normal excitability
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Blood brain barrier
a mechanism that creates a barrier between brain tissues and circulating blood; serves to protect the central nervous system
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How Blood brain barrier works
Astrocytes maintain tight junctions between endothelial cells in capillary walls. capillaries selectively permeable-prevent substances entering brain tissue. Not effective barrier for gases or fat-soluble substances. e.g. nicotine and anaesthetics
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small nonneural cells forming part of the supporting structure of the central nervous system. They are migratory and act as phagocytes to waste products of nerve tissue
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Microglia are specialised macrophages
phagocytic cells that ingest and digest cell debris and bacteria
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How microglia work
Respond to signals from neurons (important in response to disease or injury- multiply and move to infected area). remove debris and bacteria by phacocytosis. Release signalling molecule that mediate inflammation & then release growth factor
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Ependymal cells
epithelial-like cells that line the CSF-filled ventricles in the brain and the central canal of the spinal cord
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function of ependymal cells
help produce and circulate cerebrospinal fluid that bathes brains and spinal cord. possibly also neuronal stem cells - might form glial cells and neurones
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type of Glial cell in CNS
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Function of olgiodendrocytes
envelop neurones in CNS - forming insulating mylein sheaths. -Electrical insulator. speed transmission of neural impulses
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Schwann Cell
any cell that covers the nerve fibers in the peripheral nervous system and forms the myelin sheath.
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schwann cell function
outside CNS (so not glial). Form mylien sheath around axons in the PNS
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What's multiple sclerosis?
Neurological disease where patches of mylein deteriate at irregular inteverals along axons in the CNS & are replaced by scar tissue ontefering with conduction of neural impulses
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Symptons of multiple sclerosis
Fatigue, loss of coordination & balance, numbness, blurred vision & blindness& paralysis
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Three types of neurone
Unipolar, bipolar and multipolar
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Unipolar neurone
Long axon, cell body branches off side(in middle), dendrites at end of axon - afferent (sensory neurones)
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Bipolar neurone
specialized neuron observed to have only two processes present: the axon and a dendrite, arising from opposite poles of the cell body. - Retina
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Multipolar neurone
is a type of neuron that possesses a single (usually long) axon and many dendrites, allowing for the integration of a great deal of information from other neurons. In efferent (motor) nerurons and interneurones
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Afferent fibre classificaion
Classified dependent on diameter, conduction velocity and myelination. A and B are myelinated, C is non-mylenated
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Spinal cord
The major column of nerve tissue that is connected to the brain and lies within the vertebral canal and from which the spinal nerves emerge( carries impulses to and from the brain, and serves as a center for initiating & coordinating many reflex act)
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Grey matter
Large masses of cell bodies, dendrites, unmyleinated neurones and glial cells
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White matter
myelinated axons arranged in bundles - tracts of pathways
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what's rexed laminae
a scheme used to classify the structure of the spinal cord based on the cytological features of neurones in different regions of grey substance
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somatomotor pathway
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Visceromotor pathway
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Number of nerves in the spinal cord
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Number of cervical nerves
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No. of thoraic nerves
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No. of lumbar nerves
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No. of sacral nerves
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No of coccygeal nerves
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where nerves exit corresponding vertebra
Exit from below for all except cervical nerves
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Head end of spinal cord known as
Rostal end
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Tail end of spinal cord known as
Caudal end
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Peripheral nerves (PNS)
The nerves and ganglia outside of the brain and spinal cord - connects CNS to limbs and organs
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Structure of Peripheral nerves
axons wrapped in endonerium - connective tissue layers around azons. axons bundled together, axon bundles wrapped in perineurium(bundles of nerve fibres). Epineurim encloses bundles of nerves and blood vessels
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Division of PNS
into somatic and autonomic NS
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Nerves in the PNS
12 cranial nerves and 31 spinal nerves
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Cranial nerve
Each of twelve pairs of nerves that arise from the brain, not from the spinal cord, and pass through separate apertures in the skull
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Cranial nerve I
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Cranial nerve II
Optic (not part of PNS)
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Cranial nerve III
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Cranial nerve IV
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Cranial nerve V
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Cranial nerve VI
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Cranial nerve VII
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Cranial nerve VIII
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Cranial nerve IX
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Cranial nerve X
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Cranial nerve XI
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Cranial nerve XII
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Central Nervous System
The complex of nerve tissues that controls the activities of the body. In vertebrates it comprises the brain and spinal cord.
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Protection of the CNS
boney outer casing - skull/veterbral column. membranes-meninges. hydraulic buffer - cerebrospinal fluid. foreign agents - blood-brain-barried
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Each of the series of small bones forming the backbone, having several projections for articulation and muscle attachment, and a hole through which the spinal cord passes
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How nerves enter and exit CNS
through formina in sjull of between spinal vertebrae
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what vertebrae does spinal cord finish at? `
1 or 2. roots continue to extend caudally(towards tail) before emerging through foramina
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The three membranes (dura mater, arachnoid, and pia mater) that line the skull and vertebral canal and enclose the brain and spinal cord.
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Dura mater
The tough fibrous membrane covering the brain and the spinal cord and lining the inner surface of the skull. It is the outermost of the three meninges that surround the brain and spinal cord.
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Dura mater properties (all)
strong & inelastic- prevents abrasion. Highly Vasculated & innervated.
