The hepatic portal system

The capillary beds of most tissues drain into veins that lead directly back to the heart. But blood draining the intestines is an exception. The veins draining the intestine lead to a second set of capillary beds in the liver. Here the liver removes many of the materials that were absorbed by the intestine:

• Glucose is removed and converted into glycogen.
• Other monosaccharides are removed and converted into glucose.
• Excess amino acids are removed and deaminated.
  • The amino group is converted into urea.
  • The residue can then enter the pathways of cellular respiration and be oxidized for energy.
• Many nonnutritive molecules, such as ingested drugs, are removed by the liver and, often, detoxified.

The liver serves as a gatekeeper between the intestines and the general circulation. It screens blood reaching it in the hepatic portal system so that its composition when it leaves will be close to normal for the body.

Furthermore, this homeostatic mechanism works both ways. When, for example, the concentration of glucose in the blood drops between meals, the liver releases more to the blood by

• converting its glycogen stores to glucose (glycogenolysis)
• converting certain amino acids into glucose (gluconeogenesis).

Function of Blood

• transport through the body of
  • oxygen and carbon dioxide
  • food molecules (glucose, lipids, amino acids)
  • ions (e.g., Na⁺, Ca²⁺, HCO₃⁻)
  • wastes (e.g., urea)
  • hormones
  • heat
• defense of the body against infections and other foreign materials. All the WBCs participate in these defenses

The hypothalamus is a region of the brain. It secretes a number of hormones.

• Thyrotropin-releasing hormone (TRH)
• Gonadotropin-releasing hormone (GnRH)
• Growth hormone-releasing hormone (GHRH)
• Corticotropin-releasing hormone (CRH)
• Somatostatin
• Dopamine

All of these are released into the blood, travel immediately to the anterior lobe of the pituitary, where they exert their effects.

Two other hypothalamic hormones:

• Antidiuretic hormone (ADH) and
• Oxytocin

travel in neurons to the posterior lobe of the pituitary where they are released into the circulation.

Cardiac Output:

Minute Volume = Heart Rate X Stroke Volume

Heart rate, HR at rest = 65 to 85 bpm  

Each heartbeat at rest takes about .8 sec. of which .4 sec. is quiescent period.

Stroke volume, SV at rest = 60 to 70 ml.

Heart can increase both rate and volume with exercise. Rate increase is limited due to necessity of minimum ventricular diastolic period for filling. Upper limit is usually put at about 220 bpm. Maximum heart rate calculations are usually below 200. Target heart rates for anaerobic threshold are about 85 to 95% of maximum.

Terms:

End Diastolic Volume, EDV - the maximum volume of the ventricles achieved at the end of ventricular diastole. This is the amount of blood the heart has available to pump. If this volume increases the cardiac output increases in a healthy heart.

End Systolic Volume, ESV - the minimum volume remaining in the ventricle after its systole. If this volume increases it means less blood has been pumped and the cardiac output is less.

EDV - ESV = SV

SV / EDV = Ejection Fraction The ejection fraction is normally around 50% at rest and will increase during strenuous exercise in a healthy heart. Well trained athletes may have ejection fractions approaching 70% in the most strenuous exercise.

Isovolumetric Contraction Phase - a brief period at the beginning of ventricular systole when all valves are closed and ventricular volume remains constant. Pressure has risen enough in the ventricle to close the AV valves but not enough to open the semilunar valves and cause ejection of blood. 

Isovolumetric Relaxation Phase - a brief period at the beginning of ventricular diastole when all valves are closed and ventricular volume is constant. Pressure in the ventricle has lowered producing closure of the semilunar valves but not opening the AV valves to begin pulling blood into the ventricle.

Dicrotic Notch - the small increase in pressure of the aorta or other artery seen when recording a pulse wave. This occurs as blood is briefly pulled back toward the ventricle at the beginning of diastole thus closing the semilunar valves.

Preload - This is the pressure at the end of ventricular diastole, at the beginning of ventricular systole. It is proportional to the End Diastolic Volume (EDV), i.e. as the EDV increases so does the preload of the heart. Factors which increase the preload are: increased total blood volume, increased venous tone and venous return, increased atrial contraction, and the skeletal muscular pump.

Afterload - This is the impedence against which the left ventricle must eject blood, and it is roughly proportional to the End Systolic Volume (ESV). When the peripheral resistance increases so does the ESV and the afterload of the heart. 

The importance of these parameters are as a measure of efficiency of the heart, which increases as the difference between preload and afterload increases

Water: comprises 60 - 90% of most living organisms (and cells) important because it serves as an excellent solvent & enters into many metabolic reactions

• Intracellular (inside cells) = ~ 34 liters
• Interstitial (outside cells) = ~ 13 liters
• Blood plasma = ~3 liters

40% of blood is red blood cells (RBCs)

plasma is similar to interstitial fluid, but contains plasma proteins

serum = plasma with clotting proteins removed

intracellular fluid is very different from interstitial fluid (high K concentration instead of high Na concentration, for example)

• Capillary walls (1 cell thick) separate blood from interstitial fluid
• Cell membranes separate intracellular and interstitial fluids

• Loss of about 30% of body water is fatal

Ions = atoms or molecules with unequal numbers of electrons and protons:

• found in both intra- & extracellular fluid
• examples of important ions include sodium, potassium, calcium, and chloride

Ions (Charged Atoms or Molecules) Can Conduct Electricity

• Giving up electron leaves a + charge (cation)
• Taking on electron produces a - charge (anion)
• Ions conduct electricity
• Without ions there can be no nerves or excitability
  • Na⁺ and K⁺ cations  
  • Ca²⁺ and Mg²⁺ cations  control metabolism and trigger muscle contraction and secretion of hormones and transmitters

Na+ & K+ are the Major Cations in Biological Fluids

• High K+ in cells, high Na+ outside
• Ion gradients maintained by Na pump (1/3 of basal metabolism)
• Think of Na+ gradient as a Na+ battery- stored electrical energy
• K+ gradient forms a K+ battery
• Energy stored in Na+ and K+ batteries can be tapped when ions flow

• Na+ and K+ produce action potential of excitable cells

Glomerular filtration

Kidneys receive about 20% of cardiac output , this is called Renal Blood Flow (RBF) which is approximatley 1.1 L of blood. Plasma in this flow is about 625 ml . It is called Renal Plasma Flow (RPF) .
About 20 % of Plasma entering the glomerular capillaries is filtered into the Bowman`s capsule .
Glomerular filtration rate is about 125 ml/min ( which means 7.5 L/hr and thus 180 L/day) This means that the kidney filters about 180 liters of plasma every day.

The urine flow is about 1ml/min ( about 1.5 liter /day) This means that kidney reabsorbs about 178.5 liters every day .

Filtration occurs through the filtration unit , which includes :

1- endothelial cells of glomerular capillaries , which are fenestrated . Fenestrae are quite small so they prevent filtration of blood cells and most of plasma proteins .

2- Glomerular basement membrane : contains proteoglycan that is negatively charged and repels the negatively charged plasma proteins that may pass the fenestrae due to their small molecular weight like albumin . so the membrane plays an important role in impairing filtration of albumin .

3- Epithelial cells of Bowman`s capsule that have podocytes , which interdigitate to form slits .

Many forces drive the glomerular filtration , which are :

1- Hydrostatic pressure of the capillary blood , which favours filtration . It is about 55 mmHg .

2- Oncotic pressure of the plasma proteins in the glomerular capillary ( opposes filtration ) . It is about 30 mm Hg .

3- Hydrostatic pressure of the Bowman`s capsule , which also opposes filtration. It is about 15 mmHg .

The net pressure is as follows :

Hydrostatic pressure of glomerular capillaries - ( Oncotic pressure of glomerular capillaries + Hydrostatic pressure of the Bowman capsule):
55-(35+10)
=55-45
=10 mmHg .

Te glomerular filtration rate does not depend only on the net pressure , but also on an other value , known as filtration coefficient ( Kf) . The later depends on the surface area of the glomerular capillaries and the hydraulic conductivity of the glomerular capillaries.