general physiology

Hypertrophy
Hypertrophy is the increase in SIZE of a tissue due to the increase in size of the cells present. Hypertrophy is
reversible if the stimulus is removed.

Hyperplasia
An increase in cell NUMBER is called hyperplasia.

acute stress response

IMMEDIATELY AFTER surgery there is a REDUCTION in thyroid hormone secretion. This would be expected to
normalise within the first few days.

During an acute stress response there is activation of the hypothalamic–pituitary axis, which stimulates
secretion of cortisol. Cortisol has a number of functions including anti-inflammatory effects and glucose control.

There is increased secretion of antidiuretic hormone resulting in sodium and water retention.

The sympathetic nervous system is activated as part of the stress response and adrenaline release causes
tachycardia.

Hyperkalaemia
This patient has hyperkalaemia for which the classical ECG findings include peaked T-waves, loss of P-waves and
widened QRS but shortend QT complexes predisposing the patient to cardiac arrhythmias.

Delta-wave
Delta-waves are most commonly associated with Wolff–Parkinson–White syndrome. They are seen as a slurred
upstroke in the QRS complex.

Ova/ primary oocytes

The ova are developed from the primitive germ cells, which are embedded in the substance of the ovaries.

Each PRIMITIVE GERM CELL gives rise, by repeated divisions, to a number of smaller cells called OOGONIA,
from which the OVA or PRIMARY OOCYTES are developed.

Unless it is fertilised it undergoes no further development and is discharged from the uterus, but if fertilisation
take place it is retained within the uterus and develops into an embryo.
 By the enlargement and subsequent rupture of a follicle at the surface of the ovary, an ovum is liberated and
conveyed by the uterine tube to the cavity of the uterus. Human ova are extremely small, measuring about 0.1–
0.2 mm in diameter and are enclosed within the egg follicles of the ovaries.

Renal tubules
The glomerulus is the network of the capillaries at the beginning of the nephron. It produces a SELECTIVE
ultrafiltrate of the blood.

Glucose, amino acids and bicarbonate are reabsorbed along sodium in the early portion of the PROXIMAL
convoluted tubule.

Glucose is removed from the urine by secondary active transport.

The DESCENDING loop of Henle is permeable to water due to the presence of ACQUAPORIN-1. As it goes down
fluid becomes more hypertonic (max 1200mOsm/l)

The ASCENDING limb is impermeable to water. As it goes up fluid becomes hypotonic

The DISTAL convoluted tubule is RELATIVELY impermeable to water and is involved in the continual removal of
the solute, making the tubular fluid further diluted. It is not involved in glucose resorption.

The COLLECTING DUCTS are under the influence of ANTIDIURETIC HORMONE (ADH) (vasopressin) to control
water absorption. In the absence of ADH, water can enter the urine, promoting diuresis. In the presence of ADH,
aquaporins allow the collecting duct to become permeable to water allowing reabsorption and inhibiting
diuresis.

Wound healing

 Phase 1: Hemostasis Phase.

 Phase 2: Defensive/Inflammatory Phase.
 Phase 3: Proliferative Phase.
 Phase 4: Maturation/ remodeling Phase.

Bleeding occurs after tissue injury, and the first thing to occur is haemostasis. Haemostasis is achieved through
constriction of the blood vessels (vasoconstriction), platelet-plug formation and the intrinsic and extrinsic
coagulation pathways.

The INFLAMMATORY phase is dominated initially by NEUTROPHILS that appear in the first few hours and reach
a PEAK IN 24–48 h . Their main function is phagocytosis and cleaning the wound of bacteria and foreign
material. Complement activation is seen in the initial inflammatory phase. A release of cytokines and growth
factors is seen in the initial inflammatory phase of wound healing.

The REMODELLING phase (scar maturation) starts a few days after injury and can last UP TO 18 MONTHS
(from months to years)
The tensile strength of any wound will never again be as strong as the premorbid state. Wounds of the skin,
subcutaneous tissues, muscle, fascia and tendon only ever regain 80–90% of their pre-injury strength.

Risk factors

 Immunosuppression is a recognised risk factor for poor wound healing and complications.
 Low albumin in a stable patient can indicate poor nutritional status, which can delay wound healing.
 Diabetes is a recognised risk factor for poor wound healing and complications.
 Obesity is a risk factor for poor wound healing.

Hyperbaric oxygen is being used in some centres for cases of gas gangrene (as oxygen is toxic to anaerobes) but
has NOT been proved to significantly accelerate wound healing, although it may help if there is an ischaemic
element.

Clinically WOUND INFECTIONS do NOT present in the first 48 h – most commonly AFTER 3–5 DAYS,
so a high temperature commencing more than 2 days after surgery should raise the suspicion of a possible
wound infection. Wound infections following cardiac or vascular surgery are potentially very serious as they can
lead to graft failure.

Platelets appear immediately and form the platelet plug to achieve primary haemostasis.

Neutrophils appear at day 1-2 and are part of the initial inflammatory response.

Macrophages appear around days 1–2 and are involved in the inflammatory phase.

Myofibroblasts appear around days 2–4 and are important in contraction of the wound.

Endoth(re)elial cells appear around days 3–5 and migrate into the wound to form new capillaries.

Lymphocytes are not major contributors to wound healing.

Hypertrophic scarring is a complication of wound healing.

A sutured, clean surgical wound heals by primary intention. Open wounds heal by secondary intention.

In healing of secondary intention, the base of the wound has to fill with granulation tissue, and
EPITHELIALISATION occurs from the wound edges.

Significant tissue and presence of infection loss are indications for closure by secondary intention.

Type III collagen is produced during the early phase of wound healing, and is weaker than the later-appearing
type I collagen (maturation stage).
Fetal Wound healing
FETAL wounds have REDUCED pro-inflammatory signals so the inflammatory infiltrate during the early phase of
healing is inhibited. The expression of transforming GROWTH FACTOR B3, a growth factor associated with
reduced scarring, is higher in fetal wounds.

FETAL FIBROBLASTS synthesise more total COLLAGEN and more HYALURONIC acid than their adult
counterparts. They MIGRATE at a faster rate than adult fibroblasts. Their increased migration velocity during
repair is likely to affect collagen deposition and crosslinking.

Wound repair

In a CLEAN wound, damaged nerves and tendons are repaired URGENTLY (within 72 h ideally).

Devitalised wounds, ulcers and abscess cavities may heal by second intention, ie granulation from the base
upwards but leave worse scars.

Skin is preserved EXCEPT for DEVITALISED tissue, which is trimmed before wound closure.

Steroids impair wound healing at any age.

Cardiovascular drugs

Dobutamine acts on β1 receptors and acts to increase cardiac contractility and cardiac output

Noradrenaline is an α1 agonist and increases blood pressure by vasoconstriction. It is not inotropic.

Dexmedetomidine is a centrally acting α2-agonist. It has sedative and analgesic effects.

 On initial administration it can cause vasoconstriction, raising the blood pressure.

 However, continuous infusion causes vasodilatation and subsequent hypotension.

Neurogenic shock
In neurogenic shock there is a loss of sympathetic tone BELOW the lesion that causes bradycardia and loss of
vasomotor tone resulting in hypotension. Neurogenic shock does not respond to fluids as the primary problem
is loss of sympathetic tone.

Inheritance in various syndromes

In HEREDITARY SPHEROCYTOSIS there is a defect of the structural proteins in the red cells. It is inherited as an
autosomal-dominant trait.

BETA-THALASSEMIA is autosomal recessive.

CYSTIC FIBROSIS shows recessive inheritance. The gene defect is on chromosome 7 and is carried by
approximately 1 in 20 Whites.

Haemophilia is a sex-linked recessive disorder.

 HAEMOPHILIA A is caused by a deficiency clotting factor VIII.

 HAEMOPHILIA B is caused by a deficiency of clotting factor IX.

Transportation across membrane

Diffusion: Fat-soluble molecules, such as glycerol, can diffuse through the membrane easily. They dissolve in the
phospholipid bilayer and pass through it in the direction of the concentration gradient, from a high
concentration to a low concentration.

Endocytosis is the active process by which a cell consumes external material. An example of endocytosis is the
uptake of low-density lipoprotein to the liver.

Exocytosis is the active and controlled process by which a cell releases material. An example of this is the
release of acetylcholine from the pre-synaptic membrane.

Osmosis is the diffusion of water (not particles) across a membrane, in which water diffuses into a solution
having a greater solute concentration.

Phagocytosis is the process by which a cell engulfs harmful cells or material. For example neutrophils and
macrophages are phagocytes.

Hexose sugars (eg, glucose) are transported by facilitated diffusion.

Active transport systems exist for amino acids, conjugated steroids, nucleotides and water-soluble vitamins.

Simple diffusion exchange is determined by concentration gradient for low-molecular-weight molecules, such
as blood gases, sodium, water, urea, non-polar molecules such as cholesterol and steroid hormones.

Pinocytosis occurs for transfer of plasma proteins, immunoglobulins and lipoproteins.

Active transport

 Active transport is required to move molecules from an area of low concentration to one of high
concentration.
 Active transport is required to polarise the cell membrane and to maintain the resting Na + gradient.
 Active transport occurs at the expense of energy (adenosine triphosphate, ATP).
 Carrier proteins are required to transport molecules across the cell membrane.
 Active transport requires either hydrolysis of ATP (primary active transport), or a pre-existent
osmotic gradient, such as the resting intracellular/extracellular Na + gradient (secondary active
transport or coupled transport).
 An example of this latter type is when glucose is resorbed against its concentration gradient in the
kidney. The energy to drive the reabsorption is from the passage of Na + along the pre-existing
concentration gradient.

diffusion rate
 An increase in the molecular weight of the substance will decrease the diffusion rate.
 A decrease in the molecular weight of the substance will increase the diffusion rate.
 An increase in temperature will increase the diffusion rate.
 An increase in membrane permeability will increase the diffusion rate.

net filtration rate towards the extravascular space

By definition, CAPILLARIES are only one endothelial cell thick and do not contain smooth muscle.

A larger surface area will allow a larger net filtration.

As the intravascular hydrostatic pressure rises, the net filtration will increase.

As the intravascular oncotic pressure rises, the net filtration towards the extravascular space will decrease.

Hydraulic conductivity (Lp) is the filtration rate per unit of pressure across the membrane. As Lp increases, the
net filtration will increase also.

Starling’s equation
Fluid movement is determined by the net filtration pressure (capillary hydrostatic pressure − tissue hydrostatic
pressure) minus the net oncotic pressure (capillary oncotic pressure − tissue oncotic pressure)

ALBUMIN is the most important determinant of intravascular oncotic pressure.

refeeding syndrome
In malnourished patients, the commencement of feed puts the patient at risk of refeeding syndrome, which can
cause cardiac complications including cardiac arrhythmias resulting in SUDDEN CARDIAC DEATH.

Refeeding causes increased glucose availability → increased INSULIN secretion → decreased glucagon
secretion. This results in the synthesis of glycogen, fat and protein that requires PHOSPHATE and MAGNESIUM.
Additionally, insulin stimulates the absorption of POTASSIUM into the cell.
As a result, there are decreased levels of phosphate, potassium and magnesium.
Fluid solutions
PLASMA: Na+ 140 mmol/l; K+ 4 mmol/l; Ca2+ 2.5 mmol/l; Cl– 100 mmol/l; HCO3– 28 mmol/l; glucose 5 mmol/l;
osmolarity 285 mOsm/kg

HARTMANN’S ( Ringers Lactate)solution: Na+ 131 mmol/l; K+ 5 mmol/l; Ca2+ 2 mmol/l; Cl– 111 mmol/l; Lactate–
29 mmol/l; glucose 0 mmol/l; osmolarity 280 mOsm/kg. HCO3– is in the form of lactate and is metabolised to
bicarbonate in the liver.

NORMAL SALINE: Na+ 154 mmol/l; K+ 0 mmol/l; Ca2+ 0 mmol/l; Cl– 154 mmol/l; HCO3– 0 mmol/l; glucose 0
mmol/l; osmolarity 308 mOsm/kg

5% DEXTROSE: Na+ 0 mmol/l; K+ 0 mmol/l; Ca2+ 0 mmol/l; Cl– 0 mmol/l; HCO3– 0 mmol/l; glucose 278 mmol/l (50
g); osmolarity 278 mOsm/kg

cell cycle

RNA synthesis occurs in both the G1 and G2 phases.

Mitosis, not meiosis, occurs in the M phase of the eukaryotic cell cycle

Cells in the G0 phase are in the resting phase.

DNA synthesis occurs in the S phase.

The G1 phase (part of interphase) represents synthesis and growth of proteins required for DNA synthesis. The
G1 phase determines the variability of the cycle length.

INTERPHASE comprises phases G1, S and G2 when the cell is in preparation for division.

In ANAPHASE the paired chromosomes separate and are dragged to the opposite sides of the cell by the
microtubules.

In TELOPHASE, the chromatids arrive at the opposite poles of the cell and disperse after new nuclear
membranes are formed.

In CYTOKINESIS, an actin fibres forms around the centre of the cell and contracts, pinching it into two daughter
cells, each with 23 pairs of chromosomes.

The tumour-suppressor gene p53 is known as ‘the guardian of the genome’ and prevents a cell from entering
the S phase of the cell cycle.
DNA/ RNA processes
PROOFREADING refers to the process by which genetic errors are corrected.
DNA polymerases are able to detect a BASE pair mismatch and replace it with an appropriate match, allowing
replication to continue.
3´→ 5´ EXONUCLEASE activity, possessed by some DNA polymerases, enables the enzyme to replace
misincorporated NUCLEOTIDES.

RECOMBINATION refers to the process by which the combination of two DNA sequences generates a unique,
new sequence. This process occurs in meiosis.

RETROTRANSPOSITION is transposition via an RNA intermediate (transposition is the movement of a genetic

element from one site to another in a DNA molecule).

SPLICING is when the primary transcript of mRNA is processed and introns are removed, with the remaining
exons joined together. A mature transcript is formed.

qSOFA
The qSOFA assessment is a quick screening tool with three parameters to identify high-risk patients with sepsis
outside of intensive care. A point is given for each of the following;

 Glasgow Coma Score (GCS) <15,

 respiratory rate ≥22 breaths/min (normal 12–20 breaths/min)
 systolic BP ≤100 mmHg

apoptosis
Apoptosis is a highly-regulated process (‘programmed cell death’).

It is characterised histologically by nuclear condensation, fragmentation and by defects in the cell membrane.

Programmed cell death is a feature of all cells and is associated with a variety of enzymes including
endonuclease, granzyme B and ICE (interleukin (IL)-1β-converting enzyme).

In apoptosis cell integrity is preserved. The cell membrane remains intact in the process of breaking down cells
into APOPTOTIC BODIES along the cascade of programmed cell death.

Apoptosis may be either physiological (programmed cell death) or pathological. Physiological examples of
apoptosis include embryological development and cellular turnover.

apoptosis vs necrosis

Apoptosis Necrosis
Physiological or
Always pathological
pathological
 Energy dependent
Regulated process
Cell integrity intact
DNA cleavage by specific
activated enzymes
Energy independent
Non- regulated process
Cell integrity breakdown
No DNA cleavage

Vomiting

The CHEMORECEPTOR TRIGGER ZONE (CTZ) is OUTSIDE the blood–brain barrier, within the dorsal surface of
the medulla oblongata, in the FLOOR of the FOURTH ventricle.The main receptors are dopamine, histamine
(H1) and serotonin. 5HT3 antagonists (eg ondansetron), not agonists, are effective in controlling vomiting in this
context.

The VOMITING centre is present in the reticular formation of the MEDULLA.

menstrual cycle

Physiological cycle: ovulation (day 14)→secretory phase (days 14 -28)→ menstrual phase (day 0)
→proliferative phase (days 0-14)

we start to monitor menstrual cycle from menstruation (day 0)

ovulation: day 14

The SECRETORY phase of the menstrual cycle begins after ovulation occurs, days 14-28. In the secretory phase,
the endometrium is maintained under the influence of progesterone. Within the secretory phase, progesterone
peaks 7 days after ovulation (day 21). Progesterone levels can be used to confirm ovulation. There is a basal
body temperature increase (0.5°C) in the secretory phase.