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Dura mater in head
Double layered - joined except at sinuses. attatches to inside of skull. normally no epidural space between it and skull
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Dura mater in spinal cord
Not double-layered. Epidural space above containing venous plexus (congregation of multiple veins)
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Dura mater in subdural space
very thin and contains interstitial fluid
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subdural space
artificial space created by the separation of the arachnoid from the dura as the result of trauma or some ongoing pathologic process; in the healthy state, the arachnoid is tenuously attached to the dura and a naturally occurring subdural space is n
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Arachnoid mater
delicate fibrous membrane forming the middle of the three coverings of the central nervous system
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Properties of arachnoid mater
Loose fit, very vascular, delicate like spider webs - strands connect to pia mater & help support CNS, contains cerebral spinal fluid
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Pia mater
The delicate innermost membrane enveloping the brain and spinal cord.
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Properties of pia mater
Thin layer of connective tissue. clings tightly to CNS. contains small plexus of blood vessels - ensure good 02 and nutrient supply to CNS
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Noun Inflammation of the meninges caused by viral or bacterial infection.
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Ventricular system (brain)
The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.
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Cerebrospinal fluid
Clear watery fluid that fills the space between the arachnoid membrane and the pia mater
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Properties of cerebrospinal fluid
shock absorber-cushions brain & spinal cord against mechanical injury. Medium more nutrient & waste exchange between blood & brain. inside ventricles & subarachnoid space. composed of glucose & various gases
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where is most of cerebrospinal fluid produced
70% by choroid plexus in walls & roots of ventrices
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Subarachnoid space
a space in the meninges beneath the arachnoid membrane and above the pia mater that contains the cerebrospinal fluid.
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Excessive CSF due to overproduction or block of drainage in circulatory system
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Symptoms of hydrocephalus
increase ventricular pressure on CNS, expansion of head in newborns. treated by inserting shunt that drains excess into neck vein
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Study of the effects of drugs on the function of living systems
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Any chemical substance with biological effects except nutrients - medicines, poisons, mind altering, mind-altering
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What drugs target
Mainly act on proteins. bind to/block receptors, ion channels, transporters & enzymes
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proteins which recognise and respond to a chemical signal
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Binding site
The point on the outside of the cell which the chemical bind to the receptor
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Functional site
The point on the outside of a cel that when a chemical binds to, the receptor causes a response inside the cell.
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Chemical which binds to a receptor protein
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Ligand which can activate a receptor
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liquid which blocks the effect of an agonist but has no effect on the receptor activation on its own
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Selectivity of Ligands
many are capable for more than 1 receptor type. similarities in molecular structure of ligands mediate selectivity of same receptor types. Drugs act specifically at low doses of selectively at high.
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amount(conc) of agonist needed to induce a given response. higher potency = lower dose needed for effect. potency determined by characteristics of receptor activiation
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How effective a ligand binds to its receptor
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How effective a ligand activates its receptor to induce a response within the cell - agonist
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strength of receptor-ligand interaction determined by
electrical charge interactions, hydrogen bonding and hydrophobic interactions
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Law of mass action
predicts behaviors of solutions in dynamic equilibrium. rate of chamical reaction is proportional to the product of the concentrations of the reactants
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Receptor classification
Classified based on differences in how functional responses are induced with receptor binding
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Signal transduction
mechanism that converts a mechanical/chemical stimulus to a cell into a specific cellular response. Signal transduction starts with a signal to a receptor, and ends with a change in cell function.
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Ion channel
Protein channel in a cell membrane that allows passage of a specific ion down its concentration gradient. - don't have to go through hydrolipid ilayer. can be opened or shut
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Cation ion channel
positively charged ions
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Negatively charged ions
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Ion specific
Only a specific ion
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G-Protein coupled receptor
receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses
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G-Protein coupled receptor properties
most abundant type in the body. fast synaptic transmission. anchored by lipids in internal memberane. associated with GTP and GDP
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Structure of G-protein coupled receptors
trimeric structure - 3 protein subunits - alpha beta and gamma which bind to GDP and GTP
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G-protein receptor in resting state
G-protein subunit attatched to membrane in alpha-beta-gamma complex. GDP is bounf to alpha-subunit
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When agonist binds to G-protein receptor
GDP converted to GTP (P added by enzyme). Alpha-Beta-gamma complex dissociated forming an Alpha-GTP and Beta-Gamma complex
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GPCR inactivation
Activation of GTPase converts GTP-GDP. alpha-GDP combines with Beta-Gamma to form alpha-beta-gamma complex and reassociates with receptor in the membrane. GDP-alpha-beta-gamma complex ready again for GPCR activation.
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GPCR effectors - G proteins target 2nd messengers systems
Adenyl cyclase, phospholipase C and ion channels
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Adenyl Cyclase
Enzyme. forms cyclic 3'5' adenosine monophosphate (cAMP) from ATP. Phosphodiesterase turns cAMP to 5'AMP
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Gi effect on adenylyl cyclase
Inhibits - decrease cAMP levels
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Gs effect on adenylyl cyclase
stimulate - increases cAMP levels
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what do cAMP and protein kinases regulate function of?
Enzymes and ion channels
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Who the Agonist-Receptor-G-protein pathway works
Agonist binds to receptor. G-proteins are activated. Binds to adenyl cyclase. ATP->cAMP. either activates or inactivates protein kinases to produce different response.
