Applied Physiology

Acid-base

pH = -log10[H+]

Normal range is 7.36 - 7.44

Base-Deficit: Amount of acid/alkali required to restore 1l of blood to a normal pH (at pCO2 of 5.3kPa at 37'C).

Base-deficit = -[HCO3 - 24.8 + (16.2 x (pH - 7.4))]

 

Normal ranges

pH: 7.36 - 7.44 pCO2 pO2 HCO3-: 22 - 28 BE -2 +2

 

Sources of H+

1. Lungs: CO2 + H2O <-> H2CO3 <-> HCO3- + H+

2. Anaerobic metabolism (generating lactic acid from pyruvate) 3. Generation of ketone bodies: acetone, acetoacetate, B-hydroxybutyrate

Sources of Buffer / Bases

1. Bicarbonate system 2. Phosphate system 3. Plasma proteins 4. Hemoglobin

 

Organs involved in regulating acid-base balance

1. Respiratory 2. Kidneys: HCO control 3. Blood: plasma protein buffer 4. Bone

5. Liver: produce HCO3 and ammonia

 

Acidosis Alkalosis 

Effects 1. Respiratory o Oxygen: Right shift of curve

(reduced O2 affinity, increased tendency to oxygenate tissue)

o Pulmonary hypertension 2. Cardiac

o Decreased myocardial contractility

o Resistance to catecholamines o Cardiac arrythmias o Increased sympathetic activity

3. Proteins o Denatured

Workup 1. ABG - o pH o pCO2 o HCO3: Loss from gut, depletion

through buffering, impaired generation

2. Chloride (chloride retained at expense of bicarbonate); hypercholraemia results in low bicarbonate and thus generates acidosis

o May be due to dehydration o Can be due to defects in

tubular function 3. Serum lactate: Metabolic acidosis -

classified by Cohen + Woods

1. Common disorders - liver disease, renal failure, DKA, malignancy, short-bowel

2. Drugs/toxins: paracetamol / salicylate, metformin, epinephrine

3. Inborn error of metabolism: pyruvate dehydrogenase deficiency

o Type A: From Tissue hypoxia - anaerobic metabolism of pyruvate to lactate (any cause of shock)

o Type B: Not due to Hypoxia

Causes:

1. Addition of bicarbonate o Iatrogenic o Milk-Alkali syndrome

2. Loss of chloride (with gain of bicarbonate)

o Vomiting o Diuretics

3. Hypokalaemia - shift of protons into cell

Urine dipstick - ketones Calculate anion gap (Na + K) - (HCO3

- + Cl-)

o Normal Anion Gap: HCO replaced with chloride ions to maintain electrochemical neutrality

2. Addisons (hypoaldosteronism - hyperkalaemic acidosis)

3. RTA: - group of conditions that exhibit renal tubular dysfunction in presence of normal GFR

Type I (distal) - loss of ability to excrete acid at CCD; leads to acidosis

Type II (proximal) - loss of HCO3 resorptive capacity; leads to acidosis

Type IV: Hypoaldosteronism - hyperkalaemic acidosis

4. Ileal conduit 5. Carbonic anhydrase inhibitor

o Increased Anion Gap:

7. MUDPALES - Methanol, Uraemia, DKA, Paraldehyde, Alcohol, Lactic acidosis, Ethyl glycol, Salicylates

Check renal functrion

Action potential

Action potential

 

Equilibrium potential (of an ion): PD at which ion ceases to flow down electrochemical gradient (Nernst equation)

Resting membrane potential: PD across cell membrane (calculated by Goldman equation) - takes into account equilibrium potentials of all ions

Normal cell RMP = -70mV (interior of cell is negatively charged with respect to exterior)N/K pump 3/2 helps maintain ionic balance

Action Potential

Rapid change in membrane potential (depolarisation) following a stimulus with rapid return to resting membrane potentialAll-or-none phenomenon

Depolarisation = Na influx (opening of Voltage-gated Na channels)Repolarisation = K efflux (opening of Voltage-gated K channels)Ionic balance maintained by 3Na/2K-ATPase

Refractory Period: Period of time after AP that AP cannot be propagated

Myelination

- Increased condution velocitySaltatory conduction at nodes of Ranvier

Types of Nerve Fibres

1. Group A - largest myelinated 2. Group B - Myelinated autonomic preganglionic 3. Group C - Unmyelinated postganglionic fibres

Drugs affecting neurotransmission

1. Na-channel blockers - LAs 2. K-channel blockers - Tetraethylammonium

 

Bile

~500mls bile secreted per day in the liverSecreted into liver canaliculi by hepatocytesRelease stimulated by CCK, gastrin, secretin

Function

1. Emulsification of fat (ADEK vitamins) 2. Aids in absorption

 

Composition of bile

1. Water - 97% 2. Bile Salts - 0.7% - Cholic/Chenodeoxycholic acid 3. Bile Pigments - 0.2%: bilirubin/biliverdin 4. Other 2%: Fatty acids, cholesterol, lecithin

Bilirubin / Jaundice

Normal Metabolism Jaundice Classification

1. Broken down Hb in reticuloendothelial system

2. Reaches liver bound to albumin 3. Taken up into liver via transporter 4. Conjugated to bilirubin-Digluconuride 5. CBili enters bile and into gut and out

into poo 6. Small amount enters circulation and

reaches urine / small amount in gut converted to urobilinogen and out into urine

Pre-hepatic

Haemolytic anaemia Increased cell turnover -

cancer/lymphoma

Hepatocellular

Failure of uptake: Gilbert's Failure of conjugation: Crigler-Najjar Infections - CMV, Hepatitis Autoimmune

Post-hepatic

Cholestasis / obstruction / biliary atresia

Investigations in jaundice

1. FBC2. Reticulocyte count 3. Clotting4. LFTS5. Virology

6. Autoantibody

Calcium Balance

Calcium

Normal level 2.2 - 2.6mmol/l Distribution: (1) 50% unbound and ionised (2) 40% bound to plasma proteins (3) 5%

associated with anions 99% found in bone

Organ systems regulating control

1. Gut 2. Kidneys 3. Skeletal system

Hormone regulation

Increases Calcium concentration Reduces Calcium concentration

1. PTH o Produced by parathyroid glands:

84AA o Effects:

3. Bone: stimulates osteoclasts [IL-1] + releases calcium and phosphate into circulation

4. Kidney: (1) increased calcium resorption, increased phosphate loss (2) stimulates 1-alpha-OH activity of kidney

oVitamin D

o Formed from cholesterol, metabolised in liver and kidney

o Effects:

3. Bone: stimulate osteoblast proliferation

4. Kidney: calcium + phosphate resorption

5. Gut: Enhances gut absorption of calcium + phosphate

1. Calcitonin o From thyroid

parafollicular cells: 32AA

o Effects

3. Bone: Inhibit osteoclast activity

4. Kidney: Increases calcium excretion

Hypercalcaemia Hypocalcaemia 

Aetiology

Primary hyperparathyroidism (adenoma of PTH gland)

Malignancy: bronchogenic carcinoma, secondaries to bone

Renal calculi, pancreatitis Renal transplant with tertiary

hyperparathyroidism

Post thyroid surgery (removal of parathyroid glands)

Consequences / clinical features

Calculi - renal Increased gastric acid

secretion Risk of pancreatitis Constipation Impairment of tubular

function - polyuria, polydipsia, dehydration

Tiredness, lethargy, psychosis

ECG: shortened QT, increased PR, heart block, flattened T-waves

Neuromuscular irritability - parasthesia (Chvostek's facial tap; Trousseau's arm spasm)

Muscular cramps Tetany

Management

Acute hypercalcaemia (3.0-3.5mmol/l)

1. Identify and treat cause 2. Cardiac monitoring 3. Rehydration; to prevent

overload, CVP monitoring; frusemide for calcium diuresis

4. Bisphosphonate infusion (Pamidronate - rapidly reduce serum calcium)

5. Calcitonin 6. High dose steroids 7. Urgent surgery in cases due

to hyperparathyroidism

1. Identify and treat cause 2. Cardiac monitoring 3. Adequate fluid resuscitation 4. 10ml 10% calcium gluconate

+ 10-40mls in saline infusion over 4-8hours

5.

