General Physiology Flashcards
(184 cards)
1
Q
Structure of cell membrane
A
- Phospholipid bilayer
- Hydrophobic lipid tails on inside
- Hydrophilic phosphate groups on outside
2
Q
Contents of cytoplasm
A
- Water (70-85%)
- Electrolytes - potassium, magnesium, sulphate and bicarbonate
- Proteins
- Lipids
- Carbohydrates
3
Q
What supports the structure of the cytoplasm
A
- Actin filaments
- Cytoskeleton of tubulin microtubules
4
Q
What surrounds the cell nucleus
A
Double phospholipid membrane which is penetrated by nuclear pores
5
Q
What protein is DNA wrapped around within the nucleus
A
Histone
6
Q
How is mRNA formed
A
- DNA unwinds from histone when gene is activated
- Two strands separate
- Transcription factor enzyme binds to the promoter region
- Allows RNA polymerase to produce complimentary copies of the gene
7
Q
How is energy derived from glucose
A
- Enters cell via facilitated diffusion under control of insulin
- Inside the cell glucose is phosphorylated to glucose-6-phosphate
- Either stored as a polymer (glycogen) or immediately for energy via glycolysis
8
Q
What maintains the resting potential of a cell
A
Na/K ATPase
9
Q
What is the average cell resting potential
A
-70mV
10
Q
What causes an action potential
A
When a stimulus alters the resting potential of the cell by a significant enough amount to cause depolarisation
11
Q
Outline the physiology of the action potential
A
- Stimulus alters resting potential of the cell membrane
- Alters the permeability to sodium ions (via voltage-gated sodium channels)
- Sodium influx into the cell
- Membrane potential continues to increase
- Peaks at +50mV
12
Q
How is the cell repolarised
A
Depolarisation causes voltage-gated potassium channels which causes potassium to move out of the cell to compensate for the Na influx
13
Q
What is the refractory period
A
Time taken for resting potential of the cell to be re-established
14
Q
What causes the action potential plateau in cardiac and smooth muscle cells
A
Slow release of calcium ions causes delay to recovery of the resting potential and allows for prolonged contraction
15
Q
What are the nodes of Ranvier
A
Bare area that transmits action potentials in myelinated neurons
16
Q
What is Saltatory conduction
A
Conduction of action potentials in myelinated nerves
17
Q
Outline the function of a synapse
A
- Action potential arrives at synapse
- Stimulates opening of calcium ion channels
- Influx of calcium draws secretory vesicles to the presynaptic membrane
- Vesicles exocytose their contnets and they travel across the synaptic cleft
- Stimulates post-synaptic receptors and alters the post-synaptic membrane to sodium 6. This change in resting potential stimulates post-synaptic action potential
18
Q
Outline the structure of the neuromuscular junction
A
- Action potential reaches terminal of the nerve and causes calcium influx
- Triggers the release of secretory vesicles of Acetycholine into the synaptic trough
- Muscle membrane of the trough has multiple Ach receptors which act as gated ion channels
- On binding Ach via nicotinic Ach receptors these channels allow sodium to flood into the cell
- This depolarises the membrane, generating an action potential
19
Q
How is the action potential transmitted through the muscle fibre
A
Via T-tubules
20
Q
Outline the mechanism of skeletal muscle contraction (excitation-contraction coupling)
A
- Action potential transmitted through muscle via T-tubules
- Depolarisation of T-tubule membrane causes release of calcium from SR in the muscle fibre
- Calcium causes actin and myosin molecule to slide over one another
- Causes muscle contraction
21
Q
Describe slow-twitch muscle fibres
A
- Type 1
- Smaller with extensive blood supply
- Contain myoglobin to act as oxygen store
- Contain mitochondira for oxidative phosphorylation
22
Q
Describe fast-twitch muscle fibres
A
- Type 2
- Larger
- Extensive sarcoplasmic reticulum for rapid release of calcium ions
