Thymus and parathyroids fail to develop owing to failure of development of the 3rd and 4th pharngeal pouches.  

Present with tetany due to hypocalcemia.  Recurrent viral and fungal infections due to T-cell deficiency.  Deletion in 22q11

Defect in early stem-cell differentiation.

Presents with recurrent viral, bacterial, fungal, and protozoal infections.  No rejection of allografts.  

Multiple causes ( failure to make MHC II antigents, defective IL-2 receptors which is most common form).  X-linked or Adenosine deaminase deficiency

Defect in CD40 ligand on CD4 T helper cells leads to inability to class switch.  

Presents early in life with severe pyogenic infections.  High levels of IgM, very low levels of IgG, IgA, and IgE.

X-linked defect in the ability to mount an IgM response to capsular polysaccharides of bacteria. 

Associated with elevated IgE and IgA and low IgM levels.  Triad of recurrent pyogenic infections, thrombocytopenic purpura, and ezcema

Wiskott- Aldrich Syndrome

WIPE  W-Wiskott  I-recurrent pyogenic Infections

P-thrombocytopenic Purpura  E-Eczema

Failure of IFN-gamma production by helper T cells.  Neutrophils fail to respond to chemotactic stimuli.

Presents with coarse faces, cold (noninflamed) staphylococcal abscesses, retained primary teeth, elevated IgE, and dermatologic problems (eczema)

Autosomal recessive.  

Defect in microtubular function and lysosomal emptying of phagocytic cells.  Presents with recurrent pyogenic infections by staphylococci and streptococci, partial albinism, and peripheral neuropathy.

Defect in microbicidal activity of neutrophils owing to lack of NADPH oxidase activity or similar enzymes. 

Presents with susceptibility to opportunistic infections with bacteria, especially Staph aureus, E. coli, and Aspergillus.  Confirm diagnosis with negative nitroblue tetrazolium dye reduction test.

Chronic mucocutaneous candidias

dysfunction of T cells

Deficiency in a specific class of immunoglobulins possibly due to a defect in isotype switching.  Selective IgA deficiency is the most common selective immunoglobulin deficiency.

Presents with sinus and lung infections; milk allergies and diarrhea common.  Anaphylaxis upon exposure to blood products containing IgA

Ataxia-Telangiectasia

B cell dysfunction

Normal numbers of circulating B cells.  Decrease plasma cells (defect in B cell maturation) and decrease Ig.

Can be acquired in 20s-30s.  Increased risk of autoimmune disease and lymphoma.

Infection with Tropheryma whippelii (gram positive); PAS-positive macrophages in intestinal lamina propria, mesenteric nodes.

Arthralgias, cardiac and neurologic symptoms are common.  Most often occurs in older men.

Due to cystic fibrosis, obstructing cancer, and chronic pancreatitis.  

Causes malabsorption of fat and fat-soluble vitamins (vitamins A, D, E, K)

Autoimmune-mediated intolerance of gliadin (wheat) leading to steatorrhea.  Associated with people of northern European descent.  

Antigliadin antibodies, blunting of villi, and lymphocytes in the lamina propria.  

Decrease mucosal absorption that primarily affects jejunum.  Serum levels of tissue transglutaminase used for screening.  Associated with dermatitis herpetiformis.

Gastric hypertrophy with protein loss, parietal cell atrophy, and increase mucous cells.  

Precancerous.  Rugae of stomach are so hypertrophied that they look like brain gyri.

Associated with dietary nitrosamines (smoked foods), type A blood.  signet ring cells, acanthosis nigricans are common features.  

Called linitis plastica when diffusely infiltrative (thickened, rigid appearance, leather bottle)

Stomach Cancer

usually adenocarcinoma.  Early aggressive local spread and node/liver mets.

Gastric ulcer- H+ secretion decreased & gastrin levels increased

H.pylori (gram -) infection in 70%; chronic NSAID use also implicated.  Gastric H+ secretion decreased b/c secreted H+ leaks back through damaged gastric mucosa.  Gastrin levels increased b/c decreased H+ secretion stimulates gastrin secretion.

Decreased sex hormones, decreased cortisol and increased mineralcorticoids. 

Sx:  Hypertension, hypokalemia

XY: decreased DHT so pseudohermaphroditism with externally phenotypic female, no internal reproductive structures due to MIF

XX:  externally phenotypic female with normal internal sex organs but lacking secondary sexual characteristics

Decreased cortisol, decreased aldosterone and corticosterone, decreased sex hormones.

Hypertension

Antibodies to TSH receptor which stimulate secretion of T3 and T4.  

High circulating thyroid hormones and low concentration of TSH

-Increase renal Na+ absorption on principal cells of late distal tubule and collecting duct

-Increase renal K+ secretion on principal cells on late distal tubule and collecting duct

-Increase renal H+ secretion (action on alpha intercalated cells of the late distal tubule and collecting duct)

MCC autoimmune destruction of adrenal cortex and causes acute adrenal crisis

Decreased adrenal glucocorticoid, androgen, and mineralocorticoid.  Increased ACTH, hypoglycemia, weight loss, nausea, vomiting, hyperpigmentation. 

Addison's Dz

Primary adrenocortical insufficiency

Decreased pubic and axillary hair in women

ECF volume contraction, hypotension, hyperkalemia, and metabolic acidosis.

Primary hyperaldosteronism (Conn's Syndrome)

aldosterone secreting tumor

Secondary Hyperaldosteronism

due to renal artery stenosis, chronic renal failure, CHF, cirrhosis, or nephrotic syndrome.  

Deficiency of ACTH, no hyperpigmentation

No volume contraction, hyperkalemia, or metabolic acidosis.

Present with hypoglycemia, weakness, nausea, and vomiting

Secondary adrenocortical insufficiency

Caused by pharmacologic doses of glucocorticoids or by primary hyperplasia of adrenal glands.

Decreased ACTH. Increased cortisol and androgen levels. 

Hyperglycemia, increased protein catabolism and muscle wasting, poor wound healing, HTN, osteoporosis, virilization of women

Increase in mineralocorticoid levels, decrease in androgen and glucocorticoid levels, increase ACTH

lack of pubic and axillary hair in women, hypoglycemia, metabolic alkalosis, hypokalemia, and hypertension.