MENSTRUATION – DAY 0 follows the secretory phase. In the absence of a pregnancy and without human
chorionic gonadotrophin (hCG), the corpus luteum demises and inhibin and progesterone levels fall.
Progesterone withdrawal leads to menstrual shedding (progesterone-withdrawal bleeding).

The endometrium is in a process of hyperplasia (building) in the PROLIFERATIVE phase (0-14 days).

Hyperthermia
 increased respiratory rate.
 cutaneous (peripheral) vasodilation.
 decrease in appetite.
 decrease in catecholamine secretion.
 reduction in skeletal muscle activity.

Hypothermia
The HYPOTHALAMUS controls thermoregulation.
 Blood viscosity increases as body temperature falls.
 shift of the oxygen dissociation curve to the left, so increasing the oxygen content of blood at a
given tension.
 decrease in brain metabolism and activity. Therapeutic cooling is one of several methods that can be
used to prevent secondary traumatic brain injury.
 Bradycardia occurs due to depression of cardiac pacemaker cells.

J-waves are positive deflections that occur between the QRS complex and ST segment. They are associated with
hypothermia.

 Symptoms of hypothermia START to appear BELOW 35°C and include shivering. Temperature
regulatory mechanisms are working to maintain core body temperature.
 Temperature at 32°C  REGULATORY MECHANISMS are still working, patients BEGIN to develop
bradycardia, hypotension and respiratory depression.
 Temperature regulatory mechanisms fail at 30°C and the condition is often life threatening after this
point.
 Below 28°C  temperature regulatory mechanisms have already failed, the patient is typically
unconscious and there is a high risk of Atrial and ventricular arrhythmias.
 Asystole and ventricular fibrillation have been noted to begin spontaneously at core temperatures
below 25-28°C.

Capacitation of sperm
Glycoprotein molecules coating the surface of the sperm cell are solubilised by uterine fluid in the UTERUS.

 Capacitation enhances motility and allows the head to penetrate an egg.

 Capacitation requires energy.
 Capacitation enables the acrosome reaction.
 Capacitation does not affect follicle-stimulating hormone (FSH) and luteinising hormone
(LH)release.

Mitochondria

 They have the ability to regenerate and replicate SPONTANEOUSLY as required.

 Mitochondria contain RNA that is coded for by their own DNA.
 Mitochondria are enclosed by a double (inner and outer) membrane.
 Mitochondria do consume ATP while simultaneously generating ATP via the electron transport
chain.
 The number of mitochondria per cell varies, with up to 2000 found in a human hepatocyte.

Substances absorption

Calcium is absorbed largely in the duodenum.

Iron is mainly absorbed in the duodenum and upper jejunum.

Vitamin B 1 (thiamine) is a water-soluble vitamin and is absorbed in the jejunum.

Phosphate is absorbed in the small intestine by both passive diffusion and active transport.

Zinc is absorbed throughout the small bowel.

The absorption of vitamin B12 in the terminal ileum is dependent on intrinsic factor. Intrinsic factor is secreted
by the parietal cells in the stomach. Therefore, following a total gastrectomy, the patient will require vitamin B 12
injections.

The predominant site of magnesium absorption appears to be the distal ileum.

The terminal ileum is also responsible for the reabsorption of bile salts. Bile salt malabsorption can cause
chronic diarrhoea.

Mechanical feedeing

With limited nutrition FOR A WEEK it is important to consider an alternative method of feeding to improve
patient outcome.

Total parenteral nutrition (TPN): In ileus the gastrointestinal tract is not functional and the patient is unlikely to
absorb any enteral feed. When commencing TPN it would be important to closely monitor magnesium,
phosphate and potassium levels, as patients that have had a prolonged period of starvation are at risk of
refeeding syndrome.

Percutaneous endoscopic gastrostomy or radiologically inserted gastrostomy (PEG) is performed in patients

that require LONG-TERM feeding and have SWALLOWING DIFFICULTIES, for example following certain types of
stroke.

A nasogastric tube would be useful for symptomatic relief of vomiting and distension in patients with post-
operative ileus. NOT FOR LONG TERM

A FEEDING JEJUNOSTOMY would require a working gastrointestinal system for absorption of feed. This is
typically done in combination with operations of the upper gastrointestinal system and avoids feed passing
through the stomach, delivering feed directly to the jejunum.

Poiseuille’s law
Maximum flow of fluid would be achieved by a short length, large diameter, low viscosity fluid and high
pressure.
Metabolic rate
Metabolic rate is affected by a number of factors including muscular exertion (most important), ingestion of
food, sex, age, height, weight, surface area, body temperature, environmental temperature, emotional state.

 Thyroid hormones and catecholamines (e.g. adrenaline and noradrenaline) will increase the
metabolic rate.
 Metabolic rate increases after a meal.
 Metabolic rate increases in a cold environment.
 Metabolic rate is greater in children compared with adults.

lymphatic system
The MOST IMPORTANT physiological function of the lymphatic system is to transport fluid and proteins away
from the interstitium, to the blood

In the absence of a lymphatic system, the interstitial fluid protein concentration would increase greatly, causing
widespread extracellular oedema.

Other LESS important functions:

 To concentrate proteins in the lymph

 To remove particulate materials from the interstitium
 To transport antigenic materials to lymph nodes
 To create negative pressure in the free interstitial fluid

Gastrin
In Zollinger–Ellison syndrome there is excessive secretion of gastrin.

Gastrin stimulates pepsinogen secretion by chief cells.

Gastrin stimulates the secretion of gastric acid by the parietal cells in the stomach.

Gastrin secretion aids digestion by increasing gastric motility.

DISTENSION of the stomach is a physiological STIMULUS for gastrin secretion and NOT an action of gastrin
itself.

JVP waveform
The normal JVP waveform consists of the a-wave (atrial contraction), c-wave (ventricular contraction), x-
descent (atrial relaxation), v-wave (atrial filling) and y-descent (ventricular filling).

The a-wave on a JVP waveform corresponds to right atrial contraction

 a-wave would be absent in patients with atrial fibrillation.
 Large a-waves occur when there is resistance to emptying of the right atrium for example in tricuspid
stenosis.
 Cannon waves are very large a waves that occur when the right atrium contracts against a closed
tricuspid valve. They are related to rhythm disturbances causing changes in the cardiac blood flow. They
occur irregularly in complete heart block.
o Cannon a waves need to be distinguished from giant a waves that occur in right heart
structural changes such as tricuspid valvulopathies, right ventricular hypertrophy, and
pulmonary hypertension.

The y-descent would be slow in tricuspid stenosis.

pH buffering
1. Intracellular: Cytoplasmic PROTEINS provide the main contribution to pH buffering of the intracellular
compartment.
2. Interstitial: In the interstitial (ie extracellular and extravascular) compartment, the BICARBONATE
system is the main mechanism of pH buffering.
3. Intravascular:
 The PHOSPHATE buffer system (HPO42– + H+ « H2PO4–) acts in the intravascular space.
 The BICARBONATE system is an intravascular buffer: CO2 + H2O « H2CO3 « H+ + HCO3– catalysed by the
enzyme carbonic anhydrase.
 The GLOBIN component of haemoglobin acts as a buffer in the intravascular space.

Obesity and cardiovascular complications

Blood volume expansion leads to left ventricular dilatation. Over time there is REDUCED COMPLIANCE of the
left ventricle and impaired left ventricle filling leading to heart failure.

Obese patients can have excess INTRAMYOCARDIAL FAT and deposition of fat within the myocytes (NOT
Purkinje fibres). This results in LV hypertrophy and diastolic dysfunction and increased ARRTHYTHMOGENOCITY.

B-receptors
Stimulation of either β1- or β2-receptors activates adenylate cyclase.

β-Adrenergic responses typically result from increased production of cAMP.

While adrenaline stimulates β1- and β2-receptors, noradrenaline predominantly stimulates α1-receptors.

β2-receptor stimulation causes systemic + muscle’s vessel vasodilation

β2-receptor stimulation also causes bronchodilation. This underpins the mechanism of salbutamol.
haemorrhagic shock

Class of haemorrhagic shock

I II III IV
Blood loss (ml) Up to 750 750–1500 1500–2000 >2000
Blood loss (% blood
Up to 15 15–30 30–40 >40
volume)
Heart rate/min <100 100–120 120–140 >140
Blood pressure Normal Normal Decreased Decreased
Pulse pressure
Normal/increased Decreased Decreased Decreased
(mmHg)
Respiratory rate
14–20 20–30 30–40 >35
(breaths/min)
Urine output (ml/h) >30ml/h 20–30 5–15 Negligible
Central nervous
Slightly anxious Mildly anxious Anxious, confused Confused, lethargic
system

nitrogen balance
A POSITIVE nitrogen balance is required in GROWTH.

Following a fracture there is a negative nitrogen balance due to increased demands from the reparative
process.

In exercise the metabolic rate and nitrogen demand of the body increases→ negative nitrogen balance

Major surgery results in iatrogenic injury and inflammation that increases the metabolic rate, increased urea
production and so ↑ nitrogen demands of the body.

Following sepsis there is a negative nitrogen balance due to the increased requirement from the inflammatory
processes.

skeletal muscle contraction

Occurs in response to depolarisation of the sarcolemma. Depolarisation of the plasma membrane triggers
passive release of calcium ions from the sarcoplasmic reticulum through specific channels along a gradient.
Contraction is sustained until the calcium ions are actively transported back into the sarcoplasmic reticulum and
relaxation occurs.

Spontaneous contractions (tetany) of skeletal muscle may occur in response to low (not high) serum calcium
levels.

BOTH thick and thin myofilaments are required to move along one another.
Burns
Patients with burns require significant fluid resuscitation, which can be calculated using the formula 2 ml ×
weight in kg × % burn, as per the latest version of the ATLS guidelines.

Adult patients with deep-partial and full-thickness burns involving more than 20% total body surface area
(TBSA) should receive initial fluid resuscitation of 2 ml/kg/%TBSA.

 In paediatric burns 3 ml/kg/%TBSA should be used.

 4 ml/kg/%TBSA is used for electrical burns.
The first half of the fluid should be given over the course of eight hours, and the remaining half is
provided over the next 16 hours.

The area of burn can be calculated using the rule of 9s or the Lund and Browder chart. Each lower limb is 18%
(9% anterior and 9% posterior). In this patient both anteriorly have lower limbs been burnt. The palms are 1.5%
each.
obstructed kidney

Over the FIRST 1–2 H there is an increase in renal blood flow due to prostaglandin release and vasodilatation
in an attempt to increase capillary hydrostatic pressure to maintain glomerular filtration rate.

However, AFTER 3–4 H this is FOLLOWED BY A SUSTAINED DECREASE in renal blood flow unless the
obstruction can be cleared.

LDL
Each particle of LDL contains one molecule of APOLIPOPROTEIN B-100, the ligand for the LDL receptor.

LDLs are formed from VLDL and IDL by successive removal of triglyceride and modification in the circulation.

The major fat in LDL is cholesterol.

Their concentration is determined mainly by the rate of hepatic synthesis and peripheral clearance;

Dietary SATURATED FAT intake correlates more strongly with LDL than dietary cholesterol intake.

It is HDL-cholesterol that is involved in reverse cholesterol transport.

Monroe–Kellie doctrine

The intracranial volume in the adult is approximately 1700 ml; consisting of 1400 ml of brain tissue, 150 ml of
cerebrospinal fluid and 150 ml of blood. There is no lymphatic system within the brain.

Normal intracranial pressure is typically considered to be between 5–15 mmHg.

The Monroe–Kellie doctrine states that the skull is a rigid structure with three components (brain tissue, CSF and
blood). If the volume of one of these components increases there is a reciprocal decrease in another to maintain
a constant ICP.

The hypothesis only applied when the skull is fused. It does NOT applies to the newborn

Urinary physiology

GFR
An ideal substance for measuring the glomerular filtration rate (GFR) should be freely filtered at the glomerulus
and neither secreted nor reabsorbed by the tubules.

GFR can be measured using the relationship GFR = UV/P for any substrate that is freely filtered and not
reabsorbed or secreted (UV is the amount of urine per minute and P is the concentration in plasma).

Creatinine is not an ideal substance for measuring GFR as a small amount is secreted by the tubules. This means
that slightly more creatinine is excreted in the urine than is filtered. Baseline creatinine is also affected by an
individual’s muscle mass.

GFR can decrease by as much as 50% before plasma creatinine rises beyond the normal range. Consequently, a
normal creatinine does not necessarily imply normal renal function, although a raised creatinine does usually
indicate impaired renal function.

Inulin (not insulin), a polysaccharide molecule, meets these criteria for an ideal substance. It can be
administered intravenously to patients to measure their GFR. However, it is too cumbersome to use in routine
clinical practice. Instead, in the clinical practice, the GFR is more commonly quantified by measuring the 24-H
URINARY CREATININE excretion.

In the normal individual the glomerular filtration rate is kept fairly constant at 120 ml/min or 180 l/day. The
entire plasma volume (about 3 litres) can therefore be filtered and processed by the kidney approximately 60
times each day. The GFR remains relatively constant through autoregulation.
After 35 years of age, GFR falls at about 1 ml/min/year. By the age of 80, GFR has fallen to about 50% of its
youthful level.

The RATE of urine production in humans is dominated by TUBULAR function and NOT GFR.

The ultrafiltrate is essentially plasma without the proteins (these are not able to cross the basement membrane
of the glomerulus).

The GFR is governed by the rate of glomerular blood flow, which is governed by the tone of BOTH the afferent
and efferent arterioles. This is kept constant over a range of blood pressures.

Glucose is able to cross the glomerular basement membrane into the ultrafiltrate. In normal individuals it is then
actively reabsorbed(facilitated diffusion). Under normal conditions the renal clearance of glucose is zero, as
glucose is completely reabsorbed in the renal tubules and not excreted. The resorption mechanism has a
maximal rate. If the glucose concentration of the serum, and consequently the ultrafiltrate is too high, then the
mechanism is overwhelmed and glycosuria occurs (as occurs in diabetes mellitus).

Vasopressin
Vasopressin (otherwise known as ADH) acts upon the distal convoluted tubule but PRIMARILY upon the
COLLECTING DUCTS. It increases reabsorption of water by increasing the permeability of the collecting ducts to
water.

ADH is released by the posterior pituitary in response to dehydration, from stimulation of

 Osmoreceptors: adjacent to the SUPRAOPTIC nucleus,

 volume receptors : aorta, atria and great veins.

Water absorption in the collecting ducts is independent of sodium concentration, and is under the control of
ADH, which causes increased permeability of the ducts. Increased ADH levels will increase the osmolality of the
urine via this method.

In the descending limb of the loop of Henle, sodium and water are passively resorbed, but the loop is highly
permeable to water and has low permability to ions, meaning the filtrate will be hypertronic with increased
osmality. The ascending limb is impermeable to water, with active sodium resorption, producing a
concentration gradient in the renal medulla, which is essential for the maintenance of water balance.

diabetes insipidus
In diabetes insipidus, appropriate water intake from thirst will ADEQUATELY COMPENSATE for the potential
excess volume loss.

Diabetes insipidus is a condition where large amounts of urine are produced due to the inability of the kidney to
concentrate urine. The cause can either be cranial which is due to the lack of ADH produced by the posterior
pituitary, or nephrogenic which is when there is adequate levels of ADH but the kidney does not respond to it.
Cranial diabetes insipidus can be caused by brain trauma or a pituitary tumour among other things.
Nephrogenic diabetes insipidus can be caused by acquired diseases such as amyloidosis, drug therapy such as
lithium or hypercalcaemia.

renal blood flow

At rest, the kidney receives 25% of the cardiac output, approximately 1.2L of blood/min.

Renal plasma flow can be measured by infusing PAH and determining its urine and plasma concentrations. PAH
is filtered by the glomeruli and secreted by the renal tubular cells, so its excretion ratio is high. The effective
renal plasma flow is equivalent to the urine clearance of PAH. PAH is not used in routine practice, where
surrogates such as haemodynamic parameters and lactate are more useful.

The renal blood flow and renal perfusion are controlled by several factors including hormones and the
sympathetic nervous system. The factors affecting renal blood flow include: blood volume (hypovolaemia
reduces renal blood flow) and catecholamines (constrict renal vessels so reducing flow).

