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Physiology for Anaesthetists > The cell membrane > Flashcards

The cell membrane Flashcards

1
Q

Describe the membrane ‘bilayer’

A

Hydrophillic phosphate head - hydrophillic fatty acid tail.

Hydrophobic core prevents movement of free water across the membrane into the cell.

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2
Q

Apart from the bilayer what other structures are found within the cell membrane and what is the function of each of these structures

A

PROTEINS

  1. PUMPS (and channels) –> transport
  2. CARRIERS –> transport
  3. ION CHANNELS –> Transport
  4. RECEPTORS –> intercellular communication
  5. ENZYMES –> Catalyse reactions on the cell’s surface
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3
Q

What is the function of transmembrane proteins

A

Allow controlled transfer of solutes and water into and out of the cell

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4
Q

What forces hold the phospholipids of the phospholipid bilayer together?

A

Van der Waals forces
Hydrogen bonds
Non-covalent interactions

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5
Q

List 5 ways that transport across the cell membrane can occur

A
  1. Diffusion
  2. Osmosis
  3. Active transport
  4. Endocytosis
  5. Exocytosis
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6
Q

Classify and define ‘diffusion’ across a cell membrane

A

Net movement of particles down their concentration gradient.

Simple: no carrier protein
Facilitated: Carrier protein

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7
Q

Describe the acetylcholine nicotinic receptor versus the muscarinic receptor structure and mechanism of receptor stimulation

A

Nicotinic
5 subunit transmembrane receptor with central channel
- Beta, Delta, alpha, gamma, alpha (clockwise from 12 o’clock (pentagonal). Ligand binding opens channel

Muscarinic
7 transmembrane protein - G-coupled protein - cAMP/Inositol triphosphate pathway.

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8
Q

Give three examples of G-protein coupled receptors

A

Muscarinic acetylcholine receptors
Adrenoreceptors
Histamine receptors

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9
Q

Describe how binding of a ligand to the G protein receptor brings about an intracellular effect

A

Ligand - receptor –> GTP replaces GDP on the alpha subunit of G-receptor complex –> binds to calcium ion channel –> Influx of calcium –> Calcium binds to calmodulin –> intracellular response.

GTPase acts on GTP-alpha complex to re-associate the alpha/gamma/beta/GDP complex attached to the seven serpentine transmembrane protein ready for the next ligand to bind.

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10
Q

Give two examples of substances with tyrosine kinase receptors

A

Insulin

Erythropoietin

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11
Q

Describe the structure of the insulin receptor

A

N-terminal (alpha subunits) - extracellular - bind insulin

Beta subunits (within cell membrane) - connect N-terminal with C - Terminal

The C-terminal is composed of Tyrosine kinase which activates Insulin receptor substrates (IRS) via phosphorylation bringing about the effects of insulin

  1. Glucose transport
  2. Protein synthesis
  3. Fat synthesis
  4. Glucose synthesis
  5. Growth and gene expression
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12
Q

How does insulin bring about the transport of glucose into cells

A

Insulin attaches to the N-terminal of the insulin receptor. Via the beta subunits which attach to intracellular tyrosine kinase –>phosphorylation of insulin receptor substrates –> insertion of the GLUT4 transporters into the cell membrane which allow for glucose absorption.

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13
Q

What are ionotropic receptors? Give 3 examples

A

Ligand gated ion channels that open and close in response to ligand binding. The binding is usually located on a different part of the protein to the ion channel = allosteric binding

Examples

  1. Nicotinic acetylcholine receptor
  2. NMDA receptor
  3. GABA receptor
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14
Q

Describe the function of a nicotinic acetylcholine receptor

A

Two acetylcholine molecules must bind to both alpha subunits on the 5 subunit receptor (beta,delta,alpha, epsilon, alpha).

This opens the central channel allowing positive ions to be transmitted through channel (Na / K / Ca)

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15
Q

Give 4 examples of intracellular receptors

A

Sex hormones
Thyroid hormones
Vit D receptors
IP3 receptors (second messenger)

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16
Q

What 3 features of capillaries allow for exchange between blood and interstitial fluid?

A
  1. Blood moves slowly through the narrow vessels (50 -100 mm/s)
  2. Large surface area for diffusion
  3. Thin walls to minimize the diffusion distance (Fick’s law)
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17
Q

Describe the basic structure of a capillary vessel

A

An endothelial tube with in a basal lamina
No tunica media. No tunica externa.

Diameter - 5 - 9 um (RBC diameter 8 um)
Length - 0.5 - 1 mm

RBCs transit capillaries in single file

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18
Q

Name and describe the different type of capillaries from a microscopic perspective. Give examples of where each type are found in the body

A

Continuous - No fenestrations (but 3 subtypes)

  1. Classic
  2. Tight junctions
  3. Sinusoidal capillaries (Liver and Spleen) - these have a discontinuous basal lamina

Fenestrated - fenestrations (100 nm in diameter)
e.g. renal glomeruli and most endocrine glands

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19
Q

Which two tissue types contain no capillaries?