 

Cardiac function

Arterial pressure | Venous pressure | ECG | Cardiac function | Cardiovascular support | Cardiopulmonary bypass

Fluid compartments | Shock | Renal failure | Potassium Balance | Calcium Balance

Thorax | Coronary circulation | Carotid circulation | Blood supply of brain

 

Cardiac output

Heart rate x stroke volume = 70mls/kg/min (approximately 5l/min)

 

Cardiac Index

Cardiac output / Body surface area = 2.2-2.5l/min/m2

 

Cardiac Cycle

Duration 0.8 - 0.9s

1. Closure of mitral valve (systole) 2. Opening aortic vavle 3. Closure aortic valve (forms "dichrotic notch" - outward momentum) 4. Opening mitral valve (ventricular filling)

 

EVD = 120mls, ESV = 40mls : Ejection fraction = 80/120 (67%)

 

In exercise

1. Phases of cycle shorten 2. Ventricular diastole disproportionately shorter - reduced filling time 3. VFT offset by "atrial kick" for more filling

 

Heart sounds

1. Mitral / Tricuspid valve closure 2. Aortic / Pulmonary valve closure 3. Rapid ventricular filling 4. Atrial contraction against stiff ventricle

 

Determinants of Cardiac output

1. Non-invasive o Pulse, HR, BP, urine output o ECG o Echo

2. Invasive o Oseophageal doppler o PiCCO - Thermodilution o Swann-Ganz Pulmonary artery catheter

Multi-lumen balloon-tipped flow-directed catheter; passed through right heart into pulmonary arteryReflects Left heart function: - "Wedge" forms continousc column of blood from left atrium (via lungs)Indications: (1) inotropic support (2) LV monitoring (3) Multi-organ failure

Parameters

Direct 1. Mean arterial pressure 2. Mean pulmonary artery pressure 3. Pulmonary artery occlusion pressure 4. Ejection fraction 5. Cardiac output - measured using indicator dilution /

thermodilution technique (volume1-temp1 vs volume2-temp2)

6. Heart rate 7. Mixed venous oxygen saturation

Derived 1. Cardiac index 2. Stroke volume 3. Systemic vascular resistance 4. Pulmonary vascular resistance 5. Oxygen delivery

Systemic Vascular resistance

(MAP - CVP)/CO X 80 = 900-1400 dyn/s/cm-5

Pulmonary vascular resistance

(MPAP - PAOP)/CO x 80 = 150-250dyn/s/cm-5

Complications of insertion: 1. Any of the central line complications 2. Cardiac arrythmias 3. Valve injury: incompetence of TV or PV 4. Pulmonary artery rupture 5. Pulmonary infarction (if balloon kept wedged too long) 6. Catheter knotting 7. Sepsis

Coagulation

Normal Coagulation / haemostatic function

Depends on

1. Normal vascular endothelium 2. Normal number and function of platelets

o Derived from megakaryocytes in BM o Release vasoconstrictive 5HT, serotonin, TXA2, ADP o Bind via phospholipid / vWF to form haemostatic plug

3. Normal amount of coagulation factors o Forms stable meshwork of cross-linked fibrin around primary platelet plug

(stable haemostatic plug)4. Essential co-factors - Vit K, calcium

o VitK: Fat soluble leads to carboxylation of factors II, VII, IX, X binding to surface of platelets

5. Balanced by fibrinolytic pathway

 

Coagulation pathway

A series of enzyme-controlled steps resulting in the conversion of soluble plasma proteins (fibrinogen) into insoluble polymerise deposit.

Ie. the formation of a clot!

1. Intrinsic cascade (APTT): components intrinsic to blood itself - clots in tube (12,11,9,10,2,1)

2. Extrinsic cascade (PT): components activated by extrinsic factors from damaged tissue (7, 10,2,1)

o Factor VII decays fastest in blood + particularly calcium dependent

 

Surgical Coagulopathy

Hypothermia - cold results in dysfunctional platelets Massive transfusion Aspirin Heparin (can lead to thrombocytopenia through immunological mechanism "HITS" -

heparin induced thrombocytopenia DIC / sepsis

 

Tests of coagulation

Bleeding Time  Time taken for earlobe to stop bleeding after it's been punctured3-5 min. Reflects platelet function

Clotting Time Time taken for blood to clot in glass tube (intrinsic pathway)4-6 min.

Activated Clotting TimeWhole blood clotting time107seconds + /- 13 seconds

Prothrombin TimeMeasure of extrinsic + common pathways9-15 seconds

Activated Partial Thromboplastin Time

Measure of intrinsic and common pathways30-40seconds

Thrombin TimeMeasure of common pathway14-16s

TEG Dynamic function of everything

TEG (Thromboelastography):

Parameter Description Indications/ Implications

R-value Time from initiation of test to initial fibrin formation and movement of pin

Coagulation factor activation

K-value Time from beginning of clot formation until amplitude of TEG reaches 20mm

Coagulation factor amplification

Alpha-angle Coagulation factor amplification

Max-Amplitude Greatest amplitude of TEG Platelet aggregation

Amplitude at 60mins Amplitude of TEG 60 minutes after maximal TEG is recorded clot lysis index

Fibrinolysis

Electrocardiography (ECG)

 

Fat / Pulmonary Embolus (PE)

Embolus

Abnormal mass of undissolved material that is carried in the bloodstream from one place to another

Components of Emboli

1. Thrombi or mixtures of thrombi and clot2. Fat: long bones,3. Atheroma - rupture of aotic plaques with emboli to mesenteric vessels4. Tumour cells5. Air: cannulae, open neck veins, dialysis6. Nitrogen: Caisson's disease7. Amniotic fluid: labour8. Infective: IE9. Foreign material - plastic tubing from broken cannulae

Pulmonary Embolus Fat Embolism Syndrome

Trigger/PDF

1. Wallo Increased ageing

o Vessel injury (limb injury)2. Flow (prolonged stasis)

o Prolonged bed resto Recent surgeryo Cardiac failure

3. Constituentso Polycythemiao Malignancyo Dehydrationo Coagulopathy - ProteinC/S, ATIII

deficiency, Factor V Leiden, Antiphospholipid antibodies, HRT, OCP

1. Local traumao Trauma / long

bone fractureso Joint

reconstruction2. Systemic

o Major burnso cardiopulmona

ry bypasso Diabeteso Pancreatitis

Pathophysiology

1. Thrombi form in deep veins / right atrium

2. Propagate3. Obstruct pulmonary artery (beyond right

ventricular outflow tract)4. Produces right ventricular strain5. Reduced blood flow to lung produces