At normal systemic blood pressure the renal vascular resistance adjusts the pressure in the renal arterioles so
that renal blood flow remains fairly constant (autoregulation). Autoregulation is impaired in shock, sepsis and
low cardiac output states.

 Blood flow in the CORTEX is much higher than in the medulla.

 In hypertensive patients there is a shift of autoregulation, so that they have a slightly reduced
renal blood flow for a given blood pressure
 Atrial natriuretic peptide causes dilatation of the AFFERENT arterioles and increases the renal
blood flow and the glomerular filtration rate.
 Prostaglandins (PGE2 and PGI2) increase the renal blood flow and the glomerular filtration rate.
 AngiotEnsin II (not angiotensinogen) are produced systemically, and within the kidney, primarily
constricts the (second) EFFERENT arterioles (more than afferent) to increase glomerular filtration
rate.
 Adenosine triphosphate (ATP) selectively vasoconstricts the AFFERENT arteriole and so
reduces the renal blood flow.
 Endothelin is a potent vasoconstrictor secreted by endothelial cells of arterioles, which decreases
the renal blood flow.
 Glucocorticoids dilate the AFFERENT arterioles and increase the renal blood flow and the
glomerular filtration rate.
 Likewise, nitric oxide also causes vasodilatation and increases the renal blood flow.
 Hypercarbia increases renal blood flow.
 Hypovolaemic shock decreases renal blood flow as intravascular circulating volume is reduced.
 Vasopressin/ ADH has NO EFFECT on the renal blood flow or perfusion.

PROXIMAL convoluted tubule

1. It is the site of PHOSPHATE REABSORPTION under control of parathyroid hormone. PTH acts to decrease
the resorption of phosphate. Reabsorption of phosphate by renal tubular cells occurs against its
electrochemical gradient, via a carrier co-transport of phosphate - sodium.
At high PTH concentration, as much as 40% of filtered phosphate may be excreted.

(note that CALCIUM reabsorption occurs in the ascending loop of Henle, distal tubule, and collecting
tubule).

2. GLUCOSE, AMINO ACIDS are also reabsorbed via secondary active transport in the PROXIMAL renal
tubule through co-transport channels driven by the sodium gradient out of the nephron.

Transport of glucose through the apical membrane of renal tubular as well as intestinal epithelial cells
depends on the presence of secondary active Na+-glucose symporters, sodium-glucose linked
transporter (SGLT)-1 and SGLT-2, which concentrate glucose inside the cells, using the energy
provided by co-transport of Na+ ions down their electrochemical gradient.

juxtaglomerular cells
In the kidney, the Juxtaglomerular cells (JG cells) are cells that synthesise, store and secrete renin. They are
specialised SMOOTH MUSCLE cells in the wall of the AFFERENT arteriole that delivers blood to the
glomerulus. In appropriately stained slides, juxtaglomerular cells are distinguished by their GRANULATED
cytoplasm.

loop of Henle

The fluid in the DESCENDING loop of Henle becomes hypertonic as water moves into the hypertonic
interstitium (sodium level increases as the descending limb travels downwards). UREA can permeate through
the descending limb of the loop of Henle.

In the distal end of the ASCENDING limb of loop of Henle fluid is HYPOTONIC regardless of the state of
hydration because of the active reabsorption of sodium chloride but not water, which is impermeable in this
tubular segment. Sodium, potassium and chloride are all co-transported OUT of the thick segment of the
ascending limb rather than into it. This forms the mechanism of the counter-current multiplier.

In dehydration, the late distal convoluted tubule and the collecting duct become more and more hypertonic in
the presence of antidiuretic hormone (ADH), which increases permeability of these tubular segments. The
glomerular filtrate and proximal tubule have the same tonicity as plasma.
Aldosterone
Aldosterone is a steroid hormone produced by the zona glomerulosa of the adrenal cortex. Its release is
stimulated mainly by the renin/ angiotensin system. Adrenocorticotropic hormone (ACTH) also causes
aldosterone production, as do hyponatraemia, hyperkalaemia and hypovolaemia.

1. At the DISTAL CONVOLUTED tubule, aldosterone acts to increase the Na+/K+ permeability of the luminal
+
surface of the cells and causes resorption of Na and H2O in exchange for K+, which is excreted into
the urine.
+
2. It also acts in the COLLECTING DUCTS to secrete H ions, thereby regulating plasma HCO3– levels.

Intercalated cells are kidney tubule epithelial cells with important roles in the regulation of acid-base
homeostasis. These cells appear in the late distal convoluted tubule or in the connecting segment, depending on
the species. They are most abundant in the collecting duct, where they can be detected all the way from the
cortex to the initial part of the inner medulla.

Aldosterone’s primary function is to act on the late distal tubule and collecting duct of nephrons in the kidney,
directly impacting sodium absorption and potassium excretion. The net effect of this process is sodium
absorption from the lumen, which allows for water absorption, assuming ADH is present to make the cells
permeable to water. This directly results in an increase in osmolality within the blood, causing water to flow
down its concentration gradient

It also indirectly affects the excretion of hydrogen ions by changing the amount of potassium in the lumen of
the nephron, causing downstream consequences on alpha-intercalated cells.

Lastly, it affects blood pressure through regulating the amount of sodium (and the chloride that diffuses with
sodium across the membranes) by increasing or decreasing the total amount of volume in the extracellular fluid
(ECF). However, this is not to be confused with the effect of anti-diuretic hormone (ADH). ADH is often
released simultaneously with aldosterone. This allows for blood pressure control by causing the release and
fusion of aquaporin channels into the membrane of the principal cells. Water will then be reabsorbed into the
ECF. Together these two hormones can cause an increase in the amount of water taken up through the
nephron, therefore increasing blood pressure

BOTH ALDOSTERONE AND ADH ACT IN DISTAL CONVOLUTED TUBULE AND COLLECTING DUCTS

Dehydration
Dehydration leads to splanchnic and visceral vasoconstriction, so renal blood flow falls. This causes a drop in
urine output and a minimum obligatory urine output of 500 ml/24 h may result.
gastro, endocrine, neuro physiology

Misc
 Glycogenesis → glycogen formation from glucose
 Glycogenolysis → lysis of glycogen and glucose formation. It occurs in the liver and is stimulated by
glucagon.
 Neoglucogenesis →glucose formation from non carbohydrate substances
 Glycolysis → Glucose is broken down during glycolysis into two pyruvate (three carbon) molecules that
enter Kreb’s cycle.

Gluconeogenesis
Gluconeogenesis is the process by which glucose is generated from non-carbohydrate sources such as glycerol,
lactate and amino acids. This process occurs during fasting and starvation.

The body is able to maintain adequate amount of circulating glucose by breakdown of glycogen
(glycogenolysis) for the first 8–12 h of starvation.

Following this, if the circulating glucose is not replenished by a meal, the body starts using other non-
carbohydrate substrates (neoglycogenesis) to produce glucose which is essential for the central nervous system.
It occurs mostly in the liver.

Insulin
Insulin is a peptide hormone released by the b-cells of the islets of Langerhans in the pancreas in response to a
raise in serum glucose. Its action include:

 stimulation of glucose and potassium UPTAKE by the cells. This reduces serum levels of K +, but not
total body K+. Hence insulin is given with dextrose solution for acute management of hyperkalaemia.
 glucogen synthesis in the liver and muscle (glycogenesis)
 inhibition of glycogenolysis and gluconeogenesis
 increased amino acid uptake-decreased proteolysis
 decreased lipolysis and proteolysis
 increased lipid synthesis – decreased lipolysis

INsulIN stimulates two things to go IN the cells: potassium and glucose

During pregnancy a relative insulin resistance can develop leading to the presentation of gestational diabetes.

Low plasma glucose inhibits insulin secretion by pancreatic beta cells.

Insulin release is stimulated by

 amino acids,
 some fatty acids, and the
  gut hormones secretin and cholecystokinin.
 β-Adrenergic stimulation.
 Vagal stimulation

Glucose will not diffuse through a cell membrane against a concentration gradient.

 Insulin facilitates the diffusion of glucose across many cell membranes including cardiac muscle cells,
skeletal muscle cells, some smooth muscle cells and adipose tissue cells.
 The uptake of glucose by the BRAIN, INTESTINAL (both small and large bowel) epithelium, reNAL
TUBULAR epithelium, NERVES and RBCs is INDEPENDENT of insulin.

Growth hormone
Growth hormone is a 191-amino acid, single-chain polypeptide hormone that is synthesised, stored and secreted
by the somatotroph cells within the lateral wings of the anterior pituitary gland, which stimulates growth and
cell reproduction in humans.

Growth hormone is an anabolic hormone promoting gluconeogenesis in the liver. GH is also LACTOGENIC

Exercise, is one of the physiological STIMULATORS of growth hormone secretion along with sleep,
hypoglycaemia and circulating estradiol. A diet rich in protein is also considered a stimulator of growth
hormone secretion.

Circulating glucocorticoids, such as cortisol, INHIBIT growth hormone secretion. Another inhibitor of growth
hormone is a carbohydrate-rich diet. Free circulating fatty acids have been found to inhibit the release of
growth hormone. Somatostatin, produced by the periventricular nuclei of the hypothalamus, is an inhibitor of
growth hormone secretion from the anterior pituitary.

HUMAN PLACENTAL LACTOGEN is also known as human chorionic somatomammotropin. It is produced by the
syncytiotrophoblast of the placenta and is homologous to normal GH. Although called as placental lactogen, its
role in lactation is not clear. Its major function is induction of resistance to insulin action in the mother.

Glucagon
Glucagon is a hormone released from the a-cells of the islets of Langerhans in the pancreas in response to

 a drop in serum glucose.

 a high serum concentration of amino acids (also stimulates the secretion of glucagon, which in turn
stimulates gluconeogenesis in the liver, ie conversion of amino acids to glucose)

Glucagon acts on the liver to stimulate breakdown of the glycogen stores, a process called glycogenolysis, by
increasing intracellular cyclic AMP levels. It also stimulates gluconeogenesis. Both of these processes have the
effect of increasing circulating levels of glucose. It is thought that glucagon has a MINOR effect in enhancing
LIPOLYSIS.
Gluca has Gon to cAMP to bring out Glucose → Glucagon elevates glucose by cAMP involvement

Hypoglycaemia
Hypoglycaemia is defined as a blood sugar below the normal range (3.5–5.5 mmol/l).

It most commonly occurs in diabetic patients who have taken their normal insulin dose when the carbohydrate
intake was low.

Other causes include an insulin secreting tumour of the pancreas (insulinoma), hypothyroidism, severe
infections, liver failure.

Brain metabolism is highly dependent on glucose as an energy source. Initial steps in brief or mild
hypoglycaemia include the release of glucagon to promote glycogenolysis, use of the glycogen stores in the liver
and gluconeogenesis. Hypoglycaemia triggers the release of adrenaline from the adrenal glands, as a stress
hormone.

Increased circulating adrenaline causes the symptoms of sweating, shaking, tachycardia and a feeling of
hunger all of which alert the patient to act upon the symptoms and have a meal. Adrenaline also acts
synergistically with glucagon in gluconeogenesis.

If the hypoglycaemia is not resolved, the brain does not have adequate support and the patient can experience
seizures and coma.

Clinical features of hypoglycaemia

5Ss and 2Cs

S Starving (feel hungry)

S Shaky (tremors)

S Sweating

S Sky-high pulse (tachycardia)

S Sleepy or irritable

C Convulsions

C Coma

Ketone bodies are produced when the body starts using fatty acids as an energy source. This occurs after a
LONG period of hypoglycaemia, or when there is not enough insulin in the body to enable the cells to uptake
and use the circulating glucose.
Adrenaline (epinephrine)
Adrenaline stimulates glycogenolysis by increasing intracellular CALCIUM levels.

Gastric physiology
GASTRIN is the main hormone that acts as a stimulant for gastric acid secretion during a meal. Gastrin release
occurs in response to the presence of luminal amino acids in the stomach. Gastrin is released by G cells found in
the gastric pits. Gastrin binds to the gastrin receptors on the parietal cells of the stomach promoting ACID +

INTRINSIC FACTOR (parietal/ oxyntic cells) and PEPSINOGEN (chief/ peptic/zymogenic cells) secretion.

Other hormones stimulating acid secretion (HCl) by the parietal cells include: acetylcholine (secreted from
postganglionic neurons) and histamine (released from enterochromaffin like cells).

Pepsin is the active form of the enzyme called pepsinogen, produced by the Chief cells of the stomach. Once
exposed to the acidic environment of the stomach, pepsinogen is converted to pepsin, which is involved in the
breakdown of proteins to amino-acids. Pepsin is a protease composed of 44 amino acids, an enzyme involved in
the breakdown of proteins. Pepsin is under the influence of an auto-catalytic process, in which the presence of
active pepsin stimulates the secretion of more pepsin

Gastric acid is secreted actively. Binding of gastrin, acetylcholine and histamine to parietal cells of the stomach
promotes an increase in intracellular cAMP, IP 3, diacylglycerol and calcium. This in turn promotes fusion of
vesicles containing H+/K+/ATPase molecules with the membrane of the parietal cells. The increase in the
transmembranous receptors, promotes proton secretion and therefore acid secretion. The proton pump (H+/K+-
ATPase) is found in the APICAL (LUMINAL) membrane of gastric parietal cells and secretes protons into the
lumen of the stomach in exchange for potassium ions.

Histamine-stimulated acid production is dependent on the proton pump. HISTAMINE binding to receptors on
the BASOLATERAL membrane of parietal cells activates adenylate cyclase leading to a high intracellular cyclic
AMP concentration and activation of protein kinase A. This process has the effect of recruiting more proton
pumps (H+/K+-ATPase) from the cytoplasm to the luminal (apical) membrane of the parietal leading to increase
acid production.

It is parasympathetic nervous system activation, via the stimulation of the vagal nerve and release of
acetylcholine, that promotes the production of gastric acid. Acetylcholine-stimulated acid production is again

dependent on the proton pump. Acetylcholine binds muscarinic (M3) receptors on the BASOLATERAL
membrane of the parietal cells, a G protein coupled receptor, and stimulates the secretion of gastric acid via
the proton pump.
One-third of the total production of gastric acid secretin is stimulated via the CEPHALIC phase in which
the anticipation/smell/taste of food signals through the vagus nerve (cranial nerve X) and not the
glossopharyngeal nerve.

Vasopressin and secretin DECREASE gastric acid secretion and have been shown to decrease
gastric blood flow. Additionally, noradrenaline decreases gastric blood flow by causing vasoconstriction of the
gastric arterioles. Similarly, hypovolaemia and shock can decrease gastric blood flow. Maintaining a good
gastric blood flow is necessary for protecting the gastric mucosa from damage from the acid gastric contents.

Vagal stimulation, acetylcholine, histamine and gastrin are all known to increase gastric acid production and
have been found to increase gastric blood flow. Acetylcholine also causes a direct vasodilator effect on the
gastric mucosa arterioles.

The gastric mucosa contains many cell subtypes, including goblet cells, acid-secreting cells (also known as
parietal or oxyntic cells), pepsin secreting cells (also known as peptic, chief or zymogenic cells) and G-cells
(gastrin-secreting cells).

 Parietal cells are involved in the secretion of gastric acid, in the form of hydrochloric acid, and
intrinsic factor.
 Chief cells, also known as peptic or zymogenic cells, produce the zymogen pepsinogen
 G-cells in the stomach produce gastrin
 Goblet cells are mucus-secreting cells, widely distributed throughout epithelial surfaces, but especially
dense in the gastrointestinal and respiratory tracts.

Gastric emptying rate

The rate of gastric emptying is influenced by two factors: volume of stomach contents and composition of
stomach contents.

In the absence of stomach distention there is little stimulation for gastric motility and therefore the rate of
emptying is slower.

Isotonic fluids are emptied at a maximal rate, hypertonic meals have a slower rate of gastric emptying. The
more hypertonic or nutrient-rich the meal is, the slower the rate of gastric emptying. Therefore with a meal of
5% glucose emptying will be faster than that of a meal containing 50% glucose.

Gastric emptying rate is ACCELERATED when a patient lies SUPINE rather than standing.(“you have to lay down
to digest”)

Fat reaching the duodenum slows gastric emptying.