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what does Phospholipase C form from PIP2?
inositol (1,4,5) trisphosphate - IP3 and diacylglycerol (DAG)
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effect of Gq on Phospholipase C
Stimulates, increasing IP3 and DAG
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Effect of Phospholipase C and IP3
Binds to IP3 receptor (ligand gated ca2+ channel on membrane of ER). IP3 increases intracellular Ca2+ opening channels & releasing Ca2+ from E.R into cell. Increased cellular Ca2+ activates protein kinases which regulate function of enzymes & ionchan
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what parts are the human ns divided into?
The CNS and the peripheral NS
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what makes up the CNS?
retina, brain and spinal cord (cerebral hemispheres, structure in core beneath the hemispheres, the brain and cerebellum and the spinal cord)
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what makes up the peripheral ns?
nerves supplying the skeletal muscles and organs
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what can the peripheral nervous system be divided into?
somatic and autonomic ns
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what can the autonomic ns be divided into?
sympathetic and parasympathetic NS
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who in 1543 dissected and described the anatomy of the brai for the first time?
Andreas vesalius
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who in 1650 established the brain tissue as the seat of the mind?
Rene descartes
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when and by who was electricity understood as the medium for signalling?
Lugi Galvani 1791
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who described the first nerve cell and when?
1833 by Ehrenberg
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who determined the topographic mapping of the body on the surface of the cortex?
1930s-50s Wilder Penfield
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when was the first correlation of damage in the brain and behaviour in man
1860s by Paul Broca - speech deficits and lower left frontal lobe damage
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Proper word for side view
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Proper word for vertical (front to back) view
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Proper word for top view
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Whats the cerebral hemisphere
Each side of the brain - can be divided into left and right
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whats the cerebellum
The cerebellum is the area of the hindbrain that controls motor movement coordination, balance, equilibrium and muscle tone
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whats the cranial cavity?
s the space formed inside the skull. The brain occupies the cranial cavity, which is lined by the meninges and which contains cerebrospinal fluid to cushion blows.
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how many bones in the cranial cavity made up of
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How many lobes for each hemisphere and name them
4 - frontal, temporal, parietal and occipital
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what does the frontal lobe do?
associated with higher mental functions - planning and language
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what does the parietal lobe process?
incoming sensation from the body
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what does the temporal lobe process?
sound - also a site for sound and memory and vision
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what does the motor cortex do?
gion of the cerebral cortex involved in the planning, control, and execution of voluntary movements
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what does the occipital lobe do?
principal area for vision
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what does the cingulate gyrus do?
Process emotion
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what are the basal ganglia and where are they located?
group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas.
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what role do the basal ganglia have?
variety of functions, including voluntary motor control, procedural learning relating to routine behaviors or "habits" such as bruxism, eye movements, and cognitive,[1] emotional functions (control movement)
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what role does the thalamus have?
principal site of processing sensory information
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what does the hypothalamus do?
One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland - important for homeostasis and endocrine control
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role of the brain stem
coordinates motor control signals sent from the brain to the body. The brainstem also controls life supporting autonomic functions of the peripheral nervous system.
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The spinal cord role
conduit (channel) for sensory inputs and motor outputs. alsoo processes these signals including the control of pain
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What causes muslces to move?
motor nerves run from the spinal cord to the muscles - functional element controlling action
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cervical enlargements gives attachment to the nerves what?
upper limbs
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lumbar enlargements gives attachment to the nerves what?
lower limbs
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whats a neuromuscular junction?
specialised synapse transferring electrical signals from the CNS to the muscles that move all elements of the body
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where is a neuromuscular junction located?
in a pit on the surface of a muscle cell
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Who does the concept of hierarchy in the motor system come from the work of and when?
Hughlings Jackson (1835-1911)
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What is heirarchy (NS)
automatic movements coded by the spinal cord and brain stem and purposeful/skiled movements initiated by the cerebellum, basal ganglia and cortex
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whats the spinal cord?
long, slender cylinder of nerve tissue that extends from the brain stem
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what's locomotion
act of self-propulsion by an animal, has many manifestations, including running, swimming, jumping and flying
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how does the spinal cord help locomotion?
contains circuits that generate rhythmic patterns for locomotion
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what are brainstem nuclei in control of?
innate behaviour - walking, grooming and feeding
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whats the cerebellum
Part of the hindbrain in vertebrates. In humans it lies between the brainstem and the cerebrum. It plays an important role in sensory perception, motor output, balance and posture- generating smooth coordinated sequences of muscle interaction
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what does damage to the cerebellum result in
poorly coordinates, robotic, inaccurate movement and loss of balance
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what are the basal ganglia?
collection of nuclei found on both sides of the thalamus, outside and above the limbic system
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what do basal ganglia do?
initiate willed movements by means of a smooth stop/go controlloer
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what movement disorder is basal ganglia most commonly associated with?
parkinsons disease
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role of primary motor cortex
located in the posterior portion of the frontal lobe. It works in association with other motor areas including premotor cortex, the supplementary motor area, posterior parietal cortex, & several subcortical brain regions, to plan & execute movements
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Who determined the site of the motor cortex as the pre-central gyrus?