V/Q mismatch (and increased physiological dead space)

1. Mechanical theoryo Damaged

vasculature releases fat droplets into circulation

o Enter pulmonary vascular bed

o Enter systemic circulation via arterio-venous shunts

o Impaction of emboli in terminal systemic vascular beds produces local ischaemia and tissue injury

2. Biochemical theoryo Stress

hormones released (steroids, catecholamines)

o Activate lipaseso Lipases

hydrolyse circulating lipids into FFAs and glycerol

o FFAs induce pulmonary damage and

increase capillary permeability

Clinical features

1. Localo Painless/painful swelling or

tenderness of calfo Phlegmasia cerulea dolens -

ischaemic cyanotic leg following massive ileo-femoral venous thrombosis

o Phlegmasia alba dolens - ischaemic cyanotic leg following massive ileo-femoral DVT with arterial spasm

2. Distalo Pulmonary embolism

1. Tachycardia, tachypnoea2. Pleuritic chest pain3. Shock (outflow

obstruction)4. Right ventricular strain5. Paradoxial embolisation

(through PFO) leading to systemic embolisation

1. Respiratory insufficiency

o Tachypnoea, cyanosis - pulmonary vascular occlusion by lipid emboli

2. Petechial rasho Distributed in

area of chest, mouth, axilla, conjunctiva - direct embolisation of cutaneous vessels

3. Cerebral featureso Encepalopathy

/ distinct peripheral weakness - microvessel embolisation

4. Pyrexia, tachycardia, retinopathy, renal impairment

Management

1. Prevento Early mobilisationo Heparino TED stockingso Intermittent pneumatic

compression (intraoperatively)o Transvenous intracaval device -

umbrella + wire filters2. Treat

o Resuscitateo Investigate

1. ABG - V/Q mismatch2. Plasma D-dimers

1. FDP from action of plasmin on fibrin clot

2. Measured by latex agglutin test

3. Misses 10% of PEs

3. ECG1. Sinus

Tachycardia2. S1Q3T3

4. CXR - exclude differentials

5. VQ scan6. Spiral CT7. Pulmonary angiography

o Specific therapy1. Thrombolysis -

Haemodynamically unstable

2. Pulmonary embolectomy

3. Anticoagulation: Heparin + warfarin

Gastrointestinal physiologyGIT Function Hormones / reflexes Notes Resection

Salivary glands

ParotidSubmandibularSublingual

Amylase (ptyalin) - breaks down starch into oligosaccharides

Saliva (under PNS control)

Hypotonic

 

Phases of swallowing

1. Oral (voluntary) o Bolus progressively

moved upwards and backwards by pressure of tongue

2. Pharyngeal o Contraction of

constrictors o Larynx pulled

upwards/forwards against epiglottis (protects airway)

o Upper oesophageal sphincter relaxes, superior constrictor contracts - food enters oesophagus

o Inhibition of medullary respiratory centre

3. Oesophageal

 

o Swallowing centre initiates primary peristaltic wave

o Relaxation of LOS (normal pressure 30mmHg)

Stomach    

Endocrine

Gastrin (gastric G-cells) of fundus: stimulate acid section, stomach contraction, pancreatic secretions

 

Exocrine

Pepsinogen (precursor for protein digestion)

Intrinsic factor (gastric parietal cells): Aids resorption of B12Water

HCl GPC (Fundus predominantly) - activates pepsin

Mucous - necks of gastric glands in pylorus

 

 

Emptying hormones

1. gastrin (GPC)

2. CCK + secretin (duodenum) 

 

Output = 2l/day

Gastric Innervation

Sympathetic: coeliac plexus PNS: vagus nerve (increased

motility)

 

1. H+ generated from CO2 dissolving in cytoplasm

2. Exchanged with K via H/K ATPase

3. HCO3- generated via dissociation and goes back into plasma

Acid secretion control

+ ACh (M2): vagus+ Gastrin : G-cells (fundus)+ Histamine: Mast cells (Rx ranitidine)- Somatostatin- Secretin- CCK

 

Phases of gastric acid secretion

Cephalic phase: thought/smell/taste - vagal activity stimulates gastrin

Dumping: early (osmotic sucking effect) / late (pancreatic insulin secretion following food)

B12 deficiency (no IF)

Achlorhydia (no Fe absorption)

secretion/HCl secretion

Gastric phase: presence of food - stimulates gastrin and HCl

Intestinal phase: presence of amino acid and food (later inhibited by release of secretin and CCK from duodenum)

 

Types of contraction

Peristalsis: Retropulsion - passes food

boluses back Vomiting [Pyloric stenosis]

Duodenum

Iron absorption (acidic environment)

CCK: stimulates GB contraction, stomach emptying, stimulates pancreatic lipase secretion

Secretin: stimulates stomach emptying, stimulates pancreatic secretion

Prinicple site to absorption of carbs, fats, protein, water, electrolytes, vitamins, minerals

Output = 1.5l/day

Absorbs 8.5l/day

Type of contraction

Segmentation Peristalsis (localised

contraction) Pendular movements

(contraction of longitudinal muscles)

 

Jejunum Folate absorption

   

Ileum B12 absorption

Bile salt uptake

Water resorption

  B12 deficiency, macrocytic anaemia

Increased bile salt production + increased incidence of gallstones (Cf Crohn's disease)

Loose/frequent stools (reduced water absorption)

Reduced Gamma-

globulin:

Pancreas Endocrine

Exocrine

(Stimulated by gastrin)

Output = 1.5L Diabetes mellitus

Insulin sensitivity - due to additional loss of glucagon

Reduced fat absorption (leads to steatorrhoea)

Reduced protein absorption - negative nitrogen balance

Reduced absorption of Fe and Ca - due to loss of alkalinisation of chyme in stomach

Large bowel

Water absorption

Mineral absorption

Expulsion of faeces

(Bacterial synthesis of vitK

Gastro-Colic reflex

Meal leads to increased activity of colon, with increase in mass contraction movements

 

Defecation

1. Distension of rectal walls (from faeces) >18mmHg intra-rectal pressure

2. Afferent impulse pass to sacral segments (S234)

3. Stimulates efferent reflex + stimulation of thalamus/cortical sensory areas producing

consicous desire to defecate

4. Efferent impulses back to myenteric plexus activating PNS

5. Leads to contraction and expulsion of faeces + relaxation of internal anal sphincter

6. Augmentation with voluntary contractions of pelvic floor muscles

 

Resistance to defecation - mediated by pudendal nerveInvoluntary defecation occurs when rectal pressure > 55mmHg due to contents or spasm.