After vagotomy and draining procedure (such as gastroenterostomy or pyloroplasty) performed, there is an
increase in the rate of gastric emptying. In the postoperative period, GASTRIC EMPTYING starts becoming
faster, and continues to increase until reaching a steady state at 2–3 months post-operation.
Secretin
Secretin is secreted by the S-cells in the DUODENUM in response to the arrival of gastric chyme, which is acidic,
reducing the pH of the intestinal lumen. Secretin binds to G-coupled protein secretin receptors in various tissues
to exert its effects. Secretin increases the release of bicarbonate from the duodenum and release of bile from
the gall-bladder. It also stimulates pepsin secretion from the stomach and insulin release from the pancreas.
Secretin inhibits gastrin release and gastric acid secretion.

SECRETIN stimulates the release of BICARBONATE in the duodenum, pancreatic and biliary ducts.

SECRETIN augments the action of cholecystokinin and therefore stimulates contraction of the gall-bladder.

Cholecystokinin
Cholecystokinin is a hormone released from the I-cells of the duodenum . The greatest stimulator of CCK
release is the presence of fatty acids and/or certain amino acids in the chyme entering the duodenum .In the
presence of fatty acids it induces contraction of the smooth muscle of the gall-bladder and relaxation of the
sphincter of Oddi allowing release of bile and pancreatic enzymes in the second part of the duodenum .

Additionally, it affects secretion of the pancreatic enzymes in response to a meal, by increasing the synthesis of
bicarbonate.

Somatostatin
Somatostatin is released from the D-cells found in the pancreas, stomach and intestine and acts to inhibit the
release of insulin, glucagon, gastrin, histamine and gastric acid.

Vasoactive intestinal peptide

The vasoactive intestinal peptide, is a 28 amino acid peptide hormone belonging to the glucagon/secretin
family. It has various roles in the intestine including: causing

 VASODILATION in the gastrointestinal resistance vessels,

 relaxation of enteric smooth muscle,
 inhibition of gastric acid secretion
 stimulation of pancreatic juice and bile secretion.

Other agents that cause gastrointestinal resistance vessel dilation include: gastrin, glucagon and
cholecystokinin.

Bile salt physiology

About 95% of bile salts are actively reabsorbed in the terminal ileum and these are excreted again from the liver
in a cycle called enterohepatic circulation.
There is a VERY SMALL amount of bile salt synthesis but the enterohepatic circulation ensures they are re-used.
The entire pool of bile salts recycles about 6–8 times per day.

Vitamin B12 is also absorbed at the terminal ileum.

Duodenum

Iron is absorbed in the duodenum, where there is also absorption of carbohydrates and amino acids.

Jejenum

The jejunum is the site of absorption of calcium, carbohydrates and amino acids.

Colon

The colon is where water and sodium is reabsorbed.

Sodium is actively absorbed in the colon with the aid of a basolateral Na+/K+ ATPase that creates an
electrochemical gradient.

Water absorption in the colon is via a passive mechanism mostly via enterocyte tight junctions, and is
dependent on the absorption of sodium and other solutes, creating electrochemical gradients.

Caecum

There is sodium and potassium absorption in the caecum.

intestinal motility
Electrical activity in the gastrointestinal tract occurs in slow waves, generated and propagated by the interstitial
cells of Cajal, relying on calcium current. These slow waves cause depolarisation of the cells in the wall of the
bowel and create a peristaltic wave.

Intestinal motility is increased after a meal due to the action of the parasympathetic nervous system.

It is increased by the action of the parasympathetic system, with acetylcholine acting at the muscarinic
receptors. However, it occurs CONTINUOUSLY and not just after a meal

 Segmentation, ie contraction of isolated segments found at intervals along the intestine mixes
the chyme with mucus and hydrolytic enzymes.
 peristalsis  moves the chyme along the intestine.

Amino acids absorption

Amino acids are absorbed in the small intestine, with the majority of absorption occurring in the jejunum and
the remainder in the ileum. They are absorbed by co-transport with Na + through sodium dependent amino acid
TRANSPORTERS.
Bicarbonate reabsorption

Bicarbonate reabsorption occurs predominantly in the proximal convoluted tubule of the kidney. In the
jejunum however, its absorption assists in the active transport of sodium against electrochemical gradients.

Water absorption

In total, 80% of water is absorbed by the SMALL intestine.

Water absorption in the colon is via a PASSIVE mechanism mostly via enterocyte tight junctions, and is
dependent on the absorption of sodium and other solutes, creating electrochemical gradients.

calcium Absorption

It takes place mostly in the proximal jejunum. Absorption of calcium occurs in the duodenum and jejunum, and
is BOTH active – under the regulation of calcitriol – and passive, through tight junctions.

PHYTIC ACID binds to calcium and forms the INSOLUBLE calcium phytate. Once all phytic acid is saturated and
formed a complex with calcium, then the excess calcium remains free and can be absorbed by the intestine.

FATTY ACIDS form INSOLUBLE calcium salts and prevent its absorption by the intestines.

Calcium absorption is much slower than that of sodium (up to 50 times slower).

Calcium is not secreted in the bowel. The kidneys filter calcium ions and there is a net average loss of 5 mmol of
calcium daily.

Fat absorption

Fat is EMULSIFIED in the proximal small intestine duodenum and jejunum) and free fatty acids are taken up
into the enterocytes, via a protein-dependent ACTIVE transport, in the form of fatty acids, glycerol and mono-
or di-glycerides.

Once in the enterocyte they reform triglycerides and are packaged with cholesterol into CHYLOMICRONS,
which are transported outside the cells. Some short chain fatty acids are transported via diffusion.

In the terminal ileum there is a significant amount fat absorption, however this ABSORPTION is
GREATEST IN THE PROXIMAL SMALL INTESTINE (duodenum, jejunum).

Amylase
Amylase is an enzyme involved in carbohydrate metabolism, produced in the pancreas and the salivary glands.
Lipase
Lipase is produced in the pancreas and is involved in fat metabolism, breaking down triglycerides into
monoglycerides and two fatty acids.

Elastase
Elastase is an enzyme produced in the acinar cells of the pancreas involved in the metabolism of proteins.

Maltase

Maltase is a carbohydrase enzyme, secreted by the VILLI of the small intestine, involved in the digestion of
carbohydrates from the diet.

Specifically, it is involved in the hydrolysis of the disaccharide maltose, by breaking down the glycosidic bond, to
two glucose molecules.

Maltase deficiency will result in a reduction in the hydrolysis of maltose, therefore there is an increased passage
of maltose in the stool as well as increased frequency of stool.

Amylase, in contrast, is a carbohydrase produced by the pancreas and the salivary glands and is involved in
hydrolysing polysaccharides into smaller carbohydrate molecules such as maltose.

Lactase

It is a deficiency in lactase, the enzyme that hydrolyses lactose to glucose and galactose, that results in the lack
of absorption of lactose.

pancreatic secretion

The cephalic phase of the pancreatic meal response accounts for about 20–25% of the total pancreatic exocrine
secretion.

The cephalic phase of pancreatic secretion involves the integration of sensory inputs, such as sight, smell and
taste of food as well as the process of mastication and the presence of certain molecules binding on receptors in
the mouth. It is under the control of the VAGUS nerve. Inputs are integrated in the brainstem and, specifically,
the dorsal vagal complex. It is transmitted down to the pancreas via the vagus nerve through cholinergic fibres
innervating the acinar cells. Stimulation of the acinar cells leads to pancreatic enzyme secretions. Therefore, a
vagotomy would interrupt this circuit of information and reduce the pancreatic secretion from the cephalic
phase.

HCO 3– secretion is mainly affected by the hormones cholecystokinin and secretin involved in the INTESTINAL
PHASE of pancreatic secretion.

Cholokystokinin release pancreatic enzymes + bile + gallbladder contraction

Secretin primarily regulates water homeostasis, release bicarbs + electrolytes from pancreas, gallbladder,
liver

Saliva
Human saliva is composed of water (99.5%) as well as electrolytes, epithelial cells, white blood cells, enzymes
and antimicrobial agents.

The enzymes include lipase and amylase, which commence the process of digestion of dietary fats and starches
respectively in the mouth. Antimicrobial agents found in saliva include IgA antibodies and lysozyme.

Normal saliva production in adults varies from 1–2 litres per day. The secretion of saliva from the salivary glands
is mediated by the autonomic nervous system.

 The submandibular glands contribute about THREE-QUARTERS of the saliva

 The parotid gland contribute about ONE-QUARTER of the saliva
 The other salivary glands only contribute a small amount of saliva to the total amount produced.

The salivary glands are supplied BOTH by the sympathetic and the parasympathetic nervous system.

 The sympathetic nervous system promotes thicker saliva production, necessary for respiration.
 The parasympathetic nervous system on the other half promotes the secretion of thinner saliva, for
facilitation of digestion.

Plasma pH in a healthy adult is in the range of 7.35–7.45, whereas saliva pH is slightly acidic and ranges from
6.2–7.4. This is very important in preventing teeth minerals from dissolving.

The concentration of potassium in saliva is higher than that found in plasma.

The salivary glands produce a HYPOTONIC solution. Saliva is made in the acinar cells of the salivary glands. It is
initially isotonic to plasma but as it moves down the salivary ducts its composition is changed, resulting to the
end saliva being secreted with a lower NaCl and a higher KHCO3 than plasma. The saliva secreted from the
glands is therefore hypotonic.

Saliva contains three main enzymes: AMYLASE that is associated with the digestion of starch, KALLIKREIN and
SALIVARY LIPASE(different than pancreatic lipase). Additionally, there are some antimicrobial agents in the
saliva such as LYSOZYME, IGA and LACTOFERRIN.

calcium
As 99% of calcium in the body is bound in the skeleton, only 1% of the total body calcium is available for
buffering changes in Ca2+ balance in the body. This 1% known as total serum calcium and is composed of three
fractions: the protein bound calcium (40–50%, most of it to ALBUMIN), the complexed calcium (10%) and the
free ionised calcium which is usually about 50%. The calcium concentration in the serum is tightly controlled in
the normal range of 2.20–2.60 mmol/l.
Calcium homeostasis is dependent on factors such as the circulating level of parathyroid hormone, vitamin D
levels, phosphate and magnesium concentration.

Iron physiology

2+
The iron in the ferrous state (Fe ) is more efficiently ABSORBED than in the ferric state (Fe3+).

In the physiological pH the iron is oxidised to the ferric state (Fe3+) which is insoluble. However, lowering the
pH assist the absorption of iron in the ferrous state in the DUODENUM AND FIRST PART OF THE JEJUNUM.

Ferritin is mainly an intracellular protein that binds to iron and stores it within the cells. Only small amounts are
found in the serum where it acts as an iron carrier. Ferritin concentration has been shown to increase in
response to stress and it is therefore considered an acute phase protein.

Most of the iron in the plasma is bound to TRANSFERRIN, which is an iron transporter protein.

Haemosiderin is an INTRACELLULAR iron storing complex, composed of ferritin, denatured ferritin and other
materials. The iron within these complexes is not readily available to supply iron when required. Haemosiderin
is most commonly found within macrophages in areas where haemorrhage has occurred.

60–70% of the iron in the body is found within haemoglobin and myoglobin molecules. The remainder is
stored intracellularly bound to ferritin with a smaller amount as haemosiderin.

Iron absorption occurs in the duodenum and first part of the jejunum with only a small rate of absorption
occurring. Only 3–6% of the ingested daily iron is actually absorbed because once the ferrous ion is oxidised to
ferric it becomes insoluble.

Androgens
Androgens are steroids produced primarily by the testes but also by the adrenal glands, specifically the zona
reticularis of the cortex, and to a lesser extent the ovaries.

The zona reticularis produces androgens, mainly dehydroepiandrosterone (DHEA). These are anabolic
hormones and are SUPRESSED during the STRESS response.

LH is produced by gonadotropes, which are basophilic cells in the anterior pituitary gland. In MEN, luteinising
hormone (LH) acts upon the interstitial (Leydig) cells in the testes and is responsible for testosterone
production that exerts BOTH intratesticular (in terms of the spermatogenesis) and endocrine activity as the
'man hormone'.

Androgens are found in both men and women. The main androgen seen in men is testosterone. Other
androgens include: dihydrotestosterone and androstenedione.

Androgens are involved in the development of the testes, act as PARACRINE hormones on the Sertoli cells
leading to spermatogenesis. Additionally, androgens stimulate the development of secondary male sexual
characteristics. They have anabolic effects by increasing protein synthesis and muscle mass. Androgens increase
erythropoiesis by stimulating erythropoietin, increasing the activity of the bone marrow and also enhancing
incorporation of iron into the red blood cells during their maturation process.

The androgens, along with the gonadotrophin hormones FSH and luteinising hormone (LH) are involved in the
stimulation and maintenance of spermatogenesis in men.

The adrenal cortex produces dehydroepiandrosterone (DHEA) which is a ‘male’ sex hormone and is only
produced in very small amounts in women. However, it is not the same as testosterone nor is it a precursor
or breakdown product of it.

Male reproduction physiology

Sertoli cells are supporting cells in the testis and do NOT produce any hormone, but rely on the diffusion of
androgens from interstitial cells of Leydig.

 The main function of the Sertoli cells is to NOURISH the developing sperm cells through the
stages of spermatogenesis.
 However during fetal life, sertoli secrete ANTI-MÜLLERIAN hormone (AMH) which determines the
male sex of the fetus.
 During puberty, Sertoli release INHIBIN and activins , which regulate FSH secretion.

Interstitial cells of the testes, also known as Leydig cells, secrete testosterone when stimulated by luteinising
hormone.

The vas deferens are a pair of coiled tubules that carry sperm from seminiferous tubules to the ejaculatory
ducts.

The prostate gland does NOT produce any hormones; however it is dependent on androgen hormones for its
growth and function. It produces prostatic fluid that mixes with the spermatozoa to increase fluidity and easy
ejaculation.

LH hormone is produced by the anterior pituitary once stimulated by gonadotrophin releasing hormone (GnRH).
In men LH acts on the interstitial cells of the testes (Leydig cells) to secrete testosterone.

Follicle-stimulating hormone (FSH) stimulates Sertoli cells to produce androgen-binding proteins and inhibin.

Follicle-stimulating hormone (FSH) and testosterone are REQUIRED for SPERMATOgenesis (division of
spermatogonia to form spermatids) and SPERMIOgenesis (maturation of spermatids to mature sperm). They
synergise to enhance the production of an androgen-binding protein by the Sertoli cells.

The androgen-binding protein causes high local concentrations of testosterone near the sperm. This high
concentration is essential for the development of normal spermatogenesis.

In men, FSH stimulates testicular growth and helps to maintain Sertoli cells (large cells in the seminiferous
tubules that nourish the developing sperm).
PTH-related protein (PTH-rP)
PTH-rP is produced by some of the carcinomas (mostly SQUAMOUS cell cancer) of lung, breast, and kidney. It
binds to and activates the parathyroid hormone (PTH) receptor mimicking actions of PTH. However, PTH-rP is
also present in the normal population, where its normal function is not known.

PTH- vitamin D- bone physiology

Control of bone resorption/deposition is by parathyroid hormone (PTH) and vitamin D 3.

PTH from the parathyroid glands is released in response to low serum calcium levels. Calcium-sensing receptors
expressed in the parathyroid glands are responsible for detecting extracellular calcium concentration. PTH
secretion by the parathyroid chief cells is stimulated or inhibited in response.

The half-life of parathyroid hormone is ~ 5 min. It is useful to measure during parathyroidectomy as a drop in
its concentration can confirm the removal of all hyper-functioning parathyroid tissue. An intra-operative PTH
drop>50% from the highest either pre-incision or pre-excision level AND return to the normal range, 10-20 MIN
AFTER PARATHYROID EXCISION was considered a surgical success.

PTH has direct effects on bone resorption and promotes calcium resorption in the kidney and bowel. It also
promotes activation of vitamin D3 by hydroxylation in the kidney to form 1,25-dihydroxyvitamin D3. Parathyroid
hormone increases bone resorption, calcium reabsorption and calcium absorption.

Vitamin D is produced in the skin by sunlight and is ingested in the diet. It first undergoes 25-hydroxylation in
the liver and then 1a-hydroxylation in the kidney to form the active 1,25-dihydroxycholecalciferol (1,25-DHCC).
This last stage is under the control of parathyroid hormone (PTH) and phosphorus. A rise in PTH or a fall in
serum phosphate increases 1,25-DHCC synthesis.