Ferrier and Sherrington
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what is the primary motor cortex - structure
***** of tissue anterior to the central sulcus
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what is the primary motor cortex called anatomically?
pre-central gyrus or area 4
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what is the primary motor cortex called functionally?
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what does stimulation of M1 lead to?
activation of somatic muscles - innervate specific parts of the body
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what's chyme
s the semifluid mass of partly digested food expelled by the stomach into the duodenum
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consistency/properties of chyme
pH 2, thin and watery, fine particles of undigested material. contains polypeptides and oligosaccharides (broken down proteins and polysaccharides my amylase in saliva)
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Biliary system
organs and ducts that are involved in the production and transport of bile
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what provides the main digestive fluid of the s.intestine?
the exocrine pancreas - empties into duodenum via pancreatic/common bile duct
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what does the pancreas secrete?
aqueous alkaline solution rich in bicarbonate - Water, HCO3(bicarbonate) and enzymes
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what makes bile?
the liver
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what enzymes does the pancreas secrete?
trypsin, chymotrypsin, amylase, lipase, nuclease
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How is the pancreas controled?
1. Parasympathetic nerves (Ach and VIP-Vasoactive intestinal peptide) 2.Gut hormones -secretin and cholecystokinin
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what does the neural and hormonal stimuli cause?
release of zymogens & bicarbonate rich water -> causes enzyme activation cascade and catalyzation of enzyme precursors to active form
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whats a zymogen
inactive enzyme precursos
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How much bile does the liver produce a day?
0.7-1.2L ^-1 per day
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What is bile needed for?
fat digestion
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What does the liver produce as well as bile
plasma proteins such as albumin(blood serum protein) and clotting factors. Hormones, cholesterol, biliverdin and bilirubin
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what do kupffer cells, found in the liver do
remove bacteria and worn out blood cells
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Steps in release of bile from gall bladder
1.Ach parasympathetic signal to gall bladder 2.cholecystokinin released as response to fat and protein in the s.intestine. 3.Causes contraction of bladder and relaxation of sphincter of oddi 4.releases stored bile into duodenum
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What does the sphincter of oddi do?
a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through the ampulla of Vater into the second part of the duodenum.
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Main role of bile
emulsification of fat globules- increases SA to volume ratio (more area for pancreatic lipase to work), makes fat water soluble, allows lipases access to fat
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what does intestinal mixing do to large fat droplets?
break theminto smaller ones
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how are micelles usefule?
vehicle for carrying water-insoluble substances through watery luminal contents & to absorptive surfaces of intestines
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what is stored in the liver
carbohydrates(glycogen), amino acids, fats
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how does the liver know when to store/release molecules
by monitoring atrial blood levels
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whats gluconeogenesis
convert amino acids to sugars
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what % of resting rate oxygen does the liver consume?
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whats a hepatocyte?
liver cell
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location & structure of the small intestine
tube that lies coiled within the abdominal cavity - extends between the stomach and large intestine
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what is the s.intestine divided into?
duodenum, jejunum and ileum
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where does most digestion and absorption of nutrients take place?
The s.intestine
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name the 4 layers of the digestive tract wall
1. mucosa (mucous membrane-epithelial, lamina propria-connective tissue, muscularis mucosa-smooth muscle) 2.sub-mucosa(connective tissue) 3.muscularis externa (smooth muscle) 4.serosal (connective tissue)
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What give the SI it's large Surface Area?
Folds, Villi and Microvilli/enterocytes-brush border
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whats an enterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon
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life span of an enterocyte
2-3 days
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how are enterocytes replaced
differentiation of simple cells from the crypts of lieberkuhn- in course of differentiation develop brush border, digestive enzymes and transporter proteins
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what causes chemical breakdown of food?
chyme mixed with pancreatic and hepatic secretion
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What is flow of material out of the stomach regulated by?
feedback signals from the duodenum
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enzymes used in contact digestion
enterokinase, disaccharidases(carb digestion) and aminopeptidases (protein digestion)
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rhythmic waves of muscular contraction and relaxation in the walls of hollow tubular organs that serve to move contents through a tube
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what is peristalsis initiated by?
stretching of intestinal walls by digesta
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how does peristalsis work to propel food?
contraction of circular muscle behind digesta, relaxation of circular muscles in front of digesta
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what makes the intestinal wall contract and relax
excitatory neurons make circular muscle contract, inhibitory neurons make circular muscles relax
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What does segmentation do?
Contraction of circular muscle at regular intervals to mix intestinal contents - crucial for effective absorption
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Parts of the large intestine
Colon, Cecum, Appendix & rectum
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what happens in the colon?
absorbs water and salt, stores faecal material
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whats the gastrocolic reflex?
mass movements of food in response to food entering the stomach
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what does faeces entering the rectum induce?
defecation reflex - internal anal sphincter to relax
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what can disrupt the digestive system?
emotions, vomiting, diarrhoea and constipation
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how do emotions alter gastric mobility?
through autonomic nerves - alter smooth muscle excitability. pain, sadness & fear decrease motility. anger and aggression increase motility
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what is vomiting
forceful expulsion of gastric contents
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what causes vomiting (the physical actions)
action of diaphragm and abdominal muscles
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what prevents vomit from moving from the oesophagus into the mouth?
pharyngoesophageal sphincter can close
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where is vomiting coordinated?