- Minimal blood supply
- No myoglobin and so appear white
23
Q
Difference between actin and myosin contraction in smooth muscle compared to skeletal muscle
A
Smooth muscle contains calmodulin in the place of troponin
24
Q
Methods of smooth muscle activation/relaxation
A
- Nervous impulse (as for skeletal muscle)
- Local tissue factors e.g. hypoxia
- Hormones
25
Method of cardiac muscle contraction
Striated - contains actin and myosin filaments which contract the same as skeletal muscle
26
What makes up an actin fibre
1. Actin
2. Tropomyosin
3. Troponin
27
How do actin and myosin filaments slide over each other on contraction
1. Tropomyosin and troponin form a complex that covers/inhibits the active site
2. When this complex binds with 4 calcium ions a change occurs which uncovers the active site
3. Myosin molecule cross-bridges contain ATPase heads which bind to the actin active site
4. ATP is used to walk the myosin along the actin
5. Calcium ions are then pumped back into the sarcoplasmic reticulum
28
List the 3 main types of blood cell
1. Erythrocyte (RBC)
2. Leucocyte (WBC)
3. Thrombocytes (platelets)
29
What is the haematocrit
Percentage of blood volume made up of erythrocytes
30
Normal haematocrit
45%
31
List the 5 types of leucocyte
- Neutrophil
- Eosinophil
- Basophil
- Lymphocyte
- Monocyte
32
Lifespan of neutrophils
Spend 14 days in the bone marrow but have a half-life of 7 hours in the blood
33
Role of neutrophils
- Major cell in acute inflammation
| - Role against bacteria
34
List the 3 types of lymphocyte
1. B cells
2. T cells
3. Natural killer cells
35
Fate and role of B cells
Once activated convert into plasma cells and produce antibodies (the humoral response)
36
Role of T-cells
Produce the cell-mediated immune response
37
Role of T-helper cells
Activate macrophages and B cells
38
Role of Basophils
Initiate immediate hypersensitivity via histamine release
39
How are thrombocytes (platelets) produced
Produced from megakaryocytes via cytoplasmic fragmentation
40
Causes of primary polycythaemia
Polycythaemia rubra vera:
- Excess erythrocyte production despite low EPO
- Due to proliferation of pluripotent stem cells
- Unknown cause
41
Diagnostic Hb in polycythaemia rubra vera (male and females)
- Male Hb >180
| - Female Hb >160
42
Secondary polycythaemia - causes with appropriate rise in EPO in response to hypoxia
- Altitude
- Cardiac disease
- Pulmonary disease
- Smoking
- Haemoglobinopathy
43
Risks of polycythaemia
- Increase in blood viscosity
| - Increase risk of clots
44
List the causes of lymphocytosis
- Viral infection
- Chronic infection e.g. TB, toxoplasmosis
- CLL, lymphoma
- Acute transient response to stress (24 hours only)
45
Causes of platelet production failure
- Aplastic anaemia
- Cytotoxic drugs
- Alcohol
- EBV, CMV
- Leukaemia, myelofibrosis, myeloma
Hereditary thrombocytopenia
46
Causes of reduced platelet survival
- Idiopathic thrombocytopenic purpura
- Heparin, penicillamine, gold
- Meningococci
- Subacute bacterial endocarditis
- Thrombotic thrombocytopenic purpura
- DIC
- Dilutional from blood transfusion
- HUS
- Extracorporeal bypass
47
What occurs in DIC
Simultaneous activation of coagulation and fibrinolytic systems:
- Widespread microvascular thrombosis
- Fibrin deposition
- Bleeding due to consumption of clotting factors
- Fibrinolysis
48
How long should aspirin and clopidogrel ideally be stopped prior to operating
7 days
49
When and why does sickle cell disease manifest itself
6 months of age - when fetal Hb levels fall to be replaced by adult Hb
50
Diagnostic investigations of sickle cell disease
1. FBC
2. Blood film
3. Sickle solubility test
4. Confirmed with Hb electrophoresis
51
Sickle cell inheritance pattern
Autosomal recessive
52
Clinical features of sickle cell
1. Haemolytic anaemia
2. Pigment gallstone formation
3. Vaso-occlusive crisis
4. Ischaemic pain in fingers, chest, kidney, liver and penis