The effects of 1,25-dihydroxyvitamin D3 complement those of PTH and serve to increase the serum calcium
levels. Its main function in calcium homeostasis includes an increase in the absorption of both calcium and
phosphate from the GUT. By the action of vitamin D, bone mineralisation and stabilisation is promoted. The
inorganic element of bone is resorbed through the actions of osteoclasts. It is laid down by osteoblasts.

Increasing levels of vitamin D inhibit the release of PTH from the parathyroid glands. This provides a negative
feedback mechanism as PTH is required for hydroxylation of vitamin D in the kidney.

Calcitonin is a peptide hormone produced in the C-cells or parafollicular cells of the thyroid gland. Calcitonin has
a half-life of 60–90 min. The C-cells sense an increase in the concentration of calcium in the serum and then
secrete calcitonin to bring about a reduction of calcium. Calcitonin 1) inhibits the action of OSTEOCLASTS and
therefore inhibits bone resorption and also 2) inhibits the REABSORPTION of calcium and phosphate ions by
the KIDNEY, promoting their excretion in the urine. Generally speaking, it opposes the effects of parathyroid
hormone. It is not involved with hydroxylation of vitamin D 3. Calcitonin can be used therapeutically for the
treatment of hypercalcaemia or osteoporosis.

In long-term hypercalcaemic syndromes the parafollicular cells can hypertrophy.

A total thyroidectomy does not actually have any significant skeletal effect. Similarly in patients with a medullary
thyroid carcinoma, in which there is an excess of calcitonin, no significant skeletal problems manifest.

 Hypercortisolism is associated with increased chances of bone fracture. Effect is due to

inhibiting of differentiation and apoptosis of OSTEOBLASTS in the bone.
 TSH ↑ bone production. Hypothyroidism causes increased bone mineral density. This is due to
the direct stimulatory effect of TSH on receptors in the OSTEOBLASTS. (hyperthyroidism 
decreased bone density)

Prolactin
Prolactin secretion is from the lactotroph cells of the anterior pituitary gland under the control of the
hypothalamus. The hypothalamic neurosecretory tuberoinfundibulum neurones of the arcuate nucleus in the
hypothalamus secrete DOPAMINE, which INHIBITS prolactin secretion from the anterior pituitary. It is the only
pituitary hormone whose control is inhibitory.

OESTROGENS stimulates the GROWTH of the lactotroph cells of the anterior pituitary leading to an increase in
prolactin secretion and also inhibit the release of dopamine, both of which lead to an increase in prolactin
concentration during pregnancy.

During pregnancy and the post-partum period PROLACTIN stimulates ENLARGEMENT of the breast mammary
glands and MILK PRODUCTION, while it inhibits gonadal activity, suppressing follicular stimulation and
menstruation.

In the post-partum period, during lactation, there are high levels of circulating prolactin hormone. The high
circulating levels of prolactin act as an inhibitor for the release of gonadotrophins [FSH and luteinising hormone
(LH)], which are necessary to stimulate follicle maturation and lead to ovulation and menstruation. This occurs in
the early post-partum period. After about 40 days post-partum, the prolactin sensitivity drops significantly and
gonadotrophins start increasing in concentration stimulating follicle maturation.

Prolactin levels can be RAISED in various conditions, some of which include physical and emotional stress,
exercise, following surgery, after a high protein meal. Pathological mechanisms leading to hyperprolactinaemia
include: a prolactin secreting tumour in the pituitary and treatment with dopamine receptor antagonists.

Cortisol

Cortisol is required in the LAST TRIMESTER, between weeks 30–32 to stimulate the production of LUNG
SURFACTANT in the fetus.

Phaeochromocytoma
Bronchodilation, tachycardia and paroxysmal hypertension are features of high circulating levels of adrenaline.

Excessive sympathetic discharge causes increased metabolism leading to weight loss.

Hepatic glucose production increases therefore giving rise to hyperglycaemia and glycosuria.

pituitary

The anterior pituitary contains five types of endocrine cells. These include somatotropes (GH); lactotropes
(PRL); gonadotropes (LH and FSH); corticotropes (ACTH) and thyrotropes (TSH). Depending upon the
histological appearance, these are classified as acidophils and basophils. Somatotropes and lactotropes are
acidophils while others are basophils.

Vasopressin (ADH) and oxytocin are synthesised in the hypothalamic nuclei and pass down axons to the
posterior pituitary where they are secreted into the systemic circulation.

Oxytocin is released by the posterior pituitary in response to suckling of the baby and is involved in the
EJECTION of milk from the breast and also CONTRACTION OF THE UTERUS back to its original, pre-pregnancy
size. The presence of increased oxytocin receptors in myometrial cells is responsible for the ONSET AND
PROGRESS OF LABOUR.

Renin –angiotensin–aldosterone system

Renin is produced by the JUXTAGLOMERULAR cells in the wall of AFFERENT arterioles, which, together with the
MACULA DENSA of the distal convoluted ducts, constitute the juxtaglomerular apparatus.

MACULA DENSA cells sense the concentration of sodium chloride in the DISTAL CONVOLUTED tubule. If the
sodium (Na+) level is low, the macula densa cells release prostaglandins, which trigger juxtaglomerular cells
lining the afferent arterioles to release renin into the bloodstream.

Renin is produced by the juxtaglomerular apparatus of the kidney in response to hypovolaemia, via three
mechanisms:

 increased catecholamine levels secondary to sympathetic stimulation from arterial receptors

 direct effect of hyponatraemia on the juxtaglomerular apparatus
 reduction of renal perfusion pressure via afferent arteriolar baroreceptors.
1
 Direct beta- -adrenoceptors stimulation

Shock leads to increase level of renin, which in turn activates angiotensin and in turn aldosterone. Renin
secretion is increased by any stimuli that decreases extracellular fluid volume, blood pressure or increase of
sympathetic output. Therefore, STIMULI that increase renin secretion include: sodium depletion, cardiac failure,
dehydration, constriction of the renal artery, hypotension, haemorrhage and an upright posture.

Renin is responsible for the conversion of angiotensinogen to angiotensin I. Angiotensin-converting enzyme is

responsible for the conversion of angiotensin I to angiotensin II (predominantly in the lungs).

The renin–angiotensin–aldosterone system is NOT ACTIVATED in patients who are induced with
ISOFLURANE and hypotensive anaesthesia is maintained. This approach is widely used to prevent
haemorrhage during surgery and has been reported as safe.
The effect of plasma potassium on renin secretion is independent and opposite of K action on aldosterone.

 Hyperkalaemia inhibits renin secretion, but stimulates aldosterone.

 Hypokalaemia stimulates renin and suppresses aldosterone.

Diuretics

 Loop of henle is a site of action of loop diuretics (Furosemide)

 PROXIMAL CONVOLUTED tubule is the site of action of CARBONIC ANHYDRASE inhibitor
diuretics.

Female reproduction
In women during menstruation, endometrial shedding happens due to a drop in estradiol and progesterone
levels. This drop in hormone levels signals the endometrium layer to shed, resulting in menstrual bleeding.

HCG is a glycoprotein hormone, produced in pregnancy, which is made by the EMBRYO soon after conception
and later by the SYNCYTIOTROPHOBLAST (part of the placenta). Its role is to prevent the disintegration of the
CORPUS LUTEUM of the ovary and thereby maintain progesterone production that is critical for a pregnancy in
humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of
the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG.

Neutralisation of hCG activity will result in disintegration of the corpus luteum, with subsequent death and
expulsion of embryo.

Progesterone is a steroid hormone produced in the luteal phase of the menstrual cycle and during pregnancy.
Progesterone is produced by the CORPUS LUTEUM and the PLACENTA and drops significantly after delivery.
Although the corpus luteum in the ovaries is the major site of progesterone production in humans,
progesterone is also produced in smaller quantities by the ovaries themselves, the adrenal glands and, during
pregnancy, the placenta.

The main cause of the change in respiration seen in pregnancy is the high levels of circulating progesterone.
This, increases the sensitivity of the respiratory centres of the hypothalamus to small increases in carbon
dioxide, A small rise in p(CO2) has the effect of a significant rise in minute ventilation and respiratory rate. This as
a result leads to hyperventilation and a lower normal p(CO2).

Progesterone inhibits lactation during pregnancy. The fall in serum progesterone with the
passage of the placenta seems to be the important event in establishment of lactogenesis. Furthermore,
progesterone administration inhibits casein and α-lactalbumin synthesis in vitro.

Once lactogenesis is initiated, PROLACTIN appears to be the key hormone in maintenance of milk
synthesis (galactopoiesis) and secretion.
Thyroid physiology
Thyroglobulin is synthesised within the follicular epithelial cells and secreted into the follicular lumen. It is an
important step in production of thyroid hormones.

Iodine is actively transported into the thyroid gland against a concentration gradient; the normal IODINE
concentration in the thyroid is 30 times greater than that in blood. Oxidation of iodine is done by thyroid
peroxidase.

Thyroid PEROXIDASE (TPO)

 first generates I2 by oxidising IODINE IONS present in the follicular lumen.

 then ‘organifies’ the generated I2 by covalently LINKING it with the TYROSINE residues present in
thyroglobulin. This step generates either a single or doubly iodinated species of tyrosine, termed
‘monoiodotyrosine (MIT)’ or ‘di-iodotyrosine (DIT),’ respectively. 1 MIT + 1 DIT produce T3, but most T3 is
produces in the periphery by T4 conversion. 2 DIT produce T4.

DEIODINASE converts T4 into T3 in PERIPHERAL tissues.

T4 is less active than T3. Its half-life is about 5-7 days (1 week). Its concentration is more than T3. Essentially
it serves as a RESERVOIR for T3 and in peripheral tissues it is converted into T3 by deiodinase enzymes.

T3 is metabolically active and has a shorter half-life. The half-life of T3 is only 1 day.

T3 is around three to five times more active on metabolism than T4. It has wide ranging effects on metabolism.
This includes increased oxygen consumption in every tissue in the body and stimulation of protein synthesis. It
affects both the synthesis and degradation of lipids, the net effect being a decrease in lipid stores. By influencing
the mechanisms by which cholesterol is eliminated from the body, it decreases plasma cholesterol levels. Owing
to its stimulatory effect on metabolic processes, it will also have the effect of increasing demand for coenzymes
and vitamins.

Thyroid hormones cause increased expression of Β-ADRENERGIC receptors in skeletal and cardiac muscle
leading to increased inotropic effect, with tachycardia and increased cardiac output.

Thyroid hormones increase oxygen consumption and the rates of ATP hydrolysis in the mitochondria, resulting
in increase in basal metabolic rate and heat production.

Thyroid hormone stimulates the mobilisation of fat from adipose tissues and increased lipolysis to cause
increased free serum fatty acids.

Thyroid hormones increase glucose absorption in the gastrointestinal system.

Thyroid hormones act in synergy with insulin for insulin-dependent glucose entry into cells.
Thyroid hormone increases glycogenolysis and gluconeogenesis in the liver, a similar action as
glucagon.

During PREGNANCY there is a TWO to THREE-FOLD increase in thyroxine-BINDING GLOBULIN

concentrations. It leads to an increase in TOTAL triiodothyronine and thyroxine concentrations.

Hyperparathyroidism
This patient has symptoms consistent with hypercalcaemia and isolated hypercalcaemia, the most common
finding in primary hyperparathyroidism, in her bloods.

The MAJORITY (85%) of primary hyperparathyroidism cases are caused by a single PTH-producing ADENOMA.
Excess PTH causes an increase in calcium resorption from the kidney and bone, leading to hyperparathyroidism.

Secondary hyperparathyroidism arises in the context of chronic kidney disease or vitamin D deficiency. Failure
of the kidneys to produce vitamin D or reabsorb calcium leads to chronically low serum calcium. This results in
hypertrophy of the parathyroid glands as they are stimulated to produce more PTH. Serum calcium remains low
as the kidneys are not able to resorb calcium in response to PTH, and therefore PTH levels remain elevated.

Tertiary hyperparathyroidism occurs post-renal transplant after a long period of low calcium, with
PARATHYROID gland stimulation and HYPERPLASIA. The parathyroid glands become AUTONOMOUS, no longer
responding to the serum calcium negative feedback loop. This results in raised PTH and raised calcium levels.

Aldosterone- Hyperaldosteronism
Aldosterone is a steroid hormone produced in the zona glomeruli adrenal cortex. Its main effect is to promote
water and sodium resorption in response to diminished circulating volume.

Excess secretion of aldosterone occurs in primary hyperaldosteronism and Conn syndrome. These are
characterised by HYPOKALAEMIA and metabolic ALKALOSIS.

Hyperaldosteronism causes alkalosis due to excretion of H+ ions.

Hyperaldosteronism causes hypokalaemia due to excretion of K+ ions.

Hyperaldosteronism causes hypertension due to sodium and water retention.

Aldosterone promotes magnesium excretion, thus hyperaldosteronism may lead to HYPOMAGNESEMIA.

Hypoaldosteronism or ACE inhibitors can cause hyper-magnesaemia and magnesium stone formation

Drugs with the suffix 'pril' are (angiotensin converting enzyme) ACE inhibitors. Lisinopril leads a reduction in
angiotensin II and aldosterone. Another similar drug of this type is ramipril.
Hyperkalaemia
“An 88-year-old woman is on the ward awaiting an emergency arthroplasty after a neck of femur fracture. She
was found at home after being on the floor for 24 hours. On the ward, she goes into cardiac arrest. Which
electrolyte abnormality is the most likely cause?” Hyperkalaemia

Hyperkalaemia causes cardiac arrest by precipitating ventricular tachycardia. This patient is a risk of multiple
factors that lead to hyperkalaemia. The long period on the floor can lead to rhabdomyolysis and renal failure.
Her fluid intake would also be low, causing acute kidney injury. These factors increase serum potassium and
can lead to ventricular tachycardia and cardiac arrest.

Addison’s disease
“A 12-year-old boy is taken to his GP with a history of increasing lethargy and fatigue. On examination he is
noted to have increased skin pigmentation in his skin creases and buccal mucosa. His blood tests show
hyperkalaemia and a mild acidosis. Which of the following tissue types is most likely atrophied?”  zona
fasciculata AND glomerulosa

The child is most likely suffering from Addison’s disease due to deficiency of glucorticoid and mineralocorticoid
hormone.

Zona FASCICULATE produces cortisol and is COMMONLY affected in Addison’s disease. 90% of the cortex is
destroyed before patients become symptomatic.

The Zona glomerulosa and fasculata are destroyed with SPARING of the zona RETICULARIS and MEDULLA.

A deficiency of aldosterone, as occurs in Addison’s disease, can produce hyperkalaemia and mild acidosis. In
primary cases adrenal cortex is defective while in secondary cases anterior pituitary does not produce enough
ACTH). Pigmentation differentiates between the two as high ACTH has a partial function
of melanin stimulating hormone.

excitable cells
The resting membrane potential of excitable cells is largely due to the selective permeability to POTASSIUM
ions. If the cell membrane were a perfect K + electrode, the membrane potential would equal the equilibrium
potential for K+ as predicted by the Nernst equation. In reality, the resting membrane potential is more positive
because of small contributions by Na+ channels, Cl– channels and non-selective cation channels.

Increasing the membranes conductance to potassium will result in K+ efflux and the membrane potential
approaching the value dictated by the potassium equilibrium potential, which is about −90 mV for neurones.

A value of +30 mV is near the Nernst potential for Na + ions.

A value of −30 mV is near the Nernst potential for Cl − ions in smooth muscle cells.
The Na+/K+ pump generates the ion gradient across the cell membrane (ie, high intracellular K +, high
extracellular Na+), BUT it is the back DIFFUSION OF K+ IONS through K+ channels that are open at rest, which
determines the RESTING membrane POTENTIAL.

Autonomic supply to the penis

P parasympathetic Points it up (erection)

S Sympathetic Shoots it out (ejaculation)

neuromuscular junction
When acetylcholine is released into the synaptic trough it attaches to acetylcholine-gated ion channels on the
postsynaptic membrane, causing them to open. The net effect of opening the channels is to allow large numbers
of SODIUM ions to pour inside the fibre. This creates a local potential inside the fibre that initiates an action
potential at the muscle membrane.