vomiting centre in the medulla
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Cause of vomiting - triggers
stimulation of back of throat, irritation of stomach, elevated intracranial pressure, rotation/acceleration of the head, intense pain, chemical agents and emotional anxiety
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benefit of diarrohea
rapid expulsion of harmful material
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negative of diarrohea
inhibits useful reabsorption and can lead to dehydration
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cause of diarrohea
excessive intestinal motility -(irritation, bacteria, virus or stress), Excessive osmotically active particles in digestive tract (retains fluid), presence of toxins from certain microorganisms
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role of oesphagus
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role of stomach
storage, milling and acid/peptic digestion
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role of S.intestine
fat, protein & carbohydrate digestion and absorption. water and electrolyte transport. bile salt transport
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Role of large intestine
storage and water reabsorption
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role of anus and rectum
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role of the mouth
apprehension, mechanical chewing, chemical (salivary amylase) breakdown
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whats mastication?
chewing - rhythmic action to break up food into smaller particles
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role of saliva
moistens food to make it easier to swallow - also contains amylase, some- anticoagulant, poison, thermoregulation, anti-bacterial
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whats deglutition?
propulsion of chewed material into the oesophagus
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is chewing automatic or willed?
automatic act initiated by a willed decision - controlled by neural 'pattern generator' in brain stem
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what does chewing do?
grind and break food to help swallowing, mix food with saliva, stimulates the taste buds - increase saliva, gastric, pancreatic and bile secretions
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Constituents of saliva
water(99.5%), Ions, mucus, alpha amylase, lysozyme
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3 glands saliva is secreted fomr
the parotid, sublingual and submaxillary
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How much saliva is secreted daily?
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How many times do we chew food
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whats bolus
Lump of chewed fod
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what happens when bolus is pushed to the back of the mouth
initiates reflex involvin 25 skeletal muscles - propel bolus into oesophagus where it is then moved by peristalasis
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what guards oesophagus at the bottom?
gastroesophageal - prevents back flow/heart burn
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what stops us inhaling food?
epiglottis (small flap of tissue) closes the opening to the airway
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muscular region of the digestive tract - extends from the oesophagus to the small intestine
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chemical digestion
bathes material in strong acid medium and attacks proteins with pepsin -chief cells in gastric glands secrete pepsinogen
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Mechanical digestion
mixing turns material into chyme
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What is gastric uice made of?
water, HCl, Pepsinogen, Intrinsic factor and Mucous
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what do parietal cells secrete?
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What secretes pepsinogen?
Chief cells
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what controls gastric secretion?
Stimulus - food arriving in stomach Activates parasympathetic nerves & hormones are released
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how is the stomach protected against acids?
protective stomach mucus - alkaline, lubricates gastric mucosa, prevents self digestion. Luminal membranes impermeable to H+ so acid can't penetrate and damage. cardiac cells secrete bicarbonate. lining replaced regulary 3-4 days
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where are fats digested ?
in the small intestine onlt
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s the region of the stomach that connects to the duodenum (the beginning of the small intestine
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Parts of the rumen
reticulum, omasum and abomasum
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role of the rumen
fermentation chamber
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where do you find lightweight low density material in the rumen?
top - straw needs longer to digest
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where do you find medium density material in the rumen?
sinks to the bottom
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where do you find high density material in the rumen?
sinks into the cranial sac - e.g. grains
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motor activity of the rumen
mixes contents, propels digested material into the omasum, removes gaseous products of fermentation, initiates rumination
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what is rumination?
chewing of cud - regurgitation, re-salivation, re-mastication, re-deglutition
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when does rumination occur?
following special A-cycle - triple contraction of reticulum propelling material into the esophagus
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B cycle
contraction and shifting inside means gas bubble moves over cardia allowing gas to escape
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Function of Kidney
Maintain water balance, regulate ocnc of ions, maintain plasma volume, excrete waste & foreign compounds, maintain osmolarity, Secrete compounds, convert Vitamin D to active form
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How is urine produced
1. filtration of plasma, 2.reabsorption of plasma 3.secretion directly into filtrate
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How many nephrons in each kidney?
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Two types of nephorn in the kidney
cortical nephron and internal juxtamedullary nephron
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location and % of cortical nephron
85% small glomeruli - mainly in cortex and medulla
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location and % of internal juxtamedullary nephron
15% large glomeruli,long loop of henle extending deep into medulla
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function of bowmans capsule
cups arend glomerulus to collect fluid
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% of water and solutes removed by the blood by glomerular filtration
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what does rate of glomerular filtration depend on?
net hydrostatic pressure, colloid pressure of blood plasma and hydraulic permeability of membranes
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osmotic pressure of glomerulus
-30mm Hg
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intracapsular pressure
-15mmHg (lower pressure so things pushed through)
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Layers of the glomerulus
Wall of glomerular capillaries, acellular basement membrane, inner layer of bowman's capsule
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renal clearance rate=
volume of blood plasma completely cleared of a substance per minute
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what is reabsorbed in the kidneys
filtered glucose and 1/2 ureas
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average clearance rate
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way to calculate renal clearance
1. infuse insulin and allow to mix 2.collect blood sample and determine plasma conc 3.determine rate of appearance in urine
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Types of transport
Passive and active
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no energy expended- down conc gradients
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requires energy, against electrochemical gradient - important substances
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what % of energy useage is taken up by sodium reabsorption?