Fluid compartments / fluid balance

Fluid Compartments of the body

70 kg man is composed of 60% water = 42litres

Intracellular space (2/3): 28L Extracellular space (1/3): 14L = Plasma (3) + Interstitial (10) + Transcellular (1)

Transcellular fluid includes: ocular fluid, CSF, synovial fluidNB. Circulating blood volume = 5l (70mls/kg), which is composed of plasma (ECF) and red cells (ICF)

 

Input sources

Food: 800mls Water: 1500mls

Metabolic oxidation: 200mls

Output sources

Urine: 1500mls Faeces: 200mls Skin/respiration (insensible): 800mls

 

Internal water balance

1. Balance between osmolarities of two compartments 2. [Microcirculation]

 

External water balance (important in Shock)

Reduced circulating volume results in reduction of blood pressure

1. Detected by carotid sinus/aortic arch [high pressure] baroreceptors: Sympathetic response

o Catecholamine response - vasoconstriction to maintain BP, increase FOC, increase cardiac output

o Stimulation of B2 adrenoceptors in kidneys kicks off RAS response 2. Decrease in renal blood flow / renal perfusion pressure: Renin-Angiotensin-

Aldosterone response o B2 stimulation releases renin; converts angiogensinogen to angiotensin I o angiotensin I converted to angiotensin II by ACE (in the lungs, also degrades

bradykinin) o Angiotensin II potent vasoconstrictor o Angiotensin II stimulates the release of aldosterone (from zona glomerulosa)

which promotes Na/water resorption from DCT 3. Stress hormone release - corticosteroids from adrenal cortex

o Salt/water retention 4. Increase in plasma osmolarity: ADH (produced in paraventricular and supraoptic

nuclei) response o Osmoreceptors detect a rise in osmolarity (from loss of volume) o Stimulates the release of vasopressin (aka anti-diuretic hormone) - potent

vasoconstrictor o ADH (via increase cAMP, aquaporin) stimulates resorption of water from

DCT/CCD 5. Reduced renal perfusion stimulates EPO production (long term)

Increase in fluid volume

1. Distention of cardiac atria [low pressure receptors] - leads to release of ANP: promotes diuresis

2. Increase in brain naturetic peptide (BNP increased in "cardiac failure")

Assessment of state of hydration

1. Clinical exam o Skin turgor o Dry mouth o Sunken eyes o Urine concentration

2. Charts o Tachycardia o Weights o Urine output o CVP measurements

Aim of fluid therapy

Satisfy basal water requirement Replace fluids lost beyond basal requirement Support arterial pressure

 

Agent Description

Na Cl K Ca Lactate pH Osm Notes

Hartmanns Compound sodium lactate

131 111 5 2 29 278 Lactate metabolised to bicarbonate = 278 mosmol/kg

Causes shift in fluids from extracellular to vascular, thus temporarily replacing lost blood volume and sustaining blood pressure until the whole blood can be transfused

N/S 154 154 5.5 300-310

154mmol/l

5% Dex 4.0 50g dextrose / 1 Litre

Dex-Sal 31 31 4.5 300 40g dextrose

Gelofusin 35g gelatine

145 145 6.25 Molecular weight > 30kDa

Starch Chains of glucose

Average Mol weight > 70kDa

Useful in cases of capillary leakage

Use limited to 1500ml/day – risk of coagulopathy

HAS

4.5% or 20%

Molecular weight 69Kda

Provides plasma expansion + carrier molecule + buffer

Dextrans

40 or 70

Colloid composed of branched polysaccharide t1/2~12h

Dextran 70 reduces platelet adhesion + interfere Xmatch

Risk of anaphylaxis

 

Liver

The Liver

30% cardiac output (70% portal vein / 30% hepatic artery from coeliac axis) 

 

Functions of the liver

1. Storage: Vitamin ADK, folate, B12, Ferritin 2. Metabolic

o Carbohydrate - glycogen storage, gluconeogenesis o Lipid: Ketone bodies, cholesterol, PLs, lipoproteins o Protein: protein synthesis

3. Endocrine o Breakdown of steroid hormones o Vitamin D metabolism

4. Coagulation o Produces clotting factors

5. Other o Generates heat o Breaks down red cells o Extramedullary haemopoesis

Liver function tests

1. Bilirubin / unconjugated bilirubin 2. Enzymes

o AST, ALT: from injured hepatocytes o ALP: raised in cholestasis

3. Plasma proteins o Albumin (alpha fetoprotein is embryonic albumin) o Globulins

4. Clotting studies

Lung disorders

Atelectasis

Absence of gas from all or part of the lung

 

Causes

1. Luminal obstruction / hypoventilation - distal gas trapping, gas absorbed (due to higher partial pressure than mixed venous blood) leading to progressive collapseof lung beyond obstruction

1. FB: sputum 2. inadvertant endobronchial intubation 3. Upper abdominal/thoracic surgery = reduced lung expansion (from pain,

spliting) leads to retained secretions and distal airways collapse

o High FiO2: (loss of "splinting" from nitrogen mixture, so when oxygen is absorbed, lung unit collapses)

o Underventilation: hypoventilation leading to progressive absorption of gas Mural

o Tumour Extra-luminal

o Compression from pleural effusion / pulmonary oedema

 

Consequences of atelectasis

1. VQ mismatch and hypoxaemia 2. Reduced lung compliance (smaller airways need more force to open - Laplace) 3. Pre-disposition to infection due to retention of secretions (vicious circle)

 

Management

1. Pre-operative anticipation o Chest exercise o Chest physiotherapy

2. Intraoperative o Humidified oxygen (improves mucociliary function) o Adequate tidal volumes - ensures good expansion o Avoid higg FiO2 (absorption atelectasis)

3. Post-operative o Sit upright o Adequate analgesia (facilitates breathing / good tidal volumes) o Early mobilisation o Breathing exercises o CPAP o Airway suction

Bronchiectasis

Localised / generalised irreversible dilation of bronchi (as result of chronic necrotising infection)

Types

1. Follicular: loss of bronchial elastic tissue and multiple lymphoid follicles 2. Atelectatic: Localised dilation of airways associated with parenchymal collapse due

to proximal airways obstructions 3. Saccular

 Magnesium balance

Magnesium

Normal levels 0.7 - 1.0 mmol/l Function - co-factor in enzymes (phosphate transfer), CNS, neuromuscular systems High magnesium levels prevent calcium cellular uptake Homeostasis maintained by kidney - freely filtered at glomerulus, reabsorbed at PCT

and TALLOH

Causes of Hypomagnaesemia

Gut loss - diarrhoea / IBD, malnutrition Renal loss - diuretics Alcoholism

Microcirculation

 

 

 

 

 

1. Capillary filtration pressure o Length of capillary: 35mmHg at start - 20mmHg at end

2. Interstitial hydrostatic pressure 3. Colloid oncotic pressure (osmotic)

o 25mmHg o Exerted by albumin, gamma-globulins

4. Interstitial oncotic pressure o Exerted by collagen, proteoglycans, hyaluronate

[Oedema][Lymphoedema]

 

Oedema

Abnormal accumulation of fluid in the intercellular spaces

May be

1. Transudate o Imbalance in hydrostatic pressures o Fluid: low protein <30g/l; specific gravity <1.020

2. Exudate o Inflammatory process o Fluid: high protein >30g/l; specific gravity >1.020 o Classification - in terms of content or formation: (1) serous - pleural,

pericardial, peritoneal (2) haemorrhagic - TB (3) Purulent - e.coli peritonitis (4) Fibrinous - pericarditis (5) Pseudomembranous

 

Classification

1. Exudate 2. Transudate

Motor Control / Muscle contraction

Components of the motor system

 

1. Cerebral cortex o Pre-central gyrus (Brodmann area 4) o Controls contralateral musculuar activity (pyramidal decussation)

2. Subcortical areas o Basal ganglia o Brainste o Cerebellum

3. Spinal cord 4. Motor neurones

o Alpha motorneurone: large diameter fibre innverating majority of worker fibre (extrafusal - not encased within connective tissue sheaths)

o Gamma motoroneurone: small fibre innervate intrafusal fibres of muscle spindle - alters initial lenght of muscle spindle and sensitivity of spindle to the stretching