Acetylcholinesterase acts within the synapsis (within SYNAPTIC TROUGH) to deactivate acetylcholine. It is then
recycled into the presynaptic neurone. It does not enter the sarcoplasmic reticulum.

cerebral blood flow

In normal physiological conditions, the cerebral blood flow (CBF) is usually maintained by both pressure and
chemical autoregulation. The pressure autoregulation is facilitated by reflex constriction or dilatation of the
precapillary cerebral vasculature in response to MAP between 50–150 mm Hg.

CSF
Most of the CSF is produced by the choroid plexus, which is situated in the ALL ventricles (lateral, third and
fourth).

CSF is absorbed directly into the cerebral venous sinuses through the ARACHNOID VILLI, or GRANULATIONS, by
a process known as mass or bulk flow.

CSF contains MORE glucose than NASAL mucus; a positive glucose dipstix test of clear nasal discharge may
indicate a CSF leak although is not a reliable test. BETA-2 TRANSFERRIN is more reliable.

When normal, the CSF contains LESS glucose than in the BLOOD.

The composition of CSF is different to plasma. Of importance to mention are the concentrations of K+, Ca2+,
bicarbonate, glucose and protein which are LOWER in CSF than in plasma.

The CSF contains LESS lactic acid than in the blood.

The CSF contains LESS protein than in the blood. It has a protein content that is approximately 0.5% that of
plasma. The low protein content of the CSF prevents some proteins and amino acids acting as ‘false
neurotransmitters’.

The pH of CSF is slightly more ACIDIC (7.33, whereas that of plasma is 7.4) due to the higher pCO2 in CSF than in
plasma. The CSF is more acidic than plasma because the pH of CSF plays a critical role in the regulation of
pulmonary ventilation and cerebral blood flow.

CSF has a LOWER potassium content than that of plasma.

Nerve fibres

Aα fibres are important for proprioception, not pain transmission.

Aβ fibres are large myelinated fibres that usually respond to light touch.

Aδ fibres are small myelinated fibres with rapid conduction responsible for the rapid sharp localised PAIN.

B fibres are not involved in pain transmission and are part of the autonomic nervous system.

C fibres are small UNmyelinated fibres with a slow conduction speed. C fibre stimulation produce a slow dull
PAIN.

autonomic nervous system

Acetylcholine and noradrenaline are the two main neurotransmitters secreted in the autonomic nervous
system..

Both parasympathetic and sympathetic preganglionic neurones are cholinergic.

Most POSTganglionic SYMPATHETIC neurones secrete adrenaline or noradrenaline. Exceptions to this is

1. sweat glands (acetylcholine)

2. adrenal medulla → direct supply from PREganglionic fibres (through acetylcholine).

Adrenaline and noradrenaline act primarily on adrenergic receptors (alpha or beta).

Almost all postganglionic parasympathetic neurones are cholinergic.

The adrenal medulla secretes both adrenaline and noradrenaline in response to sympathetic stimulation.

The PARASYMPATHETIC neurons are formed at the upper and lower (sacral S2-4) extremities of the spinal
cord, in the mid-brain and hindbrain (fibres are carried by cranial nerves III, VII, IX and X)

There is NO neuronal FEEDBACK from the postganglionic to the preganglionic neuron.

All autonomic nerves are composed of TWO neurons, which synapse in the autonomic ganglia.

 The ganglia of the sympathetic nervous system are found in a chain either side of the spine.
 The ganglia of the parasympathetic nervous system tend to lie near the target organ (eg coeliac
ganglion which supplies the foregut).

The SYMPATHETIC NERVES originate in the spinal cord from segments T1– L2. They leave the spinal cord in the
anterior roots and pass to the paired sympathetic chains. The sympathetic chain extends the entire length of the
vertebral column. The PREganglionic sympathetic neurons have their cell bodies in the INTERMEDIO-LATERAL
horn of the spinal cord.

Sympathetic innervation to the ADRENAL MEDULLA is unique in the regard that there is NO synapse at ganglia
between the spinal cord and organ. The ‘preganglionic’ neurone innervates the Chromaffin cells of the adrenal
medulla (through acetylcholine), causing direct release of catecholamines into the bloodstream.

Neuro misc
Proprioception is conveyed in the DORSAL columns.

Spinal reflex activity can be modulated by the corticospinal tract. This explains why in an upper motor neurone
lesion there is the development of ‘spastic paresis in which there is increased tone due to uninhibited reflex
loops.

The LATERAL spinothalamic tract conveys temperature + pain sensation. Most neurones of the spinothalamic
tract DECUSSATE via the anterior white commissure to the contralateral side of the cord.

Neurons
Neurons are supported by glial cells in the central nervous systems. Examples of glial cells include: astrocytes,
oligodendrocytes, microglia and ependymal cells.

Dendrites transmit stimuli towards the cell body

Axons transmit stimuli away from the cell body

Neurons transmit action potentials more rapidly if they are myelinated.

Neurones transmit more rapidly if the axons are of larger diameter.

stroke

The primary motor cortex (or M1) is located in the

 dorsal part of the precentral gyrus

 anterior bank of the central sulcus.
The primary motor cortex works in association with premotor areas to plan and execute movements. M1
contains large neurons known as Betz cells , which send long axons down the spinal cord to synapse onto
alpha-motor neurones, which connect to the muscles. A stroke affecting this region will result in
contralateral weakness.

The cerebellar vermis is a posterior, midline cerebellar structure. A stroke affecting this region would cause
postural instability.

The occipital lobe is involved in visual processing. A stroke affecting this region would cause a contralateral
hemianopia (visual field defect).

The central sulcus (also known as the Rolandic fissure) is one of the major sulci. It is a potential space and is
not part of the brain parenchyma. It therefore has no function.

The primary somatic sensory (S1) cortex in the postcentral gyrus is the first and largest cortical receiving area
for the analysis of information from somatosensory receptors. S1 cortex is necessary for the conscious
awareness: (1) that a stimulus has occurred; (2) of stimulus quality; (3) of stimulus location; (4) of stimulus
amplitude; and (5) of stimulus duration. A stroke affecting this region would cause contralateral
paraesthesia.

Pain
Descending fibres modulate nociceptive inputs via the dorsal horn. It is a site of spinal integration.

Unmyelinated C-fibres (dull pain) transmit more slowly than myelinated A-delta (sharp pain)fibres.

Opioids act on µ receptors in the central nervous system and the gastrointestinal system, thus contributing to
their side-effect of constipation.

Naloxone is the correct agent to reverse the effects of opioids.

Glycine is an inhibitory neurotransmitter.

The thalamus serves as a RELAY station, receiving pain stimuli from ascending sensory tracts.

The POSTcentral gyrus receives pain stimuli.

knee-jerk reflex
The knee-jerk reflex is the best-known example of a MONOsynaptic STRETCH reflex. Passive stretch of the
intrafusal spindle fibres through tapping the tendon with a tendon hammer results in generation of afferent
action potentials. These are transmitted via the dorsal roots of the spinal nerves to the ipsilateral ventral grey
matter where the ONLY synapse
 1. with the EFFERENT neurone. The action potential is transmitted through the ventral nerve roots via an
alpha-motor neuron, which synapses with the motor endplate of the muscle fibres of the knee
extensors.
2. with inhibitory interneurons that result in relaxation of the ipsilateral knee flexors.

The knee jerk is supplied by the L3 and L4 nerve roots.

Skin receptors
MERKEL’S skin receptors are slowly adapting skin receptors that detect pressure, texture, and low frequency
vibration and can be appropriately evaluated by static two-point discrimination.

MEISSNER corpuscles are rapidly -adaptive receptors to light touch and vibration.

PACINIAN (‘lamellar’) corpuscles are rapidly adapting and especially detect vibration.

RUFFINI corpuscles detect stretching of the skin.

FREE NERVE ENDINGS receive sharp acute, and chronic slow pain sensation.

Respiration
Rhythmic discharge of neurons in the MEDULLA and PONS (the cardiorespiratory centre) produces automatic
respiration, and so transection of the brainstem BELOW the medulla stops the respiration.

Spontaneous respiration is not dependent on the vagus nerve.

The respiratory muscles are supplied by C3–C5 segments (diaphragm) and thoracic segments for intercostal
and flat muscles of the thorax. A transection at a thoracic level will not affect all of the muscles of respiration.
Spontaneous respiration will still be possible.

(C3,4,5 keep the diaphragm alive!)

Cardiovascular + respiratory physiology

Exercise

↑CO:

 ↑↑ HR (x2)
 ↑↑↑ SV (x3)
 ↓ SVR  ↓ or normal DAP

↑BP:
 ↑↑SAP (because ↑SV, ↑ contractility- ejection velocity)
 ↓ or normal DAP because ↓SVR (β2 effect), ↓ PVR (pulmonary vascular resistance) (β2 effect)

There is approximately a two-fold increase in oxygen consumption , therefore the mixed venous blood O2
saturation falls to 50%

↑PCO2

Right shift in oxygen dissociation curve

↑ myocardial contractility

↓ End-Diastolic volume ( decreased due to the higher heart rate)

Normal mixed venous blood satO2 (SVO2)

60-80%

Normal arterial blood satO2 (SpO2)

95-100%

VO2 max
o Measured with cardiopulmonary exercise test (CPET)
o Anaerobic (lactate) threshold reached at 50% of VO2 max(50-60% in untrained; more in trained)of
VO2max
o Normal VO2 max: 35-40ml/kg/min (untrained)
o Normal anaerobic threshold: 17-20ml/kg/min (untrained)
o Cardiomyopathy is RELATIVE (NOT absolute) contraindication for CPET
o Predicts mortality and morbidity
o Triage patient to the appropriate ward (simple, HDU, ITU)
o If VO2max >20 ml/kg/min  no increase risk post-op for death/morbidity
o VO2max <15 ml/kg/min  ↑ risk post-op
o Vo2max >11 but <15 with evidence of myocardial ischaemia OR VE/ VO2 >35 ml/kg/min  HDU
o VO2max <11 ml/kg/min  ITU, Very high risk for post-op complications

Physiological hypervolaemia of pregnancy

 Late pregnancy = haemodilution: ↑blood ↓Hct,

 blood volume increased by 50% (150%) because ↑ overall RBC mass AND ↑↑↑ Plasma
 ↓Hct AND ↓ Hb concentration (30-35Hct; 10-11Hb)
 More blood loss is required (almost 30% vs 15% in normal) to produce symptoms of hypovolaemic shock
(because blood more dilutes):
o In shock blood will be diverted from the uterus to the mother’s circulation fetus is the first to suffer
o Fluid replcament must be aggressive and early
o Pregnant must be positioned left lateral so as to prevent compression of the IVC by the uterus
 pregnancy does NOT reduce the need for blood transfusion, because they have more diluted blood (for every
ml lost less RBC/ Hb lost vs normal woman) BUT have already a lower Hb level (more in normal women)
 Does NOT increase risk of pulmonary oedema
 Does NOT complicate management of head injury

Most effective defence against hypervolaemia

ANP- Due to Atria stretching

Direct mechanism:

1. ↑ Peripheral vasodilation (↓SVR)

2. ↓ aldosterone
3. ↑ GFR
Another mechanism (little effect) is venous dilation (stores the extra blood) (Lungs store ~500ml)

Baroreceptors affect pressure NOT volume

cardiac action potential

Phase 0: rapid sodium influx (depolarization)

Phase 1: efflux of potassium

Phase 2: efflux of potassium + slow influx of calcium (plateau = 500msec))

Phase 3: efflux of potassium ( closes late → hyperpolarisation)

Phase 4: sodium/ calcium efflux, POTASSIUM /chloride influx (“LEAKS”) → maintains resting potential)

SAP rises when

 ↑Arterial rigidity/↓ arterial compliance

 ↑Stroke volume
 ↑Ejection velocity (contractility-inotropic effect)
 ↑Diastolic pressure of the preceding pulse (DAP)

DAP rises when

 ↑ arterial compliance (rigidity ↓ DAP)

 ↑ SVR
 ↑ HR
mean pulmonary arterial pressure
Normal mean pulmonary arterial pressure is 15 mmHg. This is the hydrostatic pressure generated by the right
ventricle and is 1/6th that of systemic arterial pressure generated by the left ventricle.

90 mmHg is the normal systemic mean arterial pressure.

The pulmonary circulation lacks high resistance arterioles and so the pressure drop between the pulmonary
arteries and capillaries is minimised.

Cardiac output

CO = SV x HR

 ↓ when standing up (↓ venous return  baroreceptors compensatory ↑ SVR)

 ↓ when stepping out of a hot bath and stands up (peripheral vasodilation)
 ↓ baroreceptor effect in elderly- antihypertensive  vasovagal syncope/ orthostatic hypotension

↑ in sympathetic stimulation

↑ when vagus is cut/ heart transplanted

↑ in pregnancy (both early and late, max by 20 weeks)

↑ when eating (↓ in starvation)

↑ when ↑end diastoling volume (sterlings law)

↑ with decreased blood volume on the carotid sinus (baroreceptors→ inactive/ send fewer neural pulses ↓
inhibitory effect on the vasomotor center in the brainstem ↑ sympathetic  ↑CO, ↑venous return)

Cardiac output is increased only short-term when arriving at high altitude.

Flow through the vessel (poisseille law)

Directly proportional to the pressure head of flow (pressure gradient)

4
Directly proportional the r  most important

Inversely proportional to the viscosity

Inversely proportional to the length of the tube

Ejection fraction
Ratio of Stroke volume to end diastolic volume

EF= SV/EDV

Normal EF = 60%

Blood flow of important organs

Kidneys→ 420ml/100g/min, 25% of CO

Heart→ 84ml/100g/min (overall 5% of cardiac output)

Liver→ 57.7/100g/min, 25% of CO

Brain→ 54ml/100g/min, 15% of CO

Skin→ 12.8ml/100g/min (overall 5% of cardiac output)

Bronchial circulation  2% of CO

Skin, bone, heart 5%

Muscles, brain 15%

Kidney, liver 25%

Cardiac index

CO/ body surface area

Allows CO to be compared b/w different patients

2
Normal CI is 2.5-4 L/min/m

Greatest contributor of SVR

Arterioles

MAP – CVP
Systemic vascular resistance= ( cardiac output )
×80.

Histamine causes reduced peripheral resistance (via vasodilatation and increased capillary permeability),
resulting in increased cardiac output
ECG “numbers”
Small square (1mm)  0.04 sec

PR → 0.12-0.20s (120-200msec), same level as ST

Very short PR + Delta waves → Wolf-Parkinson-White

Prolonged PR  first degree block

QT →0.4sec (400msec)

 Affected by rate  adjust with QTc (QT adjusted for 60bpm rate)
 Prolonged in: hypokalaemia, hypocalcaemia, hypothermia, head injury, long QT syndrome,
amiodarone, tricyclics
 Shortened in: hypercalcaemia, hyperkalaemia, digoxin, genetic short QT

ST → 0.08 sec (80 msec; 1/5 of QT)

 Saddle shaped widespread ST elevation  pericarditis

 ST depression in subendocardial infract
 ST elevation in transmural infract

On a standard-calibration ECG trace, each ‘large square’ represents 200 ms (or 0.2 s). . By dividing 300 by the
number of large squares between R waves, the number of beats per minute is found. In this case,
300/3 = 100 bpm.

There are several methods for calculating the heart rate from an ECG. The 300 method as described in the
answers here works well for regular rhythms, but for irregular
traces, often the 6-s method is used – in 6
s (30 big boxes), count the number of R waves and multiply this by 10.

Heart blocks
Most important blocks:

At SA node  SA nodal blocks

Below AV node  infra Hisian blocks (in bundle of HIS)

3rd degree block: escape rhythm. An accessory pacemaker activates ventricles independently.
  2 rhythms in ECG. Regular P to P interval and regular R to R interval.
 VARIABLE PR interval- no relationship b/w P and QRS ( hallmark of complete block)

LBBB associated with: coronary artery disease, hypertension, dilated cardiomyopathy

Early repolarisation of ventricular fibres  “J” wave and ST elevation

Left bundle branch block

Left bundle branch block is caused by a conduction abnormality of the left bundle of His. It results in a broad
QRS complex. Left bundle branch block also results in the

 S wave ‘W’ → anterior lead

 R wave ‘M’ → lateral lead

Right bundle branch block

Right bundle branch block is caused by a conduction abnormality of the right bundle of His. It results in a broad
QRS complex.