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what % of sodium is reasbsorbed in the PCT
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what % of sodium is reabsorbed in the loop of henle
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what % of sodium is reabsorbed in the DCT
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What is reabsorbed in the PCT
Glucose, amino acids, water, urea and chloride ions
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how much phosphate can be reabsorbed?
up to normal plasma conc and no more - excess excreted
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what % of body weight is water?
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where is water in the body?
2/3 intracellular fluid 1/3 extracellular(plasma and interstitial fluid)
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What is normal fluid balance in the body? - amount of water to substrate
300mm/Litre (isotonic)
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What is the max fluid concentration in urine?
1200 mosm/Litre
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what % of sodium is removed by active transport in the PCT?
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what is the ascending loop of henle thin part permeable to?
Na+ and Cl- ions. low water permeability
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what is the ascending loop of henle thick part permeable to?
very low water permeabiity - Na+ and Cl- now activly transported out
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what is the descending loop of henle permeable to?
no active transport, impermeable to salts, highly permeable to water
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what does the DCT pump and what follows?
Transports K+, H+ and NH3 into lumen. Tranports Na+, Cl- and HCO3- out of lumen. As salts pumped, water follows
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what is the collecting duct permeable to?
water - flows from dilute urine to more concentrate interstitial fluid of renal medulla. reabsorbs NaCl by active transport. high permeability to urea
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Why concentrate and then dilute fluid in loop of henle in a counter current mechanism?
establishes vertical osmotic gradient in medulla to enable collecting tubule/duct to concentrate urine.
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what must exist for water to be reabsorbed?
osmotic gradient and tubule permeable to water
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what needs to be present for the collecting duct/tubule to be permeable to water?
antidiuretic hormone vasopressin
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where is vasopressin produced?
the hypothalamus
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where is vasopressin stored?
posterior pituitary gland
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what stimulates release of vasopressin
water deficiency- low BP, high plasma osmolarity
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how does vasopressin work
1. binds with receptor on basolateral membrane 2.activates cAMP 2nd-messenger system 3.cAMP increases luminal membrane permeability by inserting aquaporin2 water channels in the membrane
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4.water enters tubular cell from tubular lumen through water channels 5. water exits cell through a different water channel (AQP2/3) permanently positioned on basolateral border and goes into the blood
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what triggers thirst and vasopressin release?
hypothalamic osmoreceptors. further input from volume receptors that monitor bp in left atrium of heart
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how much urine is produce a minute when normall hydrates?
1ml/min isotonic urine
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what controls exit of urine from bladder?
internal urethral sphincter(involuntary) and external urethral sphincter (volountary)
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what % of filtered Na+ is reabsorbed?
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How is Na+ reabsorbed?
actively - Na+ - K+ ATPase carrier located in basolateral membrane of tubular cells. Moves Na+ against conc gradient
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what controls Na+ reabsorption?
the renin-angiotensin-aldosterone system
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renin-angiotensin-aldosterone system- how is controls Na+ reabsorption
1. renin secreted by kidney due to fall in ECF volume/BP 2.renin activates angiotensinogen to angiotensin1 3.Angiotensin1 is converted to angiotensin2 by angiotensin 4.angiotensin2 stimulates aldosterone secretion from adrenal cortex
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5.aldosterone inserts additional Na+ and Na+ - K+ ATPase carries into luminal/basolateral membranes) 6. Increases flux of Na+ ito tubular cells and blood follows passively along electrical gradient
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is any NaCl secreted in presence of full aldosterone secretion?
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How much NaCl can be secreted a day in absence of aldosterone
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is potassium reabsorption in PCT regulated?
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what % of filtered K+ is excreted in urine?
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Control of K+ secretion
Aldosterone - stimulates K+ secretion simultaneous to Na+ absorption Ac-d- normally K+ secreted, when body fluids too acidic, H+ secreted instead
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main factors controlling pH in mammals
excretion of CO2 via lungs and excretion of acid via kidneys
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Acid definition
Hydrogen containing substance that dissociate in solution to liberate free H+ (more free H+ = stronger acid)
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Substance that binds with H+ to remove it from solution
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what generates H+?
carbonic acid (H2CO3) forms from CO2 and H2O and dissociates to give free H+, inorganic acids from food breakdown and organic acids from intermediary metabolism
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How kidneys regulate pH
Can conserve or eliminate HCO3- and H+ by H+ excretion, HCO3- excretion and NH3 excretion
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A large membranous tube reinforced by rings of cartilage, extending from the larynx to the bronchial tubes and conveying air to and from the lungs; the windpipe
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The bronchioles or bronchioli are the first airway branches that no longer contain cartilage. They are branches of the bronchi. The bronchioles terminate by entering the circular sacs called alveoli.
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Any of the many tiny air sacs in the lungs where the exchange of oxygen and carbon dioxide takes place
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what cells are the trachea lined with and why?
mucus-secreting cells that lubricate it and ciliated cells with tiny hairs that beat impurities and inhaled particles and dust up and out the trachea
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how many alveoli in the lungs of a human man?