5. Motor units o Consists of motorneurone and muscle fibres it innervates o Large muscles, large units; small delicate muscles, small units

6. Receptors / afferent pathways

Reflex

Automatic response to a stimulus

 

Spinal reflex

1. Withdrawal reflex o Cutaneous nocioception connect to afferent pathway to stimulate alpha

neurones o Automatic contraction of muscle in response + polysynaptic inhibition of

antagonist muscles 2. Stretch reflex

o Reflex contraction following stretch of fibres o Mediated by muscle spindle receptors o Nuclear bag fibres (Group Ia) - o Nuclear chain fibres (Group II) o Patellar tendon stretch reflex:

(1) patellar tendon stretched (2) stretch of quadriceps muscle (3) spindle fibre stretch (4) afferents discharge back to alpha-motorneurone in ventral horn of spinal cord

Muscle Types

1. Skeletal - striated / voluntary o Type I: Slow twitch, slow fatigue (high concentration of myoglobin) - eg.

soleus o Type II: Fast twitch, fast fatigue (large reserves of glycogen) o Calcium binding protein = Troponin

2. Cardiac - striated / involuntary 3. Smooth - voluntary

o Actin/myosin filaments irregularly arranged throughout cell o Shows spontaneous o Calcium binding protein = Calmodulin

 

 

Skeletal Muscle Contraction

 

 

 

1. Action potential spreads from motor endplate to T-tubule system 2. Leads to release of Calcium from Sarcoplasmic Reticulum 3. Calcium binds troponin C on light chains 4. Leads to displacement of tropomyosin (removes steric hinderance)5. Actin and myosin can cross link 6. Filaments slide (energy generated from hydrolysis of ATP to ADP)

 

 

Cardiac Muscle Contraction

Cardiac cells are mononuclear (multi in skeletal) Nuclei centrally located Cardiac muscle fibres are branched Cardiac cells connected by intercalated disks - contract as syncitium Larger T-tubule system

 

1. Rapid depolarisation - Influx of Na 2. Partial repolarisation - closure of VSCC 3. Plateau phase - Slow inward current of Ca

o Myocytes cannot be stimulated to produce tetanic contractions o Myocytes are non-fatiguable

4. Repolarisation - closure of Ca channels 5. Placemaker potential

o Unstable membrane potentials o Decay spontaenously to produce AP o Caused by progressive reduction in membrane's permeability to K

 

 Neurotransmission and Receptors

 

 

 

ReceptorEnzyme coupling (via G-protein)

Second messenger

Effectors 

Alpha-1 Phospholipase C IP2 + DAGActivation of protein kinases

Alpha-2 Inhibition of adenyl cyclase Reduced cAMP

Beta 1/Beta 2 Stimulation of adenyl cyclase Increased cAMP Activation of protein kinases

Muscarininc

Nicotinine - Direct ion channel linkage

Pancreas / Glucose control

Pancreas anatomy

 

Pancreas

Mixed endocrine / exocrine gland Secretes 1-1.5l pancreatic juice daily

 

Function of the pancreas

1. Endocrine o Alpha cells: Glucagon o Beta Cells: Insulin

1. Carbs: - Increase glucose uptake, stimulates glycogensis 2. Proteins: Enhances AA into peripheral tissues, stimulates protein

synthesis

3. Fats: Stimulates lipid uptake 4. Potassium: into cells

o [Gamma cells: pancreatic polypeptide - reduces appetite] o Delta Cells: Somatostatin

2. Exocrine o 1 - 1.5l pancreatic juice / day o Aqueous component - water, bicarbonate o Enzymatic component - digestive enzymes

1. (1) Proteases (secreted as inactive zymogen form) - trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase

2. (2) Lipolytic - Lipase, Phospholipase A2 3. (3) Starch digestion - Amylase

Glucose metabolism

Sources

1. Diet 2. Glycogenolysis 3. Gluconeogenesis

o Lactate, glycerol, Amino acids

Blood sugar control

1. Increase BM: Catecholamines, Glucocorticoids, Somatotrophin 2. Decrease BM: Insulin

Ketosis

1. Starvation o Diabetes - (omission of insulin, infection, drug induced) o Improper utilisation of TCA components

2. Increased lipolysis and increased FFA production (readily transportable fatty acids that can be utilised by organs such as heart and brain)

3. Ketone production - acetone, acetoacetate, B-hydroxybutyrate

 

Postural changes

Standing up

Arterial pressure = HR x SV x SVR

1. Increases venous pooling 2. reduced venous return to heart 3. Reduced stroke volume and cardiac output

4. Reflex sympathetic responses [carotid baroreceptors] ensure maintained blood pressure

o Reflex tachycardia + vasoconstriction (to maintain status quo) o Reduction in vagal activity

Postural hypotension

1. Failure to increase HR o Vaso-vagal o Fixed heart rate (drugs, heart block)

2. Reduced stroke volume o Fixed afterload o Aortic stenosis o PE

3. Reduced SVR o Vasodilators o Sepsis o Autonomic failure - chronic DM

Potassium Balance

Normal 3.5-5mmol/l

Hyperkalaemia

Causes

Input Distribution  Excretion

Excess K therapy Blood transfusion

Rhabdomyolisis burns oncology Cellular (cf insulin)

Renal failure Renin-Angiotensin-

Aldosterone inhibition (aldosterone promotes Na reabsoprtion at expense of K excretion)

ACEi K-sparing diuretics Addison's disease

(adrenal insufficiency)

Consequence: VF arrest

> 6.5mmok/l needs urgent treatment (leads to arrest - hence used as cardioplegic solution)

Symptomatic ECG changes:

o Tall tented T-waves (T-pot), increased PR o Wide QRS o Sinusoidal pattern

 

Management

1. Recheck potassium 2. Cardiac monitoring 3. Pharmacological treatment

o 10ml calcium gluconate (10%) IV over 2 mins (cardioprotection) o 20U Insulin + 50ml 50% Dextrose IV (drives potassium into cells) o Nebulised salbutamol 2.5mg o Calcium resonium 15g/8hours PO

4. Dialysis (persistently high K / pH <7.2)

Hypokalaemia

Input Distribution  Excretion

Decreased oral intake / starvation

Alkalosis / insulin excess

Artefact - sampling from drip arm

GIT losses: vomiting, diarrhoea, fistula

Renal losses: Conns, cushings, diuretics, RTA

 

Management

1. Replacement

Pulse / Blood pressure

Blood pressure

MABP - Pv = HR x SV x TPR

Systolic pressure = Pressure from force of cardiac contractionDiastolic pressure = Pressure from resistance arterioles when heart is relaxedPulse pressure = Systolic - Diastolic pressureMean arterial pressure = Diastolic +1/3Pulse pressure; Eg BP 120/80 - MABP = 93

 

Systolic Diastolic Pulse pressure MABP

Exercise Increased Reduced Widened

Shock Reduced Reduced Reduced/narrow

Aortic regurgitation Increased Reduced Widened

Korotkoff sounds

1. First sound (Systolic pressure) 2. Louder 3. Softer 4. Muffled (used in pregnancy when 5th sound may be "absent") 5. Silence (Diastolic pressure)

 

