Eosinopenia:
Causes

-Corticoid effect (Cushing's syndrome or therapy).
-Stress.

Malnutrition

 A. Marasmus - calorie malnutrition 
 A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment.
 With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity. 
 B. Kwashiorkor - protein malnutrition - importance of protein quality as well as quantity
Marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.

The weight of children with severe kwashiorkor is typically 60% to 80% of normal. 
However, the true loss of weight is masked by the increased fluid retention (edema).

Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a "flaky paint" appearance.

Hair changes include overall loss of color or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.

An enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite. 

 The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
 
 
 C. Most cases of severe malnutrition are a combination of A and B usually characterized by:
 
• Failure of growth
• Behavioral changes
• Edema (kwashiorkor)
• Dermatosis
• Changes in hair
• Loss of appetite
• Liver enlargement
• Anemia
• Osteoporosis 
 

Infections caused by gonorrhea

1.  Acute urethritis.  Mostly in males.  Generally self-limiting.  Dysuria and purulent discharge.

2.  Endocervical infection.  Purulent vaginal discharge, abnormal menses, pelvic pain.  Often co-infection with other STD’s.  Some women are asymptomatic.

3.  Pelvic Inflammatory Disease (PID).  Consequence of ascending endocervical infection.  Causes salpingitis, endometriosis, bilateral abdominal pain, discharge, fever.  May lead to sterility, chronic pain, and ectopic pregnancy because of loss of fallopian cilia.

4.  Anorectal inflammation.  Mostly in homosexual men.  Pain, itching, discharge from anus.

5.  Dermatitis/arthritis.  Occurs after bacteremia.  Skin will have papules on an erythematous base which develop into necrotic pustules.  Asymmetric joint pain.  These infections are susceptible to penicillin.

6.  Neonatal infections.  Ophthalmia neonatorum is a conjunctival infection from going through infected vagina.  After one year of age, suspect child abuse.

Hepatitis C virus.

 It is most often mild and anicteric but occasionally severe with fulminant hepatic failure. It is caused an RNA virus, which may be transmitted parenterally (a cause of post-transfusion hepatitis); the route of transmission undetermined in 40%-50% of cases
a. 90% of blood transfusion-related hepatitis is caused by hepatitis C.
b. 50% progress to chronic disease.
c. Increased risk for hepatocellular carcinoma.

d. Incubation period: ranges from 2 to 26 weeks, but averages 8 weeks.
-  Antibody is detected by enzyme-linked immunosorbent,assay (ELISA). The incubation period is between 2 and weeks with peak onset of illness 6-8 weeks after infection 
- Most patients progress to chronic liver disease, specifically chronic persistent hepatitis or chronic active hepatitis 
- Cirrhosis is common in patients with chronic active hepatitis and occurs in 20%-25% of infected patients. HCV is also associated with hepatocellular carcinoma.

e. Treatment and prevention: α-interferon is used to treat chronic hepatitis C. There is currently no vaccine available.

Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema 
 >80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes 
 
 Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension 

Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
    o Minimal change disease (MCD)
    o Focal segmental glomerulosclerosis
    o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
    o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
    o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
    o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma  
    
 - Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.  

Investigations

- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.

Management

- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin. 

Nephritic Syndrome 

Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red 

Causes

1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis

Clinical Features

- Abrupt onset of :
    o Glomerular haematuria (RBC casts or dysmorphic RBC)
    o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
    o Oedema (periorbital, sacral )
    o Hypertension
    o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.

Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders 

Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria. 

EXOCRINE PANCREAS

Congenital anomalies
1. Ectopic pancreatic tissue most commonly occurs in the stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. It may be either asymptomatic or cause obstruction, bleeding, intussusception. 

2.Annular pancreas is a ring of pancreatic tissue that encircle the duodenum and may cause duodenal obstruction. 

Cystic fibrosis

Cystic fibrosis is a systemic disorder of exocrine gland secretion presenting during infancy or childhood. 
Incidence is 1:2500 in Caucasians; it is less common in Black and extremely rare in Asians. 

Pathogenesis. Cystic fibrosis shows autosomal recessive transmission; heterozygotes are unaffected. It results in a defective chloride channel, which leads to secretion of very thick mucus. 

Characteristics

- Tissues other than exocrine glands are normal, and glands are structurally normal until damaged by cystic fibrosis.
- The only characteristic biochemical abnormalities are an  elevation of sodium and chloride levels in sweat, and a decrease in water and bicarbonate secretion from pancreatic cells, resulting in a viscous secretion. 

Clinical features

- Fifteen percent of cases present with meconium ileus.
- Most cases present during the first year with steatorrhea (with resultant deficiencies of vitamins A, D, E, and K), abdominal distention, and failure to thrive.

