Transcript Pathological forms of hemoglobin. Acid

Pathological forms of
hemoglobin. Acidbase state of blood.
Hemoglobin
Hemoglobin (also spelled haemoglobin and abbreviated Hb or Hgb) is the
iron-containing oxygen-transport metalloprotein in the red blood cells of
vertebrates,and the tissues of some invertebrates.
In mammals, the protein makes up about 97% of the red blood cell's dry
content, and around 35% of the total content (including water). Hemoglobin
transports oxygen from the lungs or gills to the rest of the body (i.e. the
tissues) where it releases the oxygen for cell use.
Hemoglobin has an oxygen binding capacity of between 1.36 and 1.37 ml O2
per gram of hemoglobin, which increases the total blood oxygen capacity
seventyfold.
Hemoglobin is also found in outside red blood cells and their progenitor lines.
Other cells that contain hemoglobin include the A9 dopaminergic neurons in
the substantia nigra, macrophages, alveolar cells, and mesangial cells in the
kidney. In these tissues, hemoglobin has a non-oxygen carrying function as an
antioxidant and a regulator of iron metabolism.
Methemoglobin
• The iron ion may either be in the Fe2+ or Fe3+
state, but ferrihemoglobin (methemoglobin)
(Fe3+) cannot bind oxygen. In binding, oxygen
temporarily oxidizes (Fe2+) to (Fe3+), so iron
must exist in the +2 oxidation state to bind
oxygen. The enzyme methemoglobin reductase
reactivates hemoglobin found in the inactive
(Fe3+) state by reducing the iron center.
Carboxyhemoglobin
• The binding of oxygen is affected by molecules such as
carbon monoxide (CO) (for example from tobacco
smoking, car exhaust and incomplete combustion in
furnaces). CO competes with oxygen at the heme binding
site. Hemoglobin binding affinity for CO is 200 times
greater than its affinity for oxygen, meaning that small
amounts of CO dramatically reduce hemoglobin's ability to
transport oxygen. When hemoglobin combines with CO, it
forms a very bright red compound called
carboxyhemoglobin, which may cause the skin of CO
poisoning victims to appear pink in death, instead of white
or blue.
Acid-base homeostasis
• Acid-base homeostasis is the part of
human homeostasis concerning the proper
balance between acids and bases, in other
words, the pH. The body is very sensitive to
its pH level, so strong mechanisms exist to
maintain it. Outside the acceptable range of
pH, proteins are denatured and digested,
enzymes lose their ability to function, and
death may occur.
Mechanism
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The body's acid-base balance is tightly regulated. Several buffering
agents that reversibly bind hydrogen ions and impede any change in pH
exist. Extracellular buffers include bicarbonate and ammonia, whereas
proteins and phosphate act as intracellular buffers. The bicarbonate
buffering system is especially key, as carbon dioxide (CO2) can be
shifted through carbonic acid (H2CO3) to hydrogen ions and bicarbonate
(HCO3-) as shown below.
Acid-base imbalances that overcome the buffer system can be
compensated in the short term by changing the rate of ventilation. This
alters the concentration of carbon dioxide in the blood, shifting the
above reaction according to Le Chatelier's principle, which in turn alters
the pH. For instance, if the blood pH drops too low (acidemia), the body
will compensate by increasing breathing, expelling CO2, and shifting the
above reaction to the right such that less hydrogen ions are free; thus
the pH will rise back to normal. For alkalemia, the opposite occurs.
The kidneys are slower to compensate, but renal physiology has several
powerful mechanisms to control pH by the excretion of excess acid or
base. In responses to acidosis, tubular cells reabsorb more bicarbonate
from the tubular fluid, collecting duct cells secrete more hydrogen and
generate more bicarbonate, and leads to increased formation of the
NH3 buffer. In responses to alkalosis, the kidney may excrete more
bicarbonate by decreasing hydrogen ion secretion from the tubular
epithelial cells, and increasing rates of glutamine metabolism and
ammonia excretion.