Blood pressure monitoring

Dichrotic notch = momentary rise in arterial pressure on closure of aortic valve

1. Non-invasive o Sphygmomanometer

2. Invasive

o Direct cannulation of peripheral artery (should perform Allen's test; competence of collateral ulna arterial circulation - positive if hand still blanched 15 seconds later)

o Gives continous waveform trace after attachment to electrical transducer o Complications of art lines: haematoma, digital ischaemia, pseudoaneurysm,

AVfistula, exsanguination

 

Pulse changes along arterial tree

Occur due to changes in wall stiffness along arterial tree Radial: higher systolic, lower diastolic, higher PP, lower MAP

 

Pulses

1. Anacrotic pulse: slow rise and low amplitude in AS 2. Waterhammer pulse: Rapid rise and decline in AR 3. Pulsus Bisferiens: Mixed aortic vavle disease - "double peak" 4. Pulsus Alternans: Random variation in amplitude of arterial pressure - LVF 5. Pulsus Paradoxus

o Exaggerated >10mmHg reduction in arterial pressure on inspiration o Inspiration - reduced intrathoracic pressure - increase venous return -

increase right sided end-diastolic volume - leads to bulging into left ventricle reducing size (Bernheim effect)

o Increased pooling of blood in expanded lungs - reduced return to left side of heart

o Negative pressure transmitted to thoracic aorta o Effect is reduced pulse pressure

Paradox is (1) audible heart sounds yet (2) no palpable pulse

Causes of Pulsus Paradoxus

6.

Changes in intrathoracic pressure

Increased pooling in lungs  Reduced return to left side of heart 

o Bronchial asthma (lung hyperinflation)

o Ventilated patients (waking off sedation)

o Pulmonary embolus (+RV dysfunction)

o Asthma

o Tamponade o Constrictive

pericarditis o Pneumothorax

Renal Failure

Renal failure

Inability of kidney to excrete nitrogenous / other waste products of metabolismDevelops over hours / days / months

 

Part of nephron most susceptible to injury = Thick ascending limb of the loop of henle

1. Anatomy - reside in medulla - poorer oxygenation than cortex 2. Metabolism - Active Na/K-ATPase pumps at membrane have high energy demand

 

Acute Renal failure Chronic renal failure 

Causes 1. Pre-renal o "Circulatory"- see

cardiac function / shock / fluid balance

2. Renal o Acute tubular necrosis

(ATN) - Paracetamol o Glomerulonephritis o Reno-vascular -

NSAIDS (blocks production of vasodilatory PGE2)

o Hepato-renal syndrome

3. Post-renal - obstruction o Luminal: calculi o Mural: o Extraluminal: -

extrinsic compression from pelvic tumours, prostatic hypertrophy, Abdominal compartment syndrome

1. Pre-renal 2. Renal

o Congential: PCKD (extra-renal - cysts in liver, pancreas, spleen; berry aneurysms in circle of bruce willis, MV prolapse)

o Glomerular: GN, Diabetes, Amyloid

o Reno-vascular: hypertension, vasculitis, RAS

o Tubular/interstitial: interstitial nephritis, pyelonephritis

3. Post-renal o Chronic outflow

obstruction: calculi, prostatic enlargement, pelvic tumours

Pathophysiology

1. Parenchymal ischaemia -> reduced perfusion pressure

o Vasoconstriction of efferent arteriole (to maintain RBF);

maintains pressure across Glomerulus

o Results in reduced blood supply to tubules from efferent arteriole and vasa recta

o Worsens cortical / medullary ischaemia

2. Tubular ischaemia + necrosis leads to shedding of cells into lumen

o Results in luminal obstruction

3. Promotes "back leak" of tubular fluid into interstitium

o Increases interstitial hydrostatic pressure

o Worsens tubular fluid resorption

Recognition 1. Oliguria o <400ml/day urine

2. Reduced GFR o Raised urea /

creatinine 3. Electrolyte inbalance

o Hyponatraemia o Hyperkalaemia o Metabolic acidosis o Hypocalcaemia

4. Urine composition changes

1. Blood results o trends from previously

2. Signs / symptoms of long-standing disease

o skin pigmentation, chronic anaemia (lack of EPO), pruritis, nocturia

3. USS / imaging o Bilateral small kidneys o Scarred kidneys

Complications

1. Fluid dynamics o Acute pulmonary

oedema / fluid overload

2. Electrolyte balance o Hyperkalaemia -

arrythmias

1. Hypertension o (RAS) o Fluid retention

2. Anaemia o Deficiency in EPO o Bone marrow fibrosis

(from osteitis fibrosa cystica)

o Red cell fragility caused by uraemic toxins

3. Renal osteodystrophy o Reduced renal

production of 1-alpha-OH Vit D

o Leads to hypocalcaemia and secondary hyperparathyroidism (forming bone cysts -

osteitis fibrosa cystica) o Reduced bone

mineralisation and resultant osteomalacia

o Hyperphosphataemia due to reduced renal function

4. Uraemia o From "uraemic toxins" o Skin pigmentation,

nausea, malaise, itch 5. Neurological

 Management

1. Pre-renal o Optimise filling /

cardiac output o Careful fluid-balance:

aim for even balance (fluid charts etc)

2. Renal o Stop nephrotoxic

drugs (care with drugs undergoing renal excretion)

o Manage GN 3. Post-renal

o Catherise o Monitor urine output

 

FillFurosemide boluses (if well filled)Intropes: Dopamine (increase RBF + contractility)"Renal rescue" - GTN / Dopamine / Aminophylline / Frusemide

Optimise nutrition

Renal replacement therapy

1. Hypertension o Loop diuretics o Fluid restriction

2. Anaemia o EPO injections

3. Bone disease o Improve mineralisation o Vitamin D supplements o Gut phosphate binders

4. Diet 5. Dialysis/filtration

Investigations

U/Es Urine sodium and osmolarity

ATN- Unable to concentrate urine

Pre-renal failure 

- Unable to retain sodium

Urine Na >20 <40

Urine Osm <500 >350

Urine:plasma osmolality ratio <1.2 >1.2

ECG USS kidneys

 

 Renal function

Renal Blood flow

20-25% cardiac output (1 - 1.2 l/min) Determinants of renal blood flow

1. Autoregulated between 80-180mmHg - (1) Myogenic mechanism: increased wall tension stimulates vasoconstriction (2) Tubuloglomerular feedback - alterations in flow of blood occurs with alterations in arterial pressure leading to stimulation of juxtraglomerular apparatus.