A

Epithelium of the skin

Cartilage

20
Q

Describe how solutes/water, proteins, lipid soluble molecules are transported across the continuous capillary

A

Solutes/water - paracellular transit

Proteins - transcytosis (endosomes)

Lipid soluble - e.g. CO2 and O2 diffuse passively across the plasma membrane of endothelial cells

21
Q

Where are continuous capillaries with tight junctions found and which substances can pass freely through this type of capillary

A

Blood brain barrier
(and the thymus)

Pass freely: CO2 | O2 | NH3 | Small alcohols | Steroids | Prostaglandins

22
Q

How do the various types of molecules transit into the brain through the blood brain barrier

A
  1. CO2 / O2 / NH3 / Small alcohols / Steroids / Prostaglandins - move in and out freely
  2. Water and ions: specific channels in the apical and basal membrane
  3. Minimal vesicular transport here
  4. Larger water soluble molecules must pass through by active or passive transport
23
Q

What happens to the integrity of the blood brain barrier in the event that the astrocyte end feet are damaged by trauma/inflammation or ischaemia

A

BBB weakened and will leak. BBB will lose selective permeability

24
Q

Which endocrine organs have fenestrated capilllaries?

A

Circumventricular organs:

  • Hypothalamus
  • Pituitary

Pineal gland

Thyroid

25
Q

What type of capillary exist in the choroid plexus and how is CSF contents controlled

A

Fenestrated capillaries exist in the choroid plexus but choroid cells, which separate the capillaries from CSF have tight junctions which control the contents of CSF

26
Q

Are there fenestrated capillaries in the GIT

A

In certain places to allow peptides and polysaccharides to be absorbed

27
Q

How many layers does the filtration membrane in the glomerulus contain. Describe the layers

A
  1. Endothelial cells (fenestrated)
  2. Basement membrane
  3. Podocytes with filtration slits (visceral epithelium of Bowman’s capsule
28
Q

How does the position of the mesangial cells differ from the podocytes on a histological cross section of the cells within the bowman’s capsule

A

Mesangial cells: between endothelial cells within the basal lamina.

Podocytes: Contain podocyte processes with filtration slits and outside the basal lamina

29
Q

What is the function of the mesangial cells

A

Contraction and regulation of GFR

30
Q

Where are sinusoid capillaries found. Describe these

A

Liver, Spleen and bone marrow.

There are large gaps between the endothelial cells allowing free passage of macromolecules

31
Q

Can venules and arterioles act as exchange vessels

A

Venules can - thin wall and minimal to no smooth muscle

Arterioles - no

32
Q

What is a metarteriole

A

the arteriole that supplies a collapsed bed of capillaries yet to open

33
Q

What is a pericyte and what is the function of a pericyte

A

Spatially isolated contractile cells on capillaries

  1. Alteration luminal diameter (contractile)
  2. Synthesize constituents of the basement membrane and extracellular matrix
  3. Release vasoactive substances
  4. Regulate flow through endothelial cell junctions (esp. in inflammation)
34
Q

How is pulsatile capillary flow achieved and what is the purpose of this

A
  1. Autonomic arteriolar vasoregulation
  2. Capillary sphincters contract 12 x per minute

This ensures the perfusion path is continually changing

35
Q

Why does the skin turn white when a pointed object is dragged across the skin

A

The mechanical stimulus causes closure of pre-capillary sphincters and pericytic veins

36
Q

What is the minimum and resting transit time of a capillary

A

Minimum 1s

Resting 2s

37
Q

Give an example of how blood pressure is affected by gravity

A

Standing patient:

BP in the foot is 112 mmHg higher than at the heart

Capillary hydrostatic pressure at the foot increases from 30 mmHg to 97 mmHg when the person is ambulant

38
Q

Define hydrostatic pressure

A

The pressure measured in a fluid at that point (affected by gravity)

39
Q

Write the Starling Equation and denote the symbols

A

Q = KA[(Pc - Pi) - s(pc-pi)]

Q = Fluid movement
K = Permeability constant
A = Area of membrane
Pi = interstitial hydrostatic pressure
Pc = capillary hydrostatic pressure

s = reflection co-efficient for Albumin

pi = oncotic pressure interstitium
pc = oncotic pressure capillary
40
Q

List the pathophysiological mechanisms of oedema

A
  1. Excessive ultrafiltration
    - Arteriolar VD | Neurogenic pulm. oedema | Fluid overload | Renal failure | Loss of autoregulation | Venous obstruction/congestion | Prolonged gravity
  2. Decreased osmotic pressure
    - Malnutrition / Nephrotic syndrome / Cirrhosis / Chronic illness / Pre-eclampsia
  3. Increased capillary permeability
    - Substance P / Histamine / IL / Kinins / Burns
41
Q

Why is flow resistance less in the capillaries versus in the aorta

A

Cross sectional area

  1. Aorta = 4.5 cm2
  2. Capillaries = 4500 cm2
42
Q

How does capillary density vary between tissues

A
  1. % x more dense in heart and brain versus skeletal muscle (depends on metabolic activity of tissue)
43
Q

What is the range for transit time of blood through capillaries and what influences this

A

Normal: 0.5 to 2 s at rest

Down to 0.25s in metabolically active tissues

44
Q

What is the distribution of blood at any one time in the CVS.

A 
Aorta: 2%
Arteries: 8%
Arteriole 1%
Capillary: 5%
Venous: 54%
Heart 12%
Pulmonary 18%
45
Q

What are typical capillary pressures

A

Arterial end ± 32 mmHg

Venous end ± 15 mmHg

46
Q

Compare permeability of skeletal muscle capillaries to glomerular capillaries

A

Glomerular capillaries are 50 x more permeable

Physiology for Anaesthetists (61 decks)

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