 S wave ‘W’ → lateral lead

 R wave ‘M’ → anterior lead

Pulmonary vascular resistance

↑ when ↓O2 (Euler-Liljestrand mechanism)

↓ with exercise (pulmonary pressure rises and leads to recruitment and distension of pulmonary vessels  ↓
in resistance)

↓ with ↑FiO2

↓ with aminophylline (bronchodilator- vasodilator)

↑ at high altitude. Pulmonary arterioles constrict in response to hypoxia (known as the Euler–Liljestrand
mechanism), to re-direct blood flow to well ventilated lung regions.

↓ during space flight would, if anything, as blood flow becomes more uniform.

Supraventricular tachycardia
Arise from SA node or Atria (AF, atrial flutter, atrial tachycardia, sinus tachycardia)
May arise from AV node through

1. atrioventricular re-entrant tachycardia or

2. atrioventricular nodal re-entrant tachycardia

Sinus tachycardia = elevated resting heart rate eg in a transplanted heart with denervated heart (vagi cut)

Carotid sinus massage (dangerous if atheromatosclerosis) OR pressure in the eye OR wooden tongue
depressor can be used to restore the rhythm

Atrial fibrillation

Caused by multiple re-entrant circuits in the atrial myocardium

Sinus arrhythmia

In order for a rhythm to be in sinus rhythm, there needs to be a P wave, followed by a QRS complex and a T
wave. Sinus arrhythmia, often seen in the young, resembles a normal sinus rhythm, except that there is
beat-to-beat variation in the rate with respiration.

Myocardial blood flow

250ml/min at rest  5% of CO (same with skin)

 Very dependent on arterial pressure

 ↓ with pain
 ↓ with ADH
 No blood flow in systole
 ↑ in diastole
 ↑ with nitrates

The right coronary artery supplies a third of the blood to the left ventricular muscle – the inferior
wall.
Autoregulatory mechanisms are very important in matching metabolic demand of cardiac myocytes to blood
flow. Additionally, coronary vessels have both α- and β-adrenergic receptors so can respond to
sympathetic/parasympathetic stimulation.

Kussmaul sign
Normally during inspiration (↓ in intrathoracic pressure) the JVP drops
In impaired right ventricular filling (tamponade/ restrictive pericarditis  Paradoxical raised JVP in
inspiration

JVP waveform
: acxvy

A  atria contraction. Happens just before carotid pulse during late ventricular diastole

C right ventricular contraction and bulging of tricuspid into the RA (pressure rises). Happens same time with
carotid pulse during early ventricular systole

X rapid atrial relaxation and filling (pressure drops) during mid ventricular systole

V continued atrial filling with a closed ricuspid valve (pressure rises) during late ventricular systole

Y tricuspid opens, blood into RV, pressure drops during early ventricular diastole

Atrial fibrillation: absence of a waves

Tricuspid stenosis: high a waves, slow y

Sinoatrial heart rhythm

SA node spontaneous fires at 140/min BUT resting vagal (parasympathetic) tone reduces it to normal range
(60-100)

During sleep vagal tone is increased and sympathetic tone decreased  Slower heart rate

Inspiration increases heart rate and decreases blood pressure via stretch receptors in the lung and the
respiratory centre in the medulla.

The oculocardiac reflex (Aschner–Dagnini reflex) is a decrease in heart rate associated with compression of
the eyeball.

After a meal heart rate would be expected to increase. One possible explanation for this is a response to the
increased cardiac output required due to the increased metabolic demand (and therefore blood flow) to the
digestive tract.

Baroreceptors in the carotid and aortic sinuses produce a reflex response to hypertension by inhibiting the SA
node and decreasing the heart rate. Clinically this can be utilised by carotid sinus massage as a first step in
managing superventricular tachycardias.
Cerebral blood flow

Cerebral blood flow averages 50–100 ml per min per 100 g of brain. This is equivalent to approximately
700 ml/min or 15% of resting cardiac output on average.

Cerebral blood flow is sustained in preference to other organs to which blood flow is diminished when there is
loss of blood. Mean arterial pressure must decrease to less than 50 mmHg before there is a decrease in
cerebral blood flow. This does not occur until there is a loss of over 40% of the circulating volume in the
normal individual (2 L in a 75 kg man).

Noradrenaline would increase mean arterial blood pressure, in normal circumstances this would NOT be
expected to alter cerebral blood flow. However, in a patient with very low blood pressure it may be of help.

A reduction in p(O2) would increase cerebral blood flow. This is through autoregulatory mechanisms
that control the calibre of the arterioles.

Increase in arterial p(CO2) would increase cerebral blood flow. This is through autoregulatory mechanisms that
control the calibre of the arterioles.

Raised intracranial pressure will reduce cerebral blood flow as the increased pressure within the fixed space of
the cranial vault will result in compression of the vascular spaces and therefore increased vascular resistance.

Inspiration and heart function

Inspiration ↑ heart rate and ↓ blood pressure via stretch receptors in the lung and the respiratory centre in
medulla  blood flow to the lung is ↑ so the additional O2 can be obtained

Negative intra-thoracic pressure generated during inspiration causes increased venous return to the heart.
Blood returns to the heart from the lower limbs via the action of the calf muscle pumps, valves in the veins of
the leg, and the effect of negative intra-thoracic pressure generated during inspiration. Anything causing the
intra-thoracic pressure to become less negative will decrease the venous return to the right atrium. Tension
pneumothorax, positive pressure ventilation and forced expiration all cause this effect, and therefore reduce the
venous return.

During inspiration, the negative intrathoracic pressure causes pooling of blood in expanding
pulmonary vessels and a delay of flow to the left ventricle. Thus, systolic pressure falls as cardiac
output falls momentarily.

Inspiration: ↑HR, ↓BP, ↓cardiac output

Baroreceptors
Impulses transmitted through vagus nerve (parasympathetic)

Aortic:
  Carotid sinus (bifurcation of carotid artery)→ sinus nerve (glossophayngeal)
 Aortic arch → depressor/aortic nerve (branch of vagus nerve)

The carotid sinus nerve (Hering's nerve) is a small branch of the glossopharyngeal nerve that innervates the
carotid sinus and carotid body.

Venous:

 RA/LA (chief in Hypervolaemia),

 entrance of IVC/ SVC,
 pulmonary artery

Normally have a resting tone:

increased firing in hypertension (when stretched// “hyperfiring”): ↑ in vagal tone, ↓ sympathetic

Decreased firing in hypotension (“hypofiring”): ↓ in vagal tone , ↑ sympathetic

Cardiovascular drugs

Adenosine→ makes bradycardia

Clinically intravenous (IV) adenosine is used to terminate atrioventricular node-dependent tachycardias as its
action is to reduce signal transduction through the AVnode.

Adenosine is a naturally occurring purine nucleoside that forms from the breakdown of adenosine triphosphate
(ATP). The major therapeutic use of adenosine is as an antiarrhythmic drug for the rapid treatment of
supraventricular tachycardias. Its supression of atrioventricular conduction makes it very useful in treating
paroxysmal supraventricular tachycardia in which the AV node is part of the reentry pathway (as in Wolff-
Parkinson-White Syndrome).Adenosine is not effective for atrial flutter or fibrillation.

Verapamil (CCB) → ↓contractility, ↓conduction in AV node, bradycardia, ↓BP

Salbutamol→ beta-effect  ↑ HR, ↓SVR (b2 effect)

CVP

CVP is increased by either an increase in venous blood volume or by a decrease in venous compliance.

 A decrease in cardiac output either due to decreased heart rate or stroke volume (e.g., in ventricular
failure) results in blood backing up into the venous circulation (increased venous volume) as less blood is
pumped into the arterial circulation.  The resultant increase in thoracic blood volume increases CVP.
 An increase in total blood volume as occurs in renal failure or fluid retention through activation of the
renin-angiotensin-aldosterone system increases venous pressure.
 Venous constriction caused by sympathetic activation of veins, or by circulating vasoconstrictor substances
(e.g., catecholamines, angiotensin II) decreases venous compliance, which increases CVP.
 A shift in blood volume into the thoracic venous compartment that occurs when a person changes from
standing to supine position increases CVP.
 Arterial dilation as occurs during withdrawal of sympathetic tone or with arterial vasodilator drugs causes
increased blood flow from the arterial into the venous compartments. This increases venous blood volume
and CVP.  This is what occurs when the heart is functioning normally. 
o It is important to note, however, that arterial dilation in ventricular failure leads to a
decrease in CVP instead of an increase.  This occurs because the arterial dilation
decreases afterload on the ventricle leading to an increase in stroke volume.  Ventricular
stroke volume is more strongly influenced by afterload when the ventricular is in failure than
when it has normal function.
 CVP is also increased during a force expiration, particularly against a high resistance (as occurs with a
Valsalva maneuver) due to external compression of the thoracic vena cava as intrapleural pressure rises.
This mechanical compression of the vena cava functionally reduces the compliance of the vena cava.
 Muscle contraction, particularly of the limbs and abdomen, compresses the veins (i.e., decreases
compliance) and forces blood into the thoracic compartment, thereby increasing thoracic blood volume and
CVP.

Reduced in all types of shock EXCEPT cardiogenic

Hypertension Does NOT alter CVP

Central venous pressure (CVP) can be estimated by examining the height of the pulsation in the internal
jugular vein. The height of the pulsation (in cm) should be compared with the angle of Louis as the patient sits
at 45° to the horizontal.

 CVP is a measure of right atrial (filling) pressure as there is minimal vascular resistance between the internal
jugular vein, or the inferior vena cava (IVC) and right atrium (and the right ventricle in diastole if the
tricuspid valve is properly open).
 CVP under normal circumstances is an approximate measure of left atrial filling pressure because right
atrial pressure is similar to left atrial pressure. However, left atrial pressure might be higher under some
circumstances (eg mild LV failure). So CVP cannot be a reliable measure of left atrial pressure under all
circumstances.
 If an actual pressure in the LA was required a wedge pressure would be an estimate (it is about 0.5–1 cmH 2O
greater, generally) using a Swan–Ganz catheter. This is done less and less and echocardiography now
provides a surrogate approach.

The zero measurement of CVP is taken at the level of the right atrium. This is somewhat arbitrary and so one-
off measurements are not very useful unless there is a very low CVP indicating profound hypovolemia.

It is more useful is to measure the changes in CVP occurring during and after the administration of a bolus of
200 ml of colloid intravenously, rather than a one-off reading:

 In hypovolemia, there will be only a very small transient change in CVP.

 In normovolaemia there will be a rise in CVP, which will be sustained for 10 minutes or so.
 In hypervolemia the rise in CVP will be sustained for longer.
This is because an administered colloid bolus will distribute itself in the circulation. As starting effective
circulating volume is greater an administered colloid bolus will generate a more sustained rise of CVP as venous
capacitance will be progressively attained.

cor pulmonale

= abnormal enlargement of the right side of the heart

Histamine
↓ SVR (peripheral vasodilation) which leads to ↑ cardiac output

CO = SV x HR

BP = CO x SVR  MAP-CVP = Co X SVR  CO = (MAP-CVP)/SVR

Acidocis

↓ myocardial contractility  ↓ SV  ↓CO

SAME with alkalosis, hypoxia, ↑ lactate etc

% of blood
Total blood volume = red cell volume + plasma volume.

7% of BW: Blood volume is around 5 litres in a typical 70 kg man.

An average man has a higher blood volume than an average woman

Carotid body
Chemoreceptor

Behind carotid bifurcation

2000 ml blood /100g (same the aortic body)

Chiefly stimulated by ↓ of PaO2  ↑ ventilation

Can also be stimulated by ↑PaCO2 or ↓pH

Extracellular volume 
Higher Na, Cl, HCO3 levels than Intracellular fluid
NO

NITRIC oxide (NOT nitrous oxide)

 Relaxes smooth muscles (bronchi, vessels, GI)
 Maintains vascular integrity
 ↓ proliferation & ↓migration of smooth muscles
 Plays critical role in haemostasis  normally inhibits platelet adhesion  prevents excessive clot
 Made by macrophages, lymphocytes, neutrophils

D5W

<100 ml remain in vessels (goes to both ICF and ECF)

0.9Saline

1/4 remains in vessels (only goes to extracellular space)

Hypertonic NaCl

Like 0.9% N/S, it goes 1/4 intravascular and 3/4 extracellular. Due to its high osmolarity will draw additional
water (from the intracellular compartment) to interstitial compartment  TISSUE OEDEMA (dangerous in
brain→ brain oedema)

Hypo-Hyperthermia

The J-wave may be present on the ECG in patients with hypothermia and is an additional upward peak
immediately following the QRS complex.

Tachycardia, much like a reduction in the RR interval, is an ECG feature of hyperthermia.

Serotonin
Vasoconstriction  improves haemostasis

Released by PLTs

RBCs
Live 120 days

Broken down in spleen, liver, bone marrow

No nuclei (immature erythrocytes contain DNA but this is usually only found in the peripheral circulations in
small amounts, they are called reticulocytes (<2% of total RBCs)
No mitochondria

No aerobic metabolism

Use Glucose (independent of insulin) for ANAerobic metabolism (Cori cycle)

Cerebral blood flow

15% of cardiac output ( 700ml/min) BUT is 2% of bodyweight

↑ by hypoxia or hypercapnia, ISOFLURANE

↓ by high PaO2,

Isoflurane (general anaesthetic)

↑ cerebral blood flow

Acute blood loss

Reactive/ secondary thrombocytosis

Renin secretion is increased due to renal hypoperfusion.

The rate of oxygen extraction by the peripheral tissues is increased (right shift) in response to acute blood loss

ANS has little effect in

Brain,

Aortic balloon pump

Inflate during diastole  ↑ coronary blood flow

Deflates in systole  ↑ CO due to ↓in afterload (vacuum effect)

SUM EFFECT  ↑ in both coronary artery circulation and blood pressure

Used in post cardiothoracic surgery, in weaning a patient of the bypassing machine (when cardiac tissue was
injured perioperatively)

Dopamine
LOW  D1, D2 (splachnic vasodilation, mild inotropic)

Medium  b effect (great inotropic)

High  a effect (vasoconstriction)

PE ECG sign
S1Q3T3 (only with large embolus)

Prominent S in 1

Q in 3

Inverted T in 3

Atrial flutter
2:1 regular conduction ratio  ventricles ½ of atria rhythm

Atrial flutter is a supraventricular tachycardia caused by a re-entry circuit within the right atrium. This ECG trace
is regular (unlike atrial fibrillation) and the isoelectric line has the saw-tooth appearance typical of atrial
flutter.

Body flyid distribution

Pulmonary embolism

Sinus tachycardia is the most common ECG finding associated with pulmonary embolism.
changes associated with a large pulmonary embolus

 ‘S1Q3T3’ pattern, with a prominent S wave in lead I, a Q wave and an inverted T wave in lead III.
 T wave inversion in leads V1–V3

Pericarditis
Pericarditis is inflammation of the pericardium. Pericarditis results in

 widespread saddle-shaped S-T elevation in the limb and chest leads

 P-R depression.
  Tachycardia

myocardial infarction

Acute anterior myocardial infarction is characterised by ST elevation in leads V1–V6, with hyperacute
(peaked) T waves in these leads. ST elevation may extend to leads I and aVL. There may be reciprocal ST
depression in leads III and aVF.

The broad QRS complex left bundle branch block W and M notching pattern in the anterior and lateral
leads, respectively, can also indicate an anterior myocardial infarction.

Inferior myocardial infarction is characterised on the ST segment elevation in leads II, III and aVF, with
reciprocal ST depression in leads I and aVL.

vital capacity
Vital capacity (VC) is 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. In women
it is 50–60 ml/kg and in men 70 ml/kg.
For a 25-year-old man, who is normally fit and well and weighs 70 kg Vital capacity (5 l) = inspiratory reserve
volume (3 l) + tidal volume (0.5 l) + expiratory reserve volume (1.5 l)

Total lung capacity is vital capacity + residual volume.

Vital capacity is reduced by pain as it leads to a decrease in respiratory effort.

Vital capacity is proportional to body surface area.

Vital capacity changes with posture. It increases with standing and decreases when supine.

Vital capacity decreases with advancing age.