53
Sites of haemopoeisis in adults
Red marrow remains only in the axial skeleton, ribs, skull, proximal ends of femur and humerus
54
Sites of haemopoeisis in the fetus
- Bone marrow
- Spleen
- Liver
55
How are RBCs removed from the circulation
- Removed by macrophages in the spleen
- Broken down into haem and globin
- Haem releases iron that attaches to transferrin
- Remaining haem is converted to bilirubin
56
When does the proportion of reticulocytes in the blood stream increase
When bone marrow production of erythrocytes increases e.g. after haemorrhage
57
Laboratory evidence of haemolysis
1. Increased unconjugated bilirubin
2. Reduced serum haptoglobin
3. Morphological evidence of damage e.g. spherocytes
58
Cause of osteomyelitis in sickle cell anaemia
Salmonella
59
Treatment of hereditary spherocytosis
Splenectomy delayed until aged 10
60
Pathophysiology of hereditary spherocytosis
Defect in red cell membrane
61
Platelet survival time
8-10 days
62
List the four components of haemostasis
(1*Vascular injury with exposure of subendothelial tissue factor and collagen)
1. Vasoconstriction
2. Platelet activation
3. Coagulation mechanism
4. Fibrinolytic system
63
What mediates vasoconstriction
- Local reflexes
- Thromboxane A2 released from activated platelets
- Serotonin released from activated platelets
64
Describe the process of platelet adherence
1. Vessel injury causes loss of endothelium and exposure of collagen
2. Platelets adhere to damaged area and there is activation of the intrinsic pathway via thromboplastim
3. Damaged endothelial cells release VWf which is necessary for platelet adhesion
4. Platelet granules release ADP which is needed for platelet aggregation
65
Describe the process of platelet aggregation
1. Platelet phospholipids release arachidonic acid
2. Thromboxane A2 is produced by the arachidonic acid
3. Thromboxane A2 induces further platelet aggregation
66
What forms the platelet plug
- Platelets
- Thrombin
- Fibrin
67
What clotting factor is activated as the result of the enzyme reactions in the intrinsic and extrinsic pathway
Factor X
68
What is required for the initiation of the extrinsic pathway
Tissue thromboplastin and factor 7
69
Outline the intrinsic coag pathway
1. Subendothelial damage
2. Formation of primary complex on collagen by kininogen, prekallikrein, factor 12
3. Prekallikrein is converted to kallikrein and factor 12 is activated
4. Factor 12 activates factor 11
5. Factor 11 activates factor 9
6. Activated factor 9 forms tenase complex with factor 8a
7. Activates factor 10
70
Outline the extrinsic coag pathway
1. Tissue damage
2. Factor 7 binds to tissue factor
3. Activates factor 9
4. Activated factor 9 and factor 7 activated factor 10
71
Outline the common coag pathway
1. Activated factor 10 causes conversion of prothrombin to thrombin
2. Thrombin hydrolyses fibrinogen bonds to form fibrin
3. Thrombin also activates factor 13 to form cross-links between fibrin molecules
72
How is fibrin removed
Via the fibrinolytic system during the repair process in blood vessels and healing wounds
73
Outline the fibrinolytic system
1. Tissue plasminogen activator is released by endothelial cells
(regulated by plasminogen-activator inhibitor 1 from endothelial cells)
2. Permits conversion of plasminogen to plasmin
3. Plasmin breaks down fibrin into fibrin degradation products
74
What minimum platelet count is required for surgical haemostasis
70
75
At what platelet count does spontaneous bleeding occur
20
76
What does a prolonged bleeding time imply
- Thrombocytopenia
- Platelet defects
- Failure of vascular contraction
77
What does Prothrombin time (PT) test and thus detect
- Integrity of the extrinsic pathway and common pathway
| - Detects deficiencies in factors 1, 2, 5, 7, and 10
78
What does the activated partial thromboplastin time (APTT) test and detect
Intrinsic system (i.e. all factors except factor 7)
