BM108

• Leucocytes


  • Mainly white blood cells that develop from specialised connective tissues (marrow) of certain bones
  • They function to defend the body against infection and disease. They make up the majority of the immune system
• Erythrocytes


  • Haematocrit refers the to volume of blood that is composed of RBC (40-65%)
  • There's an average of ~250 mil haemoglobin molecules, and each molecule contains 4 protein subunits (2 α- and 2 β-chains). Each protein subunit contains 1 heme molecule that binds to 1 O2 molecule
  • In total, each haemoglobin can bind to 4 O2 molecules
  • Biconcave (~6.8-7.2 μm) in structure to increase surface area, which increases the efficiency of gas exchange
  • RBC is needed because the amount of O2 dissolved in the plasma is insufficient to support a vertebrates basal metabolic rate, let alone strenuous activity
  • O2 is poorly soluble in plasma
  • Capillaries are the site of gas and nutrient exchange, so it's important that they are the width of a RBC (smallest) and one cell thick
• Platelets


  • Derived from bone marrow - cell fragments without a nucleus
  • Known as thrombocytes in other vertebrates
  • It plays a crucial role in the formation of blood clots
  • When a blood vessel is injured, platelets secrete a substance that causes them to clump together and bind to the collagen fibres in the surrounding connective tissue at the wound (plug), to prevent blood loss. Other platelet secretions interact with plasma proteins, the precipitate from the solution of fibrous protein fibrin form a meshwork of threadlike-fibres that wrap between platelets and RBC
• Heart anatomy


  1. Blood pathway: vena cava → right atrium → right ventricle → pulmonary artery → lungs → pulmonary vein → left atrium → left ventricle → aorta

  2. The contraction of the atria and ventricles make a heartbeat - "lub-DUB" sound

  3. 2 phases of heart pumping cycle - systole, when the heart contracts and pushes blood out of its chambers; and diastole, the period between contractions when the heart (myocardium) relaxes and the chambers fill with blood
• Cardiac muscle


  • When cellular [Ca2+] increases, it signals contraction in the cardiac, smooth and skeletal muscles
• Human heart

  • Myogenic, meaning it has signalling mechanisms (stimulus originate within myocardium) that initiates heart contractions, and is not reliant on neural stimulation
  • Myogenic initiation is due to excitation waves (electrical impulse/action potentials) that are conducted by specialised cardiac muscle cells that travel along the myocardium layer of the heart
  • Sinoatrial node (SAN) - specialised patch of muscle near the opening of the vena cava, in the right atrial wall that initiates the excitation wave that acts as the stimulus for heart contraction
  • The excitation wave travels across the atrial walls at 1ms-1, causing them to contract immediately, almost simultaneously (atrial systole)
  • There's a fibrous ring (non-conducting tissue) that prevents the flow of excitation waves from atria to ventricles
  • Atrioventricular node (AVN) - specialised patch of muscle in the septum of the atrioventricular wall that receives the excitation wave from the SAN (0.1s delay - allowing atria to empty and for ventricles to fill, preventing overlap of atrial and ventricular systole)
  • Atrioventricular bundle - Purkinje tissue that connects the atrium and ventricle, running along the septum
  • Bundle of His - continuation of atrioventricular bundle, found in the septum, it transmits the electrical impulse from the AV bundle to the Purkinje fibres in the ventricles
  • Purkinje fibres - specialised muscle fibres that carry excitation wave from AV node, down the septum, and up the walls of the ventricles in 5ms-1 (ventricular systole)
• Neurogenic heart


  • Relies on the nerve from the brain to initiate cardiac movement. Its often found in lower invertebrates like annelids and arthropods. The heartbeat is initiated by the ganglion situated near the heart
• Electrocardiogram (ECG)


  • Records the excitation impulse trace
  • Magnitude - number of muscle cells that are alive (cardiac muscles - atrial and ventricular, conducting muscles - SAN, AVN, Bundle of His, and Purkinje fibres)
  • Pattern - direction of movement of excitation wave
  • An abnormal ECG is an indication of more muscle cells (higher voltage)/less muscle cells (low voltage)/damaged SAN or AVN (abnormal pattern)
  • P-wave (atrial depolarisation) - excitation wave through atrial wall (magnitude is smaller as atrial walls are thin due to lesser muscle cells)
  • QRS-wave (ventricular depolarisation) - excitation wave down then up ventricles (magnitude higher as ventricles have more muscle cells)
  • T-wave (ventricular repolarisation) - residual excitation waves at the top of Purkinje fibres that are absorbed by fibrous tissue
• Blood pressure


  Pressure exerted by blood pushing against the vessel walls
• Cardiac output


  Determined by venous return and neural and hormonal controls
• Resting heart rate


  Controlled by the cardioinhibitory centre via the vagus nerves - stroke volume is controlled by venous return (end diastolic volume)
• Under stress


  The cardioacceleratory center increases heart rate and stroke volume - end systolic volume decreases and MAP increases
• Pressure gradient


  • The difference in pressure between the beginning and end of vessel
  • Blood flows from an area of high pressure to an area of low pressure (no pressure = no blood flow)
  • When the heart contracts, it exerts pressure on blood, which is the main driving force for flow through a vessel. Due to resistance in the vessel, the pressure drops as blood flows (arteries have the highest pressure, while capillaries have the lowest)
  • Maintenance of this pressure requires the cooperation of the heart, blood vessels, and kidneys along with supervision from the brain
  • If the change in pressure in a vessel is great, then the flow of blood in that vessel is great
• Resistance