Males have on average a 20–25% greater vital capacity than females.

pulmonary ventilation

The respiratory centre is located in the medulla.

Carotid body chemoreceptors respond to hypoxia to stimulate the respiratory centres in the medulla. This
increases pulmonary ventilation.

1. Acidosis ↑ ventilation. Alkalosis does not stimulate chemoreceptors

2. Hypoxia ↑ ventilation
3. Hypercapnia ↑ ventilation (leads to the stimulation of central chemoreceptors)
Central chemoreceptors, located in the ventral medulla, are the most important stimulus for respiration.

They respond to increased H+ concentration of cerebral extracellular fluid (which is directly linked to
CSF). H+/HCO3– cannot easily cross the blood–brain barrier, but CO 2 does so readily. This frees H+ ions, causing a
low CSF pH and stimulates the central chemoreceptors to fire.

Decreased arterial pH stimulates peripheral chemoreceptors in the aortic arch and carotid bodies to fire, but
these are less important in stimulating respiration.

Chemoreceptors respond to increased Pa(CO2), not decreased p(CO2).

Peripheral chemoreceptors in the aortic arch and carotid bodies are sensitive to arterial oxygen levels. In
hypoxia, they will stimulate the respiratory centres to increase ventilation, leading to a decreased p(CO2) and a
subsequent respiratory alkalosis.

Hyperventilation causes hypocapnia, which causes cerebral vasoconstriction leading to decreased cerebral
blood flow. This mechanism can be used therapeutically in hypocapnic ventilation to treat cerebral oedema.

Basal metabolic rate increases during hyperventilation.

Hyperventilation causes hypocapnia. The loss of CO2 causes a respiratory alkalosis. As pH increases, calcium
ions have a greater affinity for albumin binding, decreasing the level of free serum calcium. This is because H+
ions compete with calcium ions for albumin binding sites, and the loss of H + results in more binding sites for
calcium ions to occupy. This hypocalcaemia is what causes the perioral and digital paraesthesia seen in
hyperventilating patients.

Pulmonary gas exchange

Gas exchange can occur in the final 7 branches of the bronchoalveolar tree

The CONDUCTING zone is made up of the FIRST 16 branches. Its function is to warm and moisten air, filter air,
and assist in phonation.

About 1.5–2% of O2 is dissolved in plasma.

CO2 is much more water soluble than oxygen.

Pulmonary oedema decreases rate of diffusion. According to Fick’s Law, rate of diffusion is proportional to
surface area and concentration gradient and inversely proportional to diffusion distance. Pulmonary oedema
increases the diffusion distance as there is more fluid in the extracellular space between the alveoli and the
capillaries.

A hyperbaric gas mixture (assuming at least the same concentration of O2 as air) would increase partial pressure
of O2 and increase rate of gas exchange.
COPD does NOT affect rate of diffusion as the diffusion distance does not change. COPD does cause air
trapping as there is airway collapse on expiration.

Increase in ventilatory rate will maintain a high O2 gradient to assist gas exchange.

Exercise increases tidal volume and respiratory rate, increasing pulmonary ventilation.

In a normal person each 100 ml of blood contains about 15 g of haemoglobin and each gram of haemoglobin
can bind to 1.34 ml of oxygen when it is 100% saturated (15 × 1.34 = 20 ml O2/100 ml blood ).

pulse oximetry

 Carbon MONOXIDE binds to haemoglobin to form carboxyhaemoglobin. The presence of

carboxyhaemoglobin leads to INACCURACY in the pulse oximeter, as it will read a falsely high oxygen
saturation.

 Fails to indicate adequate tissue oxygen delivery. Adequate oxygen delivery to tissues depends on overall
haemoglobin content as well as cardiac output. For example, a patient in shock may have adequate O 2
saturation, but oxygen delivery to tissues will be poor as tissue perfusion is inadequate.

The relationship between oxygen carriage and pulse oximetry is a sigmoid curve.

The adequacy of ventilation is better reflected by the p(CO2).

oxygen-haemoglobin dissociation curve

The oxygen-haemoglobin dissociation curve is sigmoidal. Haemoglobin becomes saturated at high partial
pressures of oxygen. Haemoglobin’s affinity for oxygen is high when oxygen tension is very high and also where
it is very low. This produces the two plateaus of the curve. The steep section between the plateaus reflects a
decreased affinity for oxygen, and in this range oxygen dissociates and is delivered to tissues when it is required.

Surrounding environmental factors affect haemoglobins’ affinity for oxygen relative to its partial pressure. This is
the Bohr effect in metabolically active tissue, the oxygen-haemoglobin dissociation shifts to the right, ie for a
given partial pressure of O2, oxygen will more readily dissociate. This situation means more oxygen is delivered
into the tissues.

Active metabolic tissue will have a decreased pH (lactic acid production), increased temperature, increased 2,3-
DPG levels and increased CO2 levels. → CURVE TO THE RIGHT

The INVERSE of any of these factors will shift the curve to the LEFT. A shift of the oxygen dissociation curve to
the left is characteristic of fetal haemoglobin.

MYOGLOBIN is to the LEFT of adult Hb. (keeps oxygen for when its needed for the muscle)
FETAL HB curve is to the LEFT of adult Hb curve. When compared with adult haemoglobin, fetal haemoglobin is
composed of two alpha and two gamma chains, instead of the usual two alpha and two beta chains of adult
haemoglobin. This arrangement assists in the transfer of oxygen across the placenta from the maternal to the
fetal circulation. The corollary of this is that fetal tissue oxygen levels have to be low to permit the release of
oxygen from the haemoglobin.

Calcium does NOT affect the oxygen–haemoglobin dissociation curve.

Anaemia will NOT affect the oxygen–haemoglobin dissociation curve.

pleural fluid
The normal amount of pleural fluid is 2–10 ml. It acts as a lubricant to allow the visceral and parietal layers to
move smoothly against each other during respiration.

Carboxyhaemoglobin
Carbon monoxide has a high affinity than oxygen for haem groups. It binds to the intracellular cytochrome
system, causing cellular dysfunction.

The amount needed to cause poisoning is low enough that it does NOT alter the amount of oxygen physically
dissolved in the plasma and hence the PaO2. HOWEVER, ABGs will usually reveal a metabolic acidosis in
patients with serious poisoning.

At a 50% carboxyhaemoglobin level the patient will experience hallucinations, ataxia, coma then death.

Carbon monoxide has a 240-fold greater affinity for haemoglobin than oxygen.

Carboxyhaemoglobin does not readily dissociate, UNLIKE oxyhaemoglobin.

Total lung capacity

Total lung capacity is vital capacity + residual volume.

Functional residual capacity

The FRC is the volume of air in the lungs at the end of passive expiration. Functional residual capacity is
residual volume + expiratory reserve volume.

Emphysematous lungs are more compliant, resulting in a greater FRC.

Fibrosing alveolitis (idiopathic pulmonary fibrosis) is a restrictive lung disease. FRC is reduced.

General anaesthesia reduces FRC by approximately 20% due to loss of inspiratory muscle tone.

FRC is reduced in obesity.

FRC is reduced following abdominal surgery due to postoperative pain causing splinting of the diaphragm

FRC decreases when someone is supine and INCREASES ON STANDING.

FRC is less than 50% of the vital capacity. It is approximately 2.5 litres in a healthy adult man
The residual volume (and therefore functional residual capacity and total lung capacity) cannot be measured
directly by spirometry. They are measured by either whole body plethysmography, or by using the helium
dilution or nitrogen wash-out techniques.

Spirometry traces

Spirometry traces are easy to understand if you remember the following two rules:

(1) There are four lung volumes and five capacities that you need to remember.

(2) A capacity is made up of two or more lung volumes.

The four lung volumes are:

(1) Tidal volume = volume of air inspired or expired with each normal breath in quiet breathing; approximately
500 ml.

(2) Residual volume = that volume of air that remains in the lung after forced expiration.

(3) Inspiratory reserve volume = extra volume of air that can be inspired over and above the normal tidal
volume. (3L)

(4) Expiratory reserve volume = extra volume of air that can be expired by forceful expiration after the end of a
normal tidal expiration (1.5L)

The five lung capacities are:

(1) Functional residual capacity = that volume of air that remains in the lung at the end of quiet expiration.
Equal to the sum of the residual volume and the expiratory reserve volume.

(2) Inspiratory capacity = inspiratory reserve volume + tidal volume.

(3) Expiratory capacity = expiratory reserve volume + tidal volume.

(4) Vital capacity = inspiratory reserve volume + tidal volume + expiratory reserve volume (or total lung capacity
– residual volume).

(5) Total lung capacity = vital capacity + residual volume.

The residual volume (and therefore functional residual capacity and total lung capacity) cannot be measured
directly by spirometry. They are measured by either whole body plethysmography, or by using the helium
dilution or nitrogen wash-out techniques.

post-operative pain

Pain causes shallower breathing and causes V/Q mismatch as less air is reaching the alveoli that are being
perfused.

FRC is decreased by pain.

Minute ventilatory volume (the product of tidal volume and respiratory rate) will decrease. Although
respiratory rate may increase, tidal volume decreases significantly.

Tidal volume decreases as the patient takes shallower breaths when they are in pain.

Lung compliance should NOT be affected

Compliance
Compliance is the ease with which the lungs expand in relation to a change in the transmural pressure (the
pressure difference between the alveoli and the intrapleural space).

Lungs are generally more compliant when they are at lower volume ie they expand more easily when
transmural pressure increases. If the transmural pressure is 0 (ie no difference between the alveoli and the
intrapleural pressures), the lungs would collapse due to their property of elastic recoil. This is due to the
presence of structural proteins such as elastin. Elastance is the inverse of compliance.

Compliance changes depending on whether the lung is inflating or deflating. This is known as hysteresis .
The compliance at any given pressure during deflation is larger than during inflation.

Surfactant is produced by type II pneumocytes and helps prevent alveolar collapse by lowering the surface
tension between water molecules in the surface layer. In this way it helps to reduce the work of breathing
(makes the lungs more compliant) and permits the lungs to be more easily inflated.

Compliance is pathologically increased in emphysema. Loss of structural proteins that support the lungs means
that a change in pressure elicits a larger change in volume than in non-emphysematous lungs. However, the
airways collapse on exhalation as they are less well supported, causing hyperinflation and air trapping.

In comparison, compliance decreases (ie ‘stiffer’ lungs) in disease states such as pulmonary fibrosis and
pulmonary oedema.

A decrease in elastic fibres will increase compliance.

High surface tension will decrease lung compliance. Surfactant, produced by type II pneumocytes, decreases
the surface tension of alveolar fluid and increases compliance.

An open pneumothorax will decrease lung compliance.

Pulmonary contusion → decreases lung compliance.

PEFR
A Wright’s peak flow meter is used to measure PEFR and is a handy bedside test.

PEFR should be greater than 520–700 l/min in men and 400 l/min in women.

Regular exercise will improve PEFR.

PEFR is decreased in obstructive lung disease. Collapse of small airways on expiration causes air trapping and
decreases PEFR. This makes PEFR measurement clinically relevant, particularly in the acutely asthmatic patient
and can be used to assess severity of an asthma attack.

Forced vital capacity (FVC)

FVC is the amount of air expelled during forced expiration following a maximal inspiration. It is reduced in
restrictive disease.

Valsalva manoeuvre
The Valsalva manoeuvre is forced expiration against a closed glottis. When the intrathoracic pressure is
increased as occurs in Valsalva’s manoeuvre, there is resultant decrease in venous return to the right atrium. In
the normal subject this results in a ↑ CVP, diminished pulse pressure and decreased cardiac output.

When SUSTAINED this results in a mild tachycardic response and a rise in the diastolic BP.

Carotid sinus massage

Carotid sinus massage is a technique where pressure is applied to the carotid sinus and can be used to treat SVT
and diagnose carotid sinus syncope. However, it carries a 1–2% risk of stroke.

The diving reflex

The (mammalian) diving reflex is a response to COLD exposure to the face AND breath-holding. It causes
bradycardia and peripheral vasoconstriction.

It can be used to treat SVT.

The Heimlich manoeuvre
The Heimlich manoeuvre is a technique to treat asphyxiation. The patient’s upper abdomen is rapidly
compressed from behind to cause forced exhalation.

The Jendrassik manoeuvre

The Jendrassik manoeuvre involves clenching the teeth and pulling interlocked fingers against each other. It
reinforces tendon reflexes.

carbon dioxide is transported

70% of the carbon dioxide is transported to the lungs in the form of BICARBONATE ions. O2 combines with
water to form carbonic acid (H2CO3 this is catalysed by carbonic anhydrase), which then dissociates to form a H +
ion and HCO3–.

Carbaminohaemoglobin is carbon dioxide bound to haemoglobin. Carbamino compounds only account for 5–
10% of CO2 in the blood.

In the dissolved state, in the water of the plasma and cells, only accounts for 5–10% of CO2 transport.

CO2 is about 20 times more soluble than oxygen at equal partial pressures.

CO2 diffuses passively into red blood cells.

Carbon dioxide does NOT bind to albumin.

pulmonary vessels
The pulmonary vessels can accommodate up to 500 ml (1 small bottle of water) in an adult man under normal
resting conditions. This means that cardiac output can be increased quickly before there is a match in the
venous return, as the blood stored in the pulmonary vessels act as a reservoir for the left ventricle.

Hypoxic pulmonary vasoconstriction

 results in decreased blood flow to poorly ventilated alveoli, improving matching of blood flow to
ventilation. The mechanism of hypoxic pulmonary vasoconstriction does NOT require central nervous
system (CNS) input as it can occur in an isolated lung.
 is important in the perinatal period. When the newborn baby makes the transition from placental
to air breathing, it is important for pulmonary vascular resistance to fall precipitously within a few
seconds. As a consequence, pulmonary blood flow dramatically increases from its value of only about
15% of the cardiac output in utero. The increase in pulmonary blood flow is assisted by closure of
both the ductus arteriosus and the foramen ovale.
 occurs independently of venous O2 content.
Shunt
A right-left shunt refers to oxygen-poor blood from the right heart that has entered the left heart without
undergoing gas exchange in the alveolar capillaries (ie it is shunted away from sites of gas exchange). The
physiological shunt is the sum of the anatomical shunt (blood passing from the right ventricle to the systemic
circulation via normal anatomical pathways, eg the bronchial vessels, without passing through the pulmonary
alveolar capillaries), and the pathological shunt ie the element of pulmonary alveolar capillary blood that has
passed through non-aerated or poorly aerated alveoli. Therefore the physiological shunt is always at least as
great as or greater than the anatomical shunt.
There is always a shunt even in a healthy adult due to normal anatomical shunting ie the return of blood via
pathways which bypass pulmonary circulation eg bronchial veins and Thebesian veins.

The difference in carbon dioxide tension between arterial and venous blood is small and much less than the
difference in oxygen tension. When shunted blood mixes with blood which has passed through ventilated
alveoli, the overall partial pressure of O2 in the mixed blood is an intermediary of the two. The greater the
degree of shunting, the lower the overall pO2. This DOES NOT AFFECT CO2 AS MUCH, due the similar pCO2
levels in shunted blood and blood that has undergone gas exchange. Shunting therefore affects arterial oxygen
tension more than carbon dioxide tension.

Breathing pure oxygen cannot correct for the normal anatomical shunt, which is always present.

dead space

Physiological dead space (aeration but poor perfusion; high V/Q ratio) results in higher arterial carbon dioxide
tension as carbon dioxide is not removed via gas exchange.

Tracheostomy bypasses the anatomical dead space above the level of the tracheostomy.

Adrenaline relaxes bronchial smooth muscle, making it a potent bronchodilator. This INCREASES anatomical
dead space.

A subject STANDING as opposed to lying supine INCREASES anatomical dead space.

Anatomical dead space INCREASES as the SIZE of the subject increases.

Increasing lung volume (eg during INSPIRATION) will INCREASE anatomical dead space.

lining of the respiratory tract

Dynein is a family of cytoskeletal motor proteins that control the beat of the cilia. It is absent in
Kartagener’s syndrome (primary ciliary dyskinesia).
The respiratory tract produces about 100 ml of mucus a day.
The mucociliary elevator moves at 2 cm/min.

Unlike bronchi, bronchioles do not have cartilage in their walls.

Bronchioles are up to 1 mm in diameter.