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what do type 1 alveolar cells (pneumocytes) do?
site of gas exchange
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what do type 2 alveolar cells (pneumocytes) do?
secrete pulmonary surfactant - fluid with low surface tension to allow alveolar surfaces to separate - facilitates alveolar expansion
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why is their elastin in alveoli?
to allow the alveoli to stretch
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alveolar septum
the thin wall which separates the alveoli from each other in the lungs
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lung compliance
measure of the ease of expansion of the lungs and thorax, determined by pulmonary volume and elasticity. A high degree of compliance indicates a loss of elastic recoil of the lungs, as in old age or emphysema
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pleural sac
double-walled, closed sac that separates each lung from the thoracic wall in air-breathing verterbrates
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role of the parietal pleura
lines the wall of the chest cage and covers the upper surface of the diaphragm
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role of the pulmonary pleura
tightly covers surface of lungs
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where is serious fluid located and what is its role?
inside the pleural cavity- lubricates the pleura surfaces,allows lungs to slide freely over the inner surface of the thoracic wall during breating, high a high surface tension - prevents lungs from collapsing during expiration
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what is a punctured lung?
damage to the pleura- air enters pleural cavity and lung does not inflate when pressure is reduced
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Pressure inside a lung
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role of diaphragm during exhalation
diaphragm relaxes (more dome shaped upwards) Ribcage move down and inward
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Role of diaphragm durin inhalation
Diaphragm contracts(flattens) and ribcage moved upward and out
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which intercostal muscles contract during expiration?
Internal intercostals contract, external intercostals relax
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which intercostal muscles contract during inspiration?
Internal intercostals relax, external intercostals contract
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How inspiration occurs- mechanics of ventilation
pressure in thoracic cavity falls, walls of lungs are pulled outwards due to adherence to visceral pleura. Alveoli expand and pressure falls below atmospheric pressure so gas enters
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How expiration occurs- mechanics of ventilation
Pressure in thoracic cavity rises. Alveoli are compressed and pressure rises above atmospheric pressure so gas is expelled
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inspiratory reserve volume
the maximal amount of additional air that can be drawn into the lungs by determined effort after normal inspiration - 3000ml
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Tidal volume
normal volume of air displaced between normal inspiration and expiration when extra effort is not applied -500ml
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expiratory reserve volume
the additional amount of air that can be expired from the lungs by determined effort after normal expiration—1500ml
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residual volume
the amount of gas remaining in the lung at the end of a maximal exhalation. 1000ml
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functional residual capacity
Functional residual capacity (FRC) refers to the volume of air left in the lungs after a normal, passive exhalation. It is mainly determined by the balance between the forces of the lung and chest wall.- expiratory reserve and residual volume 2500ml
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vital capacity
s the maximum amount of air a person can expel from the lungs after a maximum inhalation. It is equal to the sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume. - 5000ml
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what is atmospheric pressure?
760mm Hg (at sea level)
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whats the intra-alveolar pressure?
pressure within the alveoli
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whats the intrapleural pressure
pressure within the pleural sac - pressure exerted outside the lungs within the thoracic cavity. usually less than atmospheric at 756mm Hg
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Dead space
refers to the part of the respiratory system that has no alveoli, and in which little or no exchange of gas between air and blood takes place.
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what parts of the respiratory system are dead space?
upper parts of the airway, trachea and bronchi - also for non functional/dead/diseased alveoli
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partial pressure
hypothetical pressure of that gas if it alone occupied the volume of the mixture at the same temperature
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how to convert % into partial pressure
for each gas, multiply its fraction % by the total pressure
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why is partial pressure important?
there is a partial pressure gradient between alveoli and blood which causes gases to move between the two
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what happens in the alveoli with gas exchange?
gases move down concentration (partial pressure gradients). Oxygenated blood goes to the heart via the pulmonary vein, deoxygenated blood comes from the tissues via the heart and pulmonary artery
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What keeps alveolar has concentrations constant?
residual volume and deadspace
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Does bound gas have an effect of partial pressure?
no they are in dynamic equilibrium - most gas (94-9% is carried in bound form)
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whats haemoglobin
O2 carrying pigment in erythrocytes - a tetramer of 4 polypeptudes (2xalpha 2xbeta) each with a haem (Fe2+) group
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How many O2s do each haemoglobin molecule bind to?
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what is the effect of binding each O2 to haemoglobin on the molecule?
relaxes molecule and increases subsequent affinity
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what is the haemoglobin dissociation curve affected by?
Partial pressure of O2, pH (Bohr effect), temperature and 2,3 diphosphoglycerate (DPG)
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Why haemoglobin drops of O2
Tissues do work which cause increase temo, low pH, Low PO2, High PCO2 and use ATP to produce DPG. This all lowers HB affinity of O2 so O2 will be dropped
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effect of pH on the haemoglobin dissociation curve (lowering pH)
Lowering the pH shifts the curve to the right. causes metabolically active tissue t have a low pH, high temp and produce 2,3-DPG. all of which moves curve to the right and encourages dissociation
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effect of temp on the haemoglobin dissociation curve
raising the temp shifts the curve to the right
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effect of 2,3diphosphatephoglycerate on the haemoglobin dissociation curve
2,3 DPG causes the curve to shift to the right -
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how does 2,3DPG effect O2
reduces binding of O2 to Hb by separating the subunits - is a product of glycolysis
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Haldane effect
Deoxygenation of the blood increases its ability to carry carbon dioxide; this property is the Haldane effect. Conversely, oxygenated blood has a reduced capacity for carbon dioxide.
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How is CO2 carried and what % of each?
Dissolved 5-10%, Carbamino compounds (25-30%), Bicarbonate (60-70%)
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carbamino compound
Any of various carbamic acid derivatives formed by the combination of carbon dioxide with an amino acid or a protein, such as hemoglobin forming carbaminohemoglobin.
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what can be adjusted in respiration
frequency of ventilation, depth of ventilation, amount of gas carried in the blood, rate at which blood circulates and perfusion of individual tissues
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what controls the frequency, depth and regularity of ventilation?
the brain - medullary respiratory centre
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what are the main regulating factors?
Blooc PCO2 and [H+] and bloog PO2
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what mainly controls respiration in the brain - central pattern generator
Pons and medulla
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where do the pons and medulla recieve information from?
chemo-receptors in aorta and carotid, stretch receptors in intercostal muscles and cerebral cortex
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two medullary respiratory centres in the pons
apneustic and pneumotaxic
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Stages of control of basic rhythm in medulla
1. input from areas including PONS. Cause medulla to send message to spinal cord, spinal cord phrenic nerve sends message to diaphragm.
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what happens if vagus nerve is cut above pons
Lowers frequency and causes deeper inspiration
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what happens if vagus nerve is cut mid-pons
Apenusis- abnormal pattern of breathing characterized by deep, gasping inspiration with a pause at full inspiration followed by a brief, insufficient release
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what happens if vagus nerve is cut between pons and medulla
gasping inspiration, irregular respiration
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what happens if vagus nerve is cut below medullla
no change - no voluntary resp
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What does the cortex control
voluntary respiration - not involved in involuntary
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Pneumotaxic centre control
Terminates inspiration; switches between inspiration and expiration (‘brakes inspiration”)
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Apneustic centre control
prevents inspiratory neurons from being ‘turned off
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Ventral respiratory group
Inactive during normal breathing; regulates amplitude and frequency; expiratory and inspiratory signals
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Dorsal respiratory group
mainly inspiratory signals via phrenic nerve to diaphragm
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overview of what pons and medulla do
Pons = Switching; Medulla = Amplitude and frequency
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3 factors that influence magnitude of ventilation
PCO2, H+ and PO2
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Peripheral chemoreceptors
principally to detect variation of the oxygen concentration in the arterial blood, whilst also monitoring arterial carbon dioxide and pH - aortic bodies and carotid bodies
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central chemoreceptors
detect the changes in pH of nearby cerebral spinal fluid (CSF) that are indicative of altered oxygen or carbon dioxide concentrations available to brain tissues
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Carotid bodies function
Monitor [H+] and [O2]. afferent nerves go to medulla
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Aortic bodies function
monitor [O2]. afferent nerves go to medulla and pons via vagus nerve
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what medulla and pons do with information from carotid and aortic bodies
integrate this information with - information on blood pH monitored by the medulla - voluntary control from the higher centres of the brain
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how do central chemoreceptors monitor cerebral arterial PCO2
PCO2 by monitoring pH (H+ ions) in ECF
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what does raising the inspired CO2 do?
Increases respiratory minute volume - increases rate an depth of ventilation
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What is acidosis?
when the pH falls below 7.35
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causes of respiratory acidosis
Respiratory depression (drugs, alcohol) Asthmatic airway constriction Fibrosis, pneumonia Emphysema (Chronic Obstructive Pulmonary Disease). Alveolar hyperventilation = CO2 retention
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cause of metabolic acidosis
Raised H+ intake - Lactic acidosis (anaerobic metabolism) Ketosis (elevated fat/protein catabolism) Diarrhoea (excess HCO3- excretion) Poisons (methanol, ethylene glycol) Medicines (aspirin)
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What is alkalosis
When the pH rises about 7.42/5
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causes of respiratory alkalosis
Anxiety [can be partially adjusted by re-breathing a bag of air] Incorrectly adjusted artificial ventilator, Hypperventilation - excess CO2 loss
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causes of metabolic alkalosis
Excessive vomiting (loss of stomach acid) Excess bicarbonate ingestion (antacids)
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Low PO2 - oxygen deficiency in tissues
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Effects of Hypoxia
Shortness of breath - Headache - Dizziness - Nausea - Fatigue Confusion High-altitude pulmonary oedema (fluid accumulation in lungs)
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What is Hypoxic hypoxia
when PO2 of arterial blood is reduced - causes by altitude without pressurisation and gaseous suffocation
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Anaemic hypoxia
PO2 of arterial blood is normal but carrying capacity is reduced due to low Hb. May be symptomless, except during stress or exercise -Severe haemorrhage - Iron-deficiency anaemia - Blood cell diseases
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What is Ischaemic (circulatory) hypoxia
PO2 and Hb of blood are normal but blood flow to a particular tissue is compromised. -Mechanical injury/trauma - Circulatory damage (e.g. Frost bite) - Thrombosis (e.g. coronary thrombosis
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what is histotoxic hypoxia
PO2 and Hb of blood are normal, and circulation is normal but cells cannot use the supplied oxygen -e.g. cellular poisoninc e.g. cyanide
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effect of H2S (hydrogen sulphide
inhibits cellular respiration >1000 ppm (parts per million) causes collapse withl loss of breathing
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