79
What is haemophilia A
Inherited deficiency of factor 8
80
Haemophilia A inheritance pattern
X-linked recessive affecting males and carried by females
81
Haemophilia clotting test results
- APTT increased
- PT normal
- Bleeding time normal
82
What is Von Willebrand disease
- Due to deficiency of VWf
- Vascular endothelium releases reduced amounts of factor 8
- Defective interaction of platelets with endothelium
83
Von Willebrand disease clotting test results
- APTT increased
- PT normal
- Bleeding time increased
84
What clotting factors is vitamin K required for the production of
2, 7, 9, 10
85
Vitamin K deficiency clotting test results
- APTT increased
- PT increased
- Bleeding time normal
86
What confirms the diagnosis of DIC
- Thrombocytopenia
- Decreased fibrinogen
- Elevated fibrin degradation products
- Prolonged PT, APTT, TT
- Fragmented RBCs
87
Describe the role of antithrombin 3
- Inhibitor of thrombin
| - Action potentiated by heparin
88
Inheritance pattern of congenital antithrombin 3 deficiency
Autosomal dominant
89
Where and how are Proteins C and S made
- In the liver
| - Dependant on vitamin K
90
Function of Protein C
- Degrades factor Va and 8a
- Inactivates plasminogen-activator inhibitor 1
- Thus promotes fibrinolysis
91
Function of Protein S
Co-factor of Protein C and enhances its activity
92
Symptoms of inherited protein C deficiency
- PE
- Superficial thrombophlebitis
- Cerebral venous thrombosis
93
Mechanism of action of heparin
Potentiates the action of antithrombin 3
94
Monitoring of heparin
APTT - aim for 2-2.5x normal
95
Side effects of heparin
- Thrombocytopenia
- Hypersensitivity reactions
- Alopecia
- Osteoporosis
96
What clotting factors does heparin inhibit
7a, 9a, 10a, 11a, kallikrein, plasmin
97
What clotting factor does LMWH inhibit
Factor 10a
98
Heparin half-life
1 hour
99
Mechanism of action of warfarin
- Vitamin K antagonist
| - Interferes with factors 2, 7, 9, 10
100
Drug of choice for anticoagulation in pregnancy and why
Heparin - does not cross placenta
101
Mechanism of action of NOACs
Direct inhibitors of activated factor 10
102
Management of haemophilia A
- Factor 8 concentrate
| - Desmopressin in mild disease
103
Management of haemophilia B
- Prothrombin complex concentrate
| - Factor 9 concentrate
104
Treatment of antithrombin 3 deficiency
- Antithrombin 3 concentrate
| - Anticoagulation
105
Treatment of protein C deficiency
- Replacement
| - Anticoagulate with warfarin
106
Management of DIC
- Fluid resus
- FFP
- Cryoprecipitate
- Platelets
107
Reversal of heparin
IV Protamine - 1mg for every 100units
108
Shelf life of RBCs
42 days at 4 degrees
109
Storage of RBCs results in loss of
- Granulocyte and platelet function
| - Factors 5 and 8
110
Biochemical changes from RBC storage
- Increased lactate
- Increased potassium
- Increased phosphate
- Decrease in pH
- Haemolysis
111
Make up of platelet transfusion
Platelets suspended in plasma
112
Contents of FFP
Contains all clotting factors
113
Contents of cryoprecipitate
- Factor 8 (primarily)
- Fibrinogen
- Von Willebrand factor
114
Fast reversal of Warfarin
Human prothrombin complex (reversal within 1 hour)
115
Indications for platelet transfusion
- Haemorrhage in presence of thrombocytopenia
- Thrombocytopenia prior to invasive procedures
- Consumptive coagulopathy e.g. DIC
116
Indications for FFP transfusion
- Replace clotting factors in major haemorrhage
- Liver disease, rapid reversal of warfarin
- DIC
- Prophylaxis in patients with clotting defects
117
Indications for cryoprecipitate transfusion
- Haemophilia
- Von Willebrands disease
- Fibrinogen deficiency e.g. DIC
118
Cause of immediate haemolytic transfusion reaction
ABO incompatibility
119
Symptoms of immediate haemolytic transfusion reaction
- Pyrexia
- Dyspnoea
- Chest pain
- Severe loin pain
- Collapse/hypotension
- Haemoglobinuria
- Oliguria
- Jaundice
- DIC
120
When does delayed haemolytic transfusion reaction occur