2. SNS: alpha-1 stimulation - afferent arteriole contraction: reduced blood flow 3. Angiotensin II: efferent arteriole constriction (ACEi cause dilation, and reduced blood

flow) 4. PGE2 PGI2: efferent arteriole constriction (NSAIDs cause renal failure by inhibiting PG

production)

Measured by para-aminohippuric acid (PAH): - completely eliminated through processof filtration and secretion by tbubules (PAH clearance = Renal plasma flow)

Renal blood flow = Renal plasma flow / (1 - Haematocrit)

 

Renal Clearance

Volume of plasma from which all of a substance has been removed and excreted in urine per unit time

Clearance = [Urine] x Volume / [Plasma] Substance

1. Freely filtered (see below) 2. Not secreted / reabsorbed / metabolised 3. Must not inherently alter GFR

 

Glomerular Filtration Determinants

1. Molecular size - cut off 40Angstroms 2. Molecular charge (BM is negatively charged)

Measurement of GFR

1. Inulin clearance (must undergo continous iv infusion) 2. 24hour urinary creatinine (anhydride of creatine - ie without the water) excretion

(some secretion of creatinine into tubules) 3. 51CrEDTA

Estimation of GFR

1. Cockcroft-Gault formula

 

The Nephron

1. Glomerulus 2. Proximal convoluted tubule

o Major site of reabsorping solutes (70%): - Na, Cl, K, glucose, amino acids + phosphate, lactate

3. Loop of Henle o Resorption of solute (20%): - Na, Cl, K o Water resorption in thin descending loop (Thich ascending loop is

impermeable to water) o Forms counter-current mutiplication system - concentrates urine

1. Fluid enters LOH which is isotonic with plasma 2. Decending limb permable to water; water progressively absorbed

down limb (into nephron) making interstitium more concentrated 3. Ascending limb impermeable to water but permeable to sodium -

passive diffusion of NaCl down concentration gradient, this dilutes tubular fluid

4. Distal convoluted tubule o Resorption of solute (10%) - Na, K o Secretion: variable amounts of K / H o Reabsorption of water - distal portions

5. Cortical collecting duct o Water reabsorption (via Aquaporin-mediated V2 receptor: Vasopressin,

produced in supraoptic and paraventricular nuclei, stored in posterior pituitary)

o Also leads to increased NaCl reabsorption by thick ascending limb - by increasing concentration of interstitium around loop of Henle.

 

Glucose and the Nephron

Filtered glucose normally completely resorbed by kidney

Above filtration load, glucose starts to appear in urine (saturated resorptive capacity)

 Respiratory function

Respiratory function | Respiratory failure | Airways Adjuncts | NIV | IV |

Acid base | PE / Fat Embolus | Pneumothorax | Flail Chest | Chest drain | Lung disorders

 

Respiration

1. Cellular: process of converting glucose into energy (can be aerobic or anaerobic)

2. Physiological: process of gas exchange

 

Control of respiration

1. Cerebral cortex - voluntary control 2. Brainstem - pons and medulla: autonomic control

o Medullary respiratory centre (Reticular formation) 1. Dorsal group: inspiration 2. Ventral group: expiration

o Apneustic area - prolongs inspiratory phase o Pneumotaxic area - Inhibits inspiratory area - "fine tunes"

respiratory 3. Chemoreceptors

o Central: ventral surface of medulla - sensitive to PaCO2 (which diffuses across BBB as H+)

o Peripheral: carotid/aortic bodies - sensitive to PaO2, pH, PaCO2

4. Mechanoceptors

o Pulmonary stretch receptors (Hering-Breuer inflation reflex - distension leads to slowing of inspiration/increase expiratory time)

o J-receptor (located airways close to capillaries) - stimulate respiration following increase in pulmonary blood flow

 

Oxygen dissocation curve

1. Sigmoidal curve: Progressive co-operative binding of oxygen

2. Bohr effect = Right shift of curve (reduce oxygen affinity)

o Acidosis o Increased temperature o DPG

3. Fetal ODC - right shifted (has higher affinity) to extract maternal blood

Pulse Oximetry

1. Measures haemoglobin saturation and pulse rate

2. Works on principle of spectrophotometry - differing amount of light absorbed by saturated and unsaturated Hb molecules

3. Sources of error (1) poor peripheral perfusion (2) unreliable below 70% sats (3) Ambient light (4) Nail varnish/pigments - jaundice (5) irregular cardiac rhythms

Gas diffusion

1. Fluid lining alveoli 2. Alveolar epithelium 3. Interstitial space 4. Basement membrane of capillary endothelium 5. Capillary endothelium

6. Plasma 7. Red cell membrane

 

 

Oxygen delivery

Equivalent to total oxygen capacity of blood x cardiac output

DO2 = [(Hb x sats x 1.34)1 + (0.03 x PaO2)2] x Cardic output = 200ml/L arterial blood

 

Oxygen content is determined by

1. Bound to Hb 99% o 1.34ml/g oxygen carried by haemoglobin

2. dissolved in solution 1% o Henry's Law = Gas content = product of solubility and partial

pressure of gas o Oxygen dissolved = 0.03 x PaO2

Incremental drops in pO2 from the atmosphere to blood

Alveolar-Arterial gradient:

Increased in "lung" pathology- VQ mismatch Normal in mechanical failure

Alveolar gas equation

PaO2 = PiO2 - PaCO2/R

PiO2 = Inspired PO2R = Respiratory exchange ration (0.8)

 

Oxygen therapy

1. Variable performance o Nasal cannulae o Face mask (Hudson)

2. Fixed performance o Venturi mask o Reservoir bag o Oxygen tent o CPAP o Invasive ventilation

Complications of Oxygen therapy

1. Loss of hypoxic drive 2. Absorption atelectasis (due to loss of splinting) 3. Oxygen radicals

o Direct pulmonary injury - irritates mucosa, loss of surfactant, progressive fibrosis

o Retinopathy - retrolenticular fibrosis 4. Risk of fire / explosions

 

Haemoglobin structure

Haem component + 2alpha + 2beta chains Fe2+ in protoporphoryn ring (Cf Methaemoglobin which is Fe3+ -

due to oxidation/loss of reducing enzymes) Can bind total of 4 oxygen molecules (8 atoms) Also binds: CO2, protons (H+), DPG Production in (1) Bone marrow (2) Liver + spleen (3) yolk sac in first

few weeks of gestation

 

Carbon dioxide transport

1. As bicarbonate: CO2 + H2O -- H2CO3 -- H+ + HCO3-

o Reaction catalysed by carbonic anhydrase 2. As carbanimo compounds

o formed when CO2 binds with plasma proteins (ie Haemoglobin)

3. Dissolved in solution (5%) o CO2 has x24 more solubility than oxygen

Bicarbonate generated increases intracellular osmotic pressure - resulting in increased venous haematocrit

CO2 can never be expressed as "percentage" saturations as it's solubility is not saturated!

Haldane effect : Reduced affinity for CO2 in light of increased PaO2 (downshift of CO2 dissociation curve)

 

Ventilation

Flow of gas per unit time

1. Minute ventilation = total volume of air entering respiratory tree every minute = Tidal volume x Respiratory rate

2. Alveolar ventilation = amount of gas entering alveoli each minute = (Tidal volume - dead space) x Respiratory rate

o More accurate measure of ventilation (only gas that interfaces with respiration)

o Rapid shallow breaths are inadequate (due to dead space)

Dead space = volume of gas not involved in respiration

1. anatomical - upper airways not involved in respiration; mouth, nose etc

2. Alveolar - alveoli ventilated but not perfused (shunts)

Shunt

Perfused but not ventilated Normal: bronchial circulation, cardiac thebsian veins (drain directly

into left side of heart) Pathological: Left-to-right cardiac defects (cyanotic septal defects -

tetralogy)

 

Pulmonary blood flow

1. Normal CO - 5-6l/min 2. Normal Pulmonary artery pressure = 25/8 (pulmonary vascular

resistance is approximately one tenth of systemic vascular resistance 3. Pulmonary Vascular Resistance

o falls with rising pulmonary pressure (due to distension of thin walled pulmonary vessels or to recruitment of collapsed vessels)

o Increasing radial traction reduces resistance to flow (poiseulles)

o As lung expands, radial traction forces on blood vessels increases, increasing calibre

o Controlled by (1) pulmonary artery and venous pressure (2) Lung volume (3) Pulmonary vascular smooth muscle tone (4) Hypoxia

4. Blood distribution o Standing: lowest parts of lungs have greatest flow (hydrostatic

pressure of dependent portions) o Exercise: Increased upper lobe blood flow

 

 

Respiratory concepts

1. Muscles of respiration o Diaphragm (c345) o External intercostals o Accessory muscles - SCM, scalenes, strap muscles

2. Lung

1. Determined by poiseuille's Law 2. Greatest resistance in upper airways, trachea 3. Compliance differs in inspiration and expiration - "Hysteresis" 4. Laplace Law: P = 2T/r; smaller the radius, the more the

tension 5. Increased compliance with bigger alveolar volumes (hence

CPAP) 6. Improved with surfactant (lipid-protein) from Type II

pneumocytes reducing surface tension 7. Decreased compliance with restrictive lung disease, fibrosis

o Airflow o Compliance: rate of change of volume / rate of change in

pressure = 200ml/cmH20 o Elastance: measure of elastic recoil of lung (1/compliance)

 

Respiratory assessment

1. Non-invasive o Sputum o Pulse oximetry o Capnography o Lung function

1. PEFR 2. Spirometry

Tidal Volume = 7ml/kg = 500mls

IRV = 3L ERV = 1.3L RV = Volume

remainin in lung following maximal

Obstructive airways disease: loss of flowRestrictive airways disease: loss of volume

respiration (measured by helium dilution, nitrogen washout, plethysmography)

Vital Capacity = 10-15ml/kg

Capacity = Sum of two or more volumes

FRC: Amount of gas remaining in lung at end of quiet expiration

3. Gas transfer o Imaging

1. CXR 2. CT 3. MRI 4. V/Q scanning

o Echo: assess pulmonary artery pressure and right heart function

2. Invasive o ABG o Bronchoscopy o Mediastinoscopy - performed via incision at root of neck,

permits biopsies of regional lymph nodes o Lung biopsy - open / radiologically-guided

Sodium balance

Sodium

Daily requirement: 1mmol/kg/day (cf 0.5mmol/kg/day for Potassium)

 

Distribution of Sodium in body

1. 50% extracellular 2. 45% in bone

3. 5% intracellular

Physiological role

1. Osmotic effects: internal water balance 2. Generates action potential

 

Hypontraemia Hypernatraemia 

Classification 1. Water gain o Increased intake:

polydipsia, binge drinking, TURP syndrome

o Increased retention: SIADH (lung, brain), cardiac failure, hepatic failure

2. Sodium loss (water loss) o Renal loss: Diuretics,

addisons o Gut loss: diarrhoea,

vomiting o Other: Burns, DKA

3. Pseudohyponatraemia o Due to measurement

peculiarities in presence of hyperlipidaemia

 

1. Water loss o Reduced intake: o Increased loss: Diabetes

insipidus (lack of vasopressin - cranial lack or nephrogenic insensitivity), osmotic diuresis

2. Sodium gain (over water) o Conn's / cushings o Hypertonic saline

Clinical features

Features of brain oedema - confusion, agitation, fits, reduced level of consciousness

Management 1. Overload - restrict 2. Losses - replace

Spleen

The Spleen

Size of a cupped hand; lies 9-11 ribs Forms left lateral extremity of lesser sac Ligaments - gastrosplenic, lienorenal Notched: hilum Blood supply: splenic artery

Relations

Posterior: left diaphragm anterior: stomach Inferior: splenic flexure Medially: left kidney

 

Functions of the spleen

1. Filtration - removal of old/abnormal red blood cells, white cells, platelets and cellular debris

2. Immunological - produces opsonin, antibody synthesis and protection from infection 3. Storage: 35% platelets are stored in spleen

Features in trauma to suspect splenic injury

Direct blunt trauma Guarded tender abdomen Low rib fractures (9-11 ribs) Shock Shoulder tip pain (phrenic nerve)

Systemic stress response

Stimuli

1. Trauma 2. Surgery 3. Infection 4. Hypothermia 5. Hypoglycaemia

Physiological systems involved

1. Sympathetic o Produces changes in cardiovascular endocrine and metabolic systems

2. Endocrine o ACTH release: release of cortisol / corticosterone

1. Glucose metabolism 2. Protein uptake into liver, promotion of catabolism 3. Lipolysis 4. Anti-inflammatory, immunosuppressive, anti-allergic

o GH / Somatotrophin o Glucagon o Thyroxine

3. Acute phase proteins 4. Microcirculatory changes

Valsalva

Valsalva

Forced expiration against a closed glottis (straining, defecation, coughing)

A test of physiological autonomic function Therapeutic role in termination of paroxysms of SVTs (increased vagal activity during

phase IV)

 

 

Physiological changes

1. Phase I o Rise in intrathoracic pressure o Transmitted to thoracic aorta - increase in BP

2. Phase II o Reduced venous return - fall in SV and CO o Fall in CO produced reflex tachycardia

3. Phase III o Opening glottis, sudden drop in intrathoracic pressure o Intra-arterial pressure falls as direct pressure on thoracic aorta relieved

4. Phase IV o Fall in thoracic pressure leads to improved venous return

Non-invasive ventilation

Patent airway/secretion clearing/NGT(decompress stomach)

Minimal monitoring

Saturation probe ABG/arterial line Critical care environment

 

Settings

CPAP

BiPAP

IPAP 10-20 (increase in 5cm increments) EPAP 5

BiPAP - inspired oxygen unknown due to complex interaction between gas mixing, site of O2 addition and leakageCPAP - constant oxygen flow driven

 

CPAP - Continous Positive Airways Pressure

1. Closed circuit to provide positive airways pressure throught all phases of respiratory cycle

2. Attached to Tight-fitting mask / ETT 3. Effects

o Recruitment of collapsed alveoli (prevents collapse at expiration) o Increased FRC (increases volume), improves lung compliance; reduces work

of breathing o Improves oxygenation

4. Risks: o Uncomfortable o Gastric dilation o Barotrauma to alveoli due to high pressures

 

Predictors of NIV success

Young ageLower acuity of illness (APACHE score)Able to co-operate: better neurological scoreAble to co-ordinate breathing with ventilatorLess air leak, intact dentitionImproved gas exchange

 

Adjunct treatments

Antibiotics Humidification / saline +/- bronchodilating nebules Steroids?

Coronary Thrombolysis

Effective if given within 12 hours of pain

Cannot achive re-perfusion in all casesLimited ability to detect reperfusionHigh risk of bleeding

Indications Contraindications

Presentation within 12 hours of chest pain

1. ST Elevation 2mV 2 chest leads 2. ST Elevation 1mV 2 limb leads 3. R-wave + ST depression V1-V3

(posterior infarct) 4. New LBBB

Haemorrhagic strokeCNS damage / neoplasmRecent surgery (3/52)Active internal bleedingKnown / suspected aortic dissectionKnown bleeding disorder

 

Drugs

Streptokinase - takes at least 1 hour to complete (therefore commited to CPR), can cause allergy/anaphylaxis 1.5MU in 100mls N/SalineAlteplase (R-tpa): more effective than strep, 15mg iv bolus + 0.75mg/kg/1hourReteplaseTenectplase

Percutaneous coronary intervention PCI

Recommended method for STEMIShould be achived within 90 min of medical contact

Advantages

1. Reliable re-opening of artery 2. Visual evidence of opening + calibre of vessel 3. Lower risk of bleeding