Complications are also related to pulmonary infections'and obstructive pulmonary disease as a result of viscous bronchial secretions. 

Pathology
- There is mucus plugging of the pancreatic ducts with cystic dilatation, fibrous proliferation, and atrophy. Similar pathology develops in salivary glands. 

- Lungs. Mucus impaction leads to bronchiolar dilatation an secondary infection. 
- The gastrointestinal tract shows obstruction caused mucus impaction in the intestines with areas of biliary cirrhosis, resulting from intrahepatic bile duct obstruction

Diagnosis depends on demonstrating a "sweat test" abnomality associated with at least one clinical feature In sweat test, high levels of chloride are demonstrated.

Prognosis. Mean survival is age 20; mortality is most often due to pulmonary infections. 

Degenerative changes

1. Iron pigmentation (e.g., from hemochromatosis) may be deposited within acinar and islet cells and may cause insulin deficiency. 

2. Atrophy 
a. Ischemic atrophy is due to atherosclerosis of pancreatic arteries and is usually asymptomatic. 
b. Obstruction of pancreatic ducts affects only the exocrine pancreas, which becomes small, fibrous, and nodular.

Acute hemorrhagic pancreatitis 

presents as a diffuse necrosis of the pancreas caused by the release of activated pancreatic
enzymes. Associated findings include fat necrosis and hemorrhage into the pancreas. 

Incidence. This disorder is most often associated with alcoholism and biliary tract disease.
It affects middle-aged individuals and often occurs after a large meal or excessive alcohol ingestion; approximately 50% of patients have gallstones. 

Pathogenesis. There are four theories.
- Obstruction of the pancreatic duct causes an elevated intraductal pressure, which results in leakage of enzymes from small ducts. 
- obstruction may be caused by a gallstone at the ampulla of Vater; chronic alcohol ingestion may cause duct obstruction by edema. 
- Hypercalcemia may cause activation of trypsinogen; its mechanism is unclear. Pancreatitis occurs in 20% of patients with hyperparathyroidism. 
- Direct damage to acinar cells may occur by trauma, ischemia, viruses, and drugs. 
- Hyperlipidemia may occur as a result of exogenous estrogen intake and alcohol ingestion. 

Clinical features are typically the sudden onset of acute, continuous, and intense abdominal pain, often radiating to the back and accompanied by nausea, vomiting, and fever. This syndrome frequently results in shock. 

Laboratory values reveal elevated amylase (lipase elevated after 3-4 days) and leukocytosis. Hypocalcemia is a poor prognostic sign. 

Chronic pancreatitis 

It refers to remitting and relapsing episodes of mild pancreatitis, causing progressive pancreatic damage. 

Incidence is similar to acute pancreatitis. It is also seen in patients with ductal anomalies. Almost half the cases occur without known risk factors. 

Pathogenesis is unclear; possibly, there is excess protein secretion by the pancreas, causing ductal obstruction. 

Clinical features include flareups precipitated by alcohol and overeating, and drugs. Attacks are characterized by upper abdominal pain, tenderness, fever, and jaundice. 

Laboratory values reveal elevated amylase and alkaline phosphatase, X-rays reveal calcifications in the pancreas. Chronic pancreatitis may result in pseudocyst formation, diabetes, and steatorrhea. 

Carcinoma of the pancreas 

Incidence: 
Carcinoma of the pancreas accounts for approximately 5% of all cancer deaths. Increased risk is associated with smoking. high-fat diet, and chemical exposure. There is a higher incidence in the elderly, Blacks, males, and diabetics. 

Clinical features
- The disease is usually asymptomatic until late in its course. 
- Manifestations include weight loss, abdominal pain frequently radiating to the back, weakness, malaise, anorexia, depression, and ascites.
- There is jaundice in half of the patients who have carcinoma of the head of the pancreas.
- Courvoisier's law holds that painless jaundice with a palpable gallbladder is suggestive of pancreatic cancer. 

Pathology
Carcinomas arise in ductal epithelium. Most are adenocarcinomas. 
- Carcinoma of the head of the pancreas accounts for 60% of all pancreatic cancers. 
- Carcinoma of the body (20%) and tail (5%) produce large indurated masses that spread widely to the liver and lymph nodes. 
- In 15% of patients, carcinoma involves the pancreas diffusely. 

Complications 
include Trousseau's syndrome, a migratory thrombophlebitis that occurs in 10% of patients. 

Prognosis is very poor. if resectable, the 5-year survival rate less than 5%. The usual course is rapid decline; on average death occurs 6 months after the onset of symptoms.