5-10 days post transfusion
121
Most likely blood product to cause urticaria
FFP
122
Why does urticaria occur in plasma transfusions
Patient's IgE antibody complexing with a protein present in the donor plasma
123
Why does TRALI occur
Incompatibility between donor antibodies and recipient granulocytes
124
Autologous blood predonation amount
4 units over 4 weeks
125
How much blood can safely be removed from a patient without cardiac disease
2L
126
What occurs in transfusion reaction to white blood cells and why
- Febrile reaction
- Fever and flushing soon after the start of the transfusion
- Due to recipient leucocyte antibodies
127
List the potential complications of massive blood transfusion
- Overload
- Cardiac arrhythmia due to cold blood
- Citrate toxicity causing hypocalcaemia
- Hypothermia
- Hyperkalaemia
- Metabolic acidosis from acidity of stored blood
- Haemorrhage due to coagulopathy
- DIC
- ARDS
128
When does delayed haemolytic transfusion reaction occur
5-10 days after transfusion
129
What are the signs of delayed haemolytic transfusion reaction on blood film
- Spherocytosis
| - Reticulocytosis
130
What is the fluid composition of a 70kg man
- TBW = 46L
- Intracellular water = 25L
- Extracellular water = 19L (3L = plasma, 15L = interstitial fluid, 1L = trancellular fluid)
131
What are the two types of diuresis
1. Water
| 2. Osmotic
132
Describe water diuresis
1. Excess water ingested
2. ADH suppressed
3. Collecting ducts become impermeable to water
4. Water is lost without solute
133
Describe osmotic diuresis
This results when more solute is presented to the tubules than they can reabsorb
134
Give examples of osmotic diuresis
- DM
- Mannitol (a filtered by non-reabsorbed solute)
- Inhibition of tubular function (e.g. drugs that block NaCl reabsorption)
135
What are the main cations in intracellular fluid
- K+
| - Mg2+
136
What are the main cations in extracellular fluid
Na+
137
What 2 factors determine the osmolality of the bodies fluid compartments
1. Adjustments in ADH
| 2. Thirst
138
Where in the brain is thirst and ADH secretion controlled
By the osmolality of the plasma-perfusing nuclei in the hypothalamus
139
What biochemical abnormality is associated with pure water deficiency
Hypernatraemia
140
How is pure water deficiency corrected
5% dextrose
141
Where is sodium reabsorbed in the nephron
- 65% in the PCT
- 25% in the loop of Henle
- 10% in the DCT/collecting ducts
142
What is the effect of ANP on body sodium
ANP increases excretion of Na+:
- Increases GFR
- Inhibits Na reabsorption in the collecting ducts
- Reduces secretion of renin and aldosterone
143
How should symptomatic severe (<119) hyponatraemia be treated
Hypertonic saline
144
What is the effect of aldosterone on potassium balance
- Increases renal excretion by effects on DCT
| - Exchanges for H+
145
What is the effect of acid-base balance on serum potassium concentration
Acidosis results in increased serum K+ due to reduced entry into cells and reduced urinary excretion
146
What are ECG changes associated with hyperkalaemia
- Peaked T-waves
- Loss of P-waves
- QRS widening
147
What are the ECG changes associated with hypokalaemia
- Low broad T-waves
| - U-waves
148
What catalyses the carbonic acid-bicarbonate system
Carbonic anhydrase
149
What does the Henderson-Hasselbach equation prove
That pH depends on the ration of HCO3 (kidney function) to pCO2 (respiratory function)
150
How can the Henderson-Hasselbach equation be simplified
pH = constant + (kidney function/respiratory function)
151
Describe the compensation that occurs in respiratory acidosis
- Increased bicarbonate by buffer
| - Reduced H+ by kidneys
152
How can acute and chronic CO2 retention be differentiated on ABG
- Acute = bicarb may be normal as not enough time to change
| - Chronic = pH may be normal as bicarb increased
153
List the causes of metabolic alkalosis
- Vomiting
- NG aspirations
- Gastric fistula
- Thiazides and Loop diuretic
- Cushing's syndrome
- Conn's syndrome
- Milk-alkali syndrome
154
List the GI causes of metabolic acidosis
From excessive loss of base:
- Diarrhoea
- Intestinal, biliary, pancreatic fistulae
155
What does a high base excess indicate
Metabolic alkalosis
156
What does a low base excess indicate
Metabolic acidosis
157
How is the anion gap calculated
(Na + K) - (HCO3 + Cl)
158
What is the normal anion gap
10-19
159
What causes an increased anion gap
Metabolic acidosis resulting from production of an acid
160
When does the ebb phase occur in response to trauma and what is its purpose
- First few hours (<24 hours)
| - Protective mechanism to conserve circulatory volume and minimise demands on the body
161
What modulates the ebb phase
- Catecholamines
- Cortisol
- Aldosterone
162
What physiological changes occur in the ebb phase
- Reduced O2 consumption
- Reduced enzymatic activity
- Reduced CO
- Reduced basal metabolic rate
- Reduced body temperature
- Increased production of acute phase proteins
163
When does the flow phase occur in response to trauma and what is its purpose
- >24 hours after insult
- Hypermetabolic state
- Initially catabolic (3-10 days) allowing for mobilisation of the building blocks for repair
- Later anabolic (10-60 days) with repair of tissue
164
Why is the body predisposed to gut bacteria translocation following trauma
- Gut mucosal integrity relies on amino acids (specifically Glutamine)
- This is reduced post-trauma
165
What is the primary fuel of the catabolic phase
Glucose - liver produces this from catabolism of fats and protein to maintain high serum levels
166
How much energy is supplied by 1g of carbohydrate
4.1 kcal
167
How much energy is supplied by 1g of protein
5.3 kcal
168
How much energy is supplied by 1g of fat
9.3 kcal
169
What occurs to fluid balance following surgical trauma
- ADH and aldosterone is released
- Na is retained and K excreted
- Water conserved
170
By how much does fever increase maintenance fluid requirements
By 20% for each 1 degree rise in temperature
171
How much fluid does an average adult lose over a 24 hour period
2.5 - 3L
172
Which colloids are suitable for short-term volume expansion
- Gelatin (Gelofusin)
| - Dextran
173
Which colloids are suitable for medium-term volume expansion
- Albumin
| - Pentastarch
174
Which colloids are suitable for long-term volume expansion
- Hetastarch
175
What cautions must you be aware of with Dextran use
- Interferes with cross-matching
- Interferes with coagulation (reduces factor 8, inhibits platelet aggregation)
- High incidence of allergy
176
Where are gelatins derived
Bovine collagen
177
What are the general problems associated with plasma expanders
- Dilution coagulopathy
- Allergic reactions
- Interferes with cross-matching (Dextran 70)
178
In a given volume of crystalloid, how much remains in the intravascular compartment and how much moves to the ECF
- Intravascular = 1/3rd
| - ECF = 2/3rd
179
What safety measures should be taken when using K+ containing fluids
- Urine output at least 40ml/hr
- No more than 40mmol to be added to 1L bag
- Infusion fate no faster than 40mmol/hr (typically 10mmol/hr)
180
What does the Starling Equilibrium explain
The relationship between hydrostatic pressure, oncotic pressure, and fluid flow across the capillary membrane
181
Where are the body's temperature-sensitive receptors located
Anterior hypothalamus
182
Describe the reflex vasoconstriction loop
- Direct contact with cold stimulus
- Afferent neuron = cutaneous nerve
- Centre = hypothalamus and spinal cord
- Efferent = sympathetic fibres
183
Describe the reflex vasodilatation loop
- Application of radiant heat
- Afferent neuron = cutaneous nerve
- Centre = above C5 of spinal cord
- Efferent pathway = sympathetic fibres (reduced activity)
184
Which clotting factors are produced by hepatocytes
5, 7, 9, 10, 11, 12