  • The measure of hindrance or opposition to blood flow through a vessel, caused by friction between the blood in the vessel wall
  • If resistance to flow increases, it is difficult for blood to pass through a vessel, therefore, flow rate decreases
  • Diameter ∝ 1/resistance (large diameter, low resistance)
  • Main determinants of resistance: viscosity of blood (dependent on %RBC, if %RBC increases, viscosity increases), length of blood vessel, radius of blood vessel
  • A slight change in resistance ∝ 1/r^4 produces a significant change in blood flow (flow ∝ r^4)
• Systolic pressure


  Peak pressure when blood is ejected (normal - 120 mmHg, high - >140 mmHg)
• Diastolic pressure


  Minimum pressure when blood is draining off into vessels downstream (normal - 70 mmHg, high - >90 mmHg)
• Factors affecting blood pressure

  • Peripheral vascular resistance - diameter of blood vessels
  • Cardiac output
  • Blood volume
  • Vessel elasticity
• Vascular tree


  • Arteries
  • Arterioles
  • Capillaries
  • Venules
  • Veins
• Arteries


  • Serve as rapid-transit passageways for blood from heart to organs
  • Due to its large radius, arteries offer little resistance to blood flow, and rather act as pressure reservoirs to provide a driving force for blood when heart is relaxing
  • Arterial connective tissue contains - collagen fibres (tensile strength) and elastin fibres (elasticity to arterial walls)
• Arterioles


  • Major resistance vessels that converts pulsatile systolic to diastolic pressure swings in the arteries into the non-fluctuating pressure present in the capillaries
  • Radius of arteriole can be adjusted to distribute cardiac output among systemic organs, depending on body's momentary needs and to help regulate arterial blood pressure
  • Arteriolar vasoconstriction - increased myogenic activity, O2, endothelin and sympathetic stimulation by vasopressin; angiotensin II (cold) and decreased CO2 and other metabolites
  • Arteriolar vasodilation - decreased myogenic activity, O2, sympathetic stimulation, histamine release (heat); and increased CO2, other metabolites and nitric oxide

  
• Vascular regulation


  • Intrinsic control - control of local blood flow (contraction and vasodilation)
  • Vascular smooth muscle intrinsic myogenic tone stimulates smooth muscle tone in response to pressure
  • Vascular endothelium - nitric oxide, prostacyclin, EDHF - relaxes smooth muscle
• Thermoregulation


  • Internal core temperature (37c) - abdominal and thoracic organs, central nervous system, skeletal muscles
  • Outer shell - skin and subcutaneous fat, skin temperature varies between 20c and 40c without damage
  • An increase in internal core temperature causes: increase in speed of cellular chemical reactions, overheating (more serious that cooling), nerve malfunction, irreversible protein denaturation
• Vascular regulation


  1. Intrinsic control

  2. Control of local blood flow (contraction)

  3. Control of local blood flow (vasodilation)
• Vascular smooth muscle


  • Intrinsic myogenic tone stimulates smooth muscle tone in response to pressure
• Vascular endothelium


  • Nitric oxide
  • Prostacyclin
  • EDHF
• Thermoregulation


  Regulation of heat exchange in the body
• Mechanisms of heat transfer

  • Radiation
  • Conduction
  • Convection
  • Evaporation
• Hypothalamus


  • Acts as a "thermostat" that speeds up heat loss or heat production as needed
  • Activated by thermal receptors in skin and direct stimulation through changes in blood temperature
• Water balance (renal system)

  • Formation of urine for elimination of waste
  • Regulation of blood volume and blood pressure
  • Regulation of plasma ion concentrations
  • Regulation of blood pH
• Kidney and nephron


  • Renal corpuscle (Glomerulus and Bowman's capsule)
  • Proximal convoluted tubule
  • Loop of Henle
  • Distal convoluted tubule
  • Collecting duct

  
• Renal corpuscle


  • Composed of the glomerulus and Bowman's capsule
  • Glomerulus is a cluster of capillaries enclosed by Bowman's capsule
  • Blood enters via afferent arterioles and leaves via efferent arterioles
• Proximal convoluted tubule


  • 1st segment of renal tubule
  • Convoluted portion leads into straight segment that descends into medulla and becomes loop of Henle
• Loop of Henle


  • Forms hair-pin structure that dips into medulla and then ascends toward cortex
• Distal convoluted tubule


  • Shorter and less convoluted than PCT
  • Initial segment lies next to glomerulus and is known as juxtaglomerular apparatus (JGA)
• Juxtaglomerular apparatus (JGA)


  • Distal tubule contacts afferent arteriole at renal corpuscle
  • Composed of macula densa, tubular cells, juxtaglomerular/granular cells, and mesangial cells
  • Purpose is to maintain blood pressure, ensure proper GFR and efficient sodium reabsorption
• Processes in the nephron

  • Filtration
  • Reabsorption
  • Secretion
  • Excretion
• Glomerular filtration


  • Blood (plasma) is filtered into renal tubule from glomerulus to form filtrate
  • High blood pressure in glomerulus forces fluid into renal tubule
  • Glomerular filtration rate (GFR) is the rate of filtrate production, controlled by dilation or constriction of afferent arteriole
• Processes in PCT


  1. Reabsorption (passive and active)

  2. Secretion (passive and active)

  3. Excretion
• Loop of Henle - descending limb


  • Permeable to water and urea but not solutes
  • Passive water reabsorption occurs by osmosis
• Loop of Henle - ascending loop


  • Permeable to solutes but not to water
  • Passive NaCl reabsorption in thin segment, active NaCl reabsorption in thick segment
  • Ion movement out of ascending limb results in osmolarity gradient in interstitial fluid