cystic fibrosis

People with CF inherited two copies of a defective gene — one copy from each parent. The CFTR gene is
located on the long arm (q) of chromosome 7 - 3 base pair deletion leading to absence of phenylalanine at
position 508 (DF508) of the CF transmembrane conductance regulator (CFTR) gene.

In healthy individuals, the normal protein allows movement of Na+ and Cl- ions Keeps mucus thin
and easily swept away With CF, not enough Cl- ions are pumped out Thickening of mucus in
airways and pancreatic ducts

Lung
High rate of sodium absorption and low rate of chloride secretion reduces salt and water
content in mucus, depletes peri-ciliary liquid Mucus adheres to airway surface, leads to
decreased mucus clearing Predisposition to Staph and Pseudomonas infections
Pancreas
Absence of CFTR limits function of chloride-bicarbonate exchanger to secrete bicarbonate
Leads to retention of enzymes in the pancreas, destruction of pancreatic tissue.
Intestine
Decrease in water secretion leads to thickened mucus and dessicated intraluminal contents
Obstruction of small and large intestine
 Two elevated sweat chloride concentrations on two separate days
Identification of two CF mutations
Abnormal nasal potential difference measurement

Allele-specific oligonucleotide probe analysis

The samples of DNA are spotted onto nitro-cellulose paper in narrow bands. The paper is then incubated with the
probe either for the normal or the mutant sequence. Since it does not involve an electrophoresis step, this type of
analysis is much less time-consuming (and less expensive).

Gene therapy
Since respiratory failure is the major cause of deaths (95 percent) in CF, lung cells have become the
primary target for efforts at treating CF with gene therapy.

Wernikle Korsakoff syndrome secondary to Thiamine

Deficiency

The patient’s symptoms of nausea, vomiting, respiratory distress, palpitation, dyspnea, and
edema can be explained by the metabolic manifestations of thiamine deficiency.
 Thiamine is required for the conversion of pyruvate to acetyl-CoA in the citric
acid cycle, and its deficiency leads to an accumulation of pyruvate and lactate.
Elevated levels of blood lactate, pyruvate, and alanine in the laboratory analysis
are consistent with impaired pyruvate metabolism.

The decreased level of bicarbonate suggests metabolic acidosis, which can

occur due to the accumulation of lactate and other organic acids. This can
lead to respiratory distress and compensatory tachycardia (elevated heart
rate) as the body tries to compensate for the acidosis.

The increased concentrations of pyruvate, lactate, and alanine indicate that there is a block in the
pathway leading from pyruvate toward the TCA cycle.
A deficiency in pyruvate dehydrogenase would lead to a buildup of pyruvate.
Pyruvate has three fates other than conversion to acetyl-CoA by pyruvate dehydrogenase:
conversion to oxaloacetate by pyruvate carboxylase, reduction to lactate by lactate dehydrogenase,
and transamination to the amino acid alanine.
Thus, because pyruvate builds up, an increase in lactate and alanine would be expected if pyruvate
dehydrogenase was deficient.
GP120 on the virus binds CD4 receptors on the host. A second coreceptor molecule (CCR5 or CXCR) on the
host is also required for binding.
Membranes of the virus and the host cell fuse, and viral RNA and reverse transcriptase enter the host’s
cytoplasm.

GP120 on the virus binds CD4 receptors on the host.

It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation
of the nucleotide analogue. It competes with the natural substrate dGTP and incorporates itself into viral
DNA. It is also a weak inhibitor of cellular DNA polymerase α and γ.

T also interferes with host cell DNA synthesis, it causes severe side-effects among which are:
Anemia (because of inhibition of DNA synthesis in erythroid precursor cells)
Neutropenia (because of inhibition of DNA synthesis in neutrophil generation)
Myopathy (muscle pain)

These individuals often have unusual helper T cells with a less-efficient variant of the coreceptor
CCR5, which is necessary for viral entry into helper T cells.
There are also individuals who become infected, but do not progress to AIDS. These long-term
survivors, or long-term non-progressors, include individuals who have been AIDS-free as long as
eighteen years after infection.
 type 2 diabetes mellitus
obesity, sedentary life style, and, in women

Insulin resistance as a result of a postinsulin receptor defect. The insulin levels are normal or increased as
compared with normal individuals; however, the insulin is not “recognized,” and thus the glucose levels
remain elevated

HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk
of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor
for coronary heart disease and stroke in subjects with or without diabetes.

Metabolic disorders due to acute insulin insufficiency Characterized by

Hyperglycemia,.ketonemia,ketonuria ,venous ph<7.2 bicarbonate <15mmole/l

Lack of insulin, in the face of elevated glucagon and

epinephrine, leads to high rates of hepatic glucose output, being driven by
β -oxidation of fatty acids. The latter results in an excessive production of ketone
bodies and subsequent ketoacidosis.
 They Help to Know the Functional status of the Liver as this Patient has Liver
Cirrhosis

Prothrombin Time and ALbumin levels

ammonia is a by product of amino acid metabolism.it is toxic in it form and so it is

transported to the liver where through the urea cycle it's converts to it's less toxic
form urea.
The patient has diminished liver functions secondary to cirrhosis and so the
ammonia is not being converted to urea leading to it's accumulation in the body.

urea cycle.

proteins are broken down to amino acids whose metabolism leads to production of
ammonia as a by product.increased intake of proteins leads to increased Levels of
ammonia which may accumulate to toxic levels as this pt has reduced kidney
functions secondary to